Supplementary Information for Gold-catalyzed Stereoselective Cycloisomerization of Allenoic Acids for Two Types of Common Natural γ-Butyrolactones
Zhou et al.
Supplementary Methods Materials: 1
H and 13C nuclear magnetic resonance spectra were recorded with an instrument
operated at 300 MHz for 1H NMR spectra and 75 MHz for 13C NMR spectra. CDCl3 was used as solvent in all NMR experiments. Chemical shifts (δ) are given in parts per million (ppm). Infrared spectra were recorded from the films of pure samples on sodium chloride plates on a FT-IR spectrometer. Mass and HRMS spectra were carried out in EI or ESI mode. Flash column chromatography was performed on silica gel H. Dioxane and THF were refluxed over sodium wire using diphenyl ketone as indicator and distilled right before use. CuBr2 was purchased from J & K. (S)-α,α-diphenylprolinol and (R)-α,α-diphenylprolinol were purchased from Shanghai Darui Fine Chemicals. Aldehydes were distilled right before use. AgOTs was purchased from Alfa Aesar. CBr4 used was recrystallized from EtOH, washed with ethyl ether, and dired by vacuum. Other commercially available reagents were purchased and used as received.
Synthesis of enantioenriched 4-allenoic acids. Enantioselective allenylation of terminal alkynes 1a with aldehyde 2a in the presence of amine (S)-3a (EATA) afforded the desired product (Ra)-4aa in 36% yield with 95% ee in a sealed tube at 130 oC for 15 h (Supplementary Table 1, entry 1).1 With 1.1 equiv. of benzyl pent-4-ynoate 1a, the yield of (Ra)-4aa was improved to 38% albeit with 94% ee (Supplementary Table 1, entry 2). By replacing benzyl pent-4-ynoate 1a with ethyl pent-4-ynoate 1b, the yield of 4,5-dienoate (Ra)-4ba was improved to 53% but ee dropped to 85% (Supplementary Table 1, entry 3). We then screened the effect of the loading of 1b, showing that 1.2 equiv. are the best (Supplementary Table 1, entries 4 and 5). The yield for the reaction at 120 oC in the sealed tube with 1.2 equiv. 1b is poor (Supplementary Table 1, entry 6); the reaction under reflux at 120 oC afforded (Ra)-4ba in 46% yield with 96% ee (Supplementary Table 1, entries 7-11). Thus, the optimal reaction conditions were established as follows: 20 mol% CuBr2, alkyne 1b/aldehyde 2a/amine (S)-3a = 1.2/1.5/1 in dioxane
1
under reflux (Supplementary Table 1, entry 7).
Supplementary Table 1 Synthesis of 4,5-allenoatea (Ra)-4aa and (Ra)-4ba a
1
T/oC
entry
a
(Ra)-4 yield b (%)
ee c (%)
130 d
36 ((Ra)-4aa)
95
1.1
130 d
38 ((Ra)-4aa)
94
Et (1b)
1.1
130 d
53 ((Ra)-4ba)
85
4
Et (1b)
1.2
130 d
60 ((Ra)-4ba)
93
5
Et (1b)
1.4
130 d
63 ((Ra)-4ba)
91
6
Et (1b)
1.2
120 d
49 ((Ra)-4ba)
93
7
Et (1b)
1.2
120 e
46 ((Ra)-4ba)
96
8
Et (1b)
1.1
120 e
37 ((Ra)-4ba)
95
9
Et (1b)
1.3
120 e
44 ((Ra)-4ba)
94
10
Et (1b)
1.4
120 e
47 ((Ra)-4ba)
96
11
Et (1b)
1.5
120 e
45 ((Ra)-4ba)
93
R
X (equiv.)
1
Bn (1a)
1.5
2
Bn (1a)
3
The reactions were conducted on a 1.0 mmol of (S)-3a in 3 mL of dioxane with 1.5 equiv. 2a
under nitrogen atmosphere.
b
c
Isolated yield. Determined by chiral HPLC analysis of isolated
product. d Reactions were conducted in a sealed tube. e Reactions were conducted under reflux under N2 atmosphere.
Then a series of 4-allenoic acids (Ra)-5 were prepared by treating the corresponding carboxylates (Ra)-4 with 1.5 equiv. of LiOH∙H2O in EtOH/H2O under reflux at 90 oC (Supplementary Table 2).
2
Supplementary Table 2 Synthesis of 4-allenoic acids (Ra)-5 a
2
a
(Ra)-5
t1
Entry
t2 (h)
yield b (%)
ee c (%)
8
40 ((Ra)-5a)
96
18
8
38 ((Ra)-5b)
97
n-C11H23 (2c)
17
19
46 ((Ra)-5c)
97
4e
i-Pr (2d)
15.5
12
24 ((Ra)-5d)
98
5
Cy (2e)
15
18
34 ((Ra)-5e)
97
6
Bn (2f)
17
12
34 ((Ra)-5f)
96
7
BnCH2 (2g)
17.5
18
45 ((Ra)-5g)
96
8
CH2=CH(CH2)8 (2h)
19
18
40 ((Ra)-5h)
96
9f
TBSCC(CH2)6 (2i)
18
5
42 ((Ra)-5i)
97
R
(h)
1
n-C7H15 (2a)
15
2d
n-C4H9 (2b)
3
The reactions were conducted on a 15 mmol scale of (S)-3a with 1.2 equiv. 1b and 1.5 equiv. 2 b
c
under nitrogen atmosphere. Combined yield of 2 steps. Determined by chiral HPLC analysis of d
the corresponding carboxylate of (Ra)-5. The reaction was conducted on a 25 mmol scale of e
f
(S)-3a. The reaction was conducted on a 20 mmol scale of (S)-3a. The reaction was conducted on a 7 mmol scale; Hydrolysis under a mild condition: 1.0 equiv. of LiOH∙H2O in THF/MeOH/H2O = 1:1:1 at room temperature for 5 h.
Optimization of the lactonization reaction for gram scale synthesis For gram scale synthesis of (E)-6, further adjustments for the temperature of the lactonization reaction were conducted to improve the E/Z selectivity: runing the reaction at 0 oC made no difference as compared with tht at 25 oC (Supplementary Table 3, entries 1-2), while the reaction at -20 oC gave a higher selectivity (E/Z = 98:2) (Supplementary Table 3, entry 3); when the reaction was conducted at -40 oC, a result
3
of 99:1 E/Z selectivity in 44% yield with 56% recovery of acid 5b was observed (Supplementary Table 3, entry 4). Thus, we defined the reaction temperature as -20 o
C.
Supplementary Table 3 Further optimization of the reaction conditions for racemic (E)-6b
a
a
6b
Entry
T (oC)
t (h)
1
25
2
NMR yield b (%)
E/Z b
3
100
96/4
0
12
100
97/3
3
-20
12
100
98/2
4c
- 40
17
44
99/1
AgOTs, AuCl(LB-Phos), and CHCl3 (2 mL) were stirred for 15 min under nitrogen atmosphere;
then 0.2 mmol 5b and CHCl3 (1 mL) were added.
b
1
Determined by H NMR of crude product
using 1,3,5-trimethylbenzene as internal standard. c 56% recovery of 5b was detected.
Optimization of the the synthesis of rac-xestospongiene Under the optimized conditions, the Au-catalyzed lactonization reaction of rac-5k was executed to afford racemic xestospongiene (6k) with an E/Z selectivity of 94:6 (Supplementary Table 4, entry 1). The reaction at -30 oC for 31 h led to an E/Z selectivity of 97:3 but with 11% rac-5k being recovered (Supplementary Table 4, entry 2); further lowering the temperature to -40 oC couldn’t make a better selectivity while more starting acid rac-5k was recovered even after 36 h (Supplementary Table 4, entry 3). Then, we tried to increase the loading of the catalysts. When the reaction at -20 oC with 10 mol% catalysts, 6k was formed in 99% NMR yield with a E/Z
4
selectivity of 96:4 after 20 h (Supplementary Table 4, entry 4); Reducing the temperature to -30 oC with 10 mol% catalysts gave 6k a higher 97:3 selectivity with no rac-5k recovered after 24 h (Supplementary Table 4, entry 5). Thus, we defined 10 mol% catalyst at -30 oC for 24 h as the standard reaction conditions.
Supplementary Table 4 Optimization of the reaction conditions for the cyclization of rac-5k a
rac-5k
6k Entry
a
X mol%
o
T ( C)
t (h)
b
NMR yield (%)
E/Z
b
recovery b (%)
1c
5
22
2.5
100
94:6
0
2
5
-30
31
88
97:3
11
3
5
-40
36
90
97:3
10
4d
10
-20
20
99
96:4
0
5
10
-30
24
97
97:3
0
AgOTs, AuCl(LB-Phos), and CHCl3 (2 mL) were stirred for 15 min under nitrogen atmosphere; b
1
then 0.2 mmol rac-5k and CHCl3 (1 mL) were added. Determined by H NMR of the crude c
product using 1,3,5-trimethylbenzene as internal standard. The reaction was conducted on a 1.0 mmol scale of rac-5k in 10 mL of CHCl3 under N2 atomosphere. d The reaction was conducted on a 0.1 mmol scale of rac-5k in 1.5 mL of CHCl3 under N2 atomosphere.
Kinetic resolution of racemic 8: synthesis of optically active propargylic alcohols (R)-8 and (S)-8 A
novozym-435-catalyzed
kinetic
resolution
of
9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol 8 with vinyl acetate was studied and some typical results are presented in Supplementary Table 5. We ran the reaction under the reported conditions initially:2 The treatment of racemic propargylic alcohol
5
8 with 10 w% novozym-435-catalyzed in 3 mL of vinyl acetate at 60 oC for 2.75 h afforded propargylic acetate (S)-11 in 33% NMR yield with 93 % ee and 66% NMR yield of propargylic alcohol (R)-8 (Supplementary Table 5, entry 1); shorten the time to 1.5 h led to a slightly higher ee of 94% for (S)-11 but a lower 21% yield (Supplementary Table 5, entry 2); prolonging the time to the point when acetate (S)-11 and alcohol (R)-8 were approximately equal in yield didn’t give a better ee (Supplementary Table 5, entry 3); further extending the time to 19.5 h made the yield of (S)-11 55% with 81 % ee and 45% of alcohol (R)-8 recovered in 79% ee (Supplementary Table 5, entry 4). Then the loadings of enzyme and vinyl acetate were also screened (Supplementary Table 5, entries 5-7). The ee of (S)-11 was improved to 95% with an increased yield of 37% when temperature went down to 30 oC (Supplementary Table 5, entry 8). 20% w of the catalyst used for the reaction at this temperature for 6 h led to a better result of 41% yield of acetate (S)-11 with 99% ee (Supplementary Table 5, entry 9).
6
Supplementary Table 5 Novozym-435-catalyzed kinetic resolution of racemic 8 a.
(S)-11
Entry T (oC) X (% w)b V (mL) t (h)
a
(R)-8
yieldc (%) eed (%) yieldc (%) eee (%)
1
60
10
3
2.75
33
93
66
-
2
60
10
3
1.5
21
94
77
-
3
60
10
3
11
51
86
49
86
4
60
10
3
19.5
55
81
45
79
5
60
20
3
2.75
41
89
51
-
6
60
20
6
2.75
30
91
64
-
7
60
20
6
1.75
28
93
71
-
8
30
10
3
9
37
95
60
-
9
30
20
3
6
41
99f
59
-
b
c
1
Reactions were conducted on a 0.5 mmol scale of rac-8. % by weight. Determined by H
NMR of the crude product using 1,3,5-trimethylbenzene as internal standard.
d
Determined by
chiral HPLC analysis of isolated acetate (S)-11. e Determined by chiral HPLC analysis of acetate of isolated alcohol (R)-8. f Determined by chiral GC analysis of isolated acetate (S)-11.
On the basis of these observations, we set out to explore how to get higher ees of (S)-11 and alcohol (R)-8 at the same time. For this purpose, we identified n-hexane as the solvent with the addition of different amounts of vinyl acetate for the reaction at 30 oC. Fortunately, when 20 w% of enzyme was used with 5.2 equiv. of vinyl acetate in n-hexane for 11.5 h, ee of (R)-8 reached 97% in 44% yield along with 93% ee of (S)-11 in 46% yield (Supplementary Table 6, entry 1). Reducing the reaction time to 2.5 h failed to give a better ee of (S)-11 (Supplementary Table 6, entry 2) (compare with the best result showed in Supplementary Table 5); we then prolonged the reaction time to 19 h, affording (R)-8 with 98% ee and 47% yield (Supplementary Table 6, entry 3).
7
Supplementary Table 6 Further optimization of Novozym-435-catalyzed kinetic resolution of 8 a
(S)-11
a
Entry
T (h)
1
(R)-8
yield b (%)
ee c (%)
yield b (%)
ee d (%)
11.5
46
93
44
97
2
2.5
35
97
44
-
3
19
50
92
47
98
b
1
Reactions were conducted on a 0.5 mmol scale of rac-8 at 30 oC. Determined by H NMR of
the crude product using 1,3,5-trimethylbenzene as internal standard. c Determined by chiral HPLC analysis of isolated acetate (S)-11.
d
Determined by chiral HPLC analysis of acetate of isolated
alcohol (R)-8.
Synthesis of enantioenriched 4-allenoic acids 1. Synthesis of (Ra)-benzyl 4,5-tridecadienoate (Ra)-4aa (zj-8-078)
To a flame-dried Schlenk tube with a polytetrafluoroethylene plug were added CuBr2 (0.0462 g, 0.2 mmol, 98%), (S)-3a (0.2582 g, 1 mmol，98%), 1a (0.2824 g, 1.5 mmol)/dioxane (2 mL), and octaldehyde 2a (0.1927 g, 1.5 mmol)/dioxane (1 mL) sequentially under nitrogen atmosphere. The Schlenk tube was then sealed with screwing the polytetrafluoroethylene plug tightly. The reaction was complete after being stirred in an oil bath preheated at 130 oC for 15 h as monitored by TLC. The mixture was filtrated through a short column of silica gel [eluent: Et2O (10 mL × 3)] and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL).
8
The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ diethyl ether = 100/1 (600 mL)] on silica gel to afford (Ra)-4aa (0.1089 g, 36%) as a liquid: 95% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 0.8 mL/min, λ = 214 nm, tR (major) = 9.6 min, tR (minor) = 8.5 min); [α]D20 = -54.5 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.45-7.25 (m, 5H, Ar-H), 5.19-5.04 (m, 4H, =CH × 2 + CH2), 2.53-2.41 (m, 2H, CH2), 2.37-2.25 (m, 2H, CH2), 2.00-1.87 (m, 2H, CH2), 1.43-1.18 (m, 10H, CH2 × 5), 0.87 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.8, 135.9, 128.4, 128.1, 128.0, 92.5, 89.3, 60.0, 33.3, 31.7, 29.03, 28.99, 28.7, 23.7, 22.5, 14.0; IR (neat) ν (cm−1) 3093, 3066, 3034, 2955, 2926, 2855, 1962, 1740, 1498, 1456, 1380, 1353, 1256, 1154, 1002; MS (70 ev, EI) m/z (%) 301 (M+ + 1, 2.36), 300 (M+, 2.56), 167 (100), 91 (100); HRMS calcd for C20H28O2 [M+]: 300.2089, found: 300.2090.
2. Synthesis of (Ra)-4,5-tridecadienoic acid (Ra)-5a (zj-8-039, 8-040)
Typical Procedure I: To a dry Schlenk flask were added CuBr2 (0.6768 g, 3 mmol, 99%), (S)-2-(diphenylhydroxymethyl)pyrrolidine (S)-3a (3.8707 g, 15 mmol, 98%), ethyl pent-4-ynoate 1b3 (2.2715 g, 18 mmol)/dioxane (20 mL), and octaldehyde 2a (3.5 mL, d = 0.821 g cm-3, 2.8739 g, 22.45 mmol)/dioxane (10 mL) sequentially under nitrogen atmosphere. After continuous stirring for 15 h under reflux at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature. The mixture was diluted with ether (60 mL) and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by
9
chromatography [eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3) to 50:1 (300 mL)] on silica gel to afford (Ra)-4ba (1.4870 g) as a liquid, which was then used in the next step without further characterization. Typical Procedure II: To a round-bottom flask were added (Ra)-4ba (1.4870 g, 6.25 mmol, prapared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 31 mL of H2O and 31 mL of EtOH), and LiOH∙H2O (0.4147 g, 9.375 mmol, 95%) sequentially. After continuous stirring for 8 h under reflux at 90 oC, the reaction was complete as monitored by TLC. Then the mixture was cooled down to room temperature. After evaporation to remove EtOH, the resulting mixture was acidified with an aqueous solution of hydrochloric acid (aq., 3.0 M) until pH = 1 and extracted with Et2O (20 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel gave (Ra)-5a4 (1.2547 g, 40%, 2 steps) [eluent: petroleum ether (60-90 oC)/ ethyl acetate = 15/1 (480 mL) to 10:1 (600 mL) to 5:1 (300 mL)] as an oil: 96% ee (determined by the corrsponding esterification product (R)-ethyl trideca-4,5-dienoate (Ra)-4ba); [α]D20 = -70.1 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.21 (bs, 1H, COOH), 5.27-5.04 (m, 2H, =CH × 2), 2.48 (t, J = 7.5 Hz, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.03-1.90 (m, 2H, CH2), 1.45-1.18 (m, 10H, CH2 × 5), 0.88 (t, J = 6.8 Hz, 3H, CH3);
13
C NMR (75 MHz, CDCl3) δ 203.7, 179.7, 92.9, 89.2, 33.1, 31.8, 29.1,
28.8, 23.5, 22.6, 14.1; IR (neat) ν (cm−1) 3582-2257 (COOH), 3031, 2957, 2926, 2855, 2662, 1963, 1713, 1436, 1412, 1378, 1335, 1277, 1249, 1211, 1173, 1077; MS (70 ev, EI) m/z (%) 210 (M+, 4.49), 126 (100).
Esterification for determination of the ee value of (Ra)-5a: synthesis of (Ra)-ethyl 4,5-tridecadienoate (Ra)-4ba5 (zj-8-043)
Typical Procedure III: To a Schlenk tube were added (Ra)-5a (0.0846 g, 0.4 mmol, prapared above) and DMF (4 mL). Then K2CO3 (0.1657 g, 1.2 mmol) and EtI
10
(0.04 mL, d = 1.94 g cm-3, 0.0768 g, 0.49 mmol, 99%) were added sequentially. After continuous stirring at room temperature for 8 h, the reaction was complete as monitored by TLC. After quenching with water (10 mL) and being stirred for 10 min, the aqueous solution was extracted with Et2O (15 mL × 3). The combined organic layer was washed with H2O then brine and dried over anhydrous Na2SO4. Filtration, evaporation, and column chromatography on silica gel gave (Ra)-4ba (0.0917 g, 96%) [eluent: petroleum ether (60-90 oC)/ ethyl acetate = 50/1 (450 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 0.5 mL/min, λ = 214 nm, tR (major) = 15.8 min, tR (minor) = 15.4 min); [α]D20 = -61.9 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.30-4.95 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.45-2.34 (m, 2H, CH2), 2.34-2.23 (m, 2H, CH2), 2.02-1.88 (m, 2H, CH2), 1.44-1.18 (m, 13H, CH2 × 5 + CH3), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.0, 92.4, 89.4, 60.1, 33.3, 31.7, 29.03, 28.99, 28.8, 23.8, 22.5, 14.1, 13.9; IR (neat) ν (cm−1) 2958, 2926, 2855, 1962, 1739, 1464, 1446, 1421, 1372, 1349, 1300, 1259, 1195, 1158, 1133, 1096, 1077, 1039; MS (70 ev, EI) m/z (%) 238 (M+, 5.49), 80 (100); HRMS calcd for C15H26O2 [M+]: 238.1933, found: 238.1933.
3. Synthesis of (Ra)-4,5-decadienoic acid (Ra)-5b (zj-6-047, 6-053)
Typical Procedure IV: To a dry Schlenk flask were added CuBr2 (1.1261 g, 5.0 mmol, 99%), (S)-3a (6.4555 g, 25 mmol, 98%), 1b (3.7875 g, 30 mmol)/dioxane (30 mL), and valeraldehyde 2b (4.0 mL, d = 0.81 g cm-3, 3.24 g, 37.67 mmol)/dioxane (15 mL) sequentially under nitrogen atmosphere. After continuous stirring for 18 h under reflux at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature. The mixture was filtrated through a short column of silica gel [eluent: Et2O (25 mL × 3)], and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was
11
separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL × 2)] on silica gel to afford (Ra)-4bb (2.0071 g) as a liquid, which was then used in the next step without further characterization. Following Typical Procedure II, the reaction of (Ra)-4bb (2.0071 g, 10.2 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 50 mL of H2O and 50 mL of EtOH), and LiOH·H2O (0.6768 g, 15.3 mmol, 95%) at 90 oC for 8 h afforded (Ra)-5b (1.6152 g, 38%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: 97% ee (determined by the corrsponding esterification product (Ra)-4bb); [α]D20 = -77.3 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.42 (bs, 1H, COOH), 5.26-5.08 (m, 2H, =CH × 2), 2.48 (t, J = 7.4 Hz, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.06-1.90 (m, 2H, CH2), 1.45-1.24 (m, 4H, CH2 × 2), 0.90 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.9, 92.8, 89.2, 33.1, 31.2, 28.5, 23.5, 22.1, 13.8; IR (neat) ν (cm−1) 3699-2161 (COOH), 3031, 2958, 2928, 2871, 2863, 2668, 1963, 1711, 1436, 1412, 1377, 1333, 1274, 1247, 1211, 1173; MS (70 ev, EI) m/z (%) 169 (M+ + 1, 2.39), 168 (M+, 5.55), 126 (100); HRMS calcd for C10H16O2 [M+]: 168.1150, found: 168.1148.
Esterification for determination of the ee value of (Ra)-5b: synthesis of (Ra)-ethyl 4,5-decadienoate (Ra)-4bb (zj-6-055)
Following Typical Procedure III, the reaction of (Ra)-5b (0.0839 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.0951 g, 0.61 mmol, 98%), and K2CO3 (0.2072 g, 1.5 mmol) for 14 h afforded (Ra)-4bb (0.0924 g, 94%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/1 (300 mL)] as a
12
liquid: 97% ee (HPLC conditions: Chiralcel PC-2 column, n-hexane, 0.7 mL/min, λ = 214 nm, tR (major) = 44.8 min, tR (minor) = 38.4 min); [α]D20 = -68.0 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.18-5.07 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.47-2.36 (m, 2H, CH2), 2.35-2.23 (m, 2H, CH2), 2.06-1.91 (m, 2H, CH2), 1.44-1.28 (m, 4H, CH2 × 2), 1.26 (t, J = 7.2 Hz, 3H, CH3) 0.90 (t, J = 7.1 Hz, 3H, CH3);
13
C NMR (75 MHz, CDCl3) δ 203.7, 173.0, 92.3, 89.4, 60.1, 33.4, 31.2,
28.5, 23.8, 22.1, 14.1, 13.7; IR (neat) ν (cm−1) 2959, 2929, 2875, 2859, 1963, 1738, 1466, 1444, 1418, 1372, 1350, 1300, 1250, 1159, 1097, 1052, 1033; MS (70 ev, EI) m/z (%) 197 (M+ + 1, 10.80), 196 (M+, 24.87), 81 (100); HRMS calcd for C12H20O2 [M+]: 196.1463, found: 196.1461.
4. Synthesis of (Ra)-4,5-heptadecadienoic acid (Ra)-5c (zj-4-028, 4-033)
Following Typical Procedure IV, the reaction of CuBr2 (0.6767 g, 3.0 mmol, 99%), (S)-3a (3.8698 g, 15 mmol, 98%), 1b (2.2795 g, 18 mmol)/dioxane (15 mL)， and n-dodecanal 2c (4.98 mL, d = 0.831 g cm-3, 4.1384 g, 22.49 mmol)/dioxane (10 mL) for 17 h afforded product (Ra)-4bc (1.9936 g) [(eluent: petroleum ether (60-90 oC) (500 mL) to petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2)] as a liquid, which was then submitted to next step. Following Typical Procedure II, the reaction of product (Ra)-4bc (1.9936 g, 6.78 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 33.5 mL of H2O and 33.5 mL of EtOH), and LiOH·H2O (0.4460 g, 10.17 mmol, 95%) for 19 h afforded (Ra)-5c (1.8322 g, 46%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (500 mL) to 10/1 (500 mL × 3)] as an oil: 97% ee (determined by the corrsponding esterification product (Ra)-4bc); [α]D20 = -56.5 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.39 (bs, 1H, COOH), 5.24-5.07 (m, 2H, =CH × 2), 2.48 (t, J = 7.2 Hz, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.04-1.90 (m, 2H, CH2), 1.45-1.18
13
(m, 18H, CH2 × 9), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.9, 92.8, 89.2, 33.1, 31.9, 29.6, 29.5, 29.4, 29.2, 29.1, 28.8, 23.5, 22.7, 14.1; IR (neat) ν (cm−1) 3657-2311 (COOH), 2955, 2924, 2854, 1963, 1712, 1438, 1278, 1210, 1196, 1132, 1077; MS (70 ev, EI) m/z (%) 267 (M+ + 1, 2.88), 266 (M+, 5.98), 126 (100); HRMS calcd for C17H30O2 [M+]: 266.2246, found: 266.2251.
Esterification for determination of the ee value of (Ra)-5c: synthesis of (Ra)-ethyl 4,5-heptadecadienoate (Ra)-4bc (zj-4-111)
Following Typical Procedure III, the reaction of (Ra)-5c (0.1326 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.0960 g, 0.616 mmol, 99%), and K2CO3 (0.2079 g, 1.5 mmol) for 24 h afforded (Ra)-4bc (0.1355 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 0.7 mL/min, λ = 214 nm, tR (major) = 14.2 min, tR (minor) = 13.9 min); [α]D20 = -51.0 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.19-5.07 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.47-2.37 (m, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.02-1.89 (m, 2H, CH2), 1.45-1.15 (m, 21H, CH3 + CH2 × 9), 0.88 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.1, 92.5, 89.5, 60.2, 33.4, 31.9, 29.6, 29.5, 29.3, 29.1, 28.9, 23.9, 22.6, 14.2, 14.1; IR (neat) ν (cm−1) 2956, 2925, 2854, 1963, 1739, 1466, 1372, 1350, 1300, 1250, 1159, 1097, 1038; MS (70 ev, EI) m/z (%) 294 (M+, 6.39), 80 (100); HRMS calcd for C19H34O2 [M+]: 294.2559, found: 294.2556.
5. Synthesis of (Ra)-7-methyl-4,5-octadienoic acid (Ra)-5d (zj-8-048, 8-051)
Following Typical Procedure I, the reaction of CuBr2 (0.9014 g, 4 mmol, 99%),
14
(S)-3a (5.1672 g, 20 mmol, 98%), 1b (3.7830 g, 30 mmol)/dioxane (35 mL), and isobutaldehyde 2d (2.73 mL, d = 0.79 g cm-3, 2.1567 g, 29.95 mmol)/dioxane (15 mL) for 15.5 h afforded product (Ra)-4bd (0.9565 g, 26% ) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3)] as a liquid: 98% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 12.9 min, tR (minor) = 12.2 min); [α]D20 = -66.0 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.26-5.12 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, CH2), 2.46-2.36 (m, 2H, CH2), 2.35-2.18 (m, 3H, CH + CH2), 1.26 (t, J = 7.2 Hz, 3H, CH3), 0.99 (d, J = 6.9 Hz, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 202.0, 172.9, 99.8, 90.7, 60.1, 33.3, 27.8, 23.8, 22.3, 22.2, 14.1; IR (neat) ν (cm−1) 2961, 2925, 2869, 1961, 1738, 1466, 1447, 1420, 1372, 1350, 1299, 1251, 1227, 1199, 1159, 1097, 1055, 1029; MS (70 ev, EI) m/z (%) 182 (M+, 27.17), 93 (100); HRMS calcd for C11H18O2 [M+]: 182.1307, found: 182.1310. Following Typical Procedure II, the reaction of (Ra)-4bd (0.8194 g, 4.5 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 22.5 mL of H2O and 22.5 mL of EtOH), and LiOH·H2O (0.2990 g, 6.75 mmol, 95%) for 12 h afforded (Ra)-5d (0.6317 g, 91%) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (480 mL) to 10/1 (550 mL) to 5/1 (600 mL)] as an oil: 98% ee (determined by the corrsponding esterification product (Ra)-4bd); [α]D20 = -71.8 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.90 (bs, 1H, COOH), 5.28-5.16 (m, 2H, =CH × 2), 2.48 (t, J = 7.2 Hz, 2H, CH2), 2.38-2.18 (m, 3H, CH + CH2), 0.99 (d, J = 6.9 Hz, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 202.1, 179.9, 100.3, 90.5, 33.1, 27.9, 23.5, 22.4, 22.3; IR (neat) ν (cm−1) 3749-2203 (COOH), 3036, 2961, 2923, 2869, 2661, 1961, 1713, 1412, 1382, 1364, 1297, 1251, 1212, 1169, 1107, 1080, 1049, 1018; MS (70 ev, EI) m/z (%) 154 (M+, 14.69), 67 (100); HRMS calcd for C9H14O2 [M+]: 154.0994, found: 154.0991.
Esterification for determination of the ee value of (Ra)-5d: synthesis of (Ra)-ethyl 7-methyl-4,5-octadienoate (Ra)-4bd (zj-8-063)
15
Following Typical Procedure III, the reaction of (Ra)-5d (0.0773 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.096 g, 0.616 mmol, 99%), and K2CO3 (0.2075 g, 1.5 mmol) for 11 h afforded (Ra)-4bd (0.0867 g, 95%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (800 mL)] as a liquid: 98% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 11.4 min, tR (minor) = 10.8 min); [α]D20 = -66.4 (c = 1.02, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.28-5.11 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.45-2.37 (m, 2H, CH2), 2.36-2.18 (m, 3H, CH + CH2), 1.26 (t, J = 7.1 Hz, 3H, CH3), 0.99 (d, J = 6.9 Hz, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 202.1, 173.1, 99.9, 90.7, 60.2, 33.3, 27.8, 23.9, 22.4, 22.3, 14.1.
6. Synthesis of (Ra)-6-cyclohexyl-4,5-hexadienoic acid (Ra)-5e (zj-3-175, 3-196)
Following Typical Procedure IV, the reaction of CuBr2 (0.6757 g, 3 mmol, 99%), (S)-3a (3.8745 g, 15 mmol， 98%), 1b (2.2739 g, 18 mmol)/dioxane (17 mL), and cyclohexanaldehyde 2e (2.72 mL, d = 0.926 g cm-3, 2.5187 g, 22.49 mmol)/dioxane (8 mL) for 15 h afforded product (Ra)-4be (1.1104 g ) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3)] as a liquid, which was then submitted to next step. Typical Procedure V: To a round-bottom flask were added (Ra)-4be (1.1104 g, 5.0 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 25 mL of H2O and 25 mL of EtOH), and LiOH·H2O (0.3321 g, 7.5 mmol, 95%) sequentially. After continuous stirring for 18 h under reflux at 90 oC, the reaction was complete as monitored by TLC. Then the mixture was cooled down to room temperature. After
16
evaporation to remove EtOH, the resulting mixture was extracted with 5 mL of Et2O. The organic layer was separated and the aqueous layer was acidified with an aqueous solution of hydrochloric acid (aq., 3.0 M) until pH = 1. The aqueous layer was then extracted with Et2O (20 mL × 3). The combined organic layer was washed with brine and
dried
over
anhydrous
Na2SO4.
Filtration,
evaporation,
and
column
chromatography on silica gel [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 8/1 (450 mL) to 5/1 (500 mL × 3)] gave impure (Ra)-5e (0.9991) as an oil; then the impure (Ra)-5e was purified again on silica gel [(eluent: petroleum ether (30-60 o
C)/ethyl acetate = 8/1 (270 mL) to 5/1 (500 mL × 2)] to afford pure (Ra)-5e (0.9826 g,
34%, 2 steps) as an oil: 97% ee (determined by the corrsponding esterification product (Ra)-4be); [α]D20 = -91.6 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.18 (bs, 1H, COOH), 5.26-5.11 (m, 2H, =CH × 2), 2.55-2.42 (m, 2H, CH2), 2.36-2.22 (m, 2H, CH2), 2.01-1.86 (m, 1H, CH), 1.81-1.55 (m, 5H, one proton of CH2 + CH2 × 2), 1.35-0.95 (m, 5H, one proton of CH2 + CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 202.4, 180.0, 98.9, 90.1, 37.1, 33.1, 32.9, 26.1, 26.0, 23.5; IR (neat) ν (cm−1) 3624-2266 (COOH), 3032, 2924, 2851, 2659, 1962, 1712, 1448, 1412, 1335, 1288, 1250, 1211, 1175, 1132, 1077; MS (70 ev, EI) m/z (%) 194 (M+, 2.79), 41 (100); HRMS calcd for C12H18O2 [M+]: 194.1307, found: 194.1305.
Esterification for determination of the ee value of (Ra)-5e: synthesis of (Ra)-ethyl 6-cyclohexyl-4,5-hexadienoate (Ra)-4be6 (zj-4-006)
To a reaction tube were added (Ra)-5e (0.0978 g, 0.5 mmol, prapared above), EtOH (0.09 mL, d = 0.789 g cm-3, 0.071g, 1.54 mmol), and DCM (5 mL). Then DCC (0.1160 g, 0.55 mmol, 98%) and DMAP (0.0062 g, 0.05 mmol, 98%) were added sequentially. After continuous stirring at room temperature for 6 h, the reaction was complete as monitored by TLC. After quenching with water (10 mL) with stirring for 10 min, the aqueous solution was extracted with Et2O (10 mL × 3). The combined
17
organic layer was washed with brine and dried over anhydrous Na2SO4. Filtration, evaporation, and column chromatography on silica gel gave (Ra)-4be (0.0933 g, impure) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (800 mL)] as a liquid. The impure (Ra)-4be was diluted with 10 mL of Et2O and then washed with an aqueous solution of hydrochloric acid (aq., 3.0 M) (10 mL × 3) and brine. After drying over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel gave pure (Ra)-4be (0.0817 g, 73%) [(eluent: petroleum ether (60-90 o
C)/ethyl acetate = 100/1 (800 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel
AY column, n-hexane, 0.6 mL/min, λ = 214 nm, tR (major) = 17.32 min), [α]D20 = -81.9 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.26-5.08 (m, 2H, =CH × 2), 4.13 (q, J = 7.1 Hz, 2H, OCH2), 2.48-2.36 (m, 2H, CH2), 2.35-2.22 (m, 2H, CH2), 2.01-1.84 (m, 1H, CH), 1.81-1.56 (m, 5H, one proton of CH2 + CH2 × 2), 1.36-0.95 (m, 8H, CH3 + one proton of CH2 + CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 202.4, 173.1, 98.5, 90.4, 60.2, 37.1, 33.3, 33.0, 32.9, 26.1, 26.0, 23.8, 14.1; IR (neat) ν (cm−1) 2977, 2925, 2851, 1960, 1738, 1448, 1418, 1372, 1348, 1302, 1290, 1250, 1227, 1195, 1158, 1096, 1037; MS (70 ev, EI) m/z (%) 222 (M+, 6.25), 29 (100); HRMS calcd for C14H22O2 [M+]: 222.1620, found: 222.1618;
7. Synthesis of (Ra)-7-phenyl-4,5-heptadienoic acid (Ra)-5f (zj-4-163, 4-169)
Following Typical Procedure IV, the reaction of CuBr2 (0.6763 g, 3.0 mmol, 99%), (S)-3a (3.8769 g, 15 mmol, 98%), 1b (2.2719 g, 18 mmol)/dioxane (15 mL), and phenylacetaldehyde 2f (2.69 mL, d = 1.025 g cm-3, 2.7021 g, 22.52 mmol, 98%)/dioxane (10 mL) for 17 h afforded (Ra)-4bf (1.3907 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL × 2)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bf (1.3907 g, 6.0 mmol,
18
prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 30 mL of H2O and 30 mL of EtOH), and LiOH·H2O (0.4017 g, 9.0 mmol, 95%) for 12 h afforded (Ra)-5f (1.0324 g, 34%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (420 mL) to 10/1 (500 mL × 2)] as an oil: 96% ee (determined by the corrsponding esterification product (Ra)-4bf); [α]D20 = -79.7 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.53 (bs, 1H, COOH), 7.33-7.24 (m, 2H, ArH), 7.24-7.11 (m, 3H, ArH), 5.39-5.26 (m, 1H, =CH), 5.25-5.12 (m, 1H, =CH), 3.31 (dd, J1 = 6.9 Hz, J2 = 2.7 Hz, 2H, CH2), 2.46-2.37 (m, 2H, CH2), 2.34-2.21 (m, 2H, CH2);
13
C NMR (75
MHz, CDCl3) δ 204.2, 179.7, 140.1, 128.4, 128.3, 126.1, 92.2, 89.9, 35.5, 33.0, 23.4; IR (neat) ν (cm−1) 3600-2197 (COOH), 3084, 3060, 3028, 2980, 2915, 2665, 1964, 1712, 1603, 1494, 1453, 1428, 1334, 1279, 1251, 1212, 1173, 1075, 1029; MS (70 ev, EI) m/z (%) 202 (M+, 4.51), 143 (100), 142 (100), 129 (100), 128 (100), 91 (100); HRMS calcd for C13H14O2 [M+]: 202.0994, found: 202.0997.
Esterification for determination of the ee value of (Ra)-5f: synthesis of (Ra)-ethyl 7-phenyl-4,5-heptadienoate (Ra)-4bf (zj-4-174)
Following Typical Procedure III, the reaction of (Ra)-5f (0.1017 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.096 g, 0.616 mmol, 99%), and K2CO3 (0.2075 g, 1.5 mmol) for 11 h afforded (Ra)-4bf (0.1066 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel AS-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 20.3 min, tR (minor) = 23.3 min); [α]D20 = -75.3 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.33-7.24 (m, 2H, ArH), 7.24-7.13 (m, 3H, ArH), 5.35-5.24 (m, 1H, =CH), 5.24-5.13 (m, 1H, =CH), 4.10 (q, J = 7.2 Hz, 2H, OCH2), 3.31 (dd, J1 = 7.1 Hz, J2 = 2.9 Hz, 2H, CH2), 2.42-2.22 (m, 4H, CH2 × 2), 1.23 (t, J = 7.2 Hz, 3H, CH3);
13
C NMR (75 MHz, CDCl3) δ 204.2, 172.9, 140.1, 128.3, 128.2, 126.0, 91.7,
90.2, 60.1, 35.5, 33.2, 23.7, 14.1; IR (neat) ν (cm−1) 3084, 3060, 3027, 2980, 2908,
19
2871, 2848, 1963, 1735, 1603, 1494, 1453, 1420, 1372, 1350, 1301, 1251, 1159, 1096, 1054, 1030; MS (70 ev, EI) m/z (%) 230 (M+, 10.54), 91 (100); HRMS calcd for C15H18O2 [M+]: 230.1307, found: 230.1311.
8. Synthesis of (Ra)-8-phenyl-4,5-octadienoic acid (Ra)-5g (zj-4-136, 4-139)
Following Typical Procedure IV, the reaction of CuBr2 (0.6764 g, 3.0 mmol, 99%), (S)-3a (3.8655 g, 15 mmol, 98%), 1b (2.2671 g, 18 mmol)/dioxane (15 mL), and phenylpropyl aldehyde 2g (3.0 mL, d = 1.015 g cm-3, 3.045 g, 22.7 mmol)/dioxane (10 mL) for 17.5 h afforded (Ra)-4bg (1.8685 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3) to 50/1 (500 mL × 2)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bg (1.8685 g, 7.66 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 30 mL of H2O and 30 mL of EtOH), and LiOH·H2O (0.5082 g, 11.5 mmol, 95%) for 18 h afforded (Ra)-5g (1.4516 g, 45%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (220 mL) to 10/1 (500 mL) to 5/1 (500 mL × 2)] as an oil: 96% ee (determined by the corrsponding esterification product (Ra)-4bg); [α]D20 = -71.8 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.15 (bs, 1H, COOH), 7.32-7.23 (m, 2H, ArH), 7.23-7.13 (m, 3H, ArH), 5.27-5.10 (m, 2H, =CH × 2), 2.76-2.65 (m, 2H, CH2), 2.42-2.15 (m, 6H, CH2 × 3); 13C NMR (75 MHz, CDCl3) δ 203.8, 179.7, 141.7, 128.5, 128.2, 125.8, 92.1, 89.8, 35.2, 32.9, 30.4, 23.3; IR (neat) ν (cm−1) 3696-2194 (COOH), 3087, 3062, 3027, 2974, 2920, 2856, 2660, 1963, 1713, 1603, 1496, 1454, 1435, 1411, 1336, 1278, 1250, 1211, 1175, 1133, 1078, 1030; MS (70 ev, EI) m/z (%) 216 (M+, 4.92), 129 (100), 91 (100); HRMS calcd for C14H16O2 [M+]: 216.1150, found: 216.1154.
20
Esterification for determination of the ee value of (Ra)-5g: synthesis of (Ra)-ethyl 8-phenyl-4,5-octadienoate (Ra)-4bg (zj-4-141)
Following Typical Procedure III, the reaction of (Ra)-5g (0.1081 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.096 g, 0.616 mmol, 99%), and K2CO3 (0.2079 g, 1.5 mmol) for 11 h afforded (Ra)-4bg (0.1177 g, 96%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (800 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel AS-H column, n-hexane, 0.7 mL/min, λ = 214 nm, tR (major) = 18.5 min, tR (minor) = 22.8 min); [α]D20 = -71.3 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.31-7.22 (m, 2H, ArH), 7.22-7.09 (m, 3H, ArH), 5.26-5.09 (m, 2H, =CH × 2), 4.12 (q, J = 7.3 Hz, 2H, OCH2), 2.70 (t, J = 7.7 Hz, 2H, CH2), 2.39-2.18 (m, 6H, CH2 × 3), 1.25 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.8, 173.0, 141.6, 128.4, 128.2, 125.8, 91.7, 90.1, 60.2, 35.2, 33.3, 30.4, 23.7, 14.2; IR (neat) ν (cm−1) 3085, 3062, 3027, 2979, 2924, 2855, 1963, 1737, 1603, 1496, 1454, 1372, 1349, 1300, 1250, 1196, 1158, 1133, 1096, 1077, 1030; MS (70 ev, EI) m/z (%) 244 (M+, 3.56), 129 (100), 91 (100); HRMS calcd for C16H20O2 [M+]: 244.1463, found: 244.1470.
9. Synthesis of (Ra)-4,5,15-hexadecatrienoic acid (Ra)-5h (zj-5-035, 5-056)
Following Typical Procedure IV, the reaction of CuBr2 (0.6760 g, 3.0 mmol, 99%), (S)-3a (3.8667 g, 15 mmol, 98%), 1b (2.2702 g, 18 mmol)/dioxane (15 mL), and 10-undecylenealdehyde 2h (4.6 mL, d = 0.84 g cm-3, 3.7867 g, 22.54 mmol, 98%)/dioxane (10 mL) for 19 h afforded (Ra)-4bh (2.6107 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 3) to 50/1 (500 mL)] as a liquid, which
21
was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bh (2.6107 g, 9.4 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 30 mL of H2O and 30 mL of EtOH), and LiOH·H2O (0.6235 g, 14.1 mmol, 95%) for 18 h afforded (Ra)-5h4 (1.5036 g, 40%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (600 mL) to 5/1 (540 mL)] as an oil: 96% ee (determined by the corrsponding esterification product (Ra)-4bh); [α]D20 = -60.3 (c = 1.015, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.56 (bs, 1H, COOH), 5.89-5.70 (m, 1H, =CH), 5.25-5.09 (m, 2H, 2 × =CH), 5.05-4.86 (m, 2H, =CH2), 2.56-2.42 (m, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.11-1.90 (m, 4H, 2 × CH2), 1.44-1.20 (m, 12H, 6 × CH2); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.8, 139.2, 114.1, 92.8, 89.2, 33.8, 33.1, 29.43, 29.37, 29.09, 29.07, 28.89, 28.81, 23.48; IR (neat) ν (cm−1) 3672-2224 (COOH), 3075, 2977, 2925, 2854, 2664, 1964, 1711, 1640, 1436, 1411, 1337, 1280, 1249, 1211, 1172; MS (70 ev, EI) m/z (%) 251 (M+ + 1, 2.66), 250 (M+, 3.26), 126 (100), 81 (100).
Esterification for determination of the ee value of (Ra)-5h: synthesis of (Ra)-ethyl -4,5,15-hexadecatrienoate (Ra)-4bh (zj-5-065)
Following Typical Procedure III, the reaction of (Ra)-5h (0.1020 g, 0.4 mmol)/DMF (4 mL), EtI (0.04 mL, d = 1.94 g cm-3, 0.076 g, 0.49 mmol, 98%), and K2CO3 (0.1673 g, 1.2 mmol) for 17 h afforded (Ra)-4bh (0.1100 g, 97%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (700 mL)] as a liquid: 96% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane, 0.5 mL/min, λ = 214 nm, tR (major) = 22.0 min, tR (minor) = 21.0 min); [α]D20 = -53.9 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.86-5.72 (m, 1H, =CH), 5.18-5.06 (m, 2H, 2 × =CH), 5.04-4.87 (m, 2H, =CH2), 4.12 (q, J = 7.1 Hz, 2H, OCH2), 2.45-2.36 (m, 2H, CH2), 2.34-2.22 (m, 2H, CH2), 2.09-1.90 (m, 4H, 2 × CH2), 1.44-1.19 (m, 15H, 6 × CH2 +
22
CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.9, 139.0, 114.0, 92.3, 89.4, 60.1, 33.7, 33.3, 29.32, 29.28, 29.0, 28.8, 28.7, 23.8, 14.1; IR (neat) ν (cm−1) 3076, 2978, 2926, 2854, 1962, 1738, 1640, 1462, 1444, 1371, 1348, 1299, 1249, 1159, 1096, 1037; MS (70 ev, EI) m/z (%) 278 (M+, 20.44), 279 (M+ + 1, 6.16), 154 (100); HRMS calcd for C18H30O2 [M+]: 278.2246, found: 278.2249.
10. Synthesis of (Ra)-14-(tert-butyldimethylsilyl)-4,5-tetradecadien-13-ynoic acid (Ra)-5i (zj-6-184, 6-186)
Following Typical Procedure IV, the reaction of CuBr2 (0.3155 g, 1.4 mmol, 99%), (S)-3a (1.8071 g, 7 mmol, 98%), 1b (1.0575 g, 8.4 mmol)/dioxane (25 mL), and aldehyde 2i7 (2.6397 g, 10.5 mmol; TBS: tert-butyldimethylsilyl)/dioxane (10 mL) for 18 h afforded (Ra)-4bi (1.2865 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL) to 30/1 (600 mL)] as a liquid, which was then submitted to next step. To a round-bottom flask were added (Ra)-4bi (1.2865 g, 3.55 mmol, prepared above), THF/MeOH/H2O = 1:1:1 by volume (pre-mixed by using 6.5 mL of THF, 6.5 mL of MeOH and 6.5 mL of H2O), and LiOH·H2O (0.1571 g, 3.55 mmol, 95%) sequentially. After continuous stirring for 5 h at room temperature, the reaction was complete as monitored by TLC.8 Then MeOH and THF were removed via evaporation, the resulting mixture was acidified with an aqueous solution of hydrochloric acid (aq., 1.0 M) until pH = 1. The aqueous layer was then extracted with Et2O (25 mL × 3). After being washed with brine and dried over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel gave (Ra)-5i (0.9826 g, 42%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (480 mL) to 10/1 (550 mL) to 8/1 (540 mL)] as an oil: 97% ee (determined by the corrsponding esterification
23
product (Ra)-4bi); [α]D20 = -48.7 (c = 1.025, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.92 (bs, 1H, COOH), 5.24-5.03 (m, 2H, =CH × 2), 2.45 (t, J = 7.4 Hz, 2H, CH2), 2.36-2.24 (m, 2H, CH2), 2.20 (t, J = 7.1 Hz, 2H, CH2), 2.01-1.89 (m, 2H, CH2), 1.57-1.24 (m, 8H, CH2 × 4), 0.91 (s, 9H, CH3 × 3), 0.06 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 203.7, 179.8, 108.1, 92.7, 89.3, 82.3, 33.1, 28.9, 28.7, 28.6, 28.5, 26.0, 23.4, 19.7, 16.4, -4.50; IR (neat) ν (cm−1) 3685-2304 (COOH), 2929, 2856, 2660, 2172, 1964, 1711, 1463, 1432, 1413, 1360, 1332, 1251, 1211, 1167, 1009; MS (70 ev, EI) m/z (%) 335 (M+ + 1, 11.48), 334 (M+, 6.86), 75 (100); HRMS calcd for C20H34O2Si [M+]: 334.2328, found: 334.2332.
Esterification for determination of the ee value of (Ra)-5i: synthesis of (Ra)-ethyl 14-(tert-butyldimethylsilyl)-4,5-tetradecadien-13-ynoate (Ra)-4bi (zj-6-191)
Following Typical Procedure III, the reaction of (R)-5i (0.1002 g, 0.3 mmol)/DMF (3 mL), EtI (0.03 mL, d = 1.94 g cm-3, 0.057 g, 0.366 mmol, 98%), and K2CO3 (0.1242 g, 0.9 mmol) for 11 h afforded (R)-4bi (0.1035 g, 96%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (300 mL) to 50/1 (400 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 30.5 min, tR (minor) = 29.1 min); [α]D20 = -45.3 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.19-5.00 (m, 2H, =CH × 2), 4.10 (q, J = 7.2 Hz, 2H, OCH2), 2.44-2.32 (m, 2H, CH2), 2.32-2.22 (m, 2H, CH2), 2.19 (t, J = 6.9 Hz, 2H, CH2), 2.01-1.86 (m, 2H, CH2), 1.54-1.26 (m, 8H, CH2 × 4), 1.22 (t, J = 7.1 Hz, 3H, CH3), 0.89 (s, 9H, CH3 × 3), 0.04 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.0, 108.0, 92.3, 89.5, 60.2, 33.4, 28.9, 28.7, 28.6, 28.5, 26.0, 23.8, 19.7, 16.4, 14.2, -4.5; IR (neat) ν (cm−1) 2931, 2857, 2172, 1963, 1738, 1464, 1370, 1299, 1251, 1159, 1097, 1034; MS (70 ev, EI) m/z (%) 363 (M+ + 1, 27.35), 362 (M+, 16.06), 231 (100); HRMS calcd for C22H38O2Si [M+]: 362.2641, found: 362.2646.
24
11. Esterification for determination of the ee value of (Sa)-5m: synthesis of (Sa)-ethyl 4,5-dodecadienoate (Sa)-4bm (zj-9-055)
Following Typical Procedure III, the reaction of (Sa)-5m4 (0.0982 g, 0.5 mmol)/DMF (5 mL), EtI (0.05 mL, d = 1.94 g cm-3, 0.097 g, 0.62 mmol, 99%), and K2CO3 (0.2073 g, 1.5 mmol) for 12 h afforded (Sa)-4bm (0.1091 g, 97%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (450 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OD-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 15.2 min, tR (minor) = 17.1 min); [α]D20 = +63.9 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.23-5.07 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.46-2.37 (m, 2H, CH2), 2.36-2.23 (m, 2H, CH2), 2.06-1.91 (m, 2H, CH2), 1.44-1.19 (m, 11H, CH2 × 4 + CH3), 0.89 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 173.0, 92.4, 89.4, 60.1, 33.3, 31.6, 29.0, 28.8, 28.7, 23.8, 22.5, 14.1, 14.0; IR (neat) ν (cm−1) 2957, 2927, 2856, 1963, 1738, 1465, 1446, 1372, 1350, 1300, 1251, 1196, 1180, 1159, 1097, 1076, 1039; MS (70 ev, EI) m/z (%) 224 (M+, 5.38), 80 (100); HRMS calcd for C14H24O2 [M+]: 224.1776, found: 224.1782.
Synthesis of AuCl(LB-Phos)9 (zj-7-180)
To a three-neck flask were added NaAuCl4∙2H2O (0.5230 g, 1.3 mmol, 99%) and H2O (20 mL). The solution was cooled to 0 °C by an ice bath, and S(CH2CH2OH)2 (0.4759 g, 3.9 mmol,) in H2O (5 mL) was added within 20 min. After the addition was
25
complete, the reaction mixture was stirred for 40 min at 0 oC. Then a solution of LB-Phos (0.4737 g, 1.3 mmol) in DCM (5 mL) was added dropwise at 0 °C within 20 min. Then the reaction was warmed up to room temperature. After stirring for 30 min, the reaction was complete as monitored by TLC. The reaction mixture was extracted with DCM (20 mL × 4). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 5/1 (600 mL) to 3/1 (600 mL) to 2/1 (600 mL)] on silica gel to afford AuCl(LB-Phos) (0.3971 g, 51%) as a white solid, which is stable in air and H2O: m. p. 217.5-218.7 oC (diethyl ether/dichloromethane); 1H NMR (300 MHz, CDCl3) δ 6.14 (d, 2H, J = 3.0 Hz, ArH), 3.87 (s, 3H, CH3), 3.84 (s, 6H, CH3 × 2), 2.53-2.37 (m, 2H, CH2), 2.12-1.99 (m, 2H, CH2), 1.88-1.45 (m, 10H, CH2 × 5), 1.41-1.09 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 164.5, 163.9, 92.7 (d, J = 55.2 Hz), 91.3 (d, J = 4.9 Hz), 55.44, 55.36, 35.8 (d, J = 35.9 Hz), 32.2 (d, J = 5.5 Hz), 29.3, 26.7 (d, J = 13.1 Hz), 26.4 (d, J = 15.8 Hz), 25.6; 31P NMR (121 MHz, CDCl3) δ 31.3; IR (neat) ν (cm−1) 3042, 3002, 2927, 2850, 1597, 1459, 1408, 1334, 1291, 1267, 1228, 1207, 1181, 1161, 1123, 1092, 1029, 1003; MS (70 ev, EI) m/z (%) 598 (M+ + 1, 18.14), 597 (M+, 12.34), 478 (100); Elemental analysis calcd (%) for C21H33AuClO3P: C, 42.26; H, 5.57; Found: C, 42.18; H, 5.74. Crystal data for AuCl(LB-Phos): C21H33AuClO3P, MW = 596.86, orthorhombic, space group P 21 21 21, final R indices [I > 2\s (I)], R1 = 0.0321, wR2 = 0.0701, R indices (all data) R1 = 0.0365, wR2 = 0.0667, a = 11.6086 (6) Å, b = 13.0711 (8) Å, c = 15.0247 (10) Å, α = 90o, β = 90o, γ = 90o, V = 2279.8 (2) Å3, T = 170 K, Z = 4, reflections collected/unique: 14515/4141 (Rint = 0.0544), number of observations [> 2\s (I)] 3869, parameters: 247. CCDC 1558142.
Highly stereoselective synthesis of (S,E)-6 1. Synthesis of (S,E)-5-(1-nonenyl)dihydro-2(3H)-furanone (S,E)-6a (zj-8-046)
26
Typical Procedure VI: To a dry Schlenk tube were added AgOTs (0.0142 g, 0.05 mmol, weighed in glove box, 98%), AuCl(LB-Phos) (0.0299 g, 0.05 mmol), and CHCl3 (5 mL) under nitrogen atmosphere sequentially. After stirring for 15 min, (R)-trideca-4,5-allenoic acid (Ra)-5a and CHCl3 (5 mL) were added. After being continuously stirred at 25 oC for 3 h, the reaction was complete as monitored by TLC. Filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation afforded a crude mixture of (S,E)-6a and (R,Z)-6a ((S,E)/(R,Z) = 97/3, as determined by 1H NMR analysis). Column chromatography on silica gel afforded (S,E)-6a (0.2017 g, 96%, (S,E)/(R,Z) = 98/2 as determined by 1H NMR analysis) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (400 mL) to 10/1 (550 mL)] as an oil with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 1.0 mL/min, λ = 214 nm, tR (major) = 22.73 min, tR (minor) = 20.86 min); [α]D20 = +29.6 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dt, J1 = 15.3 Hz, J2 = 7.2 Hz, 1H, =CH), 5.49 (dd, J1 = 15.3 Hz, J2 = 7.2 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.61-2.50 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.13-1.90 (m, 3H, CH2 + one proton from CH2), 1.45-1.18 (m, 10H, CH2 × 5), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6a: δ 5.72-5.62 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH);
13
C NMR (75 MHz,
CDCl3) δ 177.0, 135.6, 127.2, 81.1, 32.0, 31.6, 29.0, 28.9, 28.7, 28.64, 28.61, 22.5, 14.0; IR (neat) ν (cm−1) 2955, 2926, 2855, 1778, 1673, 1459, 1415, 1378, 1327, 1296, 1216, 1177, 1123, 1010; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o
C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6a: tR (major) =
5.83 min: 210 (M+, 2.31), 111 (100); for (R,Z)-6a: tR (minor) = 5.76 min: 210 (M+, 0.75), 111 (100). HRMS calcd for C13H22O2 [M+]: 210.1620, found: 210.1624.
2. Synthesis of (S,E)-5-(1-hexenyl)dihydro-2(3H)-furanone (S,E)-6b (zj-6-074)
27
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5b (0.1680 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6b10 (0.1563 g, 93%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL)] ((S,E)/(R,Z) = 96/4 determined by 1H NMR of crude product) as a liquid with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 1.0 mL/min, λ = 214 nm, tR (major) = 29.0 min, tR (minor) = 26.3 min); [α]D20 = +36.3 (c = 1.02, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 0.9 Hz, 1H, =CH), 5.50 (ddt, J1 = 15.5 Hz, J2 = 7.1 Hz, J3 = 1.4 Hz, 1H, =CH), 4.90 (q, J = 7.1 Hz, 1H, CH), 2.60-2.49 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.45-1.24 (m, 4H, CH2 × 2), 0.90 (t, J = 7.1 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6b: δ 5.72-5.62 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH); 13C NMR (75 MHz, CDCl3) δ 176.9, 142.0, 124.4, 81.0, 30.4, 28.6, 28.5, 21. 6; IR (neat) ν (cm−1) 2957, 2929, 2872, 2859, 1778, 1673, 1460, 1423, 1379, 1328, 1295, 1217, 1178, 1123, 1054, 1006; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o
C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6b: tR (major) =
4.47 min: 168 (M+, 1.61), 111 (100); for (R,Z)-6b tR (minor) = 4.42 min: 168 (M+, 1.83), 111 (100).
3. Synthesis of (S,E)-5-(1-tridecenyl)dihydro-2(3H)-furanone (S,E)-6c (zj-4-114)
Following Typical Procedure VI, the reaction of AgOTs (0.0143 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5c (0.2663 g,
28
1.0 mmol)/CHCl3 (5 mL) for 2.5 h afforded (S,E)-6c (0.2604 g, 98%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) [eluent: petroleum ether (30-60 oC)/ethyl acetate = 20/1 (300 mL) to 10/1 (500 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 96% ee (HPLC conditions: Chiralcel AS-H column, n-hexane/i-PrOH = 95:5, 1.0 mL/min, λ = 214 nm, tR (major) = 7.3 min, tR (minor) = 6.7 min; [α]D20 = +23.0 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dt, J1 = 15.3 Hz, J2 = 7.1 Hz, 1H, =CH), 5.49 (dd, J1 = 15.5 Hz, J2 = 7.1 Hz, 1H, =CH), 4.89 (q, J = 7.2 Hz, 1H, CH), 2.59-2.49 (m, 2H, CH2), 2.44-2.31 (m, 1H, one proton from CH2), 2.13-1.89 (m, 3H, one proton from CH2 + CH2), 1.46-1.20 (m, 18H, CH2 × 8), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6c: δ 5.72-5.62 (m, 1H, =CH), 5.30-5.20 (m, 1H, CH);
13
C NMR (75 MHz,
CDCl3) δ 177.0, 135.6, 127.2, 81.1, 32.0, 31.8, 29.53, 29.51, 29.45, 29.3, 29.2, 29.0, 28.73, 28.66, 28.6, 22.6, 14.0; IR (neat) ν (cm−1) 2925, 2854, 1779, 1672, 1461, 1422, 1378, 1327, 1300, 1216, 1176, 1123, 1010; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 o
C/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6c:
tR (major) = 4.9 min: 266 (M+, 1.24), 111 (100); for (R,Z)-6c tR (minor) = 4.8 min): 266 (M+, 2.32), 111 (100). HRMS calcd for C17H30O2 [M+]: 266.2246, found: 266.2250.
4.
Synthesis
of
(S,E)-5-(3-methyl-1-butenyl)dihydro-2(3H)-furanone
(S,E)-6d
(zj-8-058)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5d (0.1541 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6d (0.1449 g, 94%, (S,E)/(R,Z) = 99/1 determined by quantitative
13
C NMR analysis) [eluent: petroleum ether (60-90
29
o
C)/ethyl acetate = 15/1 (450 mL) to 10/1 (550 mL)] as a liquid with pleasant flavor:
98% ee (HPLC conditions: Chiralcel AS-H column, n-hexane/i-PrOH = 98/2, 1.0 mL/min, λ = 214 nm, tR (major) = 23.6 min, tR (minor) = 21.3 min); [α]D20 = +37.8 (c = 1.03, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.79 (ddd, J1 = 15.5 Hz, J2 = 6.5 Hz, J3 = 0.9 Hz, 1H, =CH), 5.50 (ddd, J1 = 15.6 Hz, J2 = 7.2 Hz, J3 = 1.4 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.62-2.50 (m, 2H, CH2), 2.47-2.25 (m, 2H, CH + one proton from CH2), 2.07-1.91 (m, 1H, one proton from CH2), 1.01 (d, J = 6.9 Hz, 6H, CH3 × 2);
13
C NMR (75 MHz, CDCl3) δ 176.9, 142.0, 124.4, 81.0, 30.4, 28.6, 28.5,
21.6; IR (neat) ν (cm−1) 2960, 2927, 2870, 1777, 1463, 1421, 1381, 1327, 1296, 1217, 1176, 1132, 1077, 1012; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o
C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6d: tR (major) =
4.06 min: 154 (M+, 6.86), 111 (100); for (R,Z)-6d tR (minor) = 3.95 min: 154 (M+, 14.95), 111 (100); HRMS calcd for C9H14O2 [M+]: 154.0994, found: 154.0996.
5.
Synthesis
of
(S,E)-5-(2-cyclohexylvinyl)dihydro-2(3H)-furanone
(S,E)-6e
(zj-4-008)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5e (0.1938 g, 1.0 mmol)/CHCl3 (5 mL) for 3 h afforded (S,E)-6e (0.1867 g, 96%, (S,E)/(R,Z) = 99/1 determined by quantitative
13
C NMR analysis) [eluent: petroleum ether (30-60
o
C)/ethyl acetate = 8/1 (500 mL)] as an oil with pleasant flavor: 96% ee (HPLC
conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 95:5, 1.0 mL/min, λ = 214 nm, tR (major) = 17.1 min, tR (minor) = 13.2 min; [α]D20 = +29.9 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.75 (ddd, J1 = 15.3 Hz, J2 = 6.6 Hz, J3 = 0.75 Hz, 1H,
30
=CH), 5.44 (ddd, J1 = 15.6 Hz, J2 = 7.2 Hz, J3 = 1.2 Hz, 1H, =CH), 4.89 (q, J = 7.1 Hz, 1H, CH), 2.60-2.46 (m, 2H, CH2), 2.46-2.31 (m, 1H, CH), 2.06-1.90 (m, 2H, CH2), 1.79-1.58 (m, 5H, one proton from CH2 + CH2 × 2), 1.36-0.98 (m, 5H, one proton from CH2 + CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 176.6, 140.3, 124.7, 80.8, 39.6, 31.89, 31.85, 28.3, 28.2, 25.5, 25.3; IR (neat) ν (cm−1) 2924, 2851, 1776, 1669, 1449, 1421, 1327, 1291, 1216, 1177, 1126, 1010; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6e: tR (major) = 5.22 min: 194 (M+, 5.91), 94 (100); for (R,Z)-6e tR (minor) = 5.08 min): 194 (M+, 11.78), 94 (100). HRMS calcd for C12H18O2 [M+]: 194.1307, found: 194.1307.
6.
Synthesis
of
(S,E)-5-(3-phenyl-1-propenyl)dihydro-2(3H)-furanone
(S,E)-6f
(zj-4-175)
To a dry Schlenk tube were added AgOTs (0.0142 g, 0.05 mmol, weighed in a glove box, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), and CHCl3 (5 mL) under nitrogen atmosphere sequentially. After being stirred at room temperature for 15 min, the resulting mixture was cooled down to -40 oC and then (Ra)-5f (0.2021 g, 1.0 mmol) and CHCl3 (5 mL) were added. After being continuously stirred at -40 oC for 6 h, the reaction was complete as monitored by TLC. The resulting mixture was warmed up to room temperature. Filtration through a short column of silica gel [eluent: Et2O (20 mL × 3) at -30oC] and evaporation afforded a crude mixture of (S,E)-6f and (R,Z)-6f ((S,E)/(R,Z) = 97/3, as determined by 1H NMR analysis). Column chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (330 mL) to 5/1 (450 mL) at -30 oC] on silica gel afforded (S,E)-6f (0.1912 g, 95%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) as an oil with pleasant flavor: 97% ee (HPLC conditions: Chiralcel IB
31
column, n-hexane/i-PrOH = 98:2, 1.0 mL/min, λ = 214 nm, tR(major) = 38.9 min, tR(minor) = 37.6 min; [α]D20 = +34.1 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.31-7.21 (m, 2H, ArH), 7.21-7.09 (m, 3H, ArH), 5.90 (dtd, J1 = 15.3 Hz, J2 = 6.8 Hz, J3 = 1.0 Hz, 1H, =CH), 5.50 (ddt, J1 = 15.5 Hz, J2 = 7.1 Hz, J3 = 1.4 Hz, 1H, =CH), 4.82 (q, J = 7.2 Hz, 1H, CH), 3.34 (d, J = 6.9 Hz, 2H, CH2), 2.49-2.36 (m, 2H, CH2), 2.34-2.18 (m, 1H, one proton from CH2), 1.95-1.79 (m, 1H, one proton from CH2); the following signals are discernible for (R,Z)-6f: δ 5.82-5.72 (m, 1H, =CH), 5.34-5.24 (m, 1H, CH);
13
C NMR (75 MHz, CDCl3) δ 176.6, 138.8, 133.2, 128.5,
128.14, 128.07, 125.9, 80.2, 37.9, 28.2, 28.1; IR (neat) ν (cm−1) 3084, 3061, 3027, 3001, 2941, 2917, 2840, 1770, 1671, 1602, 1495, 1453, 1422, 1380, 1328, 1290, 1217, 1176, 1121, 1075, 1029, 1008; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o
C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6f: tR = 4.1 min:
202 (M+, 19.17), 111 (100); HRMS calcd for C13H14O2 [M+]: 202.0994, found: 202.0995.
7.
Synthesis
of
(S,E)-5-(4-phenyl-1-butenyl)dihydro-2(3H)-furanone
(S,E)-6g
(zj-4-146)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0298 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5g (0.2156 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6g (0.2101 g, 97%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (440 mL) to 8/1 (540 mL)] ((S,E)/(R,Z) = 95/5 determined by 1H NMR of crude product) as an oil with pleasant flavor: 97% ee (HPLC conditions: Chiralcel OD-H column, n-hexane/i-PrOH = 90:10, 0.7 mL/min, λ = 214 nm, tR (major) = 27.7 min, tR (minor) = 29.9 min; [α]D20 = +25.4 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.31-7.22 (m, 2H, ArH), 7.21-7.10 (m, 3H, ArH), 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.8 Hz,
32
J3 = 1.1 Hz, 1H, =CH), 5.47 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.4 Hz, 1H, =CH), 4.83 (q, J = 7.2 Hz, 1H, CH), 2.74-2.65 (m, 2H, CH2), 2.51-2.42 (m, 2H, CH2), 2.42-2.22 (m, 3H, one proton from CH2 + CH2), 1.95-1.80 (m, 1H, one proton from CH2); the following signals are discernible for (R,Z)-6g: δ 5.72-5.62 (m, 1H, =CH), 5.11-5.01 (m, 1H, CH);
13
C NMR (75 MHz, CDCl3) δ 176.8, 141.0, 133.9, 128.2,
128.1, 128.0, 125.7, 80.6, 34.9, 33.6, 28.4, 28.3; IR (neat) ν (cm−1) 3081, 3056, 3026, 2998, 2926, 2855, 1774, 1671, 1602, 1496, 1454, 1421, 1379, 1327, 1216, 1176, 1121, 1009; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6g: tR = 4.3 min: 216 (M+, 2.67), 91 (100) ; Elemental analysis calcd (%) for C14H16O2: C, 77.75; H, 7.46; Found: C, 77.60; H, 7.47.
8. Synthesis of (S,E)-5-(dodeca-1,11-dien-1-yl)dihydro-2(3H)-furanone (S,E)-6h (zj-5-083)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 mg, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 mg, 0.05 mmol), CHCl3 (5 mL), and (Ra)-6h (0.2504 g, 1.0 mmol)/CHCl3 (5 mL) for 2.0 h afforded (S,E)-6h (0.2356 g, 94%, (S,E)/(R,Z) > 99/1 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (440 mL) to 8/1 (450 mL)] as an oil: 96% ee (SFC (supercritical fluid chromatogram): Chiralcel AD-H column, n-hexane/i-PrOH = 98/2, 0.7 mL/min, λ = 214 nm, tR (major) = 12.9 min, tR (minor) = 12.1 min); [α]D20 = +26.0 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.90-5.69 (m, 2H, =CH), 5.49 (dd, J1 = 15.3 Hz, J2 = 7.2 Hz, 1H, =CH), 5.05-4.81 (m, 3H, =CH2 + CH), 2.57-2.45 (m, 2H, CH2), 2.43-2.30 (m, 1H, one proton from CH2), 2.11-1.88 (m, 5H, one proton from CH2 + CH2 × 2), 1.45-1.17 (m, 12H, CH2 × 6); 13C NMR (75 MHz, CDCl3) δ 177.0, 139.1, 135.6, 127.3, 114.1, 81.1,
33
33.7, 32.0, 29.3, 29.0, 28.81, 28.76, 28.68, 28.65; IR (neat) ν (cm−1) 3075, 2976, 2925, 2854, 1778, 1673, 1640, 1459, 1436, 1422, 1374, 1327, 1300, 1216, 1176, 1123, 1008; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC, (70 ev, EI) m/z (%) for (S,E)-6h: tR = 4.60 min: 250 (M+, 0.42), 41 (100); Elemental analysis calcd (%) for C16H26O2: C, 76.75; H, 10.47; Found: C, 76.73; H, 10.77.
9. Synthesis of (S,E)-5-(10-(tert-butyldimethylsilyl)-1-decen-9-yn-1-yl)dihydro-2 (3H)-furanone (S,E)-6i (zj-6-188)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL) and (Ra)-5i (0.3330 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6i (0.3206 g, 96%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (480 mL) to 10/1 (850 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil: 97% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 100/1, 0.3 mL/min, λ = 214 nm, tR (major) = 29.5 min, tR (minor) = 28.5 min); [α]D20 = +17.6 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.78 (dtd, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 0.8 Hz, 1H, =CH), 5.47 (ddt, J1 = 15.3 Hz, J2 = 6.9 Hz, J3 = 1.4 Hz, 1H, =CH), 4.87 (q, J = 7.1 Hz, 1H, CH), 2.57-2.47 (m, 2H, CH2), 2.44-2.28 (m, 1H, one proton from CH2), 2.20 (t, J = 6.9 Hz, 2H, CH2), 2.10-1.87 (m, 3H, CH2 + one proton from CH2), 1.55-1.22 (m, 8H, CH2 × 4), 0.90 (s, 9H, CH3 × 3), 0.05
(s, 6H, CH3 ×
2); the following signals are discernible for (R,Z)-6i: δ 5.69-5.60 (m, 1H, =CH), 5.27-5.18 (m, 1H, CH);
13
C NMR (75 MHz, CDCl3) δ 176.9, 135.4, 127.4, 107.9,
82.3, 81.0, 31.9, 28.7, 28.6, 28.5, 28.39, 28.36, 28.3, 26.0, 19.6, 16.4, -4.6; IR (neat) ν (cm−1) 2929, 2856, 2172, 1776, 1673, 1461, 1361, 1326, 1249, 1174, 1008; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature
34
programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6i: tR (major) = 5.41 min, m/z (%) 277 (M+ - t-Bu, 10.23), 75 (100); for (R,Z)-6i: tR (minor) = 5.36 min, m/z (%) 277 (M+ - t-Bu, 8.13), 75 (100); Elemental analysis calcd (%) for C20H34O2Si: C, 71.80; H, 10.24; Found: C, 71.57; H, 10.18.
10. Synthesis of (R,E)-5-(1-decenyl)dihydro-2(3H)-furanone (R,E)-6j (zj-5-014)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol), AuCl(LB-Phos) (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Sa)-5j (0.2239 g, 1.0 mmol)/CHCl3 (5 mL) (for synthesis of compound (Sa)-5j, see page 68) for 3.0 h afforded (R,E)-6j11 (0.2094 g, 94%, (R,E)/(S,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (220 mL) to 8/1 (450 mL)] ((R,E)/(S,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 95% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 12.9 min, tR (minor) = 16.2 min); [α]D20 = -27.4 (c = 1.00, CHCl3); (Lit.10 [α]D26 = -31.2 (c = 2.237, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.9 Hz, J3 = 0.8 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.2 Hz, J2 = 7.1 Hz, J3 = 1.5 Hz, 1H, =CH), 4.89 (q, J = 7.1 Hz, 1H, CH), 2.58-2.49 (m, 2H, CH2), 2.45-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.18 (m, 12H, CH2 × 6), 0.88 (t, J = 6.9 Hz, 3H, CH3); the following signals are discernible for (S,Z)-6j: δ 5.72-5.61 (m, 1H, =CH), 5.30-5.20 (m, 1H, CH);
13
C NMR (75 MHz, CDCl3) δ 176.9, 135.4, 127.3, 80.9, 31.9, 31.7, 29.2,
29.0, 28.9, 28.7, 28.6, 28.5, 22.5, 13.9; IR (neat) ν (cm−1) 2955, 2926, 2854, 1778, 1673, 1460, 1422, 1378, 1327, 1296, 1216, 1176, 1123, 1011; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (R,E)-6j: tR (major) = 4.03 min: 224 (M+, 0.72), 111 (100); for (S,Z)-6j tR
35
(minor) = 3.99 min: 224 (M+, 1.18), 111 (100).
11. Gram scale synthesis of (S,E)-6b (zj-6-160)
To a dry Schlenk tube were added AgOTs (0.0426 g, 0.15 mmol, weighed in glove box, 98%), Au(LB-Phos)Cl (0.0896 g, 0.15 mmol), and CHCl3 (30 mL) under nitrogen atmosphere sequentially. After stirring at room temperature for 15 min, the reaction was cooled down to -20 oC and then (Ra)-5b (1.6817 g, 10.0 mmol) and CHCl3 (10 mL) (for synthesis of compound (Ra)-5b, see page 74) were added. After being continuously stirred at –20 oC for 15 h, the reaction was complete as monitored by TLC. The resulting mixture was warmed up to room temperature. Filtration through a short column of silica gel [eluent: Et2O (25 mL ×3)] and evaporation afforded a crude mixture of (S,E)-6b and (R,Z)-6b ((S,E)/(R,Z) = 98/2 determined by 1
H NMR analysis). Column chromatography on silica gel [(eluent: petroleum ether
(60-90 oC)/ethyl acetate = 15/1 (500 mL) to 10/1 (550 mL)] afforded (S,E)-6b (1.6615 g, 99%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) as a liquid with pleasant flavor: 97% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 200/1, 1.0 mL/min, λ = 214 nm, tR (major) = 26.4 min, tR (minor) = 23.7 min); [α]D20 = +37.1 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.8 Hz, J3 = 1.0 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.5 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.60-2.49 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.24 (m, 4H, CH2 × 2), 0.90 (t, J = 7.2 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6b: δ 5.70-5.62 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH); 13C NMR (75 MHz, CDCl3) δ 176.9, 135.4, 127.3, 81.0, 31.6, 30.7, 28.7, 28.5, 21.9, 13.7.
12. Synthesis of (R,E)-5-(1-octenyl)dihydro-2(3H)-furanone (R,E)-6m (zj-9-053)
36
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0300 g, 0.05 mmol), CHCl3 (5 mL), and (Sa)-5m (0.1964 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (R,E)-6m (0.1891 g, 96%, (R,E)/(S,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 7/1 (480 mL)] ((R,E)/(S,Z) = 97/3 determined by 1H NMR of crude product) as a liquid with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 97/3, 1.0 mL/min, λ = 214 nm, tR (major) = 12.5 min, tR (minor) = 14.5 min); [α]D20 = -32.6 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.81 (dt, J1 = 15.3 Hz, J2 = 7.1 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.2 Hz, 1H, =CH), 4.90 (q, J = 7.2 Hz, 1H, CH), 2.61-2.48 (m, 2H, CH2), 2.46-2.32 (m, 1H, one proton from CH2), 2.15-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.16 (m, 8H, CH2 × 4), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (S,Z)-6m: δ 5.71-5.61 (m, 1H, =CH), 5.32-5.22 (m, 1H, CH);
13
C
NMR (75 MHz, CDCl3) δ 176.8, 135.3, 127.2, 80.9, 31.8, 31.3, 28.5, 28.44, 28.41, 22.2, 13.7; IR (neat) ν (cm−1) 2956, 2927, 2856, 1777, 1673, 1459, 1420, 1379, 1327, 1216, 1179, 1132, 1076, 1009; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 o
C, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (R,E)-6m: tR (major) =
6.65 min: 196 (M+, 0.88), 111 (100); for (S,Z)-6m: tR (minor) = 6.57 min: 196 (M+, 1.68), 111 (100). HRMS calcd for C12H20O2 [M+]: 196.1463, found: 196.1466.
Synthesis of naturally occurring xestospongienes 1. Synthesis of racemic xestospongiene Synthesis of 9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol12 rac-8 (zj-7-083)
37
To a flame-dried three-neck flask equipped with a reflux condenser containing Mg turnings (2.6545 g, 110.5 mmol) was added THF (110 mL) under nitrogen atmosphere. After the reaction was initiated with a grain of I2 and a little amount of EtBr, EtBr [8.3 mL (including the EtBr used above for initiation), d = 1.46 g cm-3, 12.118 g, 111.17 mmol] was then added dropwise within 30 min. After the addition was complete, the resulting mixture was stirred for 2.5 h at room temperature, and then a stream of ethyne was bubbled through the resulting solution at -35 oC. The ethyne gas was introduced for 30 min at a rate that the temperature was kept under 10 o
C using a dry ice-acetone bath. Then the gas of ethyne was introduced for an extra 30
min before removing the dry ice-acetone bath. The resulting mixture was warmed up to
room
temperature
for
30
min
and
a
solution
of
7-((tert-butyldimethylsilyl)oxy)heptanal 7 (readily available from 1,7-heptanediol in 2 steps)13 (15.8817 g, 65 mmol) in THF (25 mL) was added dropwise within 30 min. When the reaction was complete after 12 h as monitored by TLC, a saturated aqueous solution of NH4Cl (30 mL) was added dropwise at rt. The organic layer was separated and the aqueous layer was extracted with Et2O (50 mL × 3). The combined organic layer was washed with H2O and brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (350 mL) to 50/1 (500 mL) to 15/1 (500 mL × 2)] on silica gel afforded 9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol rac-8 (14.8471 g, 85%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 4.32 (t, J = 6.6 Hz, 1H, CH), 3.57 (t, J = 6.6 Hz, 2H, CH2), 2.68 (s, 1H, OH), 2.42 (d, J = 2.1 Hz, 1H, ≡CH), 1.73-1.62 (m, 2H, CH2), 1.54-1.38 (m, 4H, CH2 × 2), 1.35-1.26 (m, 4H, CH2 × 2), 0.86 (s, 9H, CH3 × 3), 0.01 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 85.1, 72.7, 63.2, 62.0, 37.5, 32.6, 29.0, 25.9, 25.6, 24.9, 18.3, -5.3; IR (neat) ν (cm−1) 3355, 3311, 2930, 2857, 2114, 1472, 1463, 1388, 1361, 1255, 1099, 1006; MS (ESI) m/z 271 [M + H]+; HRMS (ESI) calcd. for C15H31O2Si+ [M + H]+: 271.2088, found: 271.2080.
Synthesis of 7-methoxynon-8-yn-1-ol 14 rac-9 (zj-7-106)
38
To a dry Schlenk flask were added 8 (2.9494 g, 11 mmol) and THF (33 mL) under nitrogen atmosphere. The solution was cooled to 0 °C with an ice bath, and NaH (0.4404 g, 60% dispersion in mineral oil, 11 mmol,) was added carefully. After the addition was complete, the cooling bath was removed and the resulting mixture was stirred for 30 min. Then MeI (0.83 mL, d = 2.28 g cm-3, 1.8735 g, 13.2 mmol, 99%) was added dropwise at 0 °C within 2 min. The reaction was warmed up to room temperature again by removing the ice-bath. After stirring for 5 h, the reaction was complete as monitored by TLC and then 3 M HCl (5.5 mL) was added slowly at 0 °C. The reaction was monitored by TLC again after 1.5 h to make sure that the TBS-group was removed completely. The mixture was quenched with water (11 mL) and then extracted with EtOAc (20 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 5/1 (600 mL) to 3/1 (480 mL)] on silica gel to afford 7-methoxynon-8-yn-1-ol rac-9 (1.6238 g, 88%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 3.94 (td, J1 = 6.5 Hz, J2 = 2.0 Hz, 1H, CH), 3.63 (t, J = 6.6 Hz, 2H, CH2), 3.41 (s, 3H, CH3), 2.60-2.38 (bs, 1H, OH), 2.46 (d, J = 1.8 Hz, 1H, ≡CH), 1.81-1.66 (m, 2H, CH2), 1.66-1.29 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 82.6, 73.7, 71.0, 62.7, 56.3, 35.3, 32.5, 29.0, 25.5, 25.0; IR (neat) ν (cm−1) 3384, 3299, 2934, 2859, 2822, 2112, 1465, 1336, 1107, 1092, 1058; MS (ESI) m/z 171 [M + H]+; HRMS (ESI) calcd. for C10H19O2+ [M + H]+: 171.1380, found:171.1383.
Synthesis of 7-methoxynon-8-ynal15 rac-10 (zj-7-110)
To a three-necked flask were added Fe(NO3)3∙9H2O (0.2962 g, 0.72 mmol, 98%),
39
NaCl (0.0420 g, 0.72 mmol), TEMPO (0.1146 g, 0.72 mmol, 98%), and DCM (75 mL) subsequently. An oxygen balloon was equipped and then a solution of rac-9 (1.5279 g, 9 mmol) in 15 mL of DCM was added dropwise via an addition funnel at 25 oC within 10 min in oxygen atmosphere from the balloon. The resulting mixture was stirred for 12.5 h until the reaction was complete as monitored by TLC. After filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 30/1 (500 mL) to 20/1 (500 mL) to 10/1 (500 mL)] on silica gel to afford 7-methoxynon-8-ynal rac-10 (0.9301 g, 62%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 9.76 (t, J = 1.8 Hz, 1H, CHO), 3.93 (td, J1 = 6.5 Hz, J2 = 1.7 Hz, 1H, CH), 3.41 (s, 3H, CH3), 2.40-2.41 (m, 3H, ≡CH + CH2), 1.77-1.59 (m, 4H, CH2 × 2), 1.55-1.43 (m, 2H, CH2), 1.43-1.31 (m, 2H, CH2);
13
C NMR (75 MHz, CDCl3) δ 201.7, 81.7, 73.3,
70.0, 55.5, 42.9, 34.3, 27.9, 23.9, 21.0; IR (neat) ν (cm−1) 3284, 2986, 2940, 2862, 2823, 2722, 2109, 1724, 1465, 1410, 1391, 1336, 1192, 1156, 1108, 1091; MS (ESI) m/z 169 [M + H]+; HRMS (ESI) calcd. for C10H17O2+ [M + H]+: 169.1223, found: 169.1220.
Synthesis of 1,1-dibromo-8-methoxydec-1-en-9-yne rac-1c16 (zj-7-112)
Typical Procedure VII: To a dry Schlenk flask were added aldehyde rac-10 (0.8727 g, 5.2 mmol) and DCM (55 mL, dry) under nitrogen atmosphere. The resulting solution was cooled to 0 °C with an ice bath followed by the addition of CBr4 (2.5884 g, 7.8 mmol). Then a solution of PPh3 (4.1697 g, 15.6 mmol, 98%) in DCM (20 mL) was added dropwise at 0 °C within 0.5 h. The resulting mixture was warmed up to room temperature naturally. After 1 h the reaction was complete as monitored by TLC. Then the resulting mixture was diluted with petroleum ether (75 mL) forming white precipitate. The precipitate was filtrated off and washed with petroleum ether (15 mL × 3). After combining the filtrate and evaporation, the residue
40
was purified by chromatography [eluent: petroleum ether/ethyl acetate = 100/1 (400 mL) to 50/l (500 mL) to 30/l (200 mL)] on silica gel to afford rac-1c (1.5451 g, 92%) as a liquid: 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.2 Hz, 1H, =CH), 3.93 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.41 (s, 3H, CH3), 2.45 (d, J = 2.1 Hz, 1H, ≡CH), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.77-1.66 (m, 2H, CH2), 1.53-1.27 (m, 6H, CH2 × 3),
13
C
NMR (75 MHz, CDCl3) δ 138.6, 88.6, 82.6, 73.8, 70.9, 56.4, 35.3, 32.8, 28.6, 27.6, 24.7; IR (neat) ν (cm−1) 3301, 2985, 2932, 2858, 2822, 2110, 1622, 1463, 1335, 1273, 1261, 1196, 1152, 1109; MS (EI) m/z (%) 325 {[M (81Br81Br) - H]+, 0.035}, 323 {[M (79Br81Br) - H]+, 0.069}, 321 {[M (79Br79Br) - H]+, 0.036}, 201 {[M (81Br81Br) C8H13O]+, 5.37}, 199 {[M (79Br81Br) - C8H13O]+, 12.31}, 197 {[M (79Br79Br) C8H13O]+, 5.62}, 69 (100); HRMS (EI) calcd for C11H1579Br79BrO [M - H]+: 320.9490, found: 320.9499.
Synthesis of methyl 14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate rac-4ck (zj-7-114)
To a flame-dried Schlenk tube with a polytetrafluoroethylene plug were added CuBr2 (0.1803 g, 0.8 mmol, 99%), rac-3a (1.5497 g, 6.0 mmol, 98%), rac-1c (1.2943 g, 4.0 mmol)/dioxane (6 mL), and methyl 4-oxobutanoate 2k17 (0.6965 g, 6 mmol)/dioxane (6 mL) sequentially under nitrogen atmosphere. The Schlenk tube was then sealed by screwing the polytetrafluoroethylene plug tightly. The reaction was complete after being stirred in an oil bath preheated at 130 oC for 17 h as monitored by TLC. The resulting mixture was cooled down to room temperature, diluted with Et2O (50 mL), and washed with an aqueous solution of hydrochloric acid (10 mL × 3, 3 M). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by
41
chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 15/1 (600 mL)] on silica gel to afford rac-4ck (1.0789 g, 64%, d.r. = 1.07 : 1 determined by 1H NMR) as a liquid: 1H NMR (300 MHz, CDCl3) δ 6.39 (td, J1 = 7.2 Hz, J2 = 2.4 Hz, 1H, =CH), 5.35-5.19 (m, 1H, =CH), 5.06-4.94 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), [3.32 (s, 1.43H), 3.30 (s, 1.53H), 3H, CH3], 2.51-2.28 (m, 4H, CH2 × 2), 2.16-2.02 (m, 2H, CH2), 1.70-1.18 (m, 8H, CH2 × 4); IR (neat) ν (cm−1) 2927, 2856, 2819, 1962, 1741, 1462, 1436, 1364, 1254, 1197, 1160, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na] +, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C16H2479Br79BrNaO3+ [M (79Br79Br) + Na] +: 444.9984, found: 444.9966.
Synthesis
of
14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic
acid
rac-5k
(zj-7-121)
Following Typical Procedure II, the reaction of rac-4ck (0.9959 g, 2.35 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 12 mL of H2O and 12 mL of EtOH) and LiOH∙H2O (0.1560 g, 3.525 mmol, 95%) for 1.5 h afforded rac-5k (0.9027 g, 94%, d.r. = 1.07:1 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (440 mL) to 7/1 (560 mL) to 5/1 (600 mL) to 3/1 (120 mL)] as an oil: 1
H NMR (300 MHz, CDCl3) δ 11.23 (bs, 1H, COOH), 6.38 (td, J1 = 7.3 Hz, J2 = 1.9
Hz, 1H, =CH), 5.34-5.21 (m, 1H, =CH), 5.07-4.97 (m, 1H, =CH), 3.60 (q, J = 6.7 Hz, 1H, CH), [3.33 (s, 1.45H), 3.31 (s, 1.55H), 3H, CH3], 2.56-2.44 (m, 2H, CH2), 2.41-2.28 (m, 2H, CH2), 2.15-2.03 (m, 2H, CH2), 1.71-1.23 (m, 8H, CH2 × 4); IR (neat) ν (cm−1) 3716-2200 (COOH), 3022, 2977, 2931, 2856, 2820, 2651, 1963, 1712, 1435, 1417, 1336, 1277, 1250, 1208, 1157, 1108, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (79Br81Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79BrNaO3 + [M (79Br79Br) + Na]+: 430.9828, found:430.9810.
42
Synthesis of 5-(10’,10’-dibromo-3’-methoxy-1’ (E),9’-decadien-1’-yl)dihydro-2 (3H)-furanone rac-xestospongiene (zj-7-158)
Typical Procedure VIII: To a dry Schlenk tube were added AgOTs (0.0285 g, 0.1 mmol, weighed in glove box, 98%), AuCl(LB-Phos) (0.0597 g, 0.1 mmol), and CHCl3 (5 mL) under nitrogen atmosphere sequentially. After stirring at room temperature for 15 min, the reaction was cooled down to -30 oC and then rac-5k (0.4093 g, 1.0 mmol) and CHCl3 (5 mL) were added. The reaction mixture was then continuously stirred at -30 oC for 24 h as monitored by TLC. The reaction was warmed up to room temperature. Filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation afforded a crude mixture of (E)-6k and (Z)-6k (E/Z = 97:3 determined by 1H NMR analysis). Column chromatography on silica gel [eluent: petroleum ether (60-90 oC)/ethyl acetate = 15/1 (550 mL) to 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] afforded the impure rac-xestospongiene (0.3886 g). The impure rac-xestospongiene was purified again on silica gel [eluent: petroleum ether (60-90 oC)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to 80/10/1 (540 mL × 3)] to give pure rac-xestospongiene (0.3792 g, 93%, E/Z = 99:1 determined by 1H NMR, d.r. = 1.07:1 determined by quantitative
13
C NMR
analysis) as a liquid: 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.80-5.57 (m, 2H, =CH × 2), 4.98 (q, J = 6.6 Hz, 1H, CH), 3.68-3.50 (m, 1H, CH), 3.26 (s, 3H, CH3), 2.66-2.37 (m, 3H, CH2 + one proton of CH2), 2.16-1.93 (m, 3H, CH2 + one proton of CH2), 1.67-1.17 (m, 8H, CH2 × 4); the following signals are discernible for (Z)-6k: δ 5.56-5.46 (m, 1H, CH), 5.35-5.26 (m, 1H, CH); IR (neat) ν (cm−1) 2931, 2857, 2821, 1777, 1461, 1422, 1326, 1176, 1113, 1088, 1012; MS (ESI) m/z 413 [M (81Br81Br) + H]+, 411 (M [79Br81Br) + H]+, 409 [M (79Br79Br) + H]+; HRMS (ESI) calcd for C15H2379Br79Br O3+ [M (79Br79Br) + H]+: 409.0008, found:
43
409.0007.
2. Asymmetric synthesis of xestospongienes E-H. I. Synthesis of optically active propargylic alcohols (R)-8 and (S)-8. a. Synthesis of (R)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol3 (R)-8 (zj-7-113)
Typical Procedure IX: To a three-necked flask were added rac-8 (10.8189 g, 40 mmol) and n-hexane (340 mL). Then vinyl acetate (22.2 mL, d = 0.93 g cm-3, 20.646 g, 240.07 mmol) and Novozym-435 (2.7051 g, 25% w) were added sequentially. The reaction mixture was filtrated through a short column of silica gel [eluent: Et2O (30 mL × 3)] after being stirred in an oil bath preheated at 30 oC for 21 h as monitored by TLC. After evaporation of the filtrate, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (300 mL) to 50/1 (500 mL) to 30/1 (500 mL) to 15/1 (500 mL) to 10/1 (500 mL × 2)] on silica gel to afford (S)-11 (6.6618 g, 53%) as a liquid and (R)-8 (4.3075 g, 40%) as a liquid. For (S)-11: 1H NMR (300 MHz, CDCl3) δ 5.33 (td, J1 = 6.8 Hz, J2 = 2.2 Hz, 1H, CH), 3.59 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.4 Hz, 1H, ≡CH), 2.08 (s, 3H, CH3), 1.81-1.71 (m, 2H, CH2), 1.56-1.29 (m, 8H, CH2 × 4), 0.88 (s, 9H, CH3 × 3), 0.04 (s, 6H, CH3 × 2). For (R)-8: > 99% ee (determined by the corrsponding acylation product (R)-11); [α]D20 = +2.0 (c = 0.95, CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.41-4.30 (m, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.1 Hz, 1H, ≡CH), 2.24 (bs, 1H, OH), 1.77-1.63 (m, 2H, CH2), 1.58-1.24 (m, 8H, CH2 × 4), 0.87 (s, 9H, CH3 × 3), 0.03 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 85.0, 72.8, 63.2, 62.2, 37.5, 32.7, 29.0, 25.9, 25.6, 25.0, 18.3, -5.3; IR (neat) ν (cm−1) 3402, 3312, 2931, 2858, 2112, 1471, 1461, 1389, 1361, 1256, 1100, 1006; MS (ESI) m/z 293 [M + Na]+, 271 [M + H]+; HRMS (ESI) calcd for C15H30NaO2Si+ [M + Na]+: 293.1907, found: 293.1910.
44
Acetylation
for
determination
of
the
ee
value
of
(R)-8:
synthesis
of
(R)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-yl acetate (R)-1118 (zj-7-117)
To a dry Schlenk tube were added (R)-8 (0.0802 g, 0.3 mmol, prepared above), Et2O (3 mL), DMAP (0.0128 g, 0.105 mmol), triethylamine (62 μL, d = 0.73 g cm-3, 0.0453 g, 0.448 mmol), and acetic anhydride (43 μL, d = 1.08 g cm-3, 0.0464 g, 0.455 mmol) sequentially under nitrogen atmosphere. After continuous stirring for 10 h at room temperature, the reaction was complete as monitored by TLC. After evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (250 mL)] on silica gel to afford (R)-11 (0.0897 g, 97%) as a liquid: >99% ee [GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: N2 (10.0 psi); injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 50 oC (8 min), 50 oC to 150 oC (3 oC/min, 5 min), 150 oC to 180 oC ; tR (major) = 55.9 min]; [α]D20 = +43.9 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.32 (td, J1 = 6.7 Hz, J2 = 2.2 Hz, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.4 Hz, 1H, ≡CH), 2.07 (s, 3H, CH3), 1.80-1.69 (m, 2H, CH2), 1.55-1.26 (m, 8H, CH2 × 4), 0.87 (s, 9H, CH3 × 3), 0.03 (s, 6H, CH3 × 2);
13
C NMR (75 MHz, CDCl3) δ
169.9, 81.2, 73.4, 63.7, 63.1, 34.5, 32.6, 28.8, 25.9, 25.6, 24.8, 20.9, 18.3, -5.3; IR (neat) ν (cm−1) 3312, 2932, 2858, 2123, 1746, 1472, 1463, 1371, 1232, 1098, 1022; MS (ESI) m/z 335 [M + Na]+, 313 [M + H]+; HRMS (ESI) calcd for C17H32NaO3Si+ [M + Na]+: 335.2013, found: 335.2010.
b. Synthesis of (S)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol (S)-8 (zj-7-118, zj-7-120, zj-7-140)
45
Typical Procedure X: 19 To a round-bottom flask were added (S)-11 (6.6618 g, 21.3 mmol, prepared above, see page 46) and MeOH (22 mL). Then K2CO3 (4.4087 g, 31.95 mmol) was added. The reaction was complete as monitored by TLC after being stirred at room temperature for 0.5 h. K2CO3 was filtrated off and washed with Et2O (15 mL ×5). After combining the filtrate and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (300 mL) to 50/1 (400 mL) to 30/1 (500 mL) to 10/1 (900 mL)] on silica gel to afford (R)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-ol (S)-8 (5.6511 g, 98%) as a liquid, which was then submitted to next step without further characterization: 1H NMR (300 MHz, CDCl3) δ 4.38-4.30 (m, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.46-2.39 (m, 2H, OH + ≡CH), 1.74-1.64 (m, 2H, CH2), 1.56-1.27 (m, 8H, CH2 ×4), 0.87 (s, 9H, CH3 ×3), 0.02 (s, 6H, CH3 ×2), Following Typical Procedure IX, the reaction of (S)-8 (5.6305 g, 20.8 mmol, prepared above), Novozym-435 (1.1257 g, 20% w), and vinyl acetate (11.55 mL, d = 0.93 g cm-3, 10.7415 g, 124.9 mmol) in n-hexane (190 mL) for 1.67 h afforded (S)-9-((tert-butyldimethylsilyl)oxy)non-1-yn-3-yl acetate (S)-11 (4.8175 g, 74%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/1 (500 mL × 2) to 30/1 (300 mL) to 10/1 (550 mL) to 5/1 (300 mL)] as a liquid: > 99% ee [GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: N2 (10.0 psi); injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 50 oC (8 min), 50 oC to 150 oC (3 oC/min, 5 min), 150 oC to 180 oC; tR (major) = 56.3 min]; [α]D20 = -45.5 (c = 0.995, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.32 (td, J1 = 6.6 Hz, J2 = 1.8 Hz, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.44 (d, J = 2.1 Hz, 1H, ≡CH), 2.07 (s, 3H, CH3), 1.80-1.70 (m, 2H, CH2), 1.56-1.27 (m, 8H, CH2 × 4), 0.88 (s, 9H,
46
CH3 × 3), 0.03 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 169.9, 81.2, 73.4, 63.7, 63.1, 34.4, 32.6, 28.8, 25.9, 25.6, 24.8, 20.9, 18.3, -5.3; IR (neat) ν (cm−1) 3312, 2931, 2858, 2123, 1746, 1472, 1463, 1435, 1372, 1232, 1098, 1022; MS (ESI) m/z 335 [M + Na]+, 313 [M + H]+; HRMS (ESI) calcd for C17H32NaO3Si+ [M + Na]+: 335.2013, found: 335.2014. Following Typical Procedure X, the reaction of (S)-11 (4.7490 g, 15.2 mmol, prepared above), K2CO3 (3.1471 g, 22.8 mmol), and MeOH (16 mL) for 0.5 h afforded (S)-8 (4.0801 g, 99%; 38% for 4 steps) [eluent: petroleum ether (60-90 o
C)/ethyl acetate = 50/1 (200 mL) to 30/1 (300 mL) to 15/1 (500 mL) to 10/1 (600
mL)] as a liquid: [α]D20 = -2.2 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.38-4.30 (m, 1H, CH), 3.58 (t, J = 6.5 Hz, 2H, CH2), 2.46-2.39 (m, 2H, OH + ≡CH), 1.74-1.64 (m, 2H, CH2), 1.55-1.27 (m, 8H, CH2 × 4), 0.87 (s, 9H, CH3 × 3), 0.02 (s, 6H, CH3 × 2); 13C NMR (75 MHz, CDCl3) δ 85.0, 72.7, 63.2, 62.1, 37.5, 32.6, 29.0, 25.9, 25.6, 24.9, 18.3, -5.3; IR (neat) ν (cm−1) 3398, 3312, 2931, 2858, 2115, 1470, 1463, 1388, 1360, 1255, 1100, 1006; MS (ESI) m/z 293 [M + Na]+, 271 [M + H]+; HRMS (ESI) calcd for C15H30NaO2Si+ [M + Na]+: 293.1907, found: 293.1908.
II. Synthesis of optically active propargylic alcohols (R)-1c and (S)-1c a. Synthesis of (R)-1,1-dibromo-8-methoxydec-1-en-9-yne (R)-1c Synthesis of (R)-7-methoxynon-8-yn-1-ol (R)-9 (zj-7-126, 7-129)
Typical Procedure XI: To a dry Schlenk flask were added (R)-8 (4.1179 g, 15.2 mmol) and THF (45 mL) under nitrogen atmosphere. The resulting solution was cooled to 0 °C with an ice bath, and NaH (0.6091 g, 60% dispersion in mineral oil, 15.2 mmol,) was added carefully. After the addition was complete, the resulting mixture was stirred at 0 °C for 1 h. Then the cooling bath was removed and the resulting mixture was stirred for another 1 h followed by the addition of MeI (1.15 mL, d = 0.93 g cm-3, 2.5958 g, 18.29 mmol, 99%) dropwise at 0 °C within 5 min. The
47
resulting mixture was warmed up to room temperature naturally. After 3 h with stirring, the reaction was complete as monitored by TLC. The reaction was quenched with water (5.0 mL) at 0 °C. After separation of the organic layer, the aqueous layer was extracted with Et2O (10 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1
(500
mL
× 2)
to
50/1
(500
mL)]
on
silica
gel
to
afford
(R)-tert-butyl((7-methoxynon-8-yn-1-yl)oxy)dimethylsilane (R)-12 as a liquid, which was then submitted to next step without characterization . To a round-bottom flask were added (R)-12 (prepared above) and MeOH (60 mL). Then 3.0 M HCl (1.5 mL) was added. The reaction was complete as monitored by TLC after being stirred at room temperature for 10 h. After evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 5/1 (600 mL) to 3/1 (900 mL)] on silica gel to afford (R)-9 (2.3027 g, 89%, 2 steps) as a liquid: [α]D20 = +57.8 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 3.94 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.59 (t, J = 6.6 Hz, 2H, CH2), 3.40 (s, 3H, CH3), 2.80 (bs, 1H, OH), 2.48 (d, J = 2.1 Hz, 1H, ≡CH), 1.78-1.66 (m, 2H, CH2), 1.61-1.30 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 82.2, 73.7, 70.7, 62.0, 56.0, 35.0, 32.2, 28.8, 25.3, 24.7; IR (neat) ν (cm−1) 3381, 3295, 2986, 2933, 2859, 2824, 2110, 1464, 1336, 1195, 1109, 1091, 1057; MS (ESI) m/z 193 [M + Na]+, 171 [M + H]+; HRMS (ESI) calcd for C10H18NaO2+ [M + Na]+: 193.1199, found: 193.1200.
Synthesis of (R)-7-methoxynon-8-ynal (R)-10 (zj-7-135)
Typical Procedure XII: To a three-necked flask were added Fe(NO3)3∙9H2O (0.5307 g, 1.29 mmol, 98%), NaCl (0.0751 g, 1.29 mmol), TEMPO (0.2055 g, 1.29
48
mmol, 98%), and DCM (100 mL) subsequently. An oxygen balloon was equipped and then a solution of alcohol (R)-9 (2.1921 g, 12.9 mmol) in 30 mL of DCM was added dropwise via an addition funnel at room temperature within 0.5 h in oxygen atmosphere from the balloon. The resulting mixture was stirred for 16 h until the reaction was complete as monitored by TLC. After filtration through a short column of silica gel [eluent: Et2O (20 mL × 3)] and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (200 mL) to 30/1 (500 mL) to 20/1 (500 mL) to 10/1 (440 mL)] on silica gel to afford (R)-10 (1.5245 g, 70%) as a liquid: [α]D20 = +58.8 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 9.76 (t, J = 1.5 Hz, 1H, CHO), 3.93 (td, J1 = 6.4 Hz, J2 = 1.7 Hz, 1H, CH), 3.40 (s, 3H, CH3), 2.52-2.40 (m, 3H, ≡CH + CH2), 1.77-1.60 (m, 4H, CH2 × 2), 1.55-1.30 (m, 4H, CH2 × 2);
13
C NMR (75 MHz, CDCl3) δ 202.0, 81.9, 73.4, 70.2,
55.8, 43.0, 34.5, 28.1, 24.1, 21.2; IR (neat) ν (cm−1) 3280, 2986, 2939, 2862, 2824, 2723, 2109, 1724, 1465, 1409, 1391, 1336, 1193, 1156, 1108, 1091; MS (ESI) m/z 191 [M + Na]+; HRMS (ESI) calcd for C10H16NaO2+ [M + Na]+: 191.1043, found: 191.1045. Synthesis of (R)-1,1-dibromo-8-methoxydec-1-en-9-yne (R)-1c (zj-7-137)
Following Typical Procedure VII, the reaction of (R)-10 (1.4345 g, 8.54 mmol)/DCM (90 mL), CBr4 (4.2532 g, 12.81 mmol), and PPh3 (6.8541 g, 25.62 mmol, 98%)/DCM (35 mL) for 70 min afforded (R)-1c (2.5787 g, 93%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/l (500 mL) to 30/l (500 mL)] as a liquid: [α]D20 = +29.5 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.2 Hz, 1H, =CH), 3.94 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.42 (s, 3H, CH3), 2.45 (d, J = 2.1 Hz, 1H, ≡CH), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.77-1.67 (m, 2H, CH2), 1.53-1.27 (m, 6H, CH2 × 3),
13
C NMR (75 MHz, CDCl3) δ 138.7, 88.6, 82.6, 73.8,
70.9, 56.5, 35.3, 32.8, 28.6, 27.6, 24.8; IR (neat) ν (cm−1) 3300, 2986, 2929, 2858, 2822, 2108, 1623, 1461, 1335, 1272, 1197, 1151, 1109; MS (EI) m/z (%) 325 [M
49
(81Br81Br) - H)+, 0.10], 323 [M (79Br81Br) - H)+, 0.18], 321 [M (79Br79Br) - H)+, 0.13], 214 {[M (81Br81Br) - C7H11O]+, 17.78}, 212 {[M (79Br81Br) - C7H11O]+, 33.97}, 210 {[M (79Br79Br) - C7H11O]+, 16.83}, 131 (100); HRMS (EI) calcd for C11H1579Br79BrO [M - H]+: 320.9490, found: 320.9496.
b. Synthesis of (S)-1,1-dibromo-8-methoxydec-1-en-9-yne (S)-1c Synthesis of (S)-7-methoxynon-8-yn-1-ol (S)-9 (zj-7-141, 7-142)
Following Typical Procedure XI, the reaction of (S)-8 (4.0285 g, 14.9 mmol), NaH (0.5970 g, 60% dispersion in mineral oil, 14.9 mmol), MeI (1.13 mL, d = 2.28, 2.5506 g, 17.97 mmol, 99%) afforded (S)-12 [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL × 2) to 50/1 (500 mL)] as a liquid, which was then submitted to next step without characterization. The reaction of (S)-12 (prepared above), 3.0 M HCl (1.5 mL), and MeOH (60 mL) for 7 h afforded (S)-9 (2.3743 g, 94%, 2 steps) [eluent: petroleum ether (60-90 o
C)/ethyl acetate = 10/1 (550 mL) to 6/1 (560 mL) to 5/1 (600 mL) to 3/1 (280 mL)]
as a liquid: [α]D20 = -58.1 (c = 0.985, CHCl3); 1H NMR (300 MHz, CDCl3) δ 3.94 (td, J1 = 6.6 Hz, J2 = 1.9 Hz, 1H, CH), 3.59 (t, J = 6.0 Hz, 2H, CH2), 3.41 (s, 3H, CH3), 2.98 (s, 1H, OH), 2.49 (d, J = 2.1 Hz, 1H, ≡CH), 1.78-1.64 (m, 2H, CH2), 1.63-1.29 (m, 8H, CH2 × 4);
13
C NMR (75 MHz, CDCl3) δ 82.3, 73.7, 70.8, 62.3, 56.1, 35.1,
32.3, 28.8, 25.4, 24.8; IR (neat) ν (cm−1) 3393, 3300, 2986, 2934, 2860, 2821, 2109, 1464, 1336, 1194, 1092; MS (ESI) m/z 191 [M + Na]+; HRMS (ESI) calcd for C10H18NaO2+ [M + Na]+: 193.1199, found: 193.1197.
Synthesis of (S)-7-methoxynon-8-ynal (S)-10 (zj-7-143)
50
Following Typical Procedure XII, the reaction of Fe(NO3)3∙9H2O (0.5473 g, 1.33 mmol, 98%), NaCl (0.0771 g, 1.33 mmol), TEMPO (0.2120 g, 1.33 mmol, 98%), DCM (100 mL), and (S)-9 (2.2673 g, 13.3 mmol)/DCM (30 mL) for 16 h afforded (S)-10 (1.4286 g, 64%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (300 mL) to 30/1 (530 mL) to 20/1 (500 mL) to 10/1 (330 mL)] as a liquid: [α]D20 = -59.1 (c = 0.98, CHCl3); 1H NMR (300 MHz, CDCl3) δ 9.76 (t, J = 1.8 Hz, 1H, CHO), 3.94 (td, J1 = 6.5 Hz, J2 = 2.1 Hz, 1H, CH), 3.40 (s, 3H, CH3), 2.50-2.41 (m, 3H, ≡CH + CH2), 1.77-1.59 (m, 4H, CH2 × 2), 1.55-1.30 (m, 4H, CH2 × 2); 13C NMR (75 MHz, CDCl3) δ 202.3, 82.2, 73.7, 70.6, 56.1, 43.4, 34.9, 28.5, 24.5, 21.6; IR (neat) ν (cm−1) 3282, 2985, 2939, 2862, 2824, 2722, 2108, 1724, 1464, 1411, 1391, 1336, 1156, 1108, 1091; MS (ESI) m/z 191 [M + Na]+; HRMS (ESI) calcd for C10H16NaO2+ [M + Na]+: 191.1043, found: 191.1041.
Synthesis of (S)-1,1-dibromo-8-methoxydec-1-en-9-yne (S)-1c (zj-7-146)
Following Typical Procedure VII, the reaction of (S)-10 (1.3286 g, 7.9 mmol)/DCM (90 mL), CBr4 (3.9307 g, 11.85 mmol), and PPh3 (6.3361 g, 23.7 mmol, 98%)/DCM (25 mL) afforded (S)-1c (2.3172 g, 90%) [eluent: petroleum ether (60-90 o
C)/ethyl acetate = 100/1 (500 mL) to 50/l (500 mL) to 30/l (300 mL)] as a liquid:
[α]D20 = -29.2 (c = 0.975, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.4 Hz, 1H, =CH), 3.93 (td, J1 = 6.5 Hz, J2 = 1.9 Hz, 1H, CH), 3.41 (s, 3H, CH3), 2.45 (d, J = 2.1 Hz, 1H, ≡CH), 2.10 (q, J = 7.3 Hz, 2H, CH2), 1.77-1.66 (m, 2H, CH2), 1.53-1.28 (m, 6H, CH2 × 3),
13
C NMR (75 MHz, CDCl3) δ 138.6, 88.6, 82.5, 73.8, 70.8, 56.4,
35.2, 32.8, 28.6, 27.6, 24.7; IR (neat) ν (cm−1) 3301, 2986, 2931, 2858, 2822, 2110, 1622, 1463, 1335, 1274, 1196, 1152, 1109; MS (EI) m/z (%) 325 {[M (81Br81Br) - H]+, 0.034}, 323 {[M (79Br81Br) - H]+, 0.069}, 321 {[M (79Br79Br) - H]+, 0.03}, 201 {[M (81Br81Br) - C8H13O]+, 6.70}, 199 {[M (79Br81Br) - C8H13O]+, 14.91}, 197 {[M (79Br79Br) - C8H13O]+, 6.62}, 69 (100); HRMS (EI) calcd for C11H1579Br79BrO [M -
51
H]+: 320.9490, found: 320.9475.
III. Stereodivergent synthesis of xestospongienes E~H. a. Synthesis of (5S,1’E,3’R)-6k, i.e., xestospongiene F (reported as xestospongiene E) Synthesis
of
(Ra,R)-methyl
14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate
(Ra,R)-4ck (zj-7-138)
Typical Procedure XIII: To a dry Schlenk flask were added CuBr2 (0.1735 g, 0.77 mmol, 99%), (S)-3a (1.4943 g, 5.775 mmol), (R)-1c (1.2481 g, 3.85 mmol)/dioxane (25 mL), and 2k (0.6702 g, 5.775 mmol)/dioxane (13.5 mL) sequentially under nitrogen atmosphere. After continuous stirring for 18 h under reflux at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature. The mixture was diluted with ether (60 mL) and then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified via chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (510 mL) to 15/1 (480 mL)] on silica gel to afford (Ra,R)-4ck (0.7631 g, 47%, > 99:1 d.r. determined by HPLC analysis) as a liquid: > 99% ee (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 25.9 min); [α]D20 = -21.0 (c = 0.975, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.29 (q, J = 6.1 Hz, 1H, =CH), 5.05-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.30 (s, 3H, CH3), 2.48-2.39 (m, 2H, CH2), 2.38-2.28 (m, 2H, CH2), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.70-1.25 (m, 8H, CH2 × 4); 13
C NMR (75 MHz, CDCl3) δ 204.2, 173.1, 138.6, 93.3, 90.3, 88.5, 80.2, 56.0, 51.5,
52
35.5, 33.0, 32.8, 28.8, 27.6, 25.1, 23.6; IR (neat) ν (cm−1) 2978, 2931, 2857, 2819, 1963, 1739, 1624, 1436, 1362, 1343, 1253, 1198, 1161, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+, HRMS (ESI) calcd for C16H2479Br79Br NaO3+ [(M (79Br79Br) + Na]+: 444.9984, found: 444.9989.
Synthesis of (Ra,R)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Ra,R)-5k (zj-7-144)
Following Typical Procedure II, the reaction of (Ra,R)-4ck (0.6801 g, 1.6 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 8 mL of H2O and 8 mL of EtOH), and LiOH·H2O (0.1063 g, 2.4 mmol) at 90 oC for 1.5 h afforded (Ra,R)-5k (0.6017 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: [α]D20 = -20.2 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 9.68 (bs, 1H, COOH), 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.30 (q, J = 6.1 Hz, 1H, =CH), 5.07-4.98 (m, 1H, =CH), 3.60 (q, J1 = 7.0 Hz, 1H, CH), 3.31 (s, 3H, CH3), 2.54-2.44 (m, 2H, CH2), 2.39-2.29 (m, 2H, CH2), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.71-1.22 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.3, 178.9, 138.8, 93.5, 90.2, 88.6, 80.4, 56.0, 35.5, 33.1, 32.9, 28.9, 27.7, 25.2, 23.4; IR (neat) ν (cm−1) 3752-2188 (COOH), 2978, 2933, 2858, 2822, 2660, 1964, 1713, 1624, 1435, 1336, 1278, 1251, 1208, 1157, 1109, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (81Br79Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79BrNaO3+ [M (79Br79Br) + Na] +: 430.9828, found: 430.9830.
Synthesis of (5S)-(10’,10’-dibromo-3’(R)-methoxy-1’(E),9’-decadien-1’-yl)dihydro2(3H)-furanone (5S,1’E,3’R)-6k, i.e., xestospongiene F (reported as xestospongiene E) (zj-7-188)
53
Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0597 g, 0.1 mmol), CHCl3 (5 mL), and (Ra,R)-5k (0.4096 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24 h afforded (5S,1’E,3’R)-6k,20 i.e., xestospongiene F [(0.3844 g, 94%, (5S,1’E,3’R)/(5R,1’Z,3’R) = 98:2 (determined by 1
H NMR) and > 99:1 d.r. (determined by SFC analysis)] [eluent: petroleum ether
(60-90 oC)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to 80/10/1 (540 mL × 3)] ((5S,1’E,3’R)/(5R,1’Z,3’R) = 97:3 determined by 1H NMR of crude product) as a liquid: > 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 97/3, 1.3 mL/min, λ = 214 nm, tR (major) = 15.8 min); [α]D20 = +21.9 (c = 1.01, CHCl3); [α]D20 = +27.3 (c = 0.38, MeOH); (Lit.20 [α]D20 = -44.3 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.82-5.58 (m, 2H, =CH × 2), 4.98 (q, J = 6.6 Hz, 1H, CH), 3.58 (q, J = 6.2 Hz, 1H, CH), 3.27 (s, 3H, CH3), 2.64-2.39 (m, 3H, CH2 + one proton of CH2), 2.15-1.94 (m, 3H, CH2 + one proton of CH2), 1.66-1.20 (m, 8H, CH2 × 4); the following signals are discernible for (5R,1’Z,3’R)-6k: δ 5.56-5.47 (m, 1H, =CH), 5.35-5.25 (m, 1H, CH);
13
C NMR (75
MHz, CDCl3) δ 176.6, 138.5, 134.1, 129.4, 88.2, 80.8, 79.7, 56.1, 34.8, 32.6, 28.6, 28.5, 28.2, 27.3, 24.6; IR (neat) ν (cm−1) 2974, 2931, 2857, 2817, 1777, 1460, 1421, 1326, 1296, 1214, 1176, 1112, 1091, 1012; MS (ESI) m/z 413 [M (81Br81Br) + H]+,.411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.
b. Synthesis of xestospongiene G Synthesis
of
(Sa,R)-methyl
14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate
(Sa,R)-4ck (zj-7-139)
54
Following Typical Procedure XIII, the reaction of CuBr2 (0.1736 g, 0.77 mmol, 99%), (R)-3a (1.4942 g, 5.775 mmol, 98%), (R)-1c (1.2469 g, 3.85 mmol)/dioxane (25 mL), and 2k (0.6702 g, 5.775 mmol)/dioxane (13.5 mL) at 120 oC for 18 h afforded (Sa,R)-4ck (0.7035 g, 43%, > 99:1 d.r. by HPLC analysis) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (510 mL) to 15/1 (480 mL)] as a liquid: > 99% ee, > 99:1 d.r. (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 36.6 min, tR (minor) = 25.6 min); [α]D20 = +72.2 (c = 1.025, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.4 Hz, 1H, =CH), 5.23 (q, J = 6.7 Hz, 1H, =CH), 5.04-4.94 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.32 (s, 3H, CH3), 2.51-2.43 (m, 2H, CH2), 2.40-2.31 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.69-1.23 (m, 8H, CH2 × 4); 13
C NMR (75 MHz, CDCl3) δ 204.1, 173.1, 138.7, 93.3, 90.2, 88.5, 80.2, 56.0, 51.5,
35.6, 33.1, 32.8, 28.8, 27.6, 25.0, 23.8; IR (neat) ν (cm−1) 2978, 2931, 2857, 2819, 1963, 1738, 1622, 1463, 1435, 1417, 1362, 1343, 1254, 1227, 1197, 1161, 1087, 1023; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd for C16H2479Br79BrNaO3+ [M (79Br79Br) + Na]+: 444.9984, found: 444.9965.
Synthesis of (Sa,R)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Sa,R)-5k (zj-7-145)
Following Typical Procedure II, the reaction of (Sa,R)-4ck (0.6031 g, 1.42 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 7 mL of H2O and 7 mL of
55
EtOH), and LiOH∙H2O (0.0945 g, 2.13 mmol, 95%) at 90 oC for 1.5 h afforded (Sa,R)-5k (0.5272 g, 90%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: [α]D20 = +72.3 (c = 1.00, CHCl3); 1
H NMR (300 MHz, CDCl3) δ 9.72 (bs, 1H, COOH), 6.38 (t, J = 7.1 Hz, 1H, =CH),
5.25 (q, J = 6.0 Hz, 1H, =CH), 5.06-4.97 (m, 1H, =CH), 3.60 (q, J = 6.9 Hz, 1H, CH), 3.33 (s, 3H, CH3), 2.52 (t, J = 7.1 Hz, 2H, CH2), 2.41-2.31 (m, 2H, CH2), 2.09 (q, J = 7.3 Hz, 2H, CH2), 1.70-1.22 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.2, 178.8, 138.7, 93.5, 90.2, 88.5, 80.3, 56.1, 35.6, 33.2, 32.8, 28.8, 27.7, 25.0, 23.6; IR (neat) ν (cm−1) 3618-2182 (COOH), 2978, 2933, 2858, 2820, 2658, 1964, 1712, 1435, 1334, 1250, 1205, 1156, 1109, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (81Br79Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79Br NaO3+ [M(79Br79Br) + Na]+: 430.9828, found: 430.9832.
Synthesis of (5R)-(10’,10’-dibromo-3’(R)-methoxy-1’(E),9’-decadien-1’-yl) dihydro -2(3H)-furanone xestospongiene G (zj-8-012)
Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0598 g, 0.1 mmol), CHCl3 (5 mL), and (Sa,R)-5k (0.4097 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24 h afforded xestospongiene G20 (0.3791 g, 93%, E only, > 99:1 d.r. determined by SFC analysis) [eluent: petroleum ether (60-90 o
C)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 70/7/1 (550 mL) to 40/5/1
(540 mL) to 24/3/1 (540 mL)] ((5R,1’E,3’R)/(5S,1’Z,3’R) = 97:3 determined by 1H NMR of crude product) as an oil: > 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 16.2 min); [α]D20 = -3.4 (c = 0.98, CHCl3); [α]D20 = -7.1 (c = 0.545, MeOH); (Lit.20 [α]D20 = -10.5 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.2 Hz, 1H, =CH), 5.77-5.60 (m, 2H, =CH × 2), 4.98 (q, J = 6.5 Hz, 1H, CH), 3.57 (q, J = 6.3 Hz, 1H, CH), 3.27 (s, 3H,
56
CH3), 2.61-2.37 (m, 3H, CH2 + one proton of CH2), 2.14-1.94 (m, 3H, CH2 + one proton of CH2), 1.64-1.22 (m, 8H, CH2 × 4);
13
C NMR (75 MHz, CDCl3) δ 176.5,
138.5, 133.9, 129.7, 88.2, 80.7, 79.6, 56.1, 34.7, 32.5, 28.5, 28.4, 28.1, 27.3, 24.5; IR (neat) ν (cm−1) 2976, 2932, 2857, 2820, 1778, 1461, 1420, 1325, 1296, 1214, 1177, 1108, 1092, 1012; MS (ESI): m/z 413 [M (81Br81Br) + H]+, 411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.
c. Synthesis of xestospongiene H Synthesis
of
(Ra,S)-methyl
14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate
(Ra,S)-4ck (zj-7-148)
Typical Procedure XIV (three reactions in parallel): To a dry Schlenk flask were added CuBr2 (0.0510 g, 0.226 mmol, 99%), (S)-3a (0.4380 g, 1.695 mmol, 98%), (S)-1c (0.3629 g, 1.13 mmol)/dioxane (8.3 mL), and 2k (0.1970 g, 1.695 mmol)/dioxane (3 mL) sequentially under nitrogen atmosphere; to another dry Schlenk flask were added CuBr2 (0.0508 g, 0.226 mmol, 99%), (S)-3a (0.4369 g, 1.695 mmol), (S)-1c (0.3651 g, 1.13 mmol, 98%)/dioxane (8.3 mL), and 2k (0.1961 g, 1.695 mmol)/dioxane (3 mL) sequentially under nitrogen atmosphere; to the third dry Schlenk flask were added CuBr2 (0.0508 g, 0.226 mmol, 99%), (S)-3a (0.4368 g, 1.695 mmol, 98%), (S)-1c (0.3667 g, 1.13 mmol)/dioxane (8.3 mL), and 2k (0.1971 g, 1.695 mmol)/dioxane (3 mL) sequentially under nitrogen atmosphere; the three reactions were conducted separately. After continuous stirring for 18 h at 120 oC, the reactions were complete as monitored by TLC. After cooling down to room temperature, the three resulting mixtures were combined and diluted with ether (60 mL), then washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous
57
Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 20/1 (500 mL)] on silica gel to afford (Ra,S)-4ck (0.8064 g, 60%, 99:1 d.r. determined by 1H NMR and HPLC analysis) as a liquid: > 99% ee (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 25.7 min , tR (minor) = 37.9 min); [α]D20 = -71.9 (c = 1.025, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.38 (t, J = 7.4 Hz, 1H, =CH), 5.24 (q, J = 6.5 Hz, 1H, =CH), 5.04-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.32 (s, 3H, CH3), 2.53-2.42 (m, 2H, CH2), 2.41-2.30 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.69-1.24 (m, 8H, CH2 × 4);
13
C NMR (75 MHz, CDCl3) δ 204.1, 173.1, 138.7, 93.3, 90.2, 88.5,
80.2, 56.0, 51.5, 35.6, 33.1, 32.8, 28.8, 27.6, 25.0, 23.8; IR (neat) ν (cm−1) 2977, 2931, 2857, 2818, 1963, 1740, 1436, 1363, 1250, 1198, 1161, 1109, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd for C16H2479Br79Br NaO3+ [M (79Br79Br) + Na]+: 444.9984, found: 444.9976. Synthesis of (Ra,S)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Ra,S)-5k (zj-7-151)
Following Typical Procedure II, the reaction of (Ra,S)-4ck (0.6664 g, 1.57 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 8 mL of H2O and 8 mL of EtOH), and LiOH∙H2O (0.1047 g, 2.355 mmol) at 90 oC for 1.5 h afforded (Ra,S)-5k (0.6102 g, 95%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as a liquid: [α]D20 = -72.2 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 1H NMR (300 MHz, CDCl3) δ 10.73 (bs, 1H, COOH), 6.38 (t, J = 7.4 Hz, 1H, =CH), 5.25 (q, J = 6.2 Hz, 1H, =CH), 5.07-4.97 (m, 1H, =CH), 3.60 (q, J = 6.6 Hz, 1H, CH), 3.33 (s, 3H, CH3), 2.57-2.46 (m, 2H, CH2), 2.42-2.30 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.70-1.23 (m, 8H, CH2 × 4);
58
13
C NMR (75 MHz,
CDCl3) δ 204.1, 178.8, 138.7, 93.4, 90.1, 88.5, 80.3, 56.0, 35.5, 33.1, 32.8, 28.7, 27.6, 25.0, 23.5; IR (neat) ν (cm−1) 3693-2185 (COOH), 2976, 2933, 2858, 2820, 2664, 1963, 1712, 1435, 1335, 1251, 1206, 1156, 1108, 1086; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (79Br81Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79Br NaO3+ [M (79Br79Br) + Na]+: 430.9828, found: 430.9821.
Synthesis of (5S)-(10’,10’-dibromo-3’(S)-methoxy-1’(E),9’-decadien-1’-yl)dihydro2(3H)-furanone xestospongiene H (zj-8-013)
Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0597 g, 0.1 mmol), CHCl3 (5 mL), and (Ra,S)-5k (0.4101 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24 h afforded xestospongiene H20 (0.3766 g, 92%, E only, > 99:1 d.r. determined by SFC analysis) [eluent: petroleum ether (60-90 o
C)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 70/7/1 (550 mL) to 40/5/1
(540 mL) to 24/3/1 (540 mL)] ((5S,1’E,3’S)/(5R,1’Z,3’S) = 97:3 determined by 1H NMR of crude product) as an oil: > 99% ee, > 99:1 d.r. (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 9.4 min); [α]D20 = +3.5 (c = 0.995, CHCl3); [α]D20 = +7.0 (c = 0.49, MeOH); (Lit.20 [α]D20 = +11.0 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.78-5.58 (m,
2H, =CH × 2), 4.98 (q, J = 6.8 Hz, 1H, CH), 3.57 (q, J = 6.4 Hz, 1H, CH), 3.26 (s, 3H, CH3), 2.60-2.37 (m, 3H, CH2 + one proton of CH2), 2.14-1.93 (m, 3H, CH2 + one proton of CH2), 1.66-1.19 (m, 8H, CH2 × 4);
13
C NMR (75 MHz, CDCl3) δ 176.4,
138.4, 133.8, 129.6, 88.1, 80.7, 79.5, 56.0, 34.7, 32.5, 28.5, 28.4, 28.1, 27.3, 24.5; IR (neat) ν (cm−1) 2978, 2932, 2857, 2821, 1778, 1461, 1420, 1326, 1296, 1215, 1177, 1108, 1093, 1012; MS (ESI): m/z 413 [M (81Br81Br) + H]+, 411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.
59
d. Synthesis of (5R,1’E,3’S)-6k, i.e., xestospongiene E (reported as xestospongiene F) Synthesis
of
(Sa,S)-methyl
14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate
(Sa,S)-4ck (zj-7-150)
To a dry Schlenk flask were added CuBr2 (0.1540 g, 0.682 mmol, 99%), (R)-3a (1.4957 g, 5.797 mmol, 98%), (S)-1c (1.1058 g, 3.41 mmol)/dioxane (20 mL), and 2k (0.6740 g, 5.797 mmol)/dioxane (14 mL) sequentially under nitrogen atmosphere. After continuous stirring for 18 h at 120 oC, the reaction was complete as monitored by TLC. Then the resulting mixture was cooled down to room temperature, diluted with ether (60 mL), and washed with an aqueous solution of hydrochloric acid (3 M, 10 mL × 3). The organic layer was separated and the aqueous layer was extracted with Et2O (10 mL). The combined organic layer was washed with brine and dried over anhydrous Na2SO4. After filtration and evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 20/1 (500 mL)] on silica gel to afford (Sa,S)-4ck (0.7177 g, 50%, > 99:1 d.r. determined by 1H NMR and HPLC analysis) as a liquid: > 99% ee, > 99:1 d.r. (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 14.8 min, tR (minor) = 13.5 min); [α]D20 = +21.2 (c = 0.98, CHCl3); δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.28 (q, J = 6.2 Hz, 1H, =CH), 5.04-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.9 Hz, 1H, CH), 3.30 (s, 3H, CH3), 2.47-2.39 (m, 2H, CH2), 2.38-2.28 (m, 2H, CH2), 2.10 (q, J = 7.3 Hz, 2H, CH2), 1.70-1.25 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.1, 173.1, 138.7, 93.3, 90.3, 88.5, 80.2, 55.9, 51.5, 35.5, 33.0, 32.8, 28.8, 27.6, 25.0, 23.6; IR (neat) ν (cm−1) 2981, 2931, 2857, 2819, 1963, 1740, 1436, 1363, 1254, 1198, 1161, 1109, 1087; MS (ESI) m/z 449 [M (81Br81Br) + Na]+, 447 [M (79Br81Br) + Na]+, 445 [M (79Br79Br) + Na]+; HRMS (ESI) calcd for C16H2479Br79BrNaO3+ [M (79Br79Br) + Na]+: 444.9984,
60
found: 444.9969.
Synthesis of (Sa,S)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Sa,S)-5k (zj-7-156)
Following Typical Procedure II, the reaction of (Sa,S)-4ck (0.6575 g, 1.55 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 8 mL of H2O and 8 mL of EtOH), and LiOH∙H2O (0.1031 g, 2.325 mmol) at 90 oC for 1.5 h afforded (Sa,S)-5k (0.6022 g, 95%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (360 mL)] as an oil: [α]D20 = +19.9 (c = 0.975, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.12 (bs, 1H, COOH), 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.30 (q, J = 6.1 Hz, 1H, =CH), 5.07-4.98 (m, 1H, =CH), 3.61 (q, J = 7.0 Hz, 1H, CH), 3.31 (s, 3H, CH3), 2.49 (t, J = 7.5 Hz, 2H, CH2), 2.40-2.29 (m, 2H, CH2), 2.10 (q, J = 7.2 Hz, 2H, CH2), 1.71-1.24 (m, 8H, CH2 × 4);
13
C NMR (75 MHz, CDCl3) δ 204.3, 178.9,
138.7, 93.5, 90.2, 88.5, 80.3, 56.0, 35.5, 33.1, 32.9, 28.9, 27.7, 25.1, 23.3; IR (neat) ν (cm−1) 3031-3031 (COOH), 2928, 2856, 2662, 1964, 1713, 1417, 1338, 1257, 1202, 1157, 1108, 1084; MS (ESI) m/z 435 [M (81Br81Br) + Na]+, 433 [M (79Br81Br) + Na]+, 431 [M (79Br79Br) + Na]+; HRMS (ESI) calcd. for C15H2279Br79Br NaO3
+
[M
(79Br79Br) + Na]+: 430.9828, found: 430.9825.
Synthesis of (5R)-(10’,10’-dibromo-3’(S)-methoxy-1’(E),9’-decadien-1’-yl)dihydro2(3H)-furanone (5R,1’E,3’S)-6k, i.e., xestospongiene E (reported as xestospongiene F) (zj-7-189)
61
Following Typical Procedure VIII, the reaction of AgOTs (0.0285 g, 0.1 mmol, 98%), Au(LB-Phos)Cl (0.0597 g, 0.1 mmol), CHCl3 (5 mL), and (Sa,S)-5k (0.4102 g, 1.0 mmol)/CHCl3 (5 mL) at -30 oC for 24.5 h afforded (5R,1’E,3’S)-6k,20 i.e., xestospongiene E (0.3851 g, 94%, (5R,1’E,3’S)/(5S,1’Z,3’S) = 99:1 determined by 1H NMR, > 99:1 d.r. determined by SFC analysis) [eluent: petroleum ether (60-90 o
C)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to
80/10/1 (540 mL × 3)] ((5R,1’E,3’S)/(5S,1’Z,3’S) = 97:3 determined by 1H NMR of crude product) as an oil: > 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 21.0 min, tR (minor) = 11.6 min); [α]D20 = -22.3 (c = 1.00, CHCl3); [α]D20 = -27.4 (c = 0.495, MeOH); (Lit.20 [α]D20 = +45.6 (c = 0.4, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.79-5.59 (m, 2H, =CH × 2), 4.98 (q, J = 6.6 Hz, 1H, CH), 3.58 (q, J = 6.1 Hz, 1H, CH), 3.27 (s, 3H, CH3), 2.62-2.38 (m, 3H, CH2 + one proton of CH2), 2.15-1.94 (m, 3H, CH2 + one proton of CH2), 1.67-1.16 (m, 8H, CH2 × 4); the following signals are discernible for (5S,1’Z,3’S)-6k: δ 5.56-5.48 (m, 1H, =CH), 5.35-5.25 (m, 1H, CH);
13
C NMR (75
MHz, CDCl3) δ 176.6, 138.5, 134.1, 129.5, 88.3, 80.8, 79.7, 56.2, 34.8, 32.6, 28.6, 28.5, 28.2, 27.4, 24.6; IR (neat) ν (cm−1) 2977, 2931, 2857, 2821, 1777, 1460, 1421, 1326, 1296, 1215, 1176, 1112, 1091, 1012; MS (ESI): m/z 413 [M (81Br81Br) + H]+, 411 [M (79Br81Br) + H]+, 409 [M (79Br79Br) + H]+.
e. Gram scale synthesis of (5S,1’E,3’R)-6k , i.e., xestospongiene F) Synthesis
of
(Ra,R)-methyl
14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoate
(Ra,R)-4ck (zj-7-177)
62
Following Typical Procedure XIV (four reactions in parallel), the reaction of CuBr2 (0.0676 g, 0.3 mmol, 99%), (S)-3a (0.5803 g, 2.25 mmol, 98%), (R)-1c (0.4862 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2609 g, 2.25 mmol) in dioxane/(5 mL) at 120 o
C for 18 h; the reaction of CuBr2 (0.0677 g, 0.3 mmol, 99%), (S)-3a (0.5804 g, 2.25
mmol, 98%), (R)-1c (0.4860 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2620 g, 2.25 mmol)/dioxane (5 mL) at 120 oC for 18 h; the reaction of CuBr2 (0.0677 g, 0.3 mmol, 99%), (S)-3a (0.5810 g, 2.25 mmol, 98%), (R)-1c (0.4859 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2614 g, 2.25 mmol)/dioxane (5 mL) at 120 oC for 18 h; the reaction of CuBr2 (0.0675 g, 0.3 mmol, 99%), (S)-3a (0.5810 g, 2.25 mmol, 98%), (R)-1c (0.4863 g, 1.5 mmol)/dioxane (8 mL), and 2k (0.2613 g, 2.25 mmol)/dioxane (5 mL) at 120 o
C for 18 h. The four reactions together afforded (Ra,R)-4ck (1.4779 g, 58%, > 99:1
d.r. determined by 1H NMR and HPLC analysis) [eluent: petroleum ether (60-90 o
C)/ethyl acetate = 50/1 (500 mL) to 30/1 (500 mL) to 20/1 (500 mL)] as a liquid: >
99% ee (HPLC conditions: Chiralcel IF column, n-hexane/i-PrOH = 100/1, 1.0 mL/min, λ = 214 nm, tR (major) = 14.0 min, tR (minor) = 15.0 min), [α]D20 = -21.1 (c = 0.98, CHCl3); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.2 Hz, 1H, =CH), 5.29 (q, J = 6.1 Hz, 1H, CH),5.04-4.95 (m, 1H, =CH), 3.68 (s, 3H, CH3), 3.58 (q, J = 6.7 Hz, 1H, CH),, 3.30 (s, 3H, CH3), 2.48-2.40 (m, 2H, CH2), 2.38-2.28 (m, 2H, CH2), 2.10 (q, J = 7.3 Hz, 2H, CH2), 1.69-1.25 (m, 8H, CH2 × 4);
13
C NMR (75 MHz, CDCl3) δ
204.2, 173.2, 138.7, 93.3, 90.3, 88.5, 80.2, 56.0, 51.5, 35.6, 33.1, 32.8, 28.8, 27.6, 25.1, 23.6.
Synthesis of (Ra,R)-14,14-dibromo-7-methoxy-4,5,13-tetradecatrienoic acid (Ra,R)-5k (zj-7-182)
63
To a round-bottom flask were added (Ra,R)-4ck (1.2704 g, 3.0 mmol), EtOH/H2O = 1:1 by volume (pre-mixed by using 15 mL of H2O and 15 mL of EtOH) and LiOH∙H2O (0.1460 g, 3.3 mmol, 95%) sequentially. After stirring for 1 h under reflux at 90 oC, the reaction was complete as monitored by TLC. Then the mixture was cooled down to room temperature. After evaporation to remove EtOH, the aqueous layer was acidified with an aqueous solution of hydrochloric acid (aq., 3.0 M) until pH = 1. The aqueous layer was then extracted with Et2O (30 mL × 3). The combined organic layer was washed with brine and dried over anhydrous Na2SO4, filtration, evaporation, and column chromatography on silica gel to afford (Ra,R)-5k (1.1945 g, 97%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL) to 8/1 (540 mL) to 5/1 (600 mL)] as an oil: [α]D20 = -20.6 (c = 1.01, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.37 (bs, 1H, COOH), 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.30 (q, J = 6.1 Hz, 1H, =CH), 5.07-4.98 (m, 1H, =CH), 3.60 (q, J = 6.7 Hz, 1H, CH), 3.31 (s, 3H, CH3), 2.53-2.44 (m, 2H, CH2), 2.39-2.28 (m, 2H, CH2), 2.09 (q, J = 7.2 Hz, 2H, CH2), 1.71-1.25 (m, 8H, CH2 × 4); 13C NMR (75 MHz, CDCl3) δ 204.3, 178.9, 138.7, 93.4, 90.2, 88.5, 80.3, 56.0, 35.5, 33.1, 32.9, 28.8, 27.6, 25.1, 23.3.
Gram scale Synthesis of (5S)-(10’,10’-dibromo-3’(R)-methoxy-1’(E),9’-decadien1’-yl)dihydro-2(3H)-furanone (5S,1’E,3’R)-6k, xestospongiene F (zj-8-011)
Following Typical Procedure VIII, the reaction of AgOTs (0.077 g, 0.27 mmol), Au(LB-Phos)Cl (0.1613 g, 0.27 mmol), CHCl3 (17 mL), and (Ra,R)-5k (1.1054 g, 2.7
64
mmol)/CHCl3 (10 mL) at -30 oC for 24 h afforded impure (5S,1’E,3’R)-6k20 (1.0795 g) [eluent: petroleum ether (60-90 oC)/ethyl acetate/dichloromethane = 150/10/1 (480 mL) to 100/10/1 (550 mL) to 80/10/1 (540 mL × 3)] as an oil, which was then further purified
by
chromatography
[eluent:
petroleum
ether
(60-90
o
C)/ethyl
acetate/dichloromethane = 150/10/1 (480 mL) to 70/7/1 (550 mL) to 40/5/1 (540 mL) to 24/3/1 (540 mL) to 16/2/1 (540 mL)] to give (5S,1’E,3’R)-6k, xestospongiene F (1.0371 g, 94%, (5S,1’E,3’R)/(5R,1’Z,3’R) = 98:2 determined by 1H NMR analysis, d.r. = 98:2 determined by SFC analysis) ((5S,1’E,3’R)/(5R,1’Z,3’R) = 97:3 determined by 1H NMR of crude product) as an oil: 99% ee (SFC: Chiralcel AD-H column, n-hexane/i-PrOH = 9/1, 2.0 mL/min, λ = 214 nm, tR (major) = 11.0 min, tR (minor) = 21.8 min); [α]D20 = +21.5 (c = 1.00, CHCl3); [α]D20 = +27.4 (c = 0.43, MeOH); (Lit.20 [α]D20 = -44.3 (c = 0.5, MeOH)); 1H NMR (300 MHz, CDCl3) δ 6.39 (t, J = 7.4 Hz, 1H, =CH), 5.84-5.57 (m, 2H, =CH × 2), 4.98 (q, J = 6.7 Hz, 1H, CH), 3.58 (q, J = 6.1 Hz, 1H, CH), 3.26 (s, 3H, CH3), 2.62-2.37 (m, 3H, CH2 + one proton of CH2), 2.15-1.94 (m, 3H, CH2 + one proton of CH2), 1.66-1.20 (m, 8H, CH2 × 4); the following signals are discernible for (5R,1’Z,3’R)-6k: δ 5.56-5.48 (m, 1H, =CH), 5.34-5.24 (m, 1H, CH); 13C NMR (75 MHz, CDCl3) δ 176.5, 138.5, 134.1, 129.4, 88.2, 80.7, 79.7, 56.1, 34.7, 32.6, 28.6, 28.4, 28.2, 27.3, 24.5.
Synthetic application in the synthesis of naturally occurring γ-alkylic γ-lactones 1. Synthesis of (R)-4-tetradecalactone Synthesis of (Ra)-4,5-tetradecadienoic acid (Ra)-5j (zj-4-187,4-190)
Following Typical Procedure IV, the reaction of CuBr2 (0.6764 g, 3.0 mmol, 99%), (S)-3a (3.8705 g, 15 mmol, 98%), 1b (2.2730 g, 18 mmol)/dioxane (15 mL), and nonanaldehyde 2j (4.0 mL, d = 0.8277 g cm-3, 3.1784 g, 22.38 mmol, 96%)/dioxane (10 mL) for 16 h afforded (Ra)-4bj (1.6250 g) [(eluent: petroleum ether
65
(60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (400 mL)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bj (1.6250 g, 6.45 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 25 mL of H2O and 25 mL of EtOH), and LiOH·H2O (0.4290 g, 9.675 mmol, 95%) for 18 h afforded (Ra)-5j21 (1.3001 g, 39%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (440 mL) to 10/1 (550 mL × 3) to 5/1 (600 mL)] as a liquid: 95% ee (determined by the corrsponding esterification product (Ra)-4bj); [α]D20 = -65.3 (c = 1.025, CHCl3); 1
H NMR (300 MHz, CDCl3) δ 10.35 (bs, 1H, COOH), 5.21-5.11 (m, 2H, =CH × 2),
2.48 (t, J = 7.2 Hz, 2H, CH2), 2.36-2.24 (m, 2H, CH2); 2.02-1.91 (m, 2H, CH2), 1.44-1.20 (m, 12H, CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3);
13
C NMR (75 MHz,
CDCl3) δ 203.6, 179.8, 92.9, 89.2, 33.1, 31.9, 29.4, 29.3, 29.15, 29.10, 28.8, 23.5, 22.6, 14.1; IR (neat) ν (cm−1) 3666-2167 (COOH), 3031, 2953, 2925, 2855, 2664, 1964, 1712, 1435, 1411, 1378, 1336, 1279, 1250, 1211, 1173; MS (70 ev, EI) m/z (%) 224 (M+, 8.53), 126 (100), 84 (100), 81 (100).
Esterification for determination of the ee value of (Ra)-5j: synthesis of (Ra)-ethyl 4,5-tetradeca dienoate (Ra)-4bj (zj-4-198)
Following Typical Procedure III, the reaction of (Ra)-5j (0.1345 g, 0.6 mmol), EtI (0.06 mL, d = 1.94 g cm-3, 0.1152 g, 0.74 mmol, 99%), K2CO3 (0.2512 g, 1.8 mmol), and DMF (6 mL) for 13 h afforded (Ra)-4bj (0.1358 g, 90%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (600 mL)] as a liquid: 95% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane/i-PrOH = 400:1, 0.5 mL/min, λ = 214 nm, tR (major) = 15.4 min, tR (minor) = 14.1 min); [α]D20 = -60.1 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.18-5.09 (m, 2H, =CH × 2), 4.13 (q, J = 7.0 Hz, 2H, OCH2), 2.46-2.37 (m, 2H, CH2), 2.34-2.23 (m, 2H, CH2), 2.02-1.90 (m, 2H, CH2), 1.44-1.21 (m, 15H, CH3 + CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13C NMR
66
(75 MHz, CDCl3) δ 203.6, 173.1, 92.5, 89.5, 60.2, 33.4, 31.8, 29.4, 29.3, 29.1, 28.8, 23.9, 22.6, 14.2, 14.1; IR (neat) ν (cm−1) 2956, 2926, 2854, 1963, 1739, 1465, 1447, 1420, 1372, 1350, 1300, 1250, 1159, 1097, 1055, 1037; MS (70 ev, EI) m/z (%) 252 (M+, 4.90), 80 (100); HRMS calcd for C16H28O2 [M+]: 252.2089, found: 252.2085.
Synthesis of (S,E)-5-(1-decenyl)dihydro-2(3H)-furanone (S,E)-6j (zj-5-017)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5j (0.2240 g, 1.0 mmol)/CHCl3 (5 mL) for 3.0 h afforded (S,E)-6j11 (0.2158 g, 96%, (S,E)/(R,Z) = 97/3 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (220 mL) to 8/1 (450 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 96% ee (HPLC conditions: Chiralcel OJ-H column, n-hexane/i-PrOH = 100:1, 1.0 mL/min, λ = 214 nm, tR(major) = 15.4 min, tR(minor) = 13.5 min; [α]D20 = +27.3 (c = 0.99, CHCl3); (Lit.11 [α]D26 = +30.2 (c = 2.12, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 5.81 (dtd, J1 = 15.3 Hz, J2 = 6.6 Hz, J3 = 0.9
Hz, 1H, =CH), 5.49 (ddt, J1 = 15.3 Hz, J2 = 7.2 Hz, J3 = 1.1 Hz, 1H, =CH), 4.89 (q, J = 7.2 Hz, 1H, CH), 2.58-2.48 (m, 2H, CH2), 2.46-2.31 (m, 1H, one proton from CH2), 2.11-1.89 (m, 3H, CH2 + one proton from CH2), 1.47-1.18 (m, 12H, CH2 × 6), 0.88 (t, J = 6.6 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6j: δ 5.71-5.61 (m, 1H, =CH), 5.31-5.21 (m, 1H, CH);
13
C NMR (75 MHz, CDCl3) δ 176.8, 135.2,
127.2, 80.8, 31.8, 31.5, 29.1, 28.9, 28.8, 28.5, 28.45, 28.38, 22.3, 13.8; IR (neat) ν (cm−1) 2956, 2925, 2854, 1778, 1673, 1460, 1423, 1378, 1327, 1299, 1216, 1176, 1123, 1011; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6j: tR (major) = 4.03 min: 224 (M+, 0.94), 111 (100); for (R,Z)-6j tR (minor) = 3.98 min: 224 (M+, 1.27), 111 (100).
67
Synthesis of (R)-5-decyldihydro-2(3H)-furanone (R)-4-tetradecalactone4 (zj-5-093)
Typical Procedure XV: To a reaction tube were added (S,E)-6j (0.1122 g, 0.5 mmol), EtOAc (3 mL), and Pd/C (10% on C, dry, 0.0266 g, 0.025 mmol) sequentially. Then the reaction tube was placed in an autoclave. The resulting mixture was stirred under H2 (25 atm) at room temperature for 36 h and then filtered through a short column of silica gel with Et2O (15 mL × 3). After evaporation, the residue was purified by chromatography [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL)] on silica gel to afford (R)-4-tetradecalactone22 (0.1109 g, 98%) as an oil with pleasant flavor: 93% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier = He; injector = 145 oC; detector (FID, H2) = 200 oC; oven temperature = 140 oC to 200 oC (5 oC/min); tR(major) = 61.3 min, tR(minor) = 62.9 min; [α]D20 = +28.5 (c = 0.99, CHCl3); (Lit.11 [α]D26 = +29.95 (c = 2.739, CHCl3)); 1
H NMR (300 MHz, CDCl3) δ 4.54-4.44 (m, 1H, CH), 2.59-2.48 (m, 2H, CH2),
2.39-2.26 (m, 1H, one proton from CH2), 1.93-1.78 (m, 1H, one proton from CH2), 1.78-1.67 (m, 1H, one proton from CH2), 1.67-1.53 (m, 1H, one proton from CH2), 1.51-1.18 (m, 16 H, CH2 × 8), 0.88 (t, J = 6.8 Hz, 3H, CH3);
13
C NMR (75 MHz,
CDCl3) δ 177.2, 80.9, 35.4, 31.7, 29.43, 29.39, 29.3, 29.20, 29.17, 28.7, 27.9, 25.1, 22.5, 14.0; IR (neat) ν (cm−1) 2925, 2854, 1779, 1463, 1420, 1376, 1352, 1285, 1216, 1178, 1127, 1019; MS (70 ev, EI) m/z (%) 227 (M+ + 1, 34.74), 226 (M+, 0.63), 85 (100).
2. Synthesis of (S)-4-tetradecalactone Synthesis of (Sa)-4,5-tetradecadienoic acid (Sa)-5j (zj-4-186,4-189)
Following Typical Procedure IV, the reaction of CuBr2 (0.6764 g, 3.0 mmol,
68
99%), (R)-3a (3.8711 g, 15 mmol), 1b (2.2745 g, 18 mmol)/dioxane (15 mL), and nonanaldehyde 2j (4.0 mL, d = 0.8277 g cm-3, 3.1784 g, 22.38 mmol)/dioxane (10 mL) for 16 h afforded (Sa)-4bj (1.6104 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (400 mL)] as a liquid, which was then submitted to next step without further characterization. Following Typical Procedure V, the reaction of (Sa)-4bj (1.6104 g, 6.4 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 25 mL of H2O and 25 mL of EtOH), and LiOH·H2O (0.4240 g, 9.6 mmol, 95%) for 18 h afforded (Sa)-5j21 (1.2931 g, 39%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (420 mL) to 10/1 (550 mL × 3) to 5/1 (600 mL)] as an oil: 97% ee (determined by the corrsponding esterification product (Sa)-4bj); [α]D20 = +66.5 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 10.15 (bs, 1H, COOH), 5.22-5.10 (m, 2H, =CH × 2), 2.48 (t, J = 7.4 Hz, 2H, CH2), 2.38-2.23 (m, 2H, CH2), 2.03-1.90 (m, 2H, CH2), 1.45-1.18 (m, 12H, CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 179.7, 92.9, 89.2, 33.1, 31.9, 29.4, 29.3, 29.14, 29.10, 28.8, 23.5, 22.6, 14.1; IR (neat) ν (cm−1) 3728-2188 (COOH), 3033, 2956, 2925, 2854, 2667, 1964, 1713, 1436, 1412, 1378, 1336, 1278, 1249, 1211, 1180, 1042, 1075; MS (70 ev, EI) m/z (%) 224 (M+, 6.98), 126 (100), 81 (100).
Esterification for determination of the ee value of (Sa)-5j: synthesis of (Sa)-ethyl 4,5-tetradeca dienoate (Sa)-4bj (zj-4-199)
Following Typical Procedure III, the reaction of (Sa)-5j (0.1340 g, 0.6 mmol), EtI (0.06 mL, d = 1.94 g cm-3, 0.1152 g, 0.74 mmol, 99%), K2CO3 (0.2507 g, 1.8 mmol), and DMF (6 mL) for 13 h afforded (Sa)-4bj (0.1385 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (600 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane/i-Pr = 400:1, 0.5 mL/min, λ = 214 nm, tR (major) = 8.9 min, tR (minor) = 9.4 min); [α]D20 = + 61.6 (c = 0.995, CHCl3) 1H NMR (300 MHz,
69
CDCl3) δ 5.18-5.09 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.46-2.37 (m, 2H, CH2), 2.35-2.24 (m, 2H, CH2), 2.02-1.91 (m, 2H, CH2), 1.45-1.18 (m, 15H, CH3 + CH2 × 6), 0.88 (t, J = 6.8 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.9, 92.3, 89.4, 60.1, 33.3, 31.8, 29.3, 29.2, 29.0, 28.8, 23.8, 22.5, 14.1, 13.9; IR (neat) ν (cm−1) 2957, 2926, 2855, 1963, 1739, 1464, 1418, 1372, 1349, 1300, 1249, 1159, 1097, 1038; MS (70 ev, EI) m/z (%) 252 (M+, 6.68), 80 (100); HRMS calcd for C16H28O2 [M+]: 252.2089, found: 252.2087.
Synthesis of (S)-5-decyldihydro-2(3H)-furanone (S)-4-tetradecalactone (zj-5-090)
Following Typical Procedure XV, the reaction of (R,E)-6j (0.1121 g, 0.5 mmol, prepared above, see page 35)/EtOAc (3 mL) and Pd/C (10% on C, dry, 0.0266 g, 0.025 mmol) for 36 h afforded (S)-4-tetradecalactone11 (0.1113 g, 98%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (550 mL)] as an oil with pleasant flavor: 93% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: He; injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 140 o
C to 200 oC (5 oC/min); tR(major) = 62.7 min, tR(minor) = 61.4 min; [α]D20 = -28.6 (c
= 1.01, CHCl3); (Lit.11 [α]D26 = -36.76 (c = 2.4, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 4.55-4.44 (m, 1H, =CH), 2.61-2.50 (m, 2H, CH2), 2.40-2.26 (m, 1H, one proton from CH2), 1.95-1.79 (m, 1H, one proton from CH2), 1.79-1.67 (m, 1H, one proton from CH2), 1.66-1.53 (m, 1H, one proton from CH2), 1.51-1.17 (m, 16 H, CH2 ×8), 0.88 (t, J = 6.8 Hz, 3H, CH3);
13
C NMR (75 MHz, CDCl3) δ 177.2, 80.9, 35.5, 31.7, 29.43,
29.39, 29.3, 29.20, 29.17, 28.7, 27.9, 25.1, 22.5, 14.0; IR (neat) ν (cm−1) 2956, 2922, 2853, 1754, 1471, 1425, 1384, 1186, 1023, 1008; MS (70 ev, EI) m/z (%) 227 (M+ + 1, 49.33), 226 (M+, 0.88), 85 (100).
3. Synthesis of (R)-γ-palmitolactone Synthesis of (Ra)-4,5- hexadecadienoic acid (Ra)-5l (zj-3-166,3-171)
70
Following Typical Procedure IV, the reaction of CuBr2 (0.6766 g, 3.0 mmol, 99%), (S)-3a (3.8771 g, 15 mmol, 98%), 1b (2.2785 g, 18 mmol)/dioxane (20 mL), and undecanylaldehyde 2l (3.8 mL, d = 0.825 g cm-3, 3.135 g, 17.9 mmol)/dioxane (5 mL) for 16 h afforded (Ra)-4bl (1.6328 g) [(eluent: petroleum ether (60-90 oC)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL × 2) to 20/1 (210 mL)] as a liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bl (1.6328 g, 5.83 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 29 mL of H2O and 29 mL of EtOH), and LiOH·H2O (0.3869 g, 8.745 mmol, 95%) for 18 h afforded (Ra)-5l (1.2436 g, 33%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (500 mL) to 10/1 (500 mL × 3) to 5/1 (360 mL)] as a liquid: 97% ee (determined by the corrsponding esterification product (Ra)-4al); [α]D20 = -59.8 (c = 0.99, CHCl3); 1
H NMR (300 MHz, CDCl3) δ 10.25 (bs, 1H, COOH), 5.20-5.11 (m, 2H, =CH × 2),
2.48 (t, J = 6.9 Hz, 2H, CH2), 2.36-2.24 (m, 2H, CH2); 2.02-1.91 (m, 2H, CH2), 1.44-1.17 (m, 16H, CH2 × 8), 0.88 (t, J = 6.8 Hz, 3H, CH3);
13
C NMR (75 MHz,
CDCl3) δ 203.6, 179.7, 92.9, 89.2, 33.1, 31.9, 29.64, 29.61, 29.5, 29.3, 29.15, 29.11, 28.8, 23.5, 22.7, 14.1; IR (neat) ν (cm−1) 3558-2221 (COOH), 3037, 2956, 2925, 2854, 2664, 1963, 1712, 1436, 1412, 1377, 1334, 1279, 1249, 1211, 1173, 1046, 1017; MS (70 ev, EI) m/z (%) 252 (M+, 5.43), 126 (100); HRMS calcd. for C16H28O2 [M + H+]: 252.2089, found: 252.2088.
Esterification for determination of the ee value of (Ra)-5l: synthesis of (Ra)-ethyl 4,5-hexadeca dienoate (Ra)-4al 5(zj-3-184)
71
To a Schlenk tube were added (Ra)-5l (0.0505 g, 0.2 mmol, prapared above) and DMF (2 mL). Then K2CO3 (0.0830 g, 0.6 mmol) and BnBr (0.03 mL, d = 1.43 g cm-3, 0.042 g, 0.246 mmol, 98%) were added sequentially. After continuous stirring at room temperature for 18 h, the reaction was complete as monitored by TLC. After quenching with water (10 mL) and being stirred for 10 min, the aqueous solution was extracted with Et2O (10 mL × 3). The combined organic layer was washed with H2O and brine, and dried over anhydrous Na2SO4. Filtration, evaporation, and column chromatography on silica gel gave (Ra)-4al (0.0635 g, 93%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL)] as a liquid: 97% ee (HPLC conditions: Chiralcel IA column, n-hexane, 0.8 mL/min, λ = 214 nm, tR (major) = 20.0 min, tR (minor) = 22.4 min); [α]D20 = -49.8 (c = 1.00, CHCl3); 1H NMR (300 MHz, CDCl3) δ 7.33-7.20 (m, 5H, ArH), 5.11-4.97 (m, 4H, =CH × 2 + CH2), 2.44-2.35 (m, 2H, CH2), 2.29-2.19 (m, 2H, CH2), 1.92-1.80 (m, 2H, CH2), 1.34-1.11 (m, 16H, CH2 × 8), 0.80 (t, J = 6.6 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 172.9, 136.0, 128.5, 128.1, 92.6, 89.4, 66.1, 33.4, 31.9, 29.6, 29.4, 29.3, 29.1, 28.8, 23.8, 22.7, 14.1; IR (neat) ν (cm−1) 3090, 3066, 3033, 2956, 2925, 2853, 1962, 1740, 1498, 1455, 1379, 1353, 1153; MS (70 ev, EI) m/z (%) 343 (M+ + 1, 7.75), 342 (M+, 4.17), 91 (100); HRMS calcd for C23H34O2 [M+]: 342.2559, found: 342.2552.
Synthesis of (S,E)-5-(1-dodecenyl)dihydro-2(3H)-furanone (S,E)-6l (zj-3-181)
Following Typical Procedure VI, the reaction of AgOTs (0.0142 g, 0.05 mmol, 98%), Au(LB-Phos)Cl (0.0299 g, 0.05 mmol), CHCl3 (5 mL), and (Ra)-5l (0.2524 g, 1.0 mmol)/CHCl3 (5 mL) for 2.5 h afforded (S,E)-6l (0.2492 g, 99%, (S,E)/(R,Z) = 98/2 determined by 1H NMR) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (250 mL) to 8/1 (400 mL)] ((S,E)/(R,Z) = 97/3 determined by 1H NMR of crude product) as an oil with pleasant flavor: 97% ee (HPLC conditions: Chiralcel AS-H column, hexane/i-PrOH = 95:5, 1.0 mL/min, λ = 214 nm, tR(major) = 11.8 min,
72
tR(minor) = 10.6 min; [α]D20 = +24.2 (c = 1.005, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.80 (dt, J1 = 15.3 Hz, J2 = 7.1 Hz, 1H, =CH), 5.49 (ddt, J1 = 15.0 Hz, J2 = 7.1 Hz, J3 = 1.3 Hz, 1H, =CH), 4.89 (q, J = 6.8 Hz, 1H, CH), 2.57-2.48 (m, 2H, CH2), 2.43-2.31 (m, 1H, one proton from CH2), 2.12-1.90 (m, 3H, CH2 + one proton from CH2), 1.46-1.17 (m, 16H, CH2 × 8), 0.88 (t, J = 6.8 Hz, 3H, CH3); the following signals are discernible for (R,Z)-6l: δ 5.71-5.61 (m, 1H, =CH), 5.30-5.21 (m, 1H, CH); 13
C NMR (75 MHz, CDCl3) δ 176.8, 135.3, 127.2, 80.9, 31.8, 31.6, 29.33, 29.30, 29.2,
29.1, 28.8, 28.6, 28.5, 28.4, 22.4, 13.8; IR (neat) ν (cm−1) 2925, 2854, 1778, 1672, 1462, 1421, 1376, 1325, 1300, 1216, 1176, 1123, 1009; GC-MS (GC condition: injector: 280 oC; column: DB5 column 30 m × 0.25 mm, temperature programming: 60 oC (2 min), 20 oC/min to 280 oC, 280 oC (30 min); detector: 280 oC) (70 ev, EI) m/z (%) for (S,E)-6l: tR (major) = 7.8 min: 252 (M+, 1.16), 111 (100); for (R,Z)-6l tR (minor) = 7.6 min: 252 (M+, 3.23), 111 (100); HRMS calcd. for C16H28O2 [M +]: 252.2089, found: 252.2086.
Synthesis of (R)-5-dodecyldihydro-2(3H)-furanone (R)-γ-palmitolactone (zj-5-044)
Following Typical Procedure XV, the reaction of (S,E)-6l (0.1261 g, 0.5 mmol)/EtOAc (4 mL), Pd/C (0.0128 g, 10% on C, dry, 0.012 mmol), and EtOAc (3 mL) for 60 h afforded (R)-γ-palmitolactone23 (0.1175 g, 92%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 10/1 (850 mL)] as an oil with pleasant flavor: 96% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: He; injector: 145 oC; detector (FID, H2): 200 oC; oven temperature: 130 oC to 200 oC (5 o
C/min); tR (major) = 121.3 min, tR (minor) = 124.2 min; [α]D20 = +26.9 (c = 0.99,
CHCl3); 1H NMR (300 MHz, CDCl3) δ 4.54-4.43 (m, 1H, CH), 2.57-2.48 (m, 2H, CH2), 2.38-2.26 (m, 1H, one proton from CH2), 1.92-1.81 (m, 1H, one proton from CH2), 1.79-1.67 (m, 1H, one proton from CH2), 1.65-1.53 (m, 1H, one proton from
73
CH2), 1.50-1.18 (m, 20H, CH2 × 10), 0.88 (t, J = 6.8 Hz, 3H, CH3);
13
C NMR (75
MHz, CDCl3) δ 177.1, 80.9, 35.5, 31.8, 29.52, 29.50, 29.4, 29.3, 29.2, 28.7, 27.9, 25.1, 22.5, 14.0; IR (neat) ν (cm−1) 2925, 2854, 1780, 1462, 1421, 1376, 1352, 1285, 1216, 1177, 1127, 1021; MS (70 ev, EI) m/z (%) 255 (M+ + 1, 60.83), 254 (M+, 1.65), 85 (100).
4. Gram Scale Synthesis of (R)-4-Decalactone Synthesis of (Ra)-4,5-decadienoic acid (Ra)-5b (zj-6-108,6-111)
Following Typical Procedure I, the reaction of CuBr2 (1.3514 g, 6.0 mmol, 99%), (S)-2-(pyrrolidin-2-yl)propan-2-ol (S)-3b (3.8415 g, 30 mmol), 1b (5.6719 g, 45 mmol)/dioxane (60 mL), and 2b (4.8 mL, d = 0.81 g cm-3, 3.888 g, 45.21 mmol)/dioxane (30 mL) afforded (Ra)-4bb (3.0621 g) [(eluent: petroleum ether (60-90 C)/diethyl ether = 100/1 (500 mL × 2) to 50/1 (500 mL) to 30/1 (500 mL)] as a
o
liquid, which was then submitted to next step. Following Typical Procedure V, the reaction of (Ra)-4bb (3.0621 g, 15.6 mmol, prepared above), EtOH/H2O = 1:1 by volume (pre-mixed by using 35 mL of H2O and 35 mL of EtOH), and LiOH·H2O (1.0352 g, 23.4 mmol, 95%) afforded (Ra)-5b (2.2406 g, 45%, 2 steps) [(eluent: petroleum ether (60-90 oC)/ethyl acetate = 20/1 (420 mL) to 15/1 (480 mL) to 10/1 (660 mL)] as a liquid: 98% ee (determined by the corrsponding esterification product (Ra)-4bb); [α]D20 = -77.7 (c = 0.99, CHCl3); 1H NMR (300 MHz, CDCl3) δ 11.55 (bs, 1H, COOH), 5.21-5.11 (m, 2H, =CH × 2), 2.48 (t, J = 7.4 Hz, 2H, CH2), 2.36-2.22 (m, 2H, CH2), 2.05-1.90 (m, 2H, CH2), 1.46-1.25 (m, 4H, CH2 × 2), 0.90 (t, J = 7.2 Hz, 3H, CH3); 13C NMR (75 MHz, CDCl3) δ 203.6, 180.0, 92.8, 89.2, 33.1, 31.2, 28.5, 23.4, 22.1, 13.8.
74
Esterification for determination of the ee value of (Ra)-5b: synthesis of (Ra)-ethyl 4,5-decadienoate (Ra)-4bb (zj-6-116)
Following Typical Procedure III, the reaction of (Ra)-5b (0.0831 g, 0.5 mmol)/DMF (5 mL), K2CO3 (0.2072 g, 1.5 mmol), and EtI (0.05 mL, d = 1.94 g cm-3, 0.0951 g, 0.61 mmol, 98%) for 18 h afforded (Ra)-4bb (0.0905 g, 93%) [eluent: petroleum ether (60-90 oC)/ethyl acetate = 100/1 (500 mL) to 50/1 (300 mL)] as a liquid: 98% ee (HPLC conditions: Chiralcel OZ-H column, n-hexane, 1.0 mL/min, λ = 214 nm, tR (major) = 27.1 min, tR (minor) = 24.5 min); [α]D20 = -69.6 (c = 1.04, CHCl3); 1H NMR (300 MHz, CDCl3) δ 5.20-5.08 (m, 2H, =CH × 2), 4.13 (q, J = 7.2 Hz, 2H, OCH2), 2.47-2.37 (m, 2H, CH2), 2.35-2.24 (m, 2H, CH2), 2.04-1.92 (m, 2H, CH2), 1.43-1.30 (m, 4H, CH2 × 2), 1.26 (t, J = 7.1 Hz, 3H, CH3) 0.90 (t, J = 6.9 Hz, 3H, CH3);
13
C NMR (75 MHz, CDCl3) δ 203.7, 173.0, 92.4, 89.4, 60.1, 33.4, 31.2,
28.5, 23.8, 22.1, 14.1, 13.8.
Gram Scale Synthesis of (R)-5-hexyldihydro-2(3H)-furanone (R)-4-Decalactone (zj-6-170)
Following Typical Procedure XV, the reaction of (S,E)-6b (1.1772 g, 7.0 mmol, prepared above, see page 36)/EtOAc (20 mL), and Pd/C (10% on C, dry, 0.3724 g, 0.35 mmol) for 36 h afforded (R)-4-decalactone24 (1.1635 g, 98%) [eluent: petroleum ether (60-90 oC)/diethyl ether = 5/1 (500 mL × 2) to 3/1 (400 mL)] as an oil with pleasant flavor: 94% ee (GC conditions: CP-Chirasil-DEX CB column (25 m × 0.25 mm × 0.25 μm); carrier: N2 at 10 psi; injector: 250 oC; detector (FID, H2): 250 oC; oven temperature: 60 oC to 180 oC (5 oC/min); tR(major) = 49.6 min, tR(minor) = 50.1
75
min); [α]D20 = +40.0 (c = 0.975, CHCl3); (Lit.24 [α]D26 = +31 (c = 1.2, CHCl3)); 1H NMR (300 MHz, CDCl3) δ 4.55-4.43 (m, 1H, =CH), 2.60-2.45 (m, 2H, CH2), 2.40-2.25 (m, 1H, one proton from CH2), 1.94-1.80 (m, 1H, one proton from CH2), 1.80-1.67 (m, 1H, one proton from CH2), 1.66-1.53 (m, 1H, one proton from CH2), 1.52-1.19 (m, 8 H, CH2 × 4), 0.89 (t, J = 6.9 Hz, 3H, CH3);
13
C NMR (75 MHz,
CDCl3) δ 177.2, 81.0, 35.5, 31.5, 28.7, 27.9, 25.1, 22.4, 13.9; IR (neat) ν (cm−1) 2956, 2932, 2858, 1778, 1461, 1422, 1379, 1351, 1292, 1218, 1181, 1127, 1022; MS (70 ev, EI) m/z (%) 171 (M+ + 1, 30.46), 170 (M+, 0.13), 85 (100).
76
10
7.350 7.342 7.333 7.308 7.289 7.261 7.221
8
2017-09-03 21:39:37.968 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.00
6
5.176 5.166 5.145 5.136 5.125 5.109 5.102 5.091 5.080 5.070 5.060 5.048 4.00
Supplementary Figure 1. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4aa.
77
4
2.00
2.01
2
2.00
10.31
3.00
0
PPM
2.491 2.487 2.465 2.440 2.362 2.346 2.333 2.325 2.316 2.306 2.300 2.289 2.280 2.268 1.973 1.951 1.926 1.916 1.894 1.382 1.358 1.317 1.294 1.258 0.895 0.873 0.850 -0.000
zj-8-078
Supplementary Figures
Supplementary Figure 2. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4aa.
78
200
172.751
2017-09-03 21:44:49.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 74 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-078
100
50
33.256 31.739 29.028 28.991 28.743 23.724 22.538 13.981
66.016
77.423 77.000 76.568
92.516 89.335
128.391 128.061 128.033
135.947
203.562
0
PPM
电 (mv) 压
zj-8-078 实验时间：2017-09-03,21:25:58 谱图文件:D:\浙大智达\N2000\样品\S20170903212558.org 方法文件:D:\浙大智达\N2000\djx.mtd
实验者：zj 报告时间：2017-09-04,10:31:35 积分方法:面积归一法
实验内容简介： OJ-H,214,n-hexane/i-PrOH = 200/1, 0.8
色谱图(S20170903212558.org)
1,400 1,300 1,200 1,100 1,000
电压(mv)
900 800 700 600 500 400 300 200 100 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
8.462 9.617
总计
Supplementary Figure 3. HPLC spectrum for (Ra)-4aa. 79
峰面积
含量
70784.430 1354498.625
573324.122 21785467.000
2.5642 97.4358
1425283.055
19287909.438
100.0000
电 (mv) 压
zj-8-079 实验时间：2017-09-03,21:05:00 谱图文件:D:\浙大智达\N2000\样品\S20170903210500.org 方法文件:D:\浙大智达\N2000\djx.mtd
实验者：zj 报告时间：2017-09-04,10:21:11 积分方法:面积归一法
实验内容简介： OJ-H,214,n-hexane/i-PrOH = 200/1, 0.8
色谱图(S20170903210500.org) 1,200 1,100 1,000 900
电压(mv)
800 700 600 500 400 300 200 100 0 2
4
6
8
10
12
14
16
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
8.408 9.640
总计
Supplementary Figure 4. HPLC spectrum for rac-4aa. 80
峰面积
含量
906405.375 1178140.750
15571489.000 15385857.000
50.2998 49.7002
2084546.125
30957346.000
100.0000
Supplementary Figure 5. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5a.
81
12
11.207
10
0.73
2017-05-15 10:13:03.203 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
5.188 5.172 5.157 5.140 5.125
6
zj-8-040
2.00
4
2.01
2.00
2
2.00
10.35
3.01
0
2.508 2.482 2.458 2.338 2.323 2.299 2.284 2.280 2.007 1.985 1.966 1.952 1.927 1.379 1.355 1.271 0.904 0.882 0.859 -0.000
7.265
PPM
Supplementary Figure 6. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5a.
82
179.737
200
2017-05-15 15:28:09.281 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 5336 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-040
100
50
14.064
33.127 31.841 29.111 28.826 23.494 22.630
77.423 77.000 76.577
92.883 89.216
203.672
0
PPM
Supplementary Figure 7. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4ba.
83
10
7.273
8
2017-05-10 09:27:13.648 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.167 5.152 5.136 5.121 5.103
6
4.167 4.144 4.120 4.096 2.00
4
2.00
zj-8-043
2.00
2.01
2
2.02
13.32
3.02
0
2.441 2.414 2.389 2.332 2.316 2.307 2.300 2.289 2.276 2.267 2.255 1.980 1.964 1.956 1.948 1.939 1.923 1.403 1.379 1.355 1.283 1.273 1.259 1.235 0.903 0.882 0.859 -0.000
PPM
Supplementary Figure 8. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4ba.
84
203.553
200
2017-05-10 14:27:34.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 148 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-043
100
50
33.284 31.749 29.028 28.991 28.761 23.761 22.538 14.082 13.944
60.096
77.432 77.000 76.577
92.369 89.381
172.953
0 PPM
m)v(压
zj-8-043-od-h-100-0-0.5-214 实验时间：2017-5-25,16:18:55 谱图文件:D:\zhuguangjiong\zj\20170525\zj-8-043-od-h-100-00.5-214..org
报告时间：2017-5-25,17:01:38
实验内容简介：
色谱图(zj-8-043-od-h-100-0-0.5-214..org)
1,500 1,400 1,300 1,200 1,100 1,000
800 700
15.795
电压(mv)
900
600 500 400 300
15.352
200 100 0 0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
15.352 15.795
总计
Supplementary Figure 9. HPLC spectrum for (Ra)-4ba. 85
峰面积
含量
18955.471 520920.969
279392.031 15151092.000
1.8106 98.1894
539876.439
15430484.031
100.0000
m)v(压
zj-8-020-od-h-100-0-0.5-214 实验时间：2017-5-25,15:06:21 谱图文件:D:\zhuguangjiong\zj\20170525\zj-8-020-od-h-100-00.5-214.org
报告时间：2017-5-25,16:33:57
实验内容简介：
色谱图(zj-8-020-od-h-100-0-0.5-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
800 14.978
700 600 500
15.883
电压(mv)
900
400 300 200 100 0 0
1
2
3
4
5
6
7
8
9
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
14.978 15.883
总计
Supplementary Figure 10. HPLC spectrum for rac-4ba.
86
峰面积
含量
487824.688 409940.844
11432328.000 11590101.000
49.6573 50.3427
897765.531
23022429.000
100.0000
Supplementary Figure 11. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5b.
87
11.418
12
0.97
10
2016-05-07 23:22:11.546 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
5.194 5.184 5.174 5.169 5.153 5.137 5.122 5.114
6
zj-6-053
1.97
4
1.98
2.00
2
2.00
4.10 3.03
0
PPM
2.502 2.477 2.453 2.335 2.321 2.305 2.296 2.282 2.253 2.014 1.995 1.974 1.958 1.934 1.428 1.418 1.398 1.391 1.372 1.360 1.348 1.336 1.323 1.296 1.257 0.919 0.895 0.871 0.000
7.267
Supplementary Figure 12. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5b.
88
200
179.893
2016-05-07 23:34:43.625 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 196 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
50
zj-6-053
13.797
33.146 31.206 28.476 23.485 22.134
77.423 77.000 76.568
92.782 89.207
203.691
0
PPM
Supplementary Figure 13. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bb.
89
7.304
10
8
2016-05-09 21:09:21.765 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
1.96
4
2.00
zj-6-055
2.00
2.00
2
2.00
3.03
4.01 3.00
0
2.437 2.431 2.410 2.384 2.330 2.314 2.305 2.298 2.287 2.277 2.265 2.246 2.012 1.997 1.988 1.975 1.964 1.956 1.951 1.932 1.420 1.411 1.393 1.376 1.364 1.352 1.340 1.328 1.281 1.257 1.233 0.922 0.899 0.875 -0.000
4.165 4.142 4.118 4.094
5.164 5.148 5.132 5.117 5.102
PPM
Supplementary Figure 14. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bb.
90
172.953
203.654
200
2016-05-09 21:20:30.375 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 171 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-055
100
50
14.100 13.733
33.394 31.188 28.458 23.844 22.061
60.115
77.423 77.000 76.577
92.314 89.427
0
PPM
zj-6-055-pc-2-100-0-0.7-214 实验时间：2016-06-23,13:21:42 谱图文件:D:\zhuguangjiong\zj\20160617\zj-6-055-pc-2-100-00.7-214.org
报告时间：2016-06-23,14:23:27
实验内容简介：
色谱图(zj-6-055-pc-2-100-0-0.7-214.org)
300 280 260 240 220 200
电压(mv)
180 160 140 120
44.773
100 80 60
38.427
40 20 0 -20 0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
38.427 44.773
总计
Supplementary Figure 15. HPLC spectrum for (Ra)-4bb. 91
峰面积
含量
2442.978 54326.734
90536.805 5309446.500
1.6766 98.3234
56769.713
5399983.305
100.0000
zj-6-054-pc-2-100-0-0.7-214 实验时间：2016-06-23,12:22:21 谱图文件:D:\zhuguangjiong\zj\20160617\zj-6-054-pc-2-100-00.7-214.org
报告时间：2016-06-23,14:18:40
实验内容简介：
色谱图(zj-6-054-pc-2-100-0-0.7-214.org)
800 750 700 650 600 550
电压(mv)
500 450 400 350 300 200 150 100
42.598
35.650
250
50 0 0
2
4
6
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
35.650 42.598
总计
Supplementary Figure 16. HPLC spectrum for rac-4bb. 92
峰面积
含量
127000.523 103346.539
13396767.000 13652672.000
49.5270 50.4730
230347.063
27049439.000
100.0000
Supplementary Figure 17. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5c.
93
12
0.95
10
2015-07-04 18:55:11.515 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
5.182 5.166 5.152 5.135 5.120 2.00
zj-4-033
4
2.00
2.00
2
2.00
18.52
3.00
0
2.499 2.476 2.451 2.333 2.310 2.302 2.294 2.280 2.003 1.982 1.963 1.949 1.924 1.377 1.353 1.261 0.901 0.880 0.857 -0.000
7.263
11.037
PPM
Supplementary Figure 18. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5c.
94
179.948
203.654
200
2015-07-04 16:56:15.515 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 154 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-033
100
50
33.137 31.914 29.644 29.469 29.350 29.157 29.111 28.826 23.458 22.667 14.064
92.837 89.198 77.423 77.000 76.577
0
PPM
Supplementary Figure 19. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bc.
95
10
7.272
8
2015-10-07 16:54:12.859 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
5.167 5.152 5.148 5.135 5.126 5.120 5.115 5.106 4.167 4.144 4.120 4.096 2.00
zj-4-111
4
2.00 2.00
2.02
2
2.00
21.83
3.05
0
2.441 2.435 2.418 2.414 2.409 2.391 2.388 2.332 2.316 2.307 2.300 2.289 2.279 2.276 2.267 2.249 2.002 1.979 1.963 1.954 1.947 1.922 1.373 1.352 1.283 1.259 1.235 0.902 0.881 0.858 -0.000
PPM
Supplementary Figure 20. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bc.
96
173.146
203.645
200
2015-10-07 17:16:27.390 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 359 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-111
100
50
33.449 31.887 29.635 29.607 29.451 29.322 29.129 28.862 23.880 22.649 14.192 14.073
60.243
77.423 77.000 76.577
92.507 89.473
0
PPM
zj-4-111-od-h-100-0-0.7-214 实验时间：2015-10-13,9:01:11 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-111-od-h-100-00.7-214.org
报告时间：2015-10-13,10:14:25
实验内容简介：
色谱图(zj-4-111-od-h-100-0-0.7-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
电压(mv)
900 800 700 600
14.175
500 400 300
13.918
200 100 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
13.918 14.175
12605.106 322828.813 335433.919
总计
Supplementary Figure 21. HPLC spectrum for (Ra)-4bc. 97
峰面积
含量
135971.844 8508424.000
1.5729 98.4271
8644395.844
100.0000
zj-4-110-od-h-100-0-0.7-214 实验时间：2015-10-13,9:39:25 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-110-od-h-100-00.7-214...org
报告时间：2015-10-13,10:12:11
实验内容简介：
色谱图(zj-4-110-od-h-100-0-0.7-214...org)
500 450 400 350
电压(mv)
300 250 200
13.877 14.487
150 100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
13.877 14.487
总计
Supplementary Figure 22. HPLC spectrum for rac-4bc. 98
峰面积
含量
87863.875 79448.938
1429751.875 1442813.875
49.7726 50.2274
167312.813
2872565.750
100.0000
Supplementary Figure 23. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bd.
99
10
7.319
8
2017-05-18 15:26:16.375 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
5.243 5.223 5.203 5.192 5.176 5.158 5.148 5.137 5.126 4.165 4.141 4.117 4.093 1.95
4
2.00
zj-8-048
2.00
3.01
2
3.08
0
2.438 2.432 2.411 2.388 2.338 2.334 2.327 2.323 2.319 2.316 2.306 2.294 2.289 2.281 2.273 2.269 2.267 2.258 2.255 2.248 2.236 2.225 1.281 1.257 1.233 1.005 0.982 -0.000
PPM
Supplementary Figure 24. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bd.
100
202.000
200
172.944
2017-05-18 15:39:59.125 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 217 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-048
99.805
100
50
14.064
27.750 23.789 22.290 22.235
33.265
60.096
77.423 77.000 76.577
90.687
0
PPM
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5HSRUWHGE\ 8VHU
%UHH]HXVHU %UHH]H
6$03/( ]MRGK ᵚ⸕ XO 0LQXWHV
$FTXLUHG%\ 'DWH$FTXLUHG $FT 0HWKRG 'DWH3URFHVVHG &KDQQHO 1DPH &KDQQHO 'HVF 6DPSOH6HW 1DPH
%UHH]H &67 ]JM &67 : &K$ : &K$QP
6DPSOH1DPH 6DPSOH7\SH 9LDO ,QMHFWLRQ ,QMHFWLRQ9ROXPH 5XQ7LPH &ROXPQ7\SH
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$8
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$UHD
+HLJKW ⽖ +HLJKW
5HSRUW0HWKRG ,QGLYLGXDO 5HSRUW$6& 3DJH ޡ䇑
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Supplementary Figure 25. HPLC spectrum for (Ra)-4bd. 101
ѝഭ、ᆖ䲒к⎧ᴹᵪॆᆖ⹄ウᡰ GHIDXOWV IRUFRS\
5HSRUWHGE\ 8VHU
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6$03/( 6DPSOH1DPH 6DPSOH7\SH 9LDO ,QMHFWLRQ ,QMHFWLRQ9ROXPH 5XQ7LPH &ROXPQ7\SH
,1)250$7,21
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$FTXLUHG%\ 'DWH$FTXLUHG $FT 0HWKRG 'DWH3URFHVVHG &KDQQHO 1DPH &KDQQHO 'HVF 6DPSOH6HW 1DPH
%UHH]H &67 ]JM &67 : &K$ : &K$QP
3URMHFW1DPH
$8
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+HLJKW ⽖ +HLJKW
5HSRUW0HWKRG ,QGLYLGXDO 5HSRUW$6& 3DJH ޡ䇑
3ULQWHG 35&
Supplementary Figure 26. HPLC spectrum for rac-4bd.
102
103
12
Supplementary Figure 27. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5d.
10.896
10
0.83
2017-05-22 10:20:47.734 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
5.247 5.237 5.227 5.218 5.206 5.187 5.175 5.166 2.00
zj-8-051
4
2.00
2
3.00
2.508 2.484 2.460 2.348 2.336 2.328 2.317 2.307 2.289 2.273 2.251 2.233 1.004 0.981 6.01
0
0.000
7.269
PPM
Supplementary Figure 28. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5d.
104
179.856
202.082
200
2017-05-22 14:05:49.140 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 880 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-051
100.274
100
50
27.861 23.522 22.364 22.318
33.109
77.423 77.000 76.577
90.503
0
PPM
105
10
Supplementary Figure 29. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bd.
7.295
8
2017-08-26 13:16:16.140 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
1.97
4
2.00
zj-8-063
2.02
3.02
2
3.01
6.07
5.243 5.232 5.223 5.213 5.203 5.197 5.191 5.186 5.178 5.172 5.168 5.159 5.153 5.149 5.139 5.133 5.128 4.166 4.142 4.118 4.094 2.434 2.412 2.386 2.334 2.314 2.301 2.283 2.268 2.256 2.250 2.226 2.216 2.204 1.281 1.258 1.234 1.003 0.980 -0.000
0
PPM
Supplementary Figure 30. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bd.
106
202.055
200
173.064
150
2017-08-26 13:38:39.093 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 355 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-8-063
99.878
100
50
14.119
27.805 23.862 22.355 22.299
33.348
60.179
77.423 77.000 76.577
90.742
0
PPM
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,1)250$7,21
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$FTXLUHG%\ 'DWH$FTXLUHG $FT 0HWKRG 'DWH3URFHVVHG &KDQQHO 1DPH &KDQQHO 'HVF 6DPSOH6HW 1DPH
%UHH]H &67 ]JM &67 : &K$ : &K$QP
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Supplementary Figure 31. HPLC spectrum for (Ra)-4bd. 107
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Supplementary Figure 32. HPLC spectrum for rac-4bd.
108
109
12
Supplementary Figure 33. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5e.
11.177
10
0.98
2015-06-10 23:22:36.452 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.234 5.204 5.194 7.270 5.184 5.153 5.142 5.121
8
6
1.97
zj-3-196
4
2.00
2.00
2
1.00
5.00
5.12
0
-2
2.504 2.501 2.479 2.455 2.336 2.325 2.317 2.306 2.295 2.284 2.280 2.273 2.261 1.990 1.971 1.953 1.942 1.923 1.905 1.886 1.752 1.737 1.725 1.715 1.705 1.683 1.647 1.607 1.323 1.295 1.282 1.241 1.201 1.164 1.125 1.074 1.036 0.993 -0.000
PPM
Supplementary Figure 34. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5e.
110
179.985
202.413
200
2015-06-11 12:08:23.125 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 222 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-3-196
98.867
100
50
37.144 33.091 32.934 26.068 25.985 23.467
77.423 77.000 76.577
90.126
0
PPM
111
10
Supplementary Figure 35. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4be.
7.292
8
2015-06-16 11:12:04.390 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
5.222 5.192 5.182 5.172 5.163 5.145 5.125 5.115 5.094 4.164 4.140 4.117 4.093 1.95
4
2.00
zj-4-006
2.00 2.00
2
1.03
5.02
8.25
0
PPM
2.439 2.411 2.388 2.329 2.300 2.287 2.276 2.260 1.995 1.964 1.948 1.919 1.901 1.881 1.742 1.717 1.689 1.648 1.611 1.327 1.284 1.260 1.236 1.206 1.169 1.121 1.073 1.035 0.994 0.000
Supplementary Figure 36. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4be.
112
202.386
200
173.082
2015-06-16 13:32:30.034 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 183 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
98.490
100
zj-4-006
50
14.137
37.108 33.330 32.953 32.916 26.059 25.958 23.825
60.188
77.432 77.000 76.577
90.365
0 PPM
zj-4-006-ay-100-0-0.6-214 实验时间：2015/7/9,12:05:37 报告时间：2015/7/9,18:01:10 谱图文件:D:\zhuguangjiong\zj\20150706\zj-4-006-ay-100-0-0.6214..org 实验内容简介：
色谱图(zj-4-006-ay-100-0-0.6-214..org)
500 450 400 350
250 200
17.317
电压(mv)
300
150 100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
17.317 17.317
总计
Supplementary Figure 37. HPLC spectrum for (Ra)-4be. 113
峰面积
含量
107960.531 2235.882
5137819.000 87625.016
98.3231 1.6769
110196.414
5225444.016
100.0000
zj-4-005-ay-100-0-0.6-214 实验时间：2015/7/9,11:06:55 报告时间：2015/7/9,17:59:35 谱图文件:D:\zhuguangjiong\zj\20150706\zj-4-005-ay-100-0-0.6214.org
0
1
2
3
4
5
6
7
8
9
19.367
色谱图(zj-4-005-ay-100-0-0.6-214.org)
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
17.743
电压(mv)
实验内容简介：
10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
17.743 19.367
总计
Supplementary Figure 38. HPLC spectrum for rac-4be. 114
峰面积
含量
64498.359 53120.230
2592152.750 2621561.000
49.7180 50.2820
117618.590
5213713.750
100.0000
Supplementary Figure 39. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5f.
115
12
10
1.00
2015-11-07 13:17:18.703 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
7.303 7.289 7.278 7.276 7.266 7.255 7.207 7.196 7.184 2.03
3.02
6
5.333 5.331 5.321 5.310 5.299 5.204 5.194 5.185 5.174 5.165 1.01 1.00
zj-4-169
3.328 3.319 3.305 3.296
4
2.01 2.03
2
2.443 2.439 2.416 2.393 2.309 2.299 2.288 2.278 2.267 2.256
2.00
0
0.000
10.530
PPM
Supplementary Figure 40. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5f.
116
179.679
204.236
200
2015-11-08 22:25:21.351 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 311 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-169
100
50
23.363
35.522 33.041
77.423 77.000 76.577
92.192 89.858
128.404 128.303 126.106
140.149
0
PPM
117
Supplementary Figure 41. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bf. 10 8
2015-11-11 09:52:06.906 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
2.01
2.96
7.305 7.301 7.280 7.277 7.273 7.261 7.253 7.210 7.187 7.180 7.151
6 0.96
0.98
4
2.00
zj-4-174
2.00 4.01
2 3.01
5.338 5.328 5.318 5.307 5.294 5.283 5.273 5.260 5.250 5.221 5.213 5.202 5.192 5.182 5.172 5.162 5.152 5.143 4.138 4.114 4.090 4.066 3.329 3.319 3.305 3.296 2.399 2.391 2.378 2.370 2.346 2.318 2.305 2.296 2.286 2.275 2.265 2.255 2.243 2.236 1.250 1.226 1.202 -0.000
0 PPM
Supplementary Figure 42. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bf.
118
172.852
204.178
200
2015-11-11 09:58:27.718 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 83 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-174
100
50
14.082
23.678
35.536 33.229
60.133
77.423 77.000 76.577
91.734 90.025
128.309 128.208 126.002
140.148
0 PPM
zj-4-174-as-h-100-0-1-214 实验时间：2015/11/17,11:15:06 报告时间：2015/11/17,16:56:02 谱图文件:D:\zhuguangjiong\zj\20151117\zj-4-174-as-h-100-0-1214..org 实验内容简介：
1,500
色谱图(zj-4-174-as-h-100-0-1-214..org)
1,400 1,300 1,200 1,100 1,000
800 700
20.277
电压(mv)
900
600 500 400 300
23.315
200 100
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.277 23.315
总计
Supplementary Figure 43. HPLC spectrum for (Ra)-4bf. 119
峰面积
含量
430079.688 11803.181
33621564.000 772857.188
97.7530 2.2470
441882.868
34394421.188
100.0000
zj-4-021-as-h-100-0-1-214 实验时间：2015/11/17,10:10:53 报告时间：2015/11/17,16:54:51 谱图文件:D:\zhuguangjiong\zj\20151117\zj-4-021-as-h-100-0-1214.org 实验内容简介：
1,500
色谱图(zj-4-021-as-h-100-0-1-214.org)
1,400 1,300 1,200 1,100 1,000
电压(mv)
900 800 700 600
400 300
23.115
20.907
500
200 100 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.907 23.115
总计
Supplementary Figure 44. HPLC spectrum for rac-4bf. 120
峰面积
含量
269109.406 233418.578
19191692.000 19284672.000
49.8792 50.1208
502527.984
38476364.000
100.0000
Supplementary Figure 45. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5g.
121
11.146
12
2015-10-21 10:30:39.296 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
10
0.82
8
7.293 7.269 7.244 7.190 7.166 7.142 2.00
3.02
6
1.98
5.233 5.224 5.213 5.191 5.180 5.160 5.150 5.131
zj-4-139
4
2.00
2
6.13
2.726 2.700 2.674 2.379 2.370 2.351 2.327 2.315 2.304 2.294 2.283 2.260 2.249 2.241 2.230 2.219 2.207 2.178 -0.000
0
PPM
Supplementary Figure 46. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5g.
122
179.737
203.792
200
2015-10-24 22:30:17.984 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 165 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-139
100
50
23.329
35.196 32.916 30.425
77.423 77.000 76.577
92.075 89.823
128.456 128.244 125.818
141.664
0
PPM
123
Supplementary Figure 47. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bg. 10 8
2015-10-21 10:37:43.515 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
2.07
2.95
7.294 7.288 7.282 7.270 7.267 7.254 7.246 7.233 7.221 7.192 7.167 7.156 7.141
6
5.211 5.202 5.191 5.182 5.170 5.164 5.160 5.149 5.142 5.131 5.121 4.154 4.130 4.106 4.082
1.96
zj-4-141
4
2.00 2.00
2.728 2.702 2.677 2.383 2.360 2.348 2.337 2.329 2.323 2.316 2.306 2.292 2.267 2.258 2.251 2.239 2.231 2.221 2.209 1.269 1.245 1.221 0.000
6.07
2 3.05
0 PPM
Supplementary Figure 48. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bg.
124
203.774
200
2015-10-22 13:54:41.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 142 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-141
100
50
14.156
23.706
35.214 33.256 30.425
60.179
77.423 77.000 76.577
91.661 90.062
128.401 128.198 125.753
141.646
172.999
0
PPM
zj-4-141-as-h-100-0-0.7-214 实验时间：2015-11-04,12:42:36 谱图文件:D:\zhuguangjiong\zj\20151103\zj-4-141-as-h-100-00.7-214...org
报告时间：2015-11-04,13:53:04
实验内容简介：
色谱图(zj-4-141-as-h-100-0-0.7-214...org) 2,400 2,200 2,000 1,800
1,400 1,200
18.495
电压(mv)
1,600
1,000 800 600
22.813
400 200
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
18.495 22.813
总计
Supplementary Figure 49. HPLC spectrum for (Ra)-4bg. 125
峰面积
含量
793333.813 19756.412
66945280.000 1418243.375
97.9254 2.0746
813090.225
68363523.375
100.0000
zj-4-142-as-h-100-0-0.7-214 实验时间：2015-11-04,10:35:23 谱图文件:d:\zhuguangjiong\zj\20151103\zj-4-142-as-h-100-00.7-214.org
报告时间：2015-11-04,13:52:18
实验内容简介：
色谱图(zj-4-142-as-h-100-0-0.7-214.org) 2,400 2,200 2,000 1,800
1,400
1,000 800 600
21.897
1,200
19.288
电压(mv)
1,600
400 200 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
19.288 21.897
总计
Supplementary Figure 50. HPLC spectrum for rac-4bg. 126
峰面积
含量
642363.875 492664.531
49289944.000 50444076.000
49.4214 50.5786
1135028.406
99734020.000
100.0000
Supplementary Figure 51. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5h.
127
10.564
12
10
2016-01-01 11:32:12.406 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
0.74
8
6
0.98
2.00 2.00
4
zj-5-056
2.00
2.01
2
4.07
12.20
5.878 5.856 5.845 5.834 5.822 5.800 5.788 5.777 5.766 5.743 5.185 5.169 5.154 5.138 5.123 5.021 5.016 4.964 4.946 4.912 2.502 2.479 2.454 2.334 2.319 2.295 2.281 2.258 2.071 2.049 2.026 2.002 1.981 1.963 1.944 1.374 1.352 1.279 -0.000
7.264
0
PPM
Supplementary Figure 52. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5h.
128
179.829
203.663
200
2015-12-30 10:28:21.750 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 169 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-5-056
50
33.780 33.137 29.432 29.368 29.092 29.074 28.890 28.807 23.476
77.423 77.000 76.577
92.837 89.216
114.080
139.173
0 PPM
Supplementary Figure 53. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bh.
129
7.302
10
2016-01-03 10:31:19.984 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
1.00
zj-5-065
2.00
2.00
4
2.00
2.00 2.02
2
4.10
15.28
0
5.865 5.843 5.831 5.821 5.809 5.786 5.774 5.764 5.752 5.730 5.157 5.143 5.126 5.111 5.097 5.012 5.005 4.949 4.936 4.933 4.902 4.158 4.135 4.111 4.087 2.431 2.424 2.403 2.380 2.324 2.309 2.292 2.281 2.268 2.246 2.047 2.022 1.999 1.977 1.961 1.944 1.925 1.378 1.356 1.283 1.274 1.249 1.226 -0.000
PPM
Supplementary Figure 54. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bh.
130
172.861
203.590
200
2016-01-03 10:37:37.781 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 85 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467758 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
113.979
zj-5-065
100
50
33.670 33.320 29.322 29.276 28.982 28.789 28.734 23.779 14.082
60.050
77.423 77.000 76.577
92.304 89.400
138.953
0
PPM
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Supplementary Figure 55. HPLC spectrum for (Ra)-4bh. 131
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,1)250$7,21 $FTXLUHG%\ 'DWH$FTXLUHG $FT 0HWKRG 'DWH3URFHVVHG &KDQQHO 1DPH &KDQQHO 'HVF 6DPSOH6HW 1DPH
%UHH]H &67 ]JM &67 : &K$ : &K$QP
$8
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Supplementary Figure 56. HPLC spectrum for rac-4bh. 132
Supplementary Figure 57. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5i.
133
10.920
10
0.97
2016-07-07 15:35:56.593 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
5.166 5.150 5.134 5.119 5.103
6
zj-6-186
1.97
4
2
2.00 1.98 1.97 2.04
8.07
9.00
0
5.97
PPM
2.478 2.453 2.429 2.314 2.298 2.283 2.275 2.260 2.232 2.224 2.200 2.177 1.991 1.969 1.952 1.935 1.912 1.541 1.520 1.497 1.474 1.395 1.377 1.356 1.338 1.309 1.272 0.906 0.056
7.260
Supplementary Figure 58. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5i.
134
179.783
203.654
200
2016-07-07 15:42:25.640 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 80 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
108.059
zj-6-186
100
50
0
-4.495
33.118 28.890 28.688 28.559 28.476 26.013 23.439 19.717 16.444
82.313 77.423 77.000 76.577
92.690 89.271
PPM
Supplementary Figure 59. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bi.
135
10
7.260
8
2016-07-09 16:59:28.984 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.130 5.116 5.101 5.084 5.065
6
4.131 4.107 4.083 4.059 1.95
4
2.00
zj-6-191
2
2.01 2.00 1.99 2.02
3.00
8.03
9.08
0
6.00
2.395 2.378 2.351 2.295 2.292 2.279 2.263 2.251 2.229 2.210 2.187 2.164 1.973 1.951 1.928 1.895 1.509 1.486 1.463 1.440 1.408 1.385 1.363 1.326 1.299 1.246 1.223 1.199 0.892 0.040
PPM
Supplementary Figure 60. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bi.
136
172.990
200
2016-07-09 16:57:29.625 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 215 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-191
100
50
0
-4.522
28.899 33.385 28.706 28.550 28.458 25.995 23.825 19.698 16.426 14.174
60.161
77.432 77.000 76.577
92.304 89.528
108.022
203.645
PPM
zj-6-191-oz-h-100-0-1-214 实验时间：2016-07-20,14:32:36 报告时间：2016-07-20,16:37:47 谱图文件:D:\zhuguangjiong\zj\20160719\zj-6-191-oz-h-100-0-1214.....org 实验内容简介：
色谱图(zj-6-191-oz-h-100-0-1-214.....org)
100 90 80 70
电压(mv)
60 50 40
29.112 30.525
30 20 10 0 0
2
4
6
8
10 12 14
16 18 20
22 24 26
28 30 32
34 36 38
40 42 44
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
29.112 30.525
总计
Supplementary Figure 61. HPLC spectrum for (Ra)-4bi. 137
峰面积
含量
916.083 12404.063
21239.408 1468265.625
1.4259 98.5741
13320.146
1489505.033
100.0000
zj-6-190-oz-h-100-0-1-214 实验时间：2016-07-20,9:47:40 报告时间：2016-07-20,16:39:03 谱图文件:D:\zhuguangjiong\zj\20160719\zj-6-190-oz-h-100-0-1214..org 实验内容简介：
色谱图(zj-6-190-oz-h-100-0-1-214..org)
150 140 130 120 110 100
电压(mv)
90 80 70 60
31.088
50 40
26.985
30 20 10 0 2
4
6
8
10
12
14
16
18
20
22
24
26
28
30
32
34
36
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
26.985 31.088
总计
Supplementary Figure 62. HPLC spectrum for rac-4bi. 138
峰面积
含量
12032.708 30860.033
1188864.500 1167286.250
50.4579 49.5421
42892.741
2356150.750
100.0000
139
10
Supplementary Figure 63. 1H NMR (300 MHz, CDCl3) spectrum for (Sa)-4bm.
7.299
8
2018-02-02 12:36:50.328 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.166 5.151 5.135 5.119 5.105
6
4.166 4.142 4.118 4.094 1.99
zj-9-055
4
2.00 1.99
2.00
2
2.02
11.51
3.06
0
2.440 2.413 2.409 2.387 2.331 2.310 2.299 2.288 2.275 2.248 2.005 1.982 1.966 1.958 1.950 1.925 1.443 1.427 1.408 1.384 1.359 1.337 1.313 1.282 1.258 1.234 0.907 0.885 0.862 0.000
PPM
Supplementary Figure 64. 13C NMR (75 MHz, CDCl3) spectrum for (Sa)-4bm.
140
200
173.009
150
2018-02-02 12:50:15.218 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 210 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-9-055
100
50
33.348 31.602 29.010 28.789 28.725 23.798 22.548 14.119 13.963
60.142
77.423 77.000 76.577
92.405 89.418
203.590
0
PPM
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6$03/( ]M RGK ᵚ⸕ XO 0LQXWHV
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%UHH]H &67 ]JM &67 : &K$ : &K$QP
6DPSOH1DPH 6DPSOH7\SH 9LDO ,QMHFWLRQ ,QMHFWLRQ9ROXPH 5XQ7LPH &ROXPQ7\SH
,1)250$7,21
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5HSRUW0HWKRG ,QGLYLGXDO 5HSRUW$6& 3DJH ޡ䇑
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Supplementary Figure 65. HPLC spectrum for (Sa)-4bm. 141
ѝഭ、ᆖ䲒к⎧ᴹᵪॆᆖ⹄ウᡰ 3URMHFW1DPH
GHIDXOWV IRUFRS\
5HSRUWHGE\ 8VHU
%UHH]HXVHU %UHH]H
6$03/( 6DPSOH1DPH 6DPSOH7\SH 9LDO ,QMHFWLRQ ,QMHFWLRQ9ROXPH 5XQ7LPH &ROXPQ7\SH
,1)250$7,21
]M RGK ᵚ⸕ XO 0LQXWHV
$FTXLUHG%\ 'DWH$FTXLUHG $FT 0HWKRG 'DWH3URFHVVHG &KDQQHO 1DPH &KDQQHO 'HVF 6DPSOH6HW 1DPH
%UHH]H &67 ]JM &67 : &K$ : &K$QP
$8
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$UHD +HLJKW $UHD ⽖ VHF ⽖ +HLJKW
5HSRUW0HWKRG ,QGLYLGXDO 5HSRUW$6& 3DJH ޡ䇑
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Supplementary Figure 66. HPLC spectrum for rac-4bm. 142
143
10
Supplementary Figure 67. 1H NMR (300 MHz, CDCl3) spectrum for AuCl(LB-Phos).
7.312
8
2017-01-23 13:42:44.984 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
2.00
3.865 3.843
zj-7-180
4
3.00
6.03
2.00
2
2.00
10.65 8.41
0
PPM
2.507 2.468 2.435 2.397 2.077 2.049 2.036 1.842 1.798 1.740 1.715 1.656 1.618 1.589 1.564 1.535 1.523 1.495 1.396 1.355 1.314 1.286 1.262 1.250 1.218 1.191 0.000
6.143 6.133
Supplementary Figure 68. 13C NMR (75 MHz, CDCl3) spectrum for AuCl(LB-Phos).
144
164.506 163.881
200
2017-01-23 14:42:12.859 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 986 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-180
93.040 92.304 91.312 91.247
100
50
36.087 35.609 32.263 32.190 29.340 26.748 26.574 26.537 26.326 25.627
55.436 55.362
77.423 77.000 76.577
0
PPM
Supplementary Figure 69. 31P NMR (121.5 MHz, CDCl3) spectrum for AuCl(LB-Phos).
145
200
150
100
2017-01-23 14:58:44.203 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.200 usec Relaxation delay = 2.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 121.494835 MHz F2 = 1.000000 MHz SW1 = 53571.43 Hz
50
31.313
0
zj-7-180-P
-50
-100
-150
-200 PPM
Supplementary Figure 70. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6a.
146
7.298
10
2017-05-16 22:34:25.015 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
0.02
1.02 0.02
1.00 1.00
4
zj-8-046
1.04
2.04
2
3.11
10.82
3.04
0
5.856 5.834 5.808 5.783 5.760 5.712 5.689 5.681 5.653 5.631 5.527 5.503 5.476 5.452 5.296 5.268 5.246 5.220 4.933 4.909 4.885 4.861 2.565 2.542 2.512 2.431 2.408 2.386 2.366 2.343 2.321 2.095 2.073 2.049 2.025 1.985 1.973 1.946 1.915 1.403 1.381 1.358 1.270 0.902 0.882 0.858 -0.000
PPM
147
Supplementary Figure 71. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6a. 6.0 5.8
5.856 5.834 5.808 5.783 5.760
1.00
5.6
0.02
5.712 5.689 5.681 5.653 5.631
5.527 5.503 5.476 5.452
5.4
1.02
5.296
5.2
0.02
5.268 5.246 5.220
5.0 4.933 4.909 4.885 4.861 1.00
4.8 4.6 PPM
Supplementary Figure 72. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6a.
148
177.007
200
2017-05-16 23:10:55.609 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 582 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-046
100
50
31.969 31.648 28.964 28.927 28.715 28.642 28.614 22.502 13.953
81.072 77.423 77.000 76.577
127.233
135.616
0
PPM
m)v(压
zj-8-046-oj-h-200-1-1-214 实验时间：2017-5-24,16:53:49 报告时间：2017-5-24,17:33:30 谱图文件:D:\zhuguangjiong\zj\20170524\zj-8-046-oj-h-200-1-1214..org 实验内容简介：
色谱图(zj-8-046-oj-h-200-1-1-214..org) 2,400 2,200 2,000 1,800
电压(mv)
1,600 1,400 1,200 1,000 22.732
800 600 20.863
400 200 0 0
1 2
3 4
5
6 7
8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.863 22.732
总计
Supplementary Figure 73. HPLC spectrum for (S,E)-6a. 149
峰面积
含量
16647.076 420144.281
395363.438 20229394.000
1.9169 98.0831
436791.357
20624757.438
100.0000
m)v(压
zj-8-029-oj-h-200-1-1-214 实验时间：2017-5-24,15:52:47 报告时间：2017-5-24,17:31:23 谱图文件:D:\zhuguangjiong\zj\20170524\zj-8-029-oj-h-200-1-1214..org
色谱图(zj-8-029-oj-h-200-1-1-214..org)
1
2
3
4
5
6
7
8
23.087
400 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 60 40 20 0 0
20.313
电压(mv)
实验内容简介：
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.313 23.087
总计
Supplementary Figure 74. HPLC spectrum for rac-6a. 150
峰面积
含量
57729.738 49412.555
2545566.250 2546912.000
49.9868 50.0132
107142.293
5092478.250
100.0000
151
Supplementary Figure 75. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6b. 7.333
12 10
2016-05-16 16:08:15.750 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8 6 0.03 0.03
1.02 1.00 0.99
zj-6-074
4 1.04
2.02
2
3.11 4.11 3.06
0 -2 PPM
5.856 5.854 5.834 5.831 5.809 5.805 5.783 5.780 5.761 5.758 5.710 5.685 5.649 5.624 5.538 5.534 5.528 5.515 5.510 5.505 5.487 5.482 5.478 5.463 5.459 5.454 5.297 5.268 5.250 5.221 4.931 4.907 4.884 4.860 2.558 2.534 2.526 2.504 2.432 2.410 2.388 2.368 2.345 2.323 2.104 2.082 2.060 2.041 2.034 2.012 2.000 1.986 1.970 1.943 1.912 1.404 1.394 1.381 1.365 1.353 1.342 1.330 1.309 1.285 0.920 0.897 0.873 0.000
152
Supplementary Figure 76. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6b. 6.0 5.8
5.856 5.854 5.834 5.831 5.809 5.805 5.783 5.780 5.761 5.758 5.710 5.685 5.649
1.00
5.6
0.03
5.624
5.4
1.02
5.538 5.534 5.528 5.515 5.510 5.505 5.487 5.482 5.478 5.463 5.459 5.454
5.297 5.268 5.250
5.2
0.03
5.221
5.0 4.931 4.907 4.884 4.860 0.99
4.8 PPM
Supplementary Figure 77. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6b.
153
176.869
200
2016-05-16 16:35:32.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 444 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-074
100
50
13.613
31.510 30.682 28.605 28.476 21.886
80.916 77.432 77.000 76.577
127.270
135.331
0
PPM
zj-6-074-oj-h-200-1-1-214 实验时间：2016-05-31,12:17:54 报告时间：2016-05-31,17:14:56 谱图文件:D:\zhuguangjiong\zj\20160531\zj-6-074-oj-h-200-1-1214.org
色谱图(zj-6-074-oj-h-200-1-1-214.org)
29.033
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
26.333
电压(mv)
实验内容简介：
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
26.333 29.033
总计
Supplementary Figure 78. HPLC spectrum for (S,E)-6b. 154
峰面积
含量
1418.779 27742.568
39042.988 2190942.750
1.7508 98.2492
29161.348
2229985.738
100.0000
zj-6-056-oj-h-200-1-1-214 实验时间：2016-05-31,14:08:40 报告时间：2016-05-31,17:13:13 谱图文件:D:\zhuguangjiong\zj\20160531\zj-6-056-oj-h-200-1-1214..org
色谱图(zj-6-056-oj-h-200-1-1-214..org)
29.003
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0
24.948
电压(mv)
实验内容简介：
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
24.948 29.003
总计
Supplementary Figure 79. HPLC spectrum for rac-6b. 155
峰面积
含量
23389.479 18196.986
1017822.750 1028969.125
49.7277 50.2723
41586.465
2046791.875
100.0000
156
Supplementary Figure 80. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6c. 10 8
2015-10-09 20:16:11.078 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.294
6 0.03
1.00 1.01 0.02 1.00
4 zj-4-114
1.08
2.03
2
3.28 19.65
3.08
0
5.856 5.834 5.805 5.783 5.760 5.713 5.688 5.678 5.652 5.627 5.526 5.502 5.474 5.451 5.294 5.265 5.243 5.215 4.931 4.906 4.882 4.859 2.563 2.541 2.536 2.531 2.509 2.426 2.404 2.384 2.362 2.339 2.316 2.134 2.111 2.094 2.071 2.049 2.026 2.012 1.999 1.985 1.970 1.954 1.942 1.912 1.403 1.381 1.357 1.261 0.902 0.880 0.858 0.000
PPM
157
Supplementary Figure 81. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6c. 5.856 5.834
5.8 1.00
5.805 5.783 5.760 5.713 5.688 5.678 5.652
5.6
0.03
5.627
1.01
5.4
5.526 5.522 5.502 5.498 5.474 5.471 5.455 5.451 5.447
5.294 5.265 5.243
5.2
0.02
5.215
5.0 4.931 4.906 4.882 4.859 1.00
4.8 PPM
Supplementary Figure 82. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6c.
158
200
177.007
2015-10-09 20:30:12.593 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 222 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-114
100
50
31.978 31.795 29.533 29.506 29.451 29.322 29.221 29.000 28.725 28.660 28.614 22.557 13.990
81.063 76.568
77.423 77.000
127.242
135.616
0 PPM
zj-4-114-as-h-95-5-1-214 实验时间：2015-10-12,14:36:42 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-114-as-h-95-5-1214..org
报告时间：2015-10-13,17:39:52
实验内容简介：
色谱图(zj-4-114-as-h-95-5-1-214..org)
500 450 400 350
电压(mv)
300 250 200
7.285
150
6.695
100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
6.695 7.285
总计
Supplementary Figure 83. HPLC spectrum for (S,E)-6c. 159
峰面积
含量
4003.269 84500.078
40812.492 2221214.250
1.8042 98.1958
88503.347
2262026.742
100.0000
zj-4-113-as-h-95-5-1-214 实验时间：2015-10-12,15:35:07 谱图文件:D:\zhuguangjiong\zj\20151010\zj-4-113-as-h-95-5-1214....org
报告时间：2015-10-13,17:38:42
实验内容简介：
色谱图(zj-4-113-as-h-95-5-1-214....org)
500 450 400 350
电压(mv)
300 250 200
100
7.383
6.487
150
50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
6.487 7.383
总计
Supplementary Figure 84. HPLC spectrum for rac-6c. 160
峰面积
含量
47584.324 36512.277
661526.563 671442.813
49.6280 50.3720
84096.602
1332969.375
100.0000
161
Supplementary Figure 85. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6d. 10 8
2017-06-15 23:01:01.218 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.312
6
5.827 5.824 5.805 5.802 5.775 5.773 5.754 5.751 5.486 5.481 5.462 5.457 5.434 5.430 5.410 5.406 5.371 5.340 5.308 5.283 5.267 4.936 4.912 4.888 4.864 2.575 2.549 2.543 2.519 2.462 2.439 2.417 2.397 2.375 2.352 2.345 2.318 2.300 2.273 2.051 2.022 2.010 1.995 1.980 1.964 1.953 1.922 1.021 0.998 -0.000
1.00 1.03 1.00
4
zj-8-058
2.01 2.04
2
1.23 6.04
0 PPM
Supplementary Figure 86. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6d.
162
200
141.968
176.933
150
2017-06-10 23:44:33.015 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 153 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-8-058
50
30.352 28.578 28.467 21.638
81.017 77.432 77.000 76.577
124.384
0
PPM
Supplementary Figure 87. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6d.
163
200
142.619 142.040
176.996
150
1.06 0.02
0.01
124.659 124.355
1.00
2017-06-11 08:40:34.751 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 600 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-8-058-Q
50
21.657
30.380 28.606 28.514
81.090 77.432 77.000 76.577
0
PPM
PPM 1.00
140
135
130
0.02
125
1.06
124.659 124.355
0.01
142.040 142.619
Supplementary Figure 88. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for (S,E)-6d. 164
zj-8-058-as-h-98-2-1-210 实验时间：2017-06-16,16:50:01 谱图文件:D:\zhuguangjiong\zj\20170616\zj-8-058-as-h-98-2-1214..org
报告时间：2017-06-16,18:08:14
实验内容简介：
500
色谱图(zj-8-058-as-h-98-2-1-214..org)
450 400 350
电压(mv)
300 250 200
21.268
100 50
23.628
150
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
21.268 23.628
总计
Supplementary Figure 89. HPLC spectrum for (S,E)-6d.
165
峰面积
含量
1837.642 54305.750
79774.930 7255602.500
1.0875 98.9125
56143.392
7335377.430
100.0000
zj-8-054-as-h-98-2-1-210 实验时间：2017-06-16,17:31:45 谱图文件:D:\zhuguangjiong\zj\20170616\zj-8-054-as-h-98-2-1214..org
报告时间：2017-06-16,18:09:54
色谱图(zj-8-054-as-h-98-2-1-214..org)
24.585
400 380 360 340 320 300 280 260 240 220 200 180 160 140 120 100 80 60 40 20 0
20.092
电压(mv)
实验内容简介：
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.092 24.585
总计
Supplementary Figure 90. HPLC spectrum for rac-6d. 166
峰面积
含量
39390.332 28990.822
2938623.000 2957957.000
49.8361 50.1639
68381.154
5896580.000
100.0000
167
Supplementary Figure 91. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6e. 7.347
10 8
2015-07-13 22:02:51.265 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6 1.00
zj-4-008
1.01 0.99
4 1.02
1.99
2
2.02 5.00 5.16
0 -2
5.792 5.790 5.770 5.768 5.741 5.738 5.719 5.716 5.482 5.478 5.458 5.454 5.430 5.426 5.406 5.402 4.923 4.899 4.875 4.852 2.562 2.560 2.538 2.530 2.508 2.432 2.411 2.390 2.368 2.346 2.037 2.012 2.009 2.002 1.997 1.981 1.976 1.970 1.966 1.951 1.939 1.934 1.747 1.742 1.737 1.703 1.673 1.642 1.637 1.633 1.292 1.283 1.258 1.251 1.243 1.219 1.204 1.165 1.126 1.087 1.055 0.000
PPM
Supplementary Figure 92. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6e.
168
200
176.584
2015-06-16 21:23:19.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 112 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-008
100
50
31.887 31.850 28.302 28.155 25.471 25.296
39.562
80.778 77.432 77.000 76.577
124.650
140.295
0 PPM
Supplementary Figure 93. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6e.
169
200
140.762 140.303
150
1.00
0.01
0.02
124.999 124.631
0.96
2015-06-17 09:16:54.125 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 612 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-4-008-Q
0.01
80.796 77.432 77.000 76.577 0.97
50
31.869 31.832 28.294 28.156 25.462 25.288
39.562
176.610
0
PPM
PPM 1.00
0.01
124.631
0.96
140
138
136
134
132
130
128
126
124.999
0.02
140.303 140.762
Supplementary Figure 94. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for (S,E)-6e. 170
zj-4-008-oj-h-95-5-1-214 实验时间：2015-07-23,15:56:37 谱图文件:D:\zhuguangjiong\zj\20150720\zj-4-008-oj-h-95-5-1214..org
报告时间：2015-07-23,17:03:34
实验内容简介：
色谱图(zj-4-008-oj-h-95-5-1-214..org)
300 280 260 240 220 200
电压(mv)
180 160 140 120 100
17.053
80 60
13.228
40 20 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
13.228 17.053
总计
Supplementary Figure 95. HPLC spectrum for (S,E)-6e. 171
峰面积
含量
1296.325 45912.770
24145.711 1256106.750
1.8860 98.1140
47209.095
1280252.461
100.0000
zj-4-007-oj-h-95-5-1-214 实验时间：2015-07-23,14:50:22 谱图文件:D:\zhuguangjiong\zj\20150720\zj-4-007-oj-h-95-5-1214..org
报告时间：2015-07-23,17:02:36
实验内容简介：
色谱图(zj-4-007-oj-h-95-5-1-214..org)
300 280 260 240 220 200
电压(mv)
180 160 140 120 100
60
16.968
12.760
80
40 20 0 0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
12.760 16.968
总计
Supplementary Figure 96. HPLC spectrum for rac-6e. 172
峰面积
含量
45605.098 37913.973
983555.813 964117.250
50.4990 49.5010
83519.070
1947673.063
100.0000
173
Supplementary Figure 97. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6f. 12 10 8
2015-11-11 20:09:09.156 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
2.03
2.99
6 0.02 0.02
1.00 1.02
zj-4-175
1.00
4 2.05
2
1.02
2.02
1.01
0 -2 PPM
7.285 7.280 7.275 7.263 7.258 7.253 7.190 7.185 7.173 7.165 7.156 7.146 7.141 7.118 5.947 5.944 5.925 5.922 5.902 5.898 5.897 5.893 5.874 5.871 5.851 5.848 5.798 5.779 5.764 5.753 5.727 5.537 5.533 5.528 5.514 5.509 5.504 5.486 5.481 5.477 5.463 5.458 5.453 5.333 5.304 5.282 5.251 4.858 4.833 4.809 4.786 3.354 3.331 2.422 2.414 2.405 2.391 2.292 2.272 2.270 2.250 2.227 2.204 1.933 1.907 1.903 1.891 1.877 1.872 1.865 1.861 1.846 1.835 1.830 1.803 0.000
174
Supplementary Figure 98. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6f. zj-4-175
6.0
5.947 5.944 5.925 5.922 5.902 5.898 5.897 5.893 5.874 5.871 5.851 5.848 5.798 5.779 5.764 5.753 5.727 5.537 5.533 5.528 5.514 5.509 5.504 5.486 5.481 5.477 5.463 5.458 5.453 5.333 5.304 5.282 5.251
1.00
0.02
5.5 1.02
0.02
5.0
4.858 4.833 4.809 4.786
1.00
4.5 PPM
Supplementary Figure 99. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6f.
175
200
176.581
2015-11-11 20:21:55.875 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 178 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-175
100
50
28.151 28.115
37.886
80.195 77.438 77.006 76.583
133.186 128.480 128.140 128.066 125.851
138.757
0
PPM
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Supplementary Figure 100. HPLC spectrum for (S,E)-6f. 176
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Supplementary Figure 101. HPLC spectrum for rac-6f.
177
Supplementary Figure 102. 1H NMR (300 MHz, CDCl178 3) spectrum for (S,E)-6g. 12 10
2015-10-25 14:28:43.140 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8 2.08
3.01
6
zj-4-146
1.03
0.03
1.01 0.03
1.00
4 2.07
2.00
1.03
2
3.05
0 -2 PPM
7.292 7.288 7.271 7.265 7.244 7.240 7.191 7.187 7.167 7.161 7.156 7.148 7.134 5.853 5.849 5.831 5.827 5.808 5.805 5.802 5.798 5.779 5.776 5.757 5.754 5.710 5.670 5.659 5.646 5.619 5.514 5.510 5.505 5.491 5.486 5.482 5.463 5.459 5.454 5.440 5.435 5.430 5.093 5.065 5.043 5.014 4.872 4.846 4.823 4.800 2.715 2.689 2.664 2.487 2.485 2.463 2.456 2.433 2.404 2.378 2.353 2.346 2.324 2.304 2.282 2.258 2.235 1.937 1.912 1.896 1.883 1.870 1.866 1.851 1.840 1.835 -0.000
179
Supplementary Figure 103. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6g. 5.8
5.853 5.849 5.831 5.827 5.808 5.805 5.802 5.798 5.779 5.776 5.757 5.754 5.710 5.670 5.659 5.646 5.619
1.01
5.6
0.03
5.4
1.03
5.514 5.510 5.505 5.491 5.486 5.482 5.463 5.459 5.454 5.440 5.435 5.430
5.2 5.093 5.065 5.043
5.0
0.03
5.014
4.872 4.846
4.8
4.823 4.800 1.00
PPM
Supplementary Figure 104. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6g.
180
176.841
200
2015-10-25 20:52:27.250 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 6548 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-146
100
50
34.883 33.550 28.430 28.320
80.566 77.423 77.000 76.577
133.861 128.180 128.097 128.042 125.717
141.030
0
PPM
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Supplementary Figure 105. HPLC spectrum for (S,E)-6g. 181
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Supplementary Figure 106. HPLC spectrum for rac-6g. 182
183
Supplementary Figure 107. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6h. 10 8
2016-01-13 21:37:28.187 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 5 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.365
6 2.00 1.00 3.00
zj-5-083
4 1.00
2.00
2
5.06 12.42
5.859 5.837 5.821 5.802 5.793 5.780 5.769 5.758 5.746 5.724 5.526 5.502 5.475 5.451 5.254 5.226 5.191 5.007 5.002 4.951 4.945 4.931 4.928 4.894 4.868 4.845 2.539 2.514 2.508 2.484 2.428 2.417 2.396 2.375 2.353 2.331 2.307 2.089 2.067 2.044 2.022 1.997 1.981 1.967 1.951 1.925 1.894 1.376 1.281 0.000
0 PPM
184
200
Supplementary Figure 108. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6h.
177.025
150
2016-01-14 00:40:12.750 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1357 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-5-083
50
33.697 32.006 29.285 29.000 28.816 28.761 28.679 28.651
81.081 77.423 77.000 76.568
114.052
127.288
139.109 135.635
0
PPM
Operator:Administrator Timebase:HPLC Sequence:20151027-DAD
Page 1-1 2016-1-26 2:12 下午
842 ZJ-5-83 ADH 982 214 0.7
Sample Name: Vial Number: Sample Type: Control Program: Quantif. Method: Recording Time: Run Time (min):
120
ZJ-5-83 ADH 982 214 0.7 RD5 unknown test-dad WXL 2016-1-25 10:47 21.00
Injection Volume: Channel: Wavelength: Bandwidth: Dilution Factor: Sample Weight: Sample Amount:
20151027-DAD #842 [modified by Administrator] mAU
9.0 UV_VIS_2 214.0 4 1.0000 1.0000 1.0000 UV_VIS_2 WVL:214 nm
2 - 12.887 100
80
60
40
20 4 - 16.610 1 - 12.087 0
-20 0.0
No. 1 2 3 4 Total:
3 - 14.947
min 2.0
Ret.Time min 12.09 12.89 14.95 16.61
4.0
6.0
Peak Name n.a. n.a. n.a. n.a.
8.0
10.0
12.0
14.0
16.0
Height Area Rel.Area mAU mAU*min % 2.565 0.587 1.65 108.157 32.052 90.05 0.180 0.064 0.18 8.639 2.889 8.12 119.541 35.592 100.00
18.0
Amount n.a. n.a. n.a. n.a. 0.000
21.0
Type BM MB BMB* BMB
Chromeleon (c) Dionex 1996-2006 Version 6.80 SR14 Build 4527 (238909)
defltdad/Integration
Supplementary Figure 109. SFC (supercritical fluid chromatogram) spectrum for (S,E)-6h. 185
Operator:Administrator Timebase:HPLC Sequence:20151027-DAD
Page 1-1 2016-1-26 2:08 下午
841 ZJ-5-82+- ADH 982 214 0.7
Sample Name: Vial Number: Sample Type: Control Program: Quantif. Method: Recording Time: Run Time (min):
35.0
ZJ-5-82+- ADH 982 214 0.7 RE5 unknown test-dad WXL 2016-1-25 10:25 21.00
Injection Volume: Channel: Wavelength: Bandwidth: Dilution Factor: Sample Weight: Sample Amount:
20151027-DAD #841 [modified by Administrator] mAU
9.0 UV_VIS_2 214.0 4 1.0000 1.0000 1.0000 UV_VIS_2 WVL:214 nm
30.0
1 - 11.973 2 - 12.913
25.0
20.0
15.0
10.0
5.0 3 - 15.103 4 - 16.510 0.0
-5.0 0.0
No. 1 2 3 4 Total:
min 2.0
Ret.Time min 11.97 12.91 15.10 16.51
4.0
6.0
Peak Name n.a. n.a. n.a. n.a.
8.0
10.0
12.0
14.0
16.0
Height Area Rel.Area mAU mAU*min % 25.262 6.383 47.00 23.836 6.366 46.88 1.374 0.413 3.04 1.322 0.418 3.08 51.794 13.579 100.00
Amount n.a. n.a. n.a. n.a. 0.000
21.0
Type BM MB BMB BMB
Chromeleon (c) Dionex 1996-2006 Version 6.80 SR14 Build 4527 (238909)
defltdad/Integration
Supplementary Figure 110. SFC spectrum for rac-6h.
18.0
186
187
12
Supplementary Figure 111. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6i. 7.260
10 8
2016-07-12 00:01:03.437 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6 1.03 1.00 0.03 0.03
1.00
4
zj-6-188
2
2.03 3.09
1.00
1.99 8.32 9.05
0
6.03
-2 PPM
5.829 5.827 5.807 5.805 5.784 5.779 5.756 5.754 5.733 5.732 5.688 5.666 5.650 5.629 5.603 5.509 5.504 5.500 5.486 5.481 5.476 5.458 5.453 5.449 5.435 5.430 5.425 5.262 5.238 5.214 5.186 4.906 4.882 4.858 4.835 2.542 2.511 2.485 2.404 2.382 2.361 2.339 2.316 2.221 2.198 2.175 2.077 2.055 2.033 2.018 1.988 1.976 1.950 1.931 1.920 1.515 1.491 1.467 1.426 1.391 1.376 1.351 1.330 1.300 1.277 0.901 0.051
188
Supplementary Figure 112. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6i. 6.0 5.8
5.829 5.827 5.807 5.805 5.784 5.779 5.756 5.754 5.733 5.732 5.688 5.666 5.650 5.629 5.603 5.509 5.504 5.500 5.486 5.481 5.476 5.458 5.453 5.449 5.435 5.430 5.425 5.262 5.238 5.214 5.186
1.00
5.6
0.03
5.4
1.03
5.2
0.03
5.0 4.8
1.00
4.906 4.882 4.858 4.835
4.6
zj-6-188
4.4PPM
Supplementary Figure 113. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6i.
189
200
176.933
2016-07-11 21:31:34.953 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 580 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-188
100
50
0
-4.550
28.706 28.587 31.850 28.495 28.394 28.357 28.320 25.958 19.625 16.380
82.304 80.971 77.423 77.000 76.577
107.921
127.390
135.377
PPM
zj-6-188-oj-h-100-1-0.3-214 实验时间：2016-07-14,12:49:48 谱图文件:D:\zhuguangjiong\zj\20160712\zj-6-188-oj-h-100-10.3-214.org
报告时间：2016-07-14,17:18:57
实验内容简介：
150
色谱图(zj-6-188-oj-h-100-1-0.3-214.org)
140 130 120 110 100
电压(mv)
90 80 70 60
29.487
50 40 30
28.493
20 10 0
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
28.493 29.487
总计
Supplementary Figure 114. HPLC spectrum for (S,E)-6i. 190
峰面积
含量
883.960 32668.090
26267.666 1786474.625
1.4491 98.5509
33552.050
1812742.291
100.0000
zj-6-182-oj-h-100-1-0.3-214 实验时间：2016-07-14,10:44:07 报告时间：2016-07-14,17:17:55 谱图文件:D:\zhuguangjiong\zj\20160712\zj-6-182-oj-100-1-0.3214.org 实验内容简介：
100
色谱图(zj-6-182-oj-100-1-0.3-214.org)
90 80 70
50 40
28.438
30 20
29.937
电压(mv)
60
10 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
28.438 29.937
总计
Supplementary Figure 115. HPLC spectrum for rac-6i. 191
峰面积
含量
13724.570 12299.934
524178.875 521015.469
50.1513 49.8487
26024.504
1045194.344
100.0000
192
Supplementary Figure 116. 1H NMR (300 MHz, CDCl3) spectrum for (R,E)-6j. 7.317
10
2015-11-27 22:27:30.125 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8 6 0.03
1.03
0.03
1.01
zj-5-014
1.00
4 1.05
2.00
2
3.05 12.59
3.07
0 PPM
5.856 5.853 5.833 5.831 5.810 5.807 5.805 5.802 5.782 5.780 5.759 5.757 5.703 5.683 5.661 5.647 5.625 5.533 5.528 5.523 5.510 5.505 5.500 5.482 5.478 5.472 5.458 5.454 5.449 5.295 5.273 5.245 5.216 4.929 4.905 4.882 4.858 2.558 2.533 2.527 2.504 2.428 2.406 2.384 2.364 2.341 2.319 2.095 2.072 2.050 2.039 2.024 2.010 1.984 1.942 1.910 1.384 1.359 1.305 1.270 0.904 0.882 0.858 0.000
193
Supplementary Figure 117. 1H NMR (300 MHz, CDCl3) extended spectrum for (R,E)-6j. 6.0 5.8
5.856 5.853 5.833 5.831 5.810 5.807 5.805 5.802 5.782 5.780 5.759 5.757 5.703 5.683 5.661 5.647 5.625 5.533 5.528 5.523 5.510 5.505 5.500 5.482 5.478 5.472 5.458 5.454 5.449 5.295 5.273 5.245 5.216
1.01
5.6
0.03
5.4
1.03
5.2
0.03
5.0 4.929 4.905 4.882 4.858
4.8
1.00
4.6 PPM
Supplementary Figure 118. 13C NMR (75 MHz, CDCl3) spectrum for (R,E)-6j.
194
200
176.869
2015-11-27 22:58:54.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 514 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-5-014
50
31.905 31.666 29.203 29.037 28.918 28.651 28.596 28.522 22.456 13.889
80.943 77.000 76.577
77.423
127.270
135.442
0
PPM
zj-5-014-oj-h-100-1-1-214 实验时间：2016/1/7,15:21:56 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-014-oj-100-1-1214..org
报告时间：2016/1/7,17:02:24
实验内容简介：
色谱图(zj-5-014-oj-100-1-1-214..org)
500 450 400 350
250 200 12.928
电压(mv)
300
150
16.147
100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
12.928 16.147
峰面积
含量
120117.664 3762.432
3456854.500 87297.750
97.5368 2.4631
123880.096
3544152.250
100.0000
总计
Supplementary Figure 119. HPLC spectrum for (R,E)-6j. 195
zj-5-013-oj-h-100-1-1-214 实验时间：2016/1/7,13:38:12 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-013-oj-100-1-1214.org
报告时间：2016/1/7,17:01:04
实验内容简介：
色谱图(zj-5-013-oj-100-1-1-214.org)
500 450 400 350
250 200
15.242
12.720
电压(mv)
300
150 100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
12.720 15.242
总计
Supplementary Figure 120. HPLC spectrum for rac-6j.
196
峰面积
含量
176572.141 146212.047
5660659.000 5765820.000
49.5398 50.4602
322784.188
11426479.000
100.0000
197
Supplementary Figure 121. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6b (1.6615 g). 10
2016-06-22 22:49:47.203 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.317
8 6 0.02
1.01
0.02
1.00
zj-6-160
0.99
4 1.01
2.00
2
3.03 4.09 3.03
0 PPM
5.858 5.855 5.835 5.832 5.813 5.809 5.807 5.803 5.784 5.781 5.761 5.759 5.715 5.690 5.676 5.661 5.654 5.537 5.532 5.527 5.513 5.508 5.504 5.486 5.481 5.476 5.462 5.457 5.452 5.296 5.272 5.250 5.222 4.933 4.908 4.885 4.861 2.562 2.536 2.530 2.508 2.431 2.409 2.387 2.367 2.345 2.082 2.061 2.043 2.014 1.987 1.945 1.404 1.381 1.365 1.353 1.342 1.330 1.303 1.279 0.921 0.897 0.873 0.000
198
Supplementary Figure 122. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6b (1.6615 g). 6.0 5.8
5.858 5.855 5.835 5.832 5.813 5.809 5.807 5.803 5.784 5.781 5.761 5.759 5.715 5.690 5.676 5.661 5.654 5.537 5.532 5.527 5.513 5.508 5.504 5.486 5.481 5.476 5.462 5.457 5.452 5.296 5.272 5.250 5.222
1.00
5.6
0.02
5.4
1.01
5.2
0.02
5.0 0.99
4.933 4.908 4.885 4.861
4.8 4.6 PPM
Supplementary Figure 123. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6b (1.6615 g).
199
200
176.933
150
2016-06-22 23:11:36.296 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 348 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-6-160
50
13.659
31.565 30.719 28.651 28.532 21.941
80.971 77.423 77.000 76.568
127.270
135.432
0
PPM
zj-6-160-oj-h-200-1-1-214 实验时间：2016-07-01,10:35:50 报告时间：2016-07-01,12:50:43 谱图文件:D:\zhuguangjiong\zj\20160630\ZJ-6-160-oj-h-200-1-1214.org 实验内容简介：
300
色谱图(ZJ-6-160-oj-h-200-1-1-214.org)
280 260 240 220 200
电压(mv)
180 160 140 120 100
60
23.693
40 20 0
26.387
80
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
23.693 26.387
总计
峰面积
含量
844.168 27539.016
31765.662 1969061.375
1.5876 98.4124
28383.184
2000827.037
100.0000
Supplementary Figure 124. HPLC spectrum for (S,E)-6b (1.6615 g). 200
zj-6-056-oj-h-200-1-1-214 实验时间：2016-07-01,12:14:25 报告时间：2016-07-01,12:49:09 谱图文件:D:\zhuguangjiong\zj\20160630\ZJ-6-056-oj-h-200-1-1214..org 实验内容简介：
300
色谱图(ZJ-6-056-oj-h-200-1-1-214..org)
280 260 240 220 200
电压(mv)
180 160 140 120 100
22.563
60 40 20
26.498
80
0 -20 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
22.563 26.498
总计
Supplementary Figure 125. HPLC spectrum for rac-6b. 201
峰面积
含量
21248.332 15297.864
782160.188 785722.813
49.8864 50.1136
36546.196
1567883.000
100.0000
202
Supplementary Figure 126. 1H NMR (300 MHz, CDCl3) spectrum for (R,E)-6m. 10
2018-02-01 13:25:45.546 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.362
8 6 0.03
1.00
0.04
0.97 0.97
zj-9-053
4 1.01
2.00
2
3.01 8.16
3.00
0
5.857 5.834 5.808 5.807 5.783 5.761 5.708 5.678 5.674 5.649 5.624 5.535 5.531 5.527 5.511 5.507 5.503 5.484 5.480 5.476 5.461 5.456 5.452 5.303 5.274 5.250 5.225 4.935 4.911 4.887 4.863 2.561 2.537 2.530 2.506 2.435 2.414 2.392 2.372 2.349 2.326 2.097 2.076 2.053 2.030 2.012 2.000 1.986 1.970 1.944 1.912 1.386 1.364 1.336 1.309 1.282 0.904 0.883 0.860 -0.000
PPM
203
Supplementary Figure 127. 1H NMR (300 MHz, CDCl3) extended spectrum for (R,E)-6m. 6.2 6.0 5.8
5.857 5.834 5.808 5.807 5.783 5.761 5.708 5.678 5.674 5.649 5.624
0.97
5.6
0.04
5.4
1.00
5.535 5.531 5.527 5.511 5.507 5.503 5.484 5.480 5.476 5.461 5.456 5.452 5.303 5.274 5.250 5.225
5.2
0.03
5.0 4.935 4.911 4.887 4.863
4.8
0.97
zj-9-053
4.6 4.4 PPM
Supplementary Figure 128. 13C NMR (75 MHz, CDCl3) spectrum for (R,E)-6m.
204
200
176.823
2018-02-01 14:47:06.468 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1366 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-9-053
50
13.742
31.767 31.317 28.522 28.440 28.412 22.244
80.861 77.423 77.000 76.568
127.169
135.267
0
PPM
zj-9-053-oj-h-97-3-1-214 实验时间：2018-02-02,18:50:03 谱图文件:D:\zhuguangjiong\zj\20180202\zj-9-053-oj-h-973-1-214..org
报告时间：2018-02-02,19:10:10
实验内容简介：
色谱图(zj-9-053-oj-h-97-3-1-214..org)
1,500 1,400 1,300 1,200 1,100 1,000
800 700 600
12.547
电压(mv)
900
500 400
100 0 0
1
2
3
4
5
6
7
8
9
10
11
12
14.537
200
13
14
15.315
12.208
300
15
16
17
18
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
12.208 12.547 14.537 15.315
46765.355 381413.406 10995.621 2304.944 441479.326
总计
Supplementary Figure 129. HPLC spectrum for (R,E)-6m. 205
峰面积
含量
516480.156 11254235.000 219209.844 65094.563
4.2844 93.3573 1.8184 0.5400
12055019.563
100.0000
zj-9-054-oj-h-97-3-1-214 实验时间：2018-02-02,18:12:35 谱图文件:D:\zhuguangjiong\zj\20180202\zj-9-054-oj-h-973-1-214..org
报告时间：2018-02-02,18:40:58
色谱图(zj-9-054-oj-h-97-3-1-214..org)
0
13.423
12.115
200 190 180 170 160 150 140 130 120 110 100 90 80 70 60 50 40 30 20 10 0 1
2
3
4
5
6
7
8
9
10
11
12
15.123
12.032
电压(mv)
实验内容简介：
13
14
15
16
17
18
19
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
12.032 12.115 13.423 15.123
总计
Supplementary Figure 130. HPLC spectrum for rac-6m. 206
峰面积
含量
6901.926 51452.254 41955.156 2490.805
69434.695 1499887.000 1575010.000 81123.406
2.1527 46.5016 48.8306 2.5151
102800.141
3225455.102
100.0000
207
10
Supplementary Figure 131. 1H NMR (300 MHz, CDCl3) spectrum for rac-8.
7.260
8
2016-11-20 11:33:21.545 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
4.338 4.316 4.299 1.00
4
3.588 3.566 3.544 2.00
zj-7-083
2.684 1.00
0.97
2
1.98
3.99
4.08
9.06
1.715 1.692 1.670 1.654 1.640 1.502 1.487 1.473 1.452 1.421 1.388 1.325 1.302 1.289 0.856 0.012
2.424 2.417
0
5.99
PPM
Supplementary Figure 132. 13C NMR (75 MHz, CDCl3) spectrum for rac-8.
208
200
2016-11-20 12:17:41.562 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 507 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
85.061
zj-7-083
50
0
-5.349
32.613 28.954 25.903 25.599 24.938 18.273
37.466
63.176 62.017
77.423 77.000 76.577 72.671
PPM
Supplementary Figure 133. 1H NMR (300 MHz, CDCl3) spectrum for rac-9.
209
7.295
10
8
2016-11-29 10:27:13.221 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
4
1.00
2.00
2.99
3.960 3.954 3.939 3.932 3.917 3.910 3.648 3.626 3.604 3.412 2.458 2.452
zj-7-106
2.00
2
2.00
8.32
0
1.761 1.747 1.739 1.721 1.698 1.676 1.593 1.570 1.547 1.523 1.494 1.472 1.462 1.442 1.428 1.406 1.399 1.381 1.370 1.359 1.347 1.335 -0.000
PPM
Supplementary Figure 134. 13C NMR (75 MHz, CDCl3) spectrum for rac-9.
210
200
2016-11-29 10:44:39.110 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 809 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-106
100
50
35.278 32.493 28.973 25.507 24.956
56.337
62.734
77.423 77.000 76.577 73.737 70.970
82.561
0 PPM
Supplementary Figure 135. 1H NMR (300 MHz, CDCl3) spectrum for rac-10.
211
10
9.770 9.764 9.758
0.97
8
2016-12-01 13:58:24.449 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
3.958 3.952 3.937 3.930 3.915 3.909 3.406
zj-7-110
4
1.00
3.00
2.94
2
2.04
2.04
4.03
0
PPM
2.468 2.458 2.452 2.443 2.438 2.419 2.413 1.761 1.750 1.739 1.723 1.717 1.702 1.680 1.656 1.630 1.606 1.541 1.536 1.518 1.504 1.489 1.482 1.476 1.469 1.459 1.438 1.411 1.387 1.364 1.341 1.335 1.318 1.310 0.000
7.300
Supplementary Figure 136. 13C NMR (75 MHz, CDCl3) spectrum for rac-10.
212
201.696
200
2016-12-01 16:11:24.383 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 175 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-7-110
50
23.945 21.022
27.897
34.341
42.852
55.528
81.697 77.432 77.000 76.568 73.277 69.968
0 PPM
Supplementary Figure 137. 1H NMR (300 MHz, CDCl3) spectrum for rac-1c.
213
10
7.278
8
2016-12-02 11:03:03.921 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
1.00
6
4
1.00
3.960 3.953 3.938 3.931 3.917 3.910 3.414
zj-7-112
3.00
0.96
2
2.02 2.02
6.10
0
2.455 2.448 2.137 2.113 2.089 2.065 1.759 1.749 1.737 1.722 1.700 1.685 1.678 1.497 1.487 1.473 1.449 1.422 1.399 1.388 1.377 1.367 1.345 1.331 1.314 0.000
6.408 6.384 6.360
PPM
Supplementary Figure 138. 13C NMR (75 MHz, CDCl3) spectrum for rac-1c.
214
200
2016-12-02 13:34:21.054 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 675 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-112
100
50
35.260 32.806 28.614 27.585 24.735
56.420
82.552 77.423 77.000 76.577 73.783 70.878
88.600
138.631
0
PPM
215
10
Supplementary Figure 139. 1H NMR (300 MHz, CDCl3) spectrum for rac-4ck.
8
2016-12-05 21:40:62.118 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.297
6.413 6.405 6.389 6.381 6.365 6.357
1.00
5.315 5.294 5.274 5.252 5.245 5.224 5.204 5.028 5.007 4.997 4.981 4.970 4.960 3.683 3.614 3.592 3.568 3.545 3.323 3.296 2.497 2.469 2.438 2.414 2.384 2.371 2.339 2.328 2.134 2.101 2.086 2.053 1.651 1.634 1.617 1.594 1.564 1.534 1.514 1.491 1.460 1.442 1.420 1.403 1.382 1.351 1.291 -0.000
6 1.00 1.00
zj-7-114
4 1.43 1.02 1.53
3.00 4.01
2
2.00 8.80
0 PPM
Supplementary Figure 140. 13C NMR (75 MHz, CDCl3) spectrum for rac-4ck.
216
173.165
204.178 204.104
200
2016-12-05 22:37:54.162 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 416 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-114
90.282 93.315 90.245 88.490 80.254 80.226 77.432 77.000 76.577
100
50
35.618 35.572 33.155 33.072 32.815 28.826 28.771 27.631 25.075 24.993 23.816 23.623
56.033 55.978 51.511
138.686
0 PPM
217
Supplementary Figure 141. 1H NMR (300 MHz, CDCl3) spectrum for rac-5k. 1.00
10
2016-12-08 23:54:03.046 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
11.231
8
6.410 6.404 6.386 6.380 6.362 6.355 5.330 5.312 5.291
0.97
7.292 5.289 5.263 5.242 5.221 5.054 5.044 5.023 4.996 4.986 3.637 3.616 3.593 3.570 3.331 3.305 2.536 2.512 2.482 2.458 2.396 2.374 2.364 2.351 2.341 2.329 2.319 2.295 2.128 2.122 2.105 2.099 2.080 2.075 2.056 2.050 1.695 1.693 1.659 1.640 1.630 1.607 1.579 1.550 1.521 1.502 1.490 1.478 1.446 1.426 1.403 1.378 1.343 0.000
6
zj-7-121
1.00 1.00
4 1.001.41
1.51
2
2.02 1.97 2.00 8.34
0 -2 PPM
Supplementary Figure 142. 13C NMR (75 MHz, CDCl3) spectrum for rac-5k.
218
178.790
204.242 204.114
200
2016-12-09 17:51:09.364 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 577 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
93.426 93.371 90.126 88.490
100
zj-7-121
50
35.508 35.425 33.118 33.026 32.806 32.778 28.789 28.734 27.603 25.057 24.965 23.494 23.274
55.969 55.877
80.300 77.423 77.000 76.577
138.650
0
PPM
219
Supplementary Figure 143. 1H NMR (300 MHz, CDCl3) spectrum for rac-xestospongiene ((E)-6k). 10 7.393
8
2017-01-06 00:14:09.062 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6.416 6.392 6.367
1.00
6 0.01
0.02
2.00
1.00
4
zj-7-158
1.00 3.03 3.07
2
3.02 8.52
0
5.764 5.745 5.712 5.693 5.680 5.659 5.651 5.628 5.607 5.599 5.544 5.514 5.493 5.475 5.338 5.310 5.286 5.263 5.014 4.992 4.970 4.948 3.612 3.592 3.584 3.572 3.542 3.260 2.583 2.557 2.528 2.503 2.487 2.471 2.453 2.435 2.416 2.384 2.124 2.100 2.076 2.052 2.015 1.986 1.944 1.556 1.536 1.509 1.479 1.448 1.426 1.405 1.324 1.253 0.000
PPM
220
Supplementary Figure 144. 1H NMR (300 MHz, CDCl3) extended spectrum for rac-xestospongiene ((E)-6k). 6.5 6.416 6.392 6.367
1.00
6.0 2.00
5.764 5.745 5.712 5.693 5.680 5.659 5.651 5.628 5.607 5.599 5.544 5.514 5.493 5.475
5.5 0.02 0.01
5.338 5.310 5.286 5.263
5.0
5.014 4.992 4.970 4.948
1.00
PPM
Supplementary Figure 145. 13C NMR (75 MHz, CDCl3) spectrum for rac-xestospongiene ((E)-6k).
221
176.437
200
2017-01-07 15:25:24.720 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 213 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467773 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-7-158
50
34.653 32.466 28.467 28.348 28.090 28.063 27.236 24.450
56.006
88.113 80.677 80.622 79.583 79.500 77.432 77.000 76.577
138.438 133.925 133.796 129.632 129.403
0
PPM
222 Supplementary Figure 146. Quantitative 13C NMR (75 MHz, CDCl 3) spectrum for rac-xestospongiene ((E)-6k).
176.453
200
2017-01-07 08:43:42.953 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 490 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
138.428 133.905 133.777 129.631 129.392 1.00 1.00 0.95 0.92
100
zj-7-158-Q
50
34.645 32.457 28.459 28.339 28.091 28.064 27.227 24.442
55.997
88.094 80.667 80.612 79.592 79.509 77.432 77.000 76.577
0 PPM
129 PPM 1.00 0.92
129.392 0.95
133
132
131
130
129.631 1.00
133.777
134
133.905
Supplementary Figure 147. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for racxestospongiene ((E)-6k). 223
Supplementary Figure 148. 1H NMR (300 MHz, CDCl3) spectrum for (S)-11.
224
10
8
2016-12-04 17:33:24.515 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
5.354 5.347 5.332 5.324 5.309 5.302 0.99
4
zj-7-113-1
3.611 3.590 3.568 2.00 0.95
2
2.99 1.99
8.00
8.98
0
5.98
2.447 2.439 1.799 1.775 2.082 1.746 1.724 1.528 1.506 1.462 1.435 1.418 1.375 1.351 1.328 1.314 1.302 0.883 0.038
7.260
PPM
Supplementary Figure 149. 1H NMR (300 MHz, CDCl3) spectrum for (R)-8.
225
10
7.260
8
2016-12-03 20:45:02.354 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
3.604 3.583 3.561
4
1.00
zj-7-113-2
2.00
2
0.96
0.96
1.99
8.08
9.02
0
6.01
1.736 1.725 1.713 1.699 1.682 1.660 1.525 1.502 1.480 1.450 1.440 1.428 1.398 1.344 1.333 1.321 1.308 1.296 0.873 0.028
2.446 2.439 2.244
4.364 4.345 4.325
PPM
Supplementary Figure 150. 13C NMR (75 MHz, CDCl3) spectrum for (R)-8.
226
200
150
2016-12-06 20:51:50.937 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 242 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
63.194 62.192
50
zj-7-113-2
0
-5.313
32.668 28.982 25.939 25.645 24.956 18.329
37.521
77.423 77.000 76.577 72.790
84.988
PPM
Supplementary Figure 151. 1H NMR (300 MHz, CDCl3) spectrum for (R)-11.
227
10
7.260
8
2016-12-05 16:21:48.734 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
5.344 5.336 5.321 5.314 5.299 5.292 1.00
4
2.00
3.601 3.580 3.558
zj-7-117
0.97
2
3.00 2.03
8.02
8.99
0
6.00
2.439 2.431 1.786 1.765 2.069 1.754 1.735 1.713 1.516 1.495 1.473 1.452 1.435 1.408 1.341 1.330 1.319 1.306 1.294 0.873 0.028
PPM
Supplementary Figure 152. 13C NMR (75 MHz, CDCl3) spectrum for (R)-11.
228
200
169.893
2016-12-05 16:55:27.375 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 548 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-117
100
50
0
-5.322
34.451 32.640 28.826 25.930 25.572 24.800 20.930 18.310
81.237 77.423 77.000 76.577 73.378 63.727 63.111
PPM
Data File C:\CHEM32\1\DATA\SIG10189.D Sample Name: 7-117 ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 10:18:05 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 10:18:04 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:19:39 PM (modified after loading) Sample Info : dexcb
FID1 A, Front Signal (SIG10189.D) pA 900
800
700
600
55.938
500
400
300
200
100
0 0
10
20
30
40
min
50
===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs
Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 55.938 BB 0.0854 1869.97827 310.96283 1.000e2 Totals :
1869.97827
310.96283
Supplementary Figure 153. GC spectrum for (R)-11. Instrument 1 12/13/2016 2:19:42 PM
229
Page
1 of 2
Data File C:\CHEM32\1\DATA\SIG10188.D Sample Name: 7-111-rac ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 9:09:27 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 9:09:26 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:18:41 PM (modified after loading) Sample Info : dexcb
FID1 A, Front Signal (SIG10188.D) pA 900
800
700
600
500
400
55.911 56.320
300
200
100
0 0
10
20
30
40
min
50
===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs
Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 55.911 BB 0.0877 874.01947 158.17586 49.57828 2 56.320 BB 0.0881 888.88849 154.14984 50.42172 Totals :
1762.90796
312.32570
Supplementary Figure 154. GC spectrum for rac-11. Instrument 1 12/13/2016 2:18:44 PM
230
Page
1 of 2
Supplementary Figure 155. 1H NMR (300 MHz, CDCl3) spectrum for (S)-8.
231
10
2016-12-05 14:23:14.667 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.260
8
6
0.99
3.599 3.577 3.556
4
zj-7-118
2.00
1.83
2
2.00
8.09
9.01
0
5.97
PPM
1.729 1.718 1.706 1.691 1.676 1.653 1.646 1.519 1.497 1.475 1.455 1.433 1.420 1.411 1.336 1.313 1.300 1.289 0.867 0.024
2.441 2.434
4.355 4.337 4.317
Supplementary Figure 156. 1H NMR (300 MHz, CDCl3) spectrum for (S)-11.
232
10
2016-12-07 00:04:03.078 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
5.346 5.340 5.324 5.318 5.302 5.296 1.00
4
2.00
3.604 3.583 3.561
zj-7-120-1
0.95
2
2.99 1.99
8.08
8.98
0
6.00
2.442 2.435 1.788 1.766 2.074 1.746 1.739 1.716 1.513 1.497 1.475 1.455 1.437 1.412 1.343 1.321 1.308 0.876 0.031
7.260
PPM
Supplementary Figure 157. 13C NMR (75 MHz, CDCl3) spectrum for (S)-11.
233
200
169.911
2016-12-07 00:37:37.656 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 563 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-120-1
100
50
0
-5.331
34.442 32.631 28.826 25.921 25.572 24.800 20.939 18.310
81.228 77.423 77.000 76.568 73.378 63.718 63.111
PPM
Data File C:\CHEM32\1\DATA\SIG10190.D Sample Name: 7-120-1 ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 11:32:29 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 11:32:28 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:20:26 PM (modified after loading) Sample Info : dexcb
FID1 A, Front Signal (SIG10190.D) pA 900
800
700
600
500
56.324
400
300
200
100
0 0
10
20
30
40
min
50
===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs
Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 56.324 BB 0.0918 1594.40137 262.14978 1.000e2 Totals :
1594.40137
262.14978
Supplementary Figure 158. GC spectrum for (S)-11. Instrument 1 12/13/2016 2:20:29 PM
234
Page
1 of 2
Data File C:\CHEM32\1\DATA\SIG10188.D Sample Name: 7-111-rac ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 12/13/2016 9:09:27 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 9:09:26 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC.M Last changed : 12/13/2016 2:18:41 PM (modified after loading) Sample Info : dexcb
FID1 A, Front Signal (SIG10188.D) pA 900
800
700
600
500
400
55.911 56.320
300
200
100
0 0
10
20
30
40
min
50
===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs
Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 55.911 BB 0.0877 874.01947 158.17586 49.57828 2 56.320 BB 0.0881 888.88849 154.14984 50.42172 Totals :
1762.90796
312.32570
Supplementary Figure 159. GC spectrum for rac-11. Instrument 1 12/13/2016 2:18:44 PM
235
Page
1 of 2
236
10
Supplementary Figure 160. 1H NMR (300 MHz, CDCl3) spectrum for (S)-8.
7.260
8
2016-12-17 18:07:49.345 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
0.99
3.599 3.577 3.556
4
zj-7-140
2.00
1.85
2
1.94
8.06
8.99
0
5.98
1.729 1.718 1.706 1.691 1.676 1.653 1.646 1.519 1.497 1.475 1.455 1.433 1.420 1.411 1.336 1.313 1.300 1.289 0.867 0.024
2.441 2.434
4.355 4.337 4.317
PPM
Supplementary Figure 161. 13C NMR (75 MHz, CDCl3) spectrum for (S)-8.
237
200
150
2016-12-17 17:28:50.125 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 177 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
77.423 77.000 76.577 72.726
85.034
zj-7-140
50
0
-5.331
32.640 28.964 25.921 25.627 24.947 18.301
37.484
63.185 62.100
PPM
Supplementary Figure 162. 1H NMR (300 MHz, CDCl3) spectrum for (R)-9.
238
10
7.349
8
2016-12-13 13:31:33.656 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
4
1.00
2.00
3.00
3.957 3.950 3.936 3.929 3.914 3.907 3.611 3.589 3.567 3.404 2.799 2.483 2.476
zj-7-129
0.99
0.97
2
2.01
8.09
0
1.754 1.732 1.713 1.691 1.669 1.576 1.553 1.530 1.508 1.480 1.465 1.443 1.390 1.372 1.362 1.352 1.340 1.317 0.000
PPM
Supplementary Figure 163. 13C NMR (75 MHz, CDCl3) spectrum for (R)-9.
239
200
150
2016-12-13 13:47:50.859 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 157 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-7-129
50
35.030 32.208 28.780 25.342 24.745
56.015
62.045
77.423 77.000 76.577 73.737 70.731
82.239
0
PPM
Supplementary Figure 164. 1H NMR (300 MHz, CDCl3) spectrum for (R)-10.
240
10
9.767 9.762 9.757
0.97
8
2016-12-15 09:23:14.357 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
3.957 3.952 3.936 3.930 3.915 3.909 3.402
zj-7-135
4
1.00
3.01
3.00
2
4.06
4.15
0
2.484 2.478 2.470 2.451 2.446 2.426 2.421 1.757 1.746 1.734 1.719 1.713 1.703 1.698 1.678 1.654 1.629 1.605 1.535 1.515 1.503 1.488 1.480 1.476 1.467 1.459 1.437 1.410 1.386 1.362 1.339 1.334 1.316 0.000
7.332
-2
PPM
Supplementary Figure 165. 13C NMR (75 MHz, CDCl3) spectrum for (R)-10.
241
201.972
200
2016-12-15 11:03:25.127 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 149 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-135
100
50
24.119 21.206
28.081
34.525
43.045
55.758
81.862 77.423 77.000 76.568 73.388 70.170
0
PPM
Supplementary Figure 166. 1H NMR (300 MHz, CDCl3) spectrum for (R)-1c.
242
10
6.408 6.384 6.360
7.271
8
2016-12-15 20:24:03.593 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
1.00
6
zj-7-137
4
3.961 3.954 3.940 3.933 3.918 3.911 3.416 1.00
2.99
0.94
2
2.02 2.00
6.14
0
2.452 2.445 2.137 2.114 2.089 2.065 1.761 1.751 1.739 1.723 1.708 1.686 1.525 1.488 1.474 1.425 1.399 1.378 1.367 1.345 1.314 -0.000
PPM
Supplementary Figure 167. 13C NMR (75 MHz, CDCl3) spectrum for (R)-1c.
243
200
2016-12-17 11:03:17.562 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 606 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-137
100
50
28.642 27.612 24.763
35.288 32.833
56.456
82.579 77.423 77.000 76.577 73.792 70.924
88.618
138.668
0
PPM
244
10
Supplementary Figure 168. 1H NMR (300 MHz, CDCl3) spectrum for (S)-9.
7.358
8
2016-12-19 11:02:22.781 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
4
1.00
2.00
2.98
3.958 3.952 3.937 3.930 3.914 3.908 3.607 3.585 3.563 3.405 2.983 2.491 2.484
zj-7-142
0.98
0.93
2
2.01
8.02
0
1.798 1.771 1.739 1.712 1.701 1.691 1.668 1.646 1.598 1.574 1.551 1.528 1.506 1.479 1.464 1.435 1.387 1.360 1.350 1.338 1.325 0.000
PPM
Supplementary Figure 169. 13C NMR (75 MHz, CDCl3) spectrum for (S)-9.
245
200
150
2016-12-19 11:09:49.140 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 88 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-7-142
50
35.113 32.309 28.844 25.406 24.818
56.144
62.256
77.432 77.000 76.577 73.746 70.823
82.340
0
PPM
Supplementary Figure 170. 1H NMR (300 MHz, CDCl3) spectrum for (S)-10.
246
9.768 9.762 9.756
10
0.97
2016-12-20 20:18:20.562 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
3.959 3.952 3.938 3.931 3.916 3.909 3.402
zj-7-143
4
1.00
3.00
3.00
2
4.02
4.11
0
2.487 2.480 2.476 2.451 2.446 2.427 2.421 1.758 1.735 1.725 1.714 1.703 1.678 1.654 1.628 1.604 1.540 1.534 1.503 1.487 1.480 1.457 1.436 1.409 1.394 1.373 1.362 1.333 1.309 -0.000
7.349
PPM
Supplementary Figure 171. 13C NMR (75 MHz, CDCl3) spectrum for (S)-10.
247
202.340
200
2016-12-20 21:00:28.234 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 667 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-7-143
50
24.496 21.583
28.458
34.892
43.404
56.107
82.230 77.423 77.000 76.577 73.673 70.557
0
PPM
Supplementary Figure 172. 1H NMR (300 MHz, CDCl3) spectrum for (S)-1c.
248
10
7.283
8
2016-12-20 20:00:14.265 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
0.98
4
1.00
3.957 3.951 3.936 3.929 3.914 3.908 3.410
zj-7-146
3.00
0.94
2
2.00
2.01
6.08
0
2.455 2.448 2.136 2.112 2.088 2.063 1.757 1.729 1.703 1.682 1.518 1.496 1.485 1.472 1.448 1.421 1.398 1.387 1.366 1.343 1.329 1.313 1.299 0.000
6.407 6.383 6.358
PPM
Supplementary Figure 173. 13C NMR (75 MHz, CDCl3) spectrum for (S)-1c.
249
200
2016-12-21 00:04:07.333 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 238 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-7-146
50
28.596 27.566 24.708
35.232 32.787
56.392
82.524 77.423 77.000 76.577 73.774 70.842
88.591
138.604
0
PPM
250
10
Supplementary Figure 174. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-4ck.
7.304
8
2016-12-20 14:25:48.062 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
0.99
6
5.316 5.295 5.275 5.255 5.023 5.013 5.007 4.997 4.991 4.980 4.970 1.00 1.00
zj-7-138
4
3.682 3.615 3.593 3.569 3.546 3.295 1.01
3.01 3.00
2.01
2.04
2
2.03
8.43
2.465 2.438 2.415 2.365 2.340 2.324 2.134 2.110 2.087 2.062 1.610 1.569 1.541 1.493 1.464 1.442 1.420 1.366 -0.000
6.413 6.389 6.365
0PPM
Supplementary Figure 175. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-4ck.
251
173.119
200
2016-12-20 14:52:19.000 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 411 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-138
100
51.484
50
35.545 33.045 32.797 28.798 27.612 25.057 23.596
55.951
80.190 77.423 77.000 76.577
93.297 90.264 88.471
138.649
204.160
0PPM
zj-7-138-if-100-1-1-214 实验时间：2017-03-02,12:21:23 谱图文件:D:\zhuguangjiong\zj\20170302\zj-7-138-if-100-1-1214.org
报告时间：2017-03-02,18:32:20
实验内容简介：
色谱图(zj-7-138-if-100-1-1-214.org) 3,400 3,200 3,000 2,800 2,600
2,000 1,800
25.853
电压(mv)
2,400 2,200
1,600 1,400 1,200 1,000
0 0
34.908
400 200 2
4
6
50.862
800 600
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58
时间(min)
峰号 1 2 3
峰名
保留时间
分析结果表 峰高
25.853 34.908 50.862
总计
峰面积
含量
1479945.500 950.974 1857.505
51123048.000 43397.344 191656.438
99.5423 0.0845 0.3732
1482753.979
51358101.781
100.0000
Supplementary Figure 176. HPLC spectrum for (Ra,R)-4ck. 252
zj-7-114-if-100-1-1-214 实验时间：2017-03-02,11:12:11 谱图文件:D:\zhuguangjiong\zj\20170302\zj-7-114-if-100-1-1214.org
报告时间：2017-03-02,18:33:43
实验内容简介：
色谱图(zj-7-114-if-100-1-1-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
500 400 300 200
49.057
600
33.790
700
27.790
800
25.190
电压(mv)
900
100 0 0
2 4
6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
25.190 27.790 33.790 49.057
总计
峰面积
含量
568287.688 492501.188 333279.406 173895.328
19152964.000 19221222.000 16885436.000 16834350.000
26.5667 26.6613 23.4214 23.3506
1567963.609
72093972.000
100.0000
Supplementary Figure 177. HPLC spectrum for rac-4ck. 253
Supplementary Figure 178. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-5k.
254
9.681
10
0.93
2016-12-22 22:35:00.906 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
0.98
6
0.99
5.333 5.313 5.293 5.272 5.059 5.038 5.021 5.001 4.990 0.99
zj-7-144
3.635 3.615 3.590 3.565 3.307
4
1.00
3.00
2.02
2.01
2
2.03
9.00
0PPM
2.511 2.487 2.465 2.376 2.355 2.323 2.310 2.131 2.107 2.083 2.059 1.641 1.610 1.579 1.551 1.524 1.503 1.481 1.456 1.414 1.360 1.294 1.253 -0.000
6.412 6.388 6.363
7.278
Supplementary Figure 179. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-5k.
255
200
178.893
2016-12-22 23:33:21.116 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 507 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-144
100
50
35.546 33.129 32.917 28.900 27.715 25.169 23.385
56.016
80.393 77.488 77.066 76.643
93.501 90.237 88.583
138.770
204.345
PPM
256
Supplementary Figure 180. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene F ((5S,1’E,3’R)-6k). 10 8
2017-02-20 18:13:05.000 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.356
6.413 6.388 6.364
1.00
5.764 5.745 5.712 5.693 5.684 5.663 5.632 5.611 5.552 5.515 5.486 5.335 5.316 5.285 5.259 5.015 4.992 4.973 4.949 3.613 3.592 3.572 3.551 3.265 2.586 2.565 2.536 2.517 2.480 2.462 2.440 2.418 2.394 2.125 2.102 2.077 2.053 2.030 2.014 1.988 1.957 1.574 1.520 1.481 1.447 1.425 1.405 1.324 0.000
6 0.03
2.02
0.02 1.00
zj-7-188
4 1.00 3.00 3.09
2
3.08 8.59
0 PPM
257
Supplementary Figure 181. 1H NMR (300 MHz, CDCl3) extended spectrum for xestospongiene F. 6.5 1.00
6.413 6.388 6.364
6.0 2.02
5.764 5.745 5.712 5.693 5.684 5.663 5.632 5.611 5.552 5.515 5.486
5.5
0.03 0.02
5.335 5.316 5.285 5.259
5.0
5.015 4.992 4.973 4.949
1.00
zj-7-188
PPM
Supplementary Figure 182. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F ((5S,1’E,3’R)-6k).
258
176.566
200
2017-02-20 18:23:50.750 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 161 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-188
100
50
34.754 32.576 28.587 28.458 28.201 27.337 24.551
56.135
80.759 79.712 77.423 77.000 76.577
88.232
129.439
134.090
138.512
0 PPM
Supplementary Figure 183. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F.
259
200
176.610
2017-02-21 08:53:50.578 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 605 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
138.501 135.578 134.080 129.447 1.00 0.02
100
0.03
80.750 79.730 77.423 77.000 76.577
88.223
zj-7-188-Q
50
34.746 32.568 28.578 28.450 28.220 27.328 24.553
56.135
0
PPM
PPM 134
1.00
133
132
131
130
129.447 0.02
135
134.080
136
135.578
Supplementary Figure 184. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for xestospongiene F. 260
Data File C:\CHEM32\1\DATA\2014-44651.D Sample Name: zj-7-188 ===================================================================== Acq. Operator : 系统 Sample Operator : 系统 Acq. Instrument : SFC Location : Vial 46 Injection Date : 10/03/2017 15:47:57 Inj Volume : 5.000 µl Acq. Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 10/03/2017 15:12:15 by 系统 (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 13/03/2017 09:52:48 by 系统 (modified after loading) Additional Info : Peak(s) manually integrated DAD1 A, Sig=214,16 Ref=360,100 (2014-44651.D) mAU
800
15.775
600
400
200
0 0
5
10
15
20
min
===================================================================== Area Percent Report ===================================================================== Sorted By Multiplier Dilution Do not use Multiplier
: Signal : 1.0000 : 1.0000 & Dilution Factor with ISTDs
Signal 1: DAD1 A, Sig=214,16 Ref=360,100 Peak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] % ----|-------|----|-------|----------|----------|--------| 1 15.775 VV 0.5656 1.49946e4 325.08957 100.0000 Totals :
1.49946e4
325.08957
===================================================================== *** End of Report ***
Supplementary Figure 185. SFC spectrum for xestospongiene F.
SFC 13/03/2017 09:52:52 系统
261
Page
1 of 1
Data File C:\CHEM32\1\DATA\2014-44652.D Sample Name: zj-7-158-rac-ad-h-sfc-97-3-1.3-214 ===================================================================== Acq. Operator : 系统 Sample Operator : 系统 Acq. Instrument : SFC Location : Vial 41 Injection Date : 10/03/2017 16:22:52 Inj Volume : 5.000 µl Acq. Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 10/03/2017 16:20:37 by 系统 (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_LC-TEST-2016.M Last changed : 13/03/2017 09:50:59 by 系统 (modified after loading) Additional Info : Peak(s) manually integrated DAD1 A, Sig=214,16 Ref=360,100 (2014-44652.D) mAU
400
100
21.277
16.324
14.450
200
17.388
300
0
0
5
10
15
20
min
===================================================================== Area Percent Report ===================================================================== Sorted By Multiplier Dilution Do not use Multiplier
: Signal : 1.0000 : 1.0000 & Dilution Factor with ISTDs
Signal 1: DAD1 A, Sig=214,16 Ref=360,100 Peak RetTime Type Width Area Height Area # [min] [min] [mAU*s] [mAU] % ----|-------|----|-------|----------|----------|--------| 1 14.450 MM R 0.3913 3141.53149 127.69143 24.0477 2 16.324 MF R 0.4819 3396.79004 113.02892 26.0016 3 17.388 FM R 0.5002 3149.34937 98.45376 24.1075 4 21.277 MM R 0.6807 3376.07983 78.39977 25.8431 Totals :
1.30638e4
417.57388
===================================================================== *** End of Report ***
Supplementary Figure 186. SFC spectrum for rac-xestospongiene.
SFC 13/03/2017 09:51:52 系统
262
Page
1 of 1
263
10
Supplementary Figure 187. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,R)-4ck.
7.302
8
2016-12-20 13:43:17.578 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
0.99
6
1.00 1.00
4
1.04
3.01
5.265 5.245 5.224 5.204 5.026 5.016 5.006 4.995 4.989 4.979 4.968 4.958 3.682 3.612 3.592 3.568 3.545 3.322
zj-7-139
2.99
2.02
2.02
2
2.01
8.58
0
2.497 2.469 2.446 2.393 2.384 2.372 2.362 2.350 2.340 2.311 2.125 2.101 2.077 2.053 1.647 1.627 1.604 1.584 1.564 1.533 1.506 1.484 1.447 1.428 1.405 1.382 1.344 1.333 0.000
6.406 6.382 6.357
PPM
Supplementary Figure 188. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,R)-4ck.
264
173.128
204.095
200
2016-12-20 14:07:26.343 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 389 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-139
100
51.474
50
35.600 33.146 32.787 28.761 27.603 24.974 23.807
56.006
80.226 77.432 77.000 76.577
93.306 90.227 88.471
138.668
0 PPM
电 (mv )压
zj-7-139-if-100-1-1-214 实验时间：2016-12-29,16:30:56 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-139-if-100-1-1214.org
报告时间：2016-12-29,17:41:44
实验内容简介：
色谱图(zj-7-139-if-100-1-1-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
800 36.618
电压(mv)
900
700 600 500 400
100 0 0
2
4
6
25.635
18.925
200
21.142
300
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
18.925 21.142 25.635 36.618
总计
峰面积
含量
7426.935 1433.861 2646.305 568388.500
442951.219 62236.391 77021.773 69295464.000
0.6339 0.0891 0.1102 99.1668
579895.601
69877673.383
100.0000
Supplementary Figure 189. HPLC spectrum for (Sa,R)-4ck. 265
电 (mv )压
zj-7-114-if-100-1-1-214 实验时间：2016-12-29,13:10:36 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-114-if-100-1-1214.org
报告时间：2016-12-29,17:38:32
实验内容简介：
色谱图(zj-7-114-if-100-1-1-214.org) 2,400 2,200 2,000
1,400 1,200
26.177
电压(mv)
1,600
20.037 21.892
1,800
1,000
37.362
800 600 400 200
0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
20.037 21.892 26.177 37.362
总计
峰面积
含量
1370312.625 1249851.375 792350.000 380083.000
33698112.000 34018172.000 31096976.000 30855660.000
25.9878 26.2346 23.9818 23.7957
3792597.000
129668920.000
100.0000
Supplementary Figure 190. HPLC spectrum for rac-4ck. 266
267
Supplementary Figure 191. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,R)-5k. 10 0.87
8
2016-12-22 22:43:33.593 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
9.718
6.404 6.380 7.277 6.357
0.98
5.281 5.262 5.242 5.221 5.055 5.045 5.034 5.024 5.018 5.007 4.997 4.987 3.633 3.612 3.589 3.564 3.331 2.542 2.518 2.495 2.400 2.390 2.379 2.369 2.347 2.324 2.124 2.100 2.076 2.051 1.667 1.659 1.635 1.606 1.576 1.560 1.541 1.513 1.491 1.471 1.447 1.425 1.403 1.379 1.343 1.332 1.318 1.301 1.253 0.000
6 1.00
1.00
zj-7-145
4 1.02 3.01 2.01
1.97
2
2.01 8.56
0 PPM
Supplementary Figure 192. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,R)-5k.
268
178.827
204.169
200
2016-12-23 23:14:09.655 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 599 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-145
100
50
35.600 33.164 32.843 28.807 27.658 25.029 23.550
56.061
80.337 77.432 77.000 76.577
93.527 90.153 88.536
138.723
0 PPM
269
10
Supplementary Figure 193. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene G.
6.406 6.382 6.358
7.298
8
2017-03-19 23:48:03.453 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
1.00
6
5.758 5.739 5.706 5.681 5.661 5.630 5.608 5.014 4.991 4.972 4.949 2.00 1.00
3.602 3.581 3.561 3.539 3.274
4
zj-8-012
1.00
3.00 3.00
2
3.01
8.25
0
2.594 2.570 2.541 2.487 2.466 2.424 2.401 2.378 2.125 2.102 2.077 2.053 2.018 2.002 1.976 1.945 1.598 1.566 1.549 1.528 1.503 1.484 1.448 1.428 1.402 1.340 1.323 1.254 -0.000
PPM
Supplementary Figure 194. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene G.
270
176.474
200
2017-03-22 13:21:08.143 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 412 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-8-012
100
50
34.718 32.521 28.522 28.403 28.118 27.291 24.515
56.061
80.741 79.564 77.423 77.000 76.568
88.177
129.651
133.879
138.475
0
PPM
SAMPLE Sample Name: ZJ8012 ADH912200040 Sample Type: Vial: 1:A,5 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322
INF O R MA T IO N Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 18:02:58 CST chiral_isocratic 2017/3/23 14:19:41 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
16.213
0.24 0.22 0.20 0.18 0.16
AU
0.14 0.12 0.10 0.08 0.06
11.263
0.04 0.02 0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00 16.00 Minutes
Peak Results RT
Height
% Area
29947
2316
0.39
2 16.213 7743535
229889
99.61
1
11.263
Area
Supplementary Figure 195. SFC spectrum for xestospongiene G. 271
18.00
20.00
22.00
24.00
26.00
28.00
30.00
SAMPLE
0.60
Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
10.552
9.078
Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213
INF O R MA T IO N
14.833
AU
0.40
0.30
18.726
0.50
0.20
0.10
0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00 16.00 Minutes
Peak Results RT 1
Area
Height
% Area
635306
24.26
11177453 563713
26.15
9.078 10369086
2 10.552
3 14.833 10145220 4 18.726
298583
23.73
11052066 239962
25.86
Supplementary Figure 196. SFC spectrum for rac-xestospongiene. 272
18.00
20.00
22.00
24.00
26.00
28.00
30.00
273
10
Supplementary Figure 197. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,S)-4ck.
6.406 6.381 6.357
8
0.99
2016-12-24 20:30:19.078 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
1.00 1.00
zj-7-148
4
1.01
2.99
0.01
2.99 2.00 2.00
2
2.00
8.16
0
5.266 5.245 5.225 5.204 5.027 5.016 5.006 4.996 4.990 4.979 4.968 4.959 3.682 3.615 3.592 3.568 3.546 3.323 3.296 2.497 2.469 2.446 2.394 2.384 2.373 2.362 2.352 2.340 2.329 2.125 2.102 2.077 2.053 1.617 1.604 1.585 1.534 1.514 1.484 1.460 1.448 1.428 1.405 1.382 1.345 1.320 1.302 0.000
7.300
PPM
Supplementary Figure 198. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,S)-4ck.
274
173.146
200
2016-12-24 20:56:31.031 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 428 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-148
100
51.502
50
35.609 33.146 32.787 28.761 27.612 24.984 23.807
56.015
80.236 77.432 77.000 76.577
93.306 90.236 88.471
138.677
204.095
0
PPM
电 (mv )压
zj-7-148-if-100-1-1-214 实验时间：2016-12-29,14:26:02 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-148-if-100-1-1214.org
报告时间：2016-12-29,17:43:32
实验内容简介：
色谱图(zj-7-148-if-100-1-1-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
800
25.655
电压(mv)
900
700 600 500 400
100 0 0
2
4
6
37.877
19.177
200
21.437
300
8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
19.177 21.437 25.655 37.877
总计
峰面积
含量
2891.311 3269.852 611125.375 730.933
167002.906 175523.078 34820224.000 30796.018
0.4745 0.4987 98.9392 0.0875
618017.471
35193546.002
100.0000
Supplementary Figure 199. HPLC spectrum for (Ra,S)-4ck. 275
电 (mv )压
zj-7-114-if-100-1-1-214 实验时间：2016-12-29,13:10:36 谱图文件:F:\zhuguangjiong\zj\20161229\zj-7-114-if-100-1-1214.org
报告时间：2016-12-29,17:38:32
实验内容简介：
色谱图(zj-7-114-if-100-1-1-214.org) 2,400 2,200 2,000
1,400 1,200
26.177
电压(mv)
1,600
20.037 21.892
1,800
1,000
37.362
800 600 400 200
0 0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52 54 56 58 60
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
20.037 21.892 26.177 37.362
总计
峰面积
含量
1370312.625 1249851.375 792350.000 380083.000
33698112.000 34018172.000 31096976.000 30855660.000
25.9878 26.2346 23.9818 23.7957
3792597.000
129668920.000
100.0000
Supplementary Figure 200. HPLC spectrum for rac-4ck. 276
277
Supplementary Figure 201. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,S)-5k. 10.730 0.95
10 8
2016-12-26 21:06:23.315 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6.404 6.379 6.355
0.98
6 1.00
1.00
zj-7-151
4 1.00 3.00
2
2.00 2.00 1.99 8.36
0 -2
5.280 7.291 5.259 5.238 5.218 5.053 5.043 5.032 5.026 5.022 5.016 5.006 4.995 4.985 3.637 3.615 3.594 3.571 3.331 2.539 2.512 2.488 2.396 2.386 2.375 2.365 2.353 2.326 2.319 2.122 2.099 2.075 2.050 1.669 1.648 1.629 1.617 1.607 1.576 1.559 1.532 1.512 1.491 1.470 1.446 1.424 1.401 1.379 1.350 1.342 1.318 1.299 1.280 0.000
PPM
Supplementary Figure 202. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,S)-5k.
278
200
178.781
2017-01-02 12:09:40.377 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 574 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-151
100
50
35.508 33.127 32.787 28.743 27.603 24.965 23.504
55.969
80.300 77.423 77.000 76.577
93.444 90.126 88.499
138.659
204.123
0 PPM
279
10
Supplementary Figure 203. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene H.
7.384
8
2017-03-20 23:42:22.359 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
1.00
6
1.00
5.763 5.744 5.711 5.691 5.673 5.652 5.622 5.600 5.016 4.993 4.971 4.948 2.00
4
3.605 3.584 3.563 3.541 3.263
zj-8-013
1.00
3.00
3.02
2
3.00
8.32
0
2.586 2.560 2.531 2.497 2.472 2.453 2.432 2.409 2.384 2.124 2.100 2.076 2.051 2.018 1.987 1.946 1.600 1.585 1.558 1.537 1.520 1.499 1.479 1.449 1.426 1.405 1.335 1.323 0.000
6.414 6.391 6.366
PPM
Supplementary Figure 204. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene H.
280
200
176.437
2017-03-21 00:06:53.156 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 376 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-8-013
50
34.681 32.484 28.486 28.357 28.081 27.254 24.469
56.015
80.695 79.519 77.423 77.000 76.568
88.131
129.632
133.824
138.447
0 PPM
SAMPLE Sample Name: ZJ8013 ADH912200040 Sample Type: Vial: 1:A,6 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322
INF O R MA T IO N Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 18:33:53 CST chiral_isocratic 2017/3/23 14:20:07 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
9.389
0.70
0.60
0.50
AU
0.40
0.30
0.20
0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
20.824
11.900
0.10
14.00 16.00 Minutes
Peak Results RT
Area
Height
% Area
11206012 680745
99.48
1
9.389
2
11.900
42814
2644
0.38
3 20.824
15359
822
0.14
Supplementary Figure 205. SFC spectrum for xestospongiene H. 281
18.00
20.00
22.00
24.00
26.00
28.00
30.00
SAMPLE
0.60
Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
10.552
9.078
Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213
INF O R MA T IO N
14.833
AU
0.40
0.30
18.726
0.50
0.20
0.10
0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00 16.00 Minutes
Peak Results RT 1
Area
Height
% Area
635306
24.26
11177453 563713
26.15
9.078 10369086
2 10.552
3 14.833 10145220 4 18.726
298583
23.73
11052066 239962
25.86
Supplementary Figure 206. SFC spectrum for rac-xestospongiene. 282
18.00
20.00
22.00
24.00
26.00
28.00
30.00
283
10
Supplementary Figure 207. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,S)-4ck.
8
2016-12-27 19:18:41.265 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.305
6.413 6.389 6.365
1.00
6 1.00 1.00
zj-7-150
4 2.97
0.03
1.01
3.00
2
2.02 2.01 2.00 8.25
0
5.316 5.295 5.274 5.254 5.028 5.018 5.007 4.990 4.980 4.970 4.960 3.682 3.615 3.593 3.569 3.546 3.322 3.295 2.465 2.458 2.443 2.437 2.412 2.369 2.356 2.346 2.336 2.324 2.314 2.303 2.296 2.286 2.134 2.110 2.086 2.061 1.639 1.620 1.608 1.598 1.585 1.541 1.521 1.492 1.460 1.441 1.419 1.396 1.382 1.364 1.350 1.330 -0.000
-2 PPM
Supplementary Figure 208. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,S)-4ck.
284
173.119
200
2016-12-27 19:27:13.578 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 131 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-150
100
51.484
50
35.536 33.026 32.787 28.789 27.603 25.048 23.577
55.942
80.190 77.423 77.000 76.577
93.279 90.255 88.462
138.650
204.141
0
PPM
电 (mv )压
zj-7-150-if-3-100-1-1-214 实验时间：2017-01-13,18:09:09 报告时间：2017-01-13,19:51:03 谱图文件:F:\zhuguangjiong\zj\20170113\zj-7-150-if-3-100-1-1214.org 实验内容简介：
色谱图(zj-7-150-if-3-100-1-1-214.org)
500 450 400 350
14.788
电压(mv)
300 250 200 150
0 2
3 4 5
6
25.448
13.458
50
0 1
17.810
100
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
13.458 14.788 17.810 25.448
总计
峰面积
含量
103.315 204454.266 476.592 177.939
1663.211 3509839.000 9957.236 5422.999
0.0472 99.5168 0.2823 0.1538
205212.112
3526882.446
100.0000
Supplementary Figure 209. HPLC spectrum for (Sa,S)-4ck. 285
电 (mv )压
zj-7-114-if-3-100-1-1-214 实验时间：2017-01-13,19:04:56 报告时间：2017-01-13,19:48:04 谱图文件:F:\zhuguangjiong\zj\20170113\zj-7-114-if-3-100-1-1214.org
24.965
17.665
色谱图(zj-7-114-if-3-100-1-1-214.org)
14.765
1,000 950 900 850 800 750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0
13.515
电压(mv)
实验内容简介：
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
13.515 14.765 17.665 24.965
总计
峰面积
含量
415700.125 363298.375 253848.797 144203.688
6377944.000 6413361.000 5528617.000 5590452.500
26.6744 26.8225 23.1223 23.3809
1177050.984
23910374.500
100.0000
Supplementary Figure 210. HPLC spectrum for rac-4ck. 286
Supplementary Figure 211. 1H NMR (300 MHz, CDCl3) spectrum for (Sa,S)-5k.
287
10.123
10
0.92
2017-01-01 15:32:18.046 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
0.98
6
5.332 5.311 5.291 5.271 5.048 5.037 5.027 5.021 5.011 5.000 1.00 1.00
4
3.636 3.614 3.589 3.566 3.331 3.306
zj-7-156
0.03
1.00
2.95
2.01
2.01
2
2.01
8.26
0
PPM
2.513 2.486 2.463 2.376 2.366 2.354 2.345 2.332 2.323 2.131 2.107 2.083 2.059 1.631 1.620 1.601 1.551 1.525 1.503 1.481 1.457 1.435 1.414 1.394 1.379 1.360 -0.000
7.278 6.411 6.387 6.363
Supplementary Figure 212. 13C NMR (75 MHz, CDCl3) spectrum for (Sa,S)-5k.
288
178.873
204.279
200
2017-01-01 16:11:52.703 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 660 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-156
100
50
35.517 33.081 32.861 28.853 27.658 25.112 23.338
55.969
80.327 77.423 77.000 76.577
93.472 90.163 88.527
138.714
0
PPM
289
10
Supplementary Figure 213. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene E ((5R,1’E,3’S)-6k).
7.352
8
2017-02-21 15:25:33.236 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
1.00
6
0.01
2.00 0.01
0.99
zj-7-189
4
1.00
3.00
3.07
2
3.09
8.53
5.763 5.744 5.712 5.693 5.684 5.663 5.632 5.611 5.551 5.519 5.489 5.335 5.311 5.286 5.262 5.015 4.993 4.972 4.949 3.612 3.592 3.572 3.551 3.265 2.590 2.565 2.536 2.504 2.461 2.440 2.394 2.125 2.102 2.078 2.056 2.030 1.988 1.957 1.559 1.511 1.481 1.447 1.426 1.405 1.327 0.000
6.412 6.388 6.364
0
PPM
290
Supplementary Figure 214. 1H NMR (300 MHz, CDCl3) extended spectrum for xestospongiene E. 6.5 1.00
6.412 6.388 6.364
6.0 2.00
5.763 5.744 5.712 5.693 5.684 5.663 5.632 5.611 5.551 5.519 5.489
5.5
0.01 0.01
5.335 5.311 5.286 5.262
5.0
5.015 4.993 4.972 4.949
0.99
zj-7-189
PPM
291
200
Supplementary Figure 215. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene E ((5R,1’E,3’S)-6k).
176.566
150
2017-02-21 19:08:33.231 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 971 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
88.269
100
zj-7-189
50
34.791 32.604 28.614 28.486 28.228 27.364 24.579
56.171
80.787 79.730 77.432 77.000 76.577
129.458
134.127
138.530
0 PPM
Supplementary Figure 216. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene E.
292
200
176.794
2017-03-09 09:05:55.921 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 1930 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
134.374 129.999 129.530 1.00 0.02
88.453
100
zj-7-189-Q
50
34.939 32.742 28.772 28.643 28.404 27.521 24.755
56.356
80.962 79.932 77.432 77.000 76.577
138.630
0
PPM
PPM 128 129 1.00
129.999
132
131
130
0.02
129.530
Supplementary Figure 217. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for xestospongiene E. 293
SAMPLE Sample Name: ZJ7-189 ADH912200040 Sample Type: Vial: 1:A,3 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322
INF O R MA T IO N Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 16:53:38 CST chiral_isocratic 2017/3/23 14:18:28 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
20.954
0.30
0.25
AU
0.20
0.15
0.10
0.00
2.00
4.00
6.00
8.00
10.00
12.00
17.331
0.00
11.643
9.915
0.05
14.00 16.00 Minutes
Peak Results RT
Area
Height
% Area
1
9.915
47327
3602
0.26
2
11.643
24645
1837
0.14
3 17.331
10850
486
0.06
4 20.954 17914997
315459
99.54
Supplementary Figure 218. SFC spectrum for xestospongiene E. 294
18.00
20.00
22.00
24.00
26.00
28.00
30.00
SAMPLE
0.60
Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
10.552
9.078
Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213
INF O R MA T IO N
14.833
AU
0.40
0.30
18.726
0.50
0.20
0.10
0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00 16.00 Minutes
Peak Results RT 1
Area
Height
% Area
635306
24.26
11177453 563713
26.15
9.078 10369086
2 10.552
3 14.833 10145220 4 18.726
298583
23.73
11052066 239962
25.86
Supplementary Figure 219. SFC spectrum for rac-xestospongiene. 295
18.00
20.00
22.00
24.00
26.00
28.00
30.00
296
10
Supplementary Figure 220. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-4ck.
8
2017-01-16 09:28:22.828 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.295
6.413 6.389 6.365
0.99
6 1.00 1.00
zj-7-177
4
5.316 5.296 5.275 5.255 5.028 5.018 5.007 4.997 4.980 4.970 4.960 3.684 3.613 3.593 3.569 3.546 3.324 3.297
1.00
2.98
0.02
2.98
2.467 2.460 2.438 2.416 2.370 2.360 2.347 2.337 2.325 2.315 2.293 2.134 2.110 2.086 2.061 1.640 1.621 1.609 1.600 1.591 1.541 1.515 1.493 1.460 1.440 1.418 1.396 1.364 1.355 1.330 -0.000
2.02
1.99
2
2.00 8.17
0 PPM
Supplementary Figure 221. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-4ck.
297
173.165
200
2017-01-16 10:12:53.015 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 743 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-177
100
51.520
50
35.572 33.072 32.824 28.826 27.631 25.075 23.623
55.978
80.226 77.423 77.000 76.577
93.315 90.291 88.490
138.686
204.187
0
PPM
电 (mv )压
zj-7-177-if-3-100-1-1-214 实验时间：2017-01-17,10:38:27 报告时间：2017-01-17,12:43:29 谱图文件:F:\zhuguangjiong\zj\20170117\zj-7-177-if-3-100-1-1214.org 实验内容简介：
1,500
色谱图(zj-7-177-if-3-100-1-1-214.org)
1,400 1,300 1,200 1,100 1,000
800
13.992
电压(mv)
900
700 600 500 400
100
26.337
15.022
200
18.518
300
0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
13.992 15.022 18.518 26.337
总计
峰面积
含量
632933.125 595.728 245.622 688.221
10014403.000 11957.195 4872.408 25650.504
99.5776 0.1189 0.0484 0.2551
634462.696
10056883.107
100.0000
Supplementary Figure 222. HPLC spectrum for (Ra,R)-4ck. 298
电 (mv )压
zj-7-114-if-3-100-1-1-214 实验时间：2017-01-17,11:12:52 报告时间：2017-01-17,12:44:44 谱图文件:F:\zhuguangjiong\zj\20170117\zj-7-114-if-3-100-1-1214.org 实验内容简介：
色谱图(zj-7-114-if-3-100-1-1-214.org)
500 450 400 350
150 100
26.198
200
18.515
250
15.448
14.082
电压(mv)
300
50 0 0 1
2
3 4 5
6
7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
时间(min)
峰号 1 2 3 4
峰名
保留时间
分析结果表 峰高
14.082 15.448 18.515 26.198
峰面积
含量
224085.547 193008.625 137829.547 81985.172
3595589.250 3533020.000 3136710.500 3084028.500
26.9346 26.4659 23.4971 23.1025
636908.891
13349348.250
100.0000
总计
Supplementary Figure 223. HPLC spectrum for rac-4ck. 299
Supplementary Figure 224. 1H NMR (300 MHz, CDCl3) spectrum for (Ra,R)-5k.
300
10
0.94
8
2017-01-18 15:54:22.937 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
0.98
6
5.333 5.313 5.292 5.272 5.057 5.046 5.030 5.025 5.009 4.988 1.00 1.00
4
3.634 3.614 3.590 3.567 3.306
zj-7-182
1.00
3.00
2.00
2.03
2
2.01
8.34
0
2.513 2.485 2.462 2.373 2.363 2.353 2.330 2.321 2.309 2.294 2.130 2.106 2.082 2.058 1.663 1.640 1.609 1.601 1.579 1.550 1.523 1.480 1.455 1.433 1.413 1.359 -0.000
7.281 6.411 6.387 6.362
10.373
PPM
Supplementary Figure 225. 13C NMR (75 MHz, CDCl3) spectrum for (Ra,R)-5k.
301
178.873
200
2017-01-18 16:34:27.765 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 668 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-7-182
100
50
35.499 33.072 32.852 28.844 27.649 25.103 23.320
55.951
80.327 77.423 77.000 76.577
93.444 90.163 88.517
138.705
204.279
0
PPM
302
10
Supplementary Figure 226. 1H NMR (300 MHz, CDCl3) spectrum for xestospongiene F.
8
2017-03-19 22:06:57.578 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.360
6.413 6.389 6.364
1.00
5.764 5.745 5.712 5.693 5.683 5.663 5.631 5.610 5.551 5.522 5.484 5.331 5.308 5.285 5.262 5.015 4.992 4.972 4.948 3.612 3.592 3.572 3.551 3.264 2.589 2.586 2.564 2.535 2.504 2.480 2.440 2.416 2.394 2.125 2.101 2.077 2.053 2.017 1.988 1.957 1.602 1.559 1.511 1.481 1.447 1.425 1.324 0.000
6 0.02
2.00
0.02 1.00
zj-8-011
4 0.98 3.00 3.03
2
3.04 8.34
0 PPM
303
Supplementary Figure 227. 1H NMR (300 MHz, CDCl3) extended spectrum for xestospongiene F. 6.5 6.413 6.389 6.364 1.00
6.0 2.00
5.764 5.745 5.712 5.693 5.683 5.663 5.631 5.610 5.551 5.522 5.484
5.5
0.02 0.02
5.331 5.308 5.285 5.262
5.0
5.015 4.992 4.972 4.948 1.00
zj-8-011
4.5 PPM
304
200
Supplementary Figure 228. 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F.
176.538
150
2017-03-19 22:23:06.187 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 254 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
100
zj-8-011
50
34.745 32.558 28.568 28.440 28.191 27.327 24.542
56.125
80.741 79.693 77.423 77.000 76.568
88.223
129.430
134.072
138.502
0
PPM
Supplementary Figure 229. Quantitative 13C NMR (75 MHz, CDCl3) spectrum for xestospongiene F.
305
200
176.591
2017-03-20 15:06:05.406 USER: nmr SOLVENT: CDCl3 Experiment = zgig30 Pulse length = 9.500 usec Relaxation delay = 60.000 sec NA = 884 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
138.501 135.560 134.062 129.438 0.02
1.00
88.214
100
zj-8-011-Q
50
34.737 32.558 28.569 28.441 28.202 27.319 24.543
56.126
80.732 79.721 77.432 77.000 76.577
0 PPM
PPM 134.062
0.02
134
1.00
132
130
129.438
138
136
135.560
140
138.501
Supplementary Figure 230. Quantitative 13C NMR (75 MHz, CDCl3) extended spectrum for xestospongiene F. 306
SAMPLE Sample Name: ZJ8011 ADH912200040 Sample Type: Vial: 1:A,4 Injection: 1 Injection Volume: 3.00 ul Run Time: 30.0 Minutes Sample Set Name:20170322
Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 17:32:01 CST chiral_isocratic 2017/3/23 14:19:00 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
11.032
0.70
INF O R MA T IO N
0.60
0.50
AU
0.40
0.30
9.576
0.10
21.810
0.20
0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00 16.00 Minutes
Peak Results 1 2
RT
Area
Height
% Area
9.576
259455
18854
1.62
11.032 15714231
713261
98.03
2248
0.35
3 21.810
56440
Supplementary Figure 231. SFC spectrum for xestospongiene F. 307
18.00
20.00
22.00
24.00
26.00
28.00
30.00
SAMPLE
0.60
Acquired By: Date Acquired: Acq. Method Set: Date Processed: Processing Method: Channel Name: Proc. Chnl. Descr:
System 2017/3/22 14:45:20 CST chiral_isocratic 2017/3/23 14:07:00 CST 1 PDA Ch1 214
[email protected] nm PDA Ch1 214
[email protected] nm
10.552
9.078
Sample Name: ZJ7-158 adh912214200040 Sample Type: Vial: 1:A,1 Injection: 1 Injection Volume: 5.00 ul Run Time: 30.0 Minutes Sample Set Name:20170213
INF O R MA T IO N
14.833
AU
0.40
0.30
18.726
0.50
0.20
0.10
0.00 0.00
2.00
4.00
6.00
8.00
10.00
12.00
14.00 16.00 Minutes
Peak Results RT 1
Area
Height
% Area
635306
24.26
11177453 563713
26.15
9.078 10369086
2 10.552
3 14.833 10145220 4 18.726
298583
23.73
11052066 239962
25.86
Supplementary Figure 232. SFC spectrum for rac-xestospongiene. 308
18.00
20.00
22.00
24.00
26.00
28.00
30.00
309
12
Supplementary Figure 233. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5j.
10
0.79
2015-11-18 19:01:05.359 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 16 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
5.187 5.170 5.156 5.140 5.125
6
zj-4-190
2.00
4
1.98
1.98
2
2.01
12.45
3.02
0
2.508 2.484 2.460 2.339 2.323 2.316 2.308 2.301 2.286 2.263 2.007 1.985 1.966 1.960 1.951 1.946 1.927 1.404 1.381 1.356 1.270 0.903 0.881 0.858 -0.000
10.352
PPM
Supplementary Figure 234. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5j.
310
179.774
203.645
200
2015-11-19 22:58:33.819 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 482 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-4-190
100
50
33.127 31.859 29.405 29.294 29.147 29.101 28.826 23.476 22.649 14.082
77.423 77.000 76.577
92.883 89.216
0
PPM
Supplementary Figure 235. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bj.
311
10
8
6
1.98
5.167 5.152 5.148 5.135 5.120 5.115 5.102 4.166 4.143 4.119 4.096
2015-11-19 15:57:11.375 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
4
2.00
zj-4-198
2.02
2.00
2
2.00
15.36
3.04
0
2.441 2.435 2.414 2.388 2.332 2.311 2.300 2.289 2.276 2.265 2.254 2.248 2.002 1.980 1.964 1.955 1.947 1.939 1.922 1.398 1.378 1.355 1.327 1.282 1.270 1.258 1.235 0.903 0.881 0.858 0.000
PPM
Supplementary Figure 236. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bj.
312
200
173.137
150
2015-11-19 15:57:11.375 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
100
zj-4-198
50
33.431 31.831 29.386 29.258 29.111 28.844 23.871 22.621 14.183 14.054
60.234
77.423 77.000 76.577
92.488 89.473
203.626
0
PPM
zj-4-198-oz-h-400-1-0.5-214 实验时间：2016-01-04,12:32:12 谱图文件:D:\zhuguangjiong\zj\20160104\zj-4-198-oz-h-400-10.5-214..org
报告时间：2016-01-05,17:42:24
实验内容简介：
色谱图(zj-4-198-oz-h-400-1-0.5-214..org)
1,500 1,400 1,300 1,200 1,100 1,000
800 700 600 15.428
电压(mv)
900
500 400 300 14.068
200 100 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
14.068 15.428
总计
峰面积
含量
21746.184 346879.906
377848.406 14457886.000
2.5469 97.4531
368626.090
14835734.406
100.0000
Supplementary Figure 237. HPLC spectrum for (Ra)-4bj. 313
zj-4-197-oz-h-400-1-0.5-214 实验时间：2016-01-04,11:44:12 谱图文件:d:\zhuguangjiong\zj\20160104\zj-4-197-oz-h-400-10.5-214.org
报告时间：2016-01-05,17:40:22
实验内容简介：
色谱图(zj-4-197-oz-h-400-1-0.5-214.org)
700 650 600 550 500
400 350 300 250 200
15.692
13.642
电压(mv)
450
150 100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
13.642 15.692
总计
Supplementary Figure 238. HPLC spectrum for rac-4bj. 314
峰面积
含量
197026.484 147035.156
5910192.000 5806109.000
50.4442 49.5558
344061.641
11716301.000
100.0000
315
Supplementary Figure 239. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6j. 7.365
12 10
2015-11-28 22:06:24.890 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8 6 0.03 0.03
1.03 1.01
zj-5-017
1.00
4 1.04
2.01
2
3.04 12.47
3.07
0 -2 PPM
5.853 5.851 5.831 5.828 5.809 5.805 5.802 5.800 5.780 5.777 5.758 5.754 5.705 5.680 5.669 5.644 5.615 5.534 5.530 5.525 5.511 5.506 5.501 5.483 5.479 5.474 5.459 5.455 5.450 5.295 5.276 5.248 5.220 4.928 4.904 4.880 4.856 2.555 2.552 2.530 2.523 2.521 2.500 2.429 2.408 2.387 2.367 2.342 2.321 2.093 2.071 2.049 2.036 2.027 2.007 1.995 1.981 1.964 1.949 1.938 1.907 1.384 1.359 1.269 0.902 0.881 0.858 0.000
316
6.2
Supplementary Figure 240. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6j.
6.0 5.8
5.853 5.851 5.831 5.828 5.809 5.805 5.802 5.800 5.780 5.777 5.758 5.754 5.705 5.680 5.669 5.644 5.615 5.534 5.530 5.525 5.511 5.506 5.501 5.483 5.479 5.474 5.459 5.455 5.450 5.295 5.276 5.248 5.220
1.01
5.6
0.03
5.4
1.03
5.2
0.03
5.0 4.928 4.904 4.880 4.856
4.8
1.00
4.6 PPM
Supplementary Figure 241. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6j.
317
200
176.759
150
2015-11-28 22:17:52.265 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 174 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-017
100
50
31.758 31.528 29.065 28.899 28.780 28.504 28.449 28.375 22.318 13.751
77.423 80.824 77.000 76.577
127.178
135.221
0
PPM
zj-5-017-oj-h-100-1-1-214 实验时间：2016/1/7,15:51:30 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-017-oj-100-1-1214..org
报告时间：2016/1/7,17:05:14
实验内容简介：
色谱图(zj-5-017-oj-100-1-1-214..org)
500 450 400 350
250 200 15.388
电压(mv)
300
150
13.467
100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
13.467 15.388
总计
峰面积
含量
4963.917 120397.070
83447.000 4552410.500
1.8000 98.2000
125360.987
4635857.500
100.0000
Supplementary Figure 242. HPLC spectrum for (S,E)-6j. 318
zj-5-013-oj-h-100-1-1-214 实验时间：2016/1/7,13:38:12 谱图文件:d:\zhuguangjiong\zj\20160106\zj-5-013-oj-100-1-1214.org
报告时间：2016/1/7,17:01:04
实验内容简介：
色谱图(zj-5-013-oj-100-1-1-214.org)
500 450 400 350
250 200
15.242
12.720
电压(mv)
300
150 100 50 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
12.720 15.242
总计
Supplementary Figure 243. HPLC spectrum for rac-6j. 319
峰面积
含量
176572.141 146212.047
5660659.000 5765820.000
49.5398 50.4602
322784.188
11426479.000
100.0000
320
Supplementary Figure 244. 1H NMR (300 MHz, CDCl3) spectrum for (R)-4-tetradecalactone. 10 7.304
8
2016-01-17 21:52:31.890 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
4.534 4.516 4.509 4.489 4.468 4.464 4.461 4.442
1.00
4
zj-5-093
1.03
1.99
2 1.01 1.05 0.99
16.86
3.04
0 -2
2.558 2.535 2.526 2.503 2.379 2.357 2.335 2.315 2.292 2.270 1.918 1.891 1.876 1.860 1.844 1.828 1.812 1.785 1.776 1.756 1.738 1.726 1.713 1.699 1.682 1.650 1.633 1.619 1.601 1.574 1.556 1.538 1.488 1.463 1.441 1.412 1.377 1.265 0.903 0.882 0.858 -0.000
PPM
Supplementary Figure 245. 13C NMR (75 MHz, CDCl3) spectrum for (R)-4-tetradecalactone.
321
200
177.191
150
2016-01-21 17:42:33.241 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 235 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-093
100
50
35.444 29.432 29.386 29.322 29.203 29.166 28.715 27.861 25.094 22.529 13.953
31.749
80.943 77.423 77.000 76.577
0 PPM
Supplementary Figure 246. GC spectrum for (R)-4-tetradecalactone. 322
Supplementary Figure 247. GC spectrum for rac-4-tetradecalactone. 323
324
12
Supplementary Figure 248. 1H NMR (300 MHz, CDCl3) spectrum for (Sa)-5j.
10.150
10
2015-11-19 19:34:04.156 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
0.71
5.187 5.170 5.164 5.156 5.140 5.125
6
zj-4-189
2.00
4
1.99
2.01
2
2.00
12.33
3.06
0
2.508 2.484 2.459 2.338 2.323 2.316 2.307 2.300 2.285 2.005 1.983 1.965 1.958 1.951 1.944 1.925 1.403 1.380 1.355 1.303 1.268 0.902 0.880 0.857 -0.000
7.265
PPM
Supplementary Figure 249. 13C NMR (75 MHz, CDCl3) spectrum for (Sa)-5j.
325
200
179.673
150
2015-11-18 13:13:34.671 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1019 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-4-189
100
50
33.109 31.859 29.405 29.285 29.138 29.101 28.826 23.485 22.649 14.073
77.423 77.000 76.577
92.883 89.216
203.645
0
PPM
Supplementary Figure 250. 1H NMR (300 MHz, CDCl3) spectrum for (Sa)-4bj.
326
10
7.286
8
2015-11-27 00:06:11.562 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.164 5.149 5.133 5.118 5.102
6
4.166 4.142 4.118 4.094 1.97
zj-4-199
4
2.00 2.00
2.01
2
2.00
15.22
3.00
0
2.438 2.433 2.411 2.387 2.329 2.315 2.311 2.299 2.288 2.275 2.253 2.248 2.002 1.980 1.964 1.956 1.947 1.923 1.407 1.381 1.357 1.329 1.281 1.272 1.257 1.233 0.903 0.882 0.858 -0.000
PPM
Supplementary Figure 251. 13C NMR (75 MHz, CDCl3) spectrum for (Sa)-4bj.
327
200
172.871
150
2015-11-19 19:59:08.109 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 166 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-4-199
100
50
33.302 31.758 29.313 29.184 29.019 28.752 23.770 22.529 14.064 13.917
60.050
77.423 77.000 76.577
92.314 89.372
203.599
0
PPM
zj-4-199-oz-h-400-1-0.5-214 实验时间：2015/11/25,9:50:52 谱图文件:D:\zhuguangjiong\zj\20151125\zj-4-199-oz-h-400-10.5-214..org
报告时间：2015/11/26,18:04:03
实验内容简介：
色谱图(zj-4-199-oz-h-400-1-0.5-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
800 700 600
8.873
电压(mv)
900
500 400 300
9.441
200 100 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
8.873 9.441
峰面积
含量
403421.063 6165.251
5154801.000 67059.127
98.7158 1.2842
409586.303
5219753.844
100.0000
总计
Supplementary Figure 252. HPLC spectrum for (Sa)-4bj. 328
zj-4-197-oz-h-400-1-0.5-214 实验时间：2015/11/25,9:21:13 谱图文件:d:\zhuguangjiong\zj\20151125\zj-4-197-oz-h-400-10.5-214.org
报告时间：2015/11/26,17:53:25
实验内容简介：
色谱图(zj-4-197-oz-h-400-1-0.5-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
800 700 8.900
600 500 400
9.353
电压(mv)
900
300 200 100 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
8.900 9.353
总计
Supplementary Figure 253. HPLC spectrum for rac-4bj.
329
峰面积
含量
367626.813 305268.219
4300627.000 4330028.000
49.8297 50.1703
672895.031
8630655.000
100.0000
330
Supplementary Figure 254. 1H NMR (300 MHz, CDCl3) spectrum for (S)-4-tetradecalactone. 10 8
2016-01-15 21:29:04.390 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.304
6
zj-5-090
4.534 4.515 4.509 4.489 4.468 4.464 4.442
0.99
4 1.05
1.99
2 1.01 1.02 0.96 16.73
3.06
0 -2 PPM
2.558 2.534 2.525 2.502 2.379 2.358 2.335 2.315 2.293 2.270 1.918 1.891 1.887 1.860 1.844 1.828 1.818 1.813 1.800 1.786 1.776 1.768 1.756 1.738 1.726 1.713 1.706 1.682 1.650 1.633 1.619 1.601 1.587 1.556 1.538 1.525 1.488 1.441 1.412 1.377 1.265 0.904 0.882 0.859 -0.000
Supplementary Figure 255. 13C NMR (75 MHz, CDCl3) spectrum for (S)-4-tetradecalactone.
331
200
177.182
150
2016-01-23 21:46:52.984 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 276 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-090
100
50
31.749 29.432 35.453 29.386 29.322 29.203 29.166 28.715 27.870 25.094 22.529 13.953
80.934 77.423 77.000 76.577
0
PPM
Supplementary Figure 256. GC spectrum for (S)-4-tetradecalactone. 332
Supplementary Figure 257. GC spectrum for rac-4-tetradecalactone.
333
Supplementary Figure 258. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5l.
334
10.247
10
0.86
2017-03-17 22:21:04.578 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
5.184 5.169 5.154 5.138 5.123
6
2.00
zj-3-171
4
2.03
1.96
2
2.02
17.14
3.06
0 PPM
2.503 2.480 2.457 2.333 2.311 2.297 2.282 2.004 1.982 1.964 1.958 1.949 1.944 1.925 1.400 1.376 1.353 1.262 0.902 0.880 0.857 -0.000
7.265
Supplementary Figure 259. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5l.
335
179.737
200
2015-05-28 19:00:18.625 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 2270 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-3-171
100
50
33.118 31.896 29.635 29.607 29.451 29.331 29.147 29.111 28.835 23.485 22.667 14.082
92.883 89.207 77.423 77.000 76.577
203.645
0
PPM
Supplementary Figure 260. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4al.
336
10
8
5.03
7.285 7.279 7.263 7.258 7.251 7.244 7.165
2015-06-04 16:17:03.250 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.084 5.074 5.053 5.035 5.024 5.019 5.009
6
4.00
4
zj-3-184
2
1.98 1.96
2.00
16.69
3.04
0
2.424 2.420 2.398 2.374 2.263 2.258 2.255 2.240 2.230 2.224 2.221 2.219 1.876 1.866 1.851 1.841 1.589 1.299 1.280 1.245 1.221 1.208 1.177 0.822 0.801 0.778 -0.000
PPM
Supplementary Figure 261. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4al.
337
172.905
200
spect, CDCl3, Thu Jun 05 13:56:41 2015 USER: nmr SOLVENT: Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1274 PTS1d = 32768 F1 = 75.476807 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-3-184
100
50
33.362 31.883 29.594 29.438 29.300 29.116 28.841 23.813 22.655 14.090
66.127
77.423 77.000 76.577
92.624 89.398
128.486 128.146
135.995
203.611
0
PPM
zj-3-184-ia-100-0-0.8-214 实验时间：2015/6/16,11:25:47 报告时间：2015/6/18,17:15:45 谱图文件:D:\zhuguangjiong\zj\20150612\zj-3-184-ia-100-0-0.8214.org 实验内容简介：
色谱图(zj-3-184-ia-100-0-0.8-214.org)
1,500 1,400 1,300 1,200 1,100 1,000
800 700
20.003
电压(mv)
900
600 500 400 300
22.417
200 100 0 0
1
2
3
4
5
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.003 22.417
峰面积
含量
494230.219 9328.662
21830514.000 359993.031
98.3777 1.6223
503558.881
22190507.031
100.0000
总计
Supplementary Figure 262. HPLC spectrum for (Ra)-4al. 338
zj-3-183-ia-100-0-0.8-214 实验时间：2015/6/16,10:34:25 报告时间：2015/6/18,17:14:18 谱图文件:D:\zhuguangjiong\zj\20150612\zj-3-183-ia-100-0-0.8214.org
色谱图(zj-3-183-ia-100-0-0.8-214.org)
22.137
1,000 950 900 850 800 750 700 650 600 550 500 450 400 350 300 250 200 150 100 50 0
20.627
电压(mv)
实验内容简介：
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
20.627 22.137
总计
Supplementary Figure 263. HPLC spectrum for rac-4al. 339
峰面积
含量
230837.906 199542.828
8070378.500 7934117.000
50.4257 49.5743
430380.734
16004495.500
100.0000
340
Supplementary Figure 264. 1H NMR (300 MHz, CDCl3) spectrum for (S,E)-6l. 10 8
2015-06-05 20:53:39.812 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
7.344
6 0.02
1.02
0.02
1.00 1.00
4
zj-3-181
1.00
2.00
2
3.05 16.63
3.05
0 PPM
5.851 5.828 5.802 5.777 5.756 5.703 5.680 5.666 5.641 5.618 5.532 5.528 5.523 5.508 5.505 5.500 5.481 5.477 5.472 5.457 5.453 5.449 5.296 5.274 5.245 5.223 4.926 4.902 4.878 4.855 2.554 2.552 2.530 2.522 2.500 2.426 2.405 2.384 2.363 2.340 2.317 2.112 2.093 2.070 2.048 2.022 1.994 1.964 1.937 1.906 1.382 1.359 1.264 0.902 0.880 0.857 -0.000
341
Supplementary Figure 265. 1H NMR (300 MHz, CDCl3) extended spectrum for (S,E)-6l. 5.851 5.828
5.8
5.802 5.777 5.756 1.00
5.703 5.680 5.666
5.6
0.02
5.641 5.618
5.4
1.02
5.532 5.528 5.523 5.508 5.505 5.500 5.481 5.477 5.472 5.457 5.453 5.449
5.296 5.274
5.2
0.02
5.245 5.223
5.0 4.926 4.902 4.878 4.855
4.8
1.00
PPM
Supplementary Figure 266. 13C NMR (75 MHz, CDCl3) spectrum for (S,E)-6l.
342
200
176.796
2015-06-05 21:08:17.078 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 235 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
100
zj-3-181
50
31.822 31.620 29.331 29.304 29.175 29.055 28.844 28.559 28.513 28.430 22.391 13.815
77.423 77.000 80.870 76.568
127.196
135.304
0
PPM
zj-3-181-as-h-95-5-1-214 实验时间：2015-07-21,17:15:31 谱图文件:D:\zhuguangjiong\zj\20150720\zj-3-181-as-h-95-5-1214..org
报告时间：2015-07-21,17:39:04
实验内容简介：
色谱图(zj-3-181-as-h-95-5-1-214..org)
300 280 260 240 220 200
160 140 120
11.602
电压(mv)
180
100 80 60
10.583
40 20 0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
10.583 11.602
总计
Supplementary Figure 267. HPLC spectrum for (S,E)-6l. 343
峰面积
含量
3032.685 82252.625
37218.348 2870599.500
1.2799 98.7201
85285.310
2907817.848
100.0000
zj-4-048-as-h-95-5-1-214 实验时间：2015-07-21,15:45:11 谱图文件:d:\zhuguangjiong\zj\20150720\zj-4-048-as-h-95-5-1214.org
报告时间：2015-07-21,17:37:21
实验内容简介：
色谱图(zj-4-048-as-h-95-5-1-214.org)
300 280 260 240 220 200
电压(mv)
180 160 140 120 100
10.570
60 40 20
12.017
80
0 0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
10.570 12.017
总计
Supplementary Figure 268. HPLC spectrum for rac-6l. 344
峰面积
含量
20498.037 17177.754
330317.313 336853.625
49.5101 50.4899
37675.791
667170.938
100.0000
345
10
Supplementary Figure 269. 1H NMR (300 MHz, CDCl3) spectrum for (R)-γ-palmitolactone.
8
6
4.530 4.511 4.485 4.460 4.438
2016-12-29 20:58:25.437 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
1.00
4
zj-5-044
1.00
2.00
2
1.02 1.02
1.00
20.88
3.05
0
PPM
2.553 2.529 2.520 2.497 2.375 2.353 2.331 2.311 2.289 2.266 1.914 1.888 1.873 1.856 1.825 1.800 1.782 1.767 1.754 1.737 1.712 1.698 1.681 1.649 1.631 1.599 1.581 1.554 1.536 1.487 1.487 1.462 1.444 1.411 1.393 1.262 0.903 0.881 0.858 0.000
7.300
Supplementary Figure 270. 13C NMR (75 MHz, CDCl3) spectrum for (R)-γ-palmitolactone.
346
200
177.136
150
2016-12-29 21:11:55.390 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 201 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz zj-5-044
100
50
31.785 29.515 35.462 29.497 29.396 29.331 29.212 28.715 27.870 25.103 22.548 13.963
80.916 77.423 77.000 76.577
0 PPM
Supplementary Figure 271. GC spectrum for (R)-γ-palmitolactone. 347
Supplementary Figure 272. GC spectrum for rac-γ-palmitolactone. 348
349
12
Supplementary Figure 273. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-5b.
11.552
0.98
10
2016-05-28 23:15:42.453 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 10 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
8
6
1.95
5.196 5.187 5.186 5.175 5.170 5.168 5.164 5.155 5.150 5.143 5.139 5.124
zj-6-111
4
2.00
2.00
2
2.00
4.04
3.00
0
PPM
2.504 2.479 2.455 2.335 2.321 2.305 2.297 2.282 2.277 2.260 2.015 1.990 1.974 1.967 1.958 1.934 1.418 1.400 1.390 1.372 1.359 1.347 1.335 1.322 1.301 0.919 0.895 0.871 -0.000
7.273
Supplementary Figure 274. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-5b.
350
200
179.976
2016-05-28 23:25:28.109 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 153 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-111
100
50
13.797
33.109 31.179 28.467 23.439 22.134
77.423 77.000 76.577
92.773 89.198
203.636
0
PPM
351
10
Supplementary Figure 275. 1H NMR (300 MHz, CDCl3) spectrum for (Ra)-4bb.
7.298
8
;blank line 2016-05-31 19:52:22.062 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
5.166 5.151 5.135 5.119 5.105
6
zj-6-116
4.168 4.144 4.120 4.096 1.98
4
2.00 2.01
2.00
2
2.00
3.11
4.03 3.05
0
PPM
2.440 2.434 2.416 2.412 2.409 2.390 2.387 2.331 2.316 2.300 2.289 2.272 2.254 2.012 1.988 1.975 1.956 1.935 1.420 1.391 1.375 1.363 1.351 1.339 1.330 1.282 1.258 1.235 0.922 0.899 0.876 -0.000
Supplementary Figure 276. 13C NMR (75 MHz, CDCl3) spectrum for (Ra)-4bb.
352
200
173.036
2016-05-31 20:08:51.656 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 262 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-116
100
50
14.128 13.779
23.844 22.088
33.394 31.197 28.476
60.161
77.423 77.000 76.577
92.369 89.437
203.636
PPM
zj-6-116-oz-h-100-0-1-214 实验时间：2016-06-07,14:17:17 报告时间：2016-06-07,15:56:32 谱图文件:D:\zhuguangjiong\zj\20160607\zj-6-116-oz-h-100-0-1214.org 实验内容简介：
500
色谱图(zj-6-116-oz-h-100-0-1-214.org)
450 400 350
250 200
27.083
电压(mv)
300
150
24.478
100 50 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
24.478 27.083
总计
峰面积
含量
4888.275 116701.664
144705.719 13411313.000
1.0675 98.9325
121589.939
13556018.719
100.0000
Supplementary Figure 277. HPLC spectrum for (Ra)-4bb. 353
zj-6-054-oz-h-100-0-1-214 实验时间：2016-06-07,15:06:15 报告时间：2016-06-07,15:55:26 谱图文件:D:\zhuguangjiong\zj\20160607\zj-6-054-oz-h-100-0-1214..org 实验内容简介：
500
色谱图(zj-6-054-oz-h-100-0-1-214..org)
450 400 350
200 150 100
27.017
250
22.188
电压(mv)
300
50 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35
时间(min)
峰号 1 2
峰名
保留时间
分析结果表 峰高
22.188 27.017
总计
Supplementary Figure 278. HPLC spectrum for rac-4bb. 354
峰面积
含量
125608.375 91985.625
9041449.000 9218339.000
49.5156 50.4844
217594.000
18259788.000
100.0000
355
Supplementary Figure 279. 1H NMR (300 MHz, CDCl3) spectrum for (R)-4-decalactone. 10 7.305
8
2016-06-27 15:22:23.234 USER: nmr SOLVENT: CDCl3 Experiment = zg30 Pulse length = 14.000 usec Relaxation delay = 1.000 sec NA = 8 Solvent = CDCl3 PTS1d = 32768 F1 = 300.130005 MHz F2 = 1.000000 MHz SW1 = 6188.12 Hz
6
4.539 4.520 4.514 4.494 4.474 4.469 4.448
0.98
zj-6-170
4 1.00
1.97
2 1.01 1.02 1.01 8.07
3.00
0 -2
2.562 2.538 2.530 2.507 2.384 2.362 2.340 2.320 2.297 2.275 1.922 1.891 1.864 1.849 1.832 1.822 1.790 1.759 1.742 1.734 1.711 1.686 1.656 1.638 1.624 1.606 1.588 1.561 1.543 1.491 1.465 1.447 1.415 1.395 1.380 1.345 1.337 1.326 1.294 0.911 0.888 0.865 -0.000
PPM
Supplementary Figure 280. 13C NMR (75 MHz, CDCl3) spectrum for (R)-4-decalactone.
356
177.237
200
2016-06-27 16:23:56.890 USER: nmr SOLVENT: CDCl3 Experiment = zgpg30 Pulse length = 9.500 usec Relaxation delay = 2.000 sec NA = 1022 Solvent = CDCl3 PTS1d = 32768 F1 = 75.467751 MHz F2 = 1.000000 MHz SW1 = 22727.27 Hz
150
zj-6-170
100
50
13.898
35.453 31.519 28.862 28.734 27.879 25.057 22.391
80.971 77.432 77.000 76.577
0 PPM
Data File C:\CHEM32\1\DATA\SIG10089.D Sample Name: zj-6-170 ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 7/6/2016 12:49:40 PM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC-2.M Last changed : 7/6/2016 12:49:39 PM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC-OFF.M Last changed : 7/7/2016 3:26:54 PM (modified after loading) Sample Info : dex cb
FID1 A, Front Signal (SIG10089.D) pA
250
200
150
50.095
49.595
100
50
0 0
10
20
30
40
50
===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs
Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 49.595 MF R 0.1630 509.24765 50.51576 97.03940 2 50.095 FM R 0.1153 15.53679 1.96476 2.96060 Totals :
524.78444
52.48052
Supplementary Figure 281. GC spectrum for (R)-4-decalactone. Instrument 1 7/7/2016 3:26:57 PM
357
Page
1 of 2
min
Data File C:\CHEM32\1\DATA\SIG10088.D Sample Name: zj-6-161-rac ===================================================================== Acq. Operator : Acq. Instrument : Instrument 1 Location : Vial 1 Injection Date : 7/6/2016 11:22:48 AM Inj Volume : Manually Acq. Method : C:\CHEM32\1\METHODS\DEF_GC-2.M Last changed : 7/6/2016 11:22:46 AM (modified after loading) Analysis Method : C:\CHEM32\1\METHODS\DEF_GC-OFF.M Last changed : 7/7/2016 3:25:28 PM (modified after loading) Sample Info : dex cb
FID1 A, Front Signal (SIG10088.D) pA
250
200
150
49.624 49.969
100
50
0 0
10
20
30
40
50
===================================================================== Area Percent Report ===================================================================== Sorted By : Signal Multiplier: : 1.0000 Dilution: : 1.0000 Use Multiplier & Dilution Factor with ISTDs
Signal 1: FID1 A, Front Signal Peak RetTime Type Width Area Height Area # [min] [min] [pA*s] [pA] % ----|-------|----|-------|----------|----------|--------| 1 49.624 BB 0.1094 282.17673 34.66543 50.30196 2 49.969 BB 0.1158 278.78891 32.32484 49.69804 Totals :
560.96564
66.99027
Supplementary Figure 282. GC spectrum for rac-4-decalactone. Instrument 1 7/7/2016 3:25:32 PM
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