N-Allyloxycarbonyl derivatives of D-glucosamine as

N-Allyloxycarbonyl derivatives of D-glucosamineas promotors of 1,2-trans-glucosylation in Koenigs-Knorr reactions and in Lewis acid catalyzed condensations PAULBOULLANGER, JOSEPHBANOUB,'A N D G ~ R A RDESCOTES D Universitk Lyon I , ~ c o l supkrieure e de chimie industrielle de Lyon, Unit6 associke 463, Centre national de la recherche scientijique, 43 Bd. du 11 Novembre 1918, 69622-Villeubranne CEDEX, France

Can. J. Chem. Downloaded from www.nrcresearchpress.com by China University of Petroleum on 05/28/13 For personal use only.

Received November 7, 1986 PAULBOULLANGER, JOSEPH BANOUB,and GBRARDDESCOTES. Can. J. Chem. 65, 1343 (1987). The use of suitably blocked D-glucosamine derivatives possessing the N-allyloxycarbonyl protective group of the amino function represents potential new routes to 1,2-trans-glucosylations.Both 3,4,6-tri-O-acetyl-2-N-allyloxycarbonyl-2-amino-2deoxy-a-D-glucopyranosyl bromide (2) and 1,3,4,6-tetra-O-acetyl-2-N-allyloxycarbonyl-2-amino-2-de0xy-~-~-glucopyranose (3) could be used in Koenigs-Knorr reactions or Lewis acid catalyzed condensations, respectively. Glucosides of simple alcohols and disaccharides were synthesized in good to excellent yields. The N-allyloxycarbonyl protective group was, moreover, easy to remove with Pd(0) complexes, thus affording, after acetylation, the corresponding N-acetyl-P-D-glucosamine glucosides under very smooth conditions.

JOSEPH BANOUB et GBRARDDESCOTES. Can. J. Chem. 65, 1343 (1987). PAULBOULLANGER, L'utilisation de derives de la D - g l ~ c o ~ a m i protCgCs ne sur la fonction amine par un groupement N-allyloxycarbonyle constitue une nouvelle voie d'accbs potentielle aux glucosides 1,2-trans. Le bromure de tri-0-acCtyl-3,4,6 N-allyloxycarbonyl-2-amino-2 dCsoxy-2 a-D-glucopyrannosyle (2) et le tttra-0-acCtyl-1,3,4,6 N-allyloxycarbonyl-2 amino-2 dCsoxy-2 6-D-glucopyrannose (3) peuvent etre utilists respectivement dans les reactions de type Koenigs-Knorr ou dans les condensations catalysCes par les acides de Lewis. Les glucosides d'alcools simples et les disaccharides ont CtC prCparCs avec des rendements de bons excellents. Le groupe protecteur N-allyloxycarbonyle est, de plus, facile a cliver avec les complexes du Pd(0) et conduit, aprks acktylation, aux glucosides de la N-acCtyl P-D-gl~co~amine dans des conditions trbs douces.

Introduction amino function, requested for the synthesis of natural oligosaccharides. Despite some recent improvements (lo), the The P-D-glucosides of N-acetyl glucosamine are widely phthalimido cleavage still remains a rather drastic procedure, distributed in living organisms where they constitute important which causes the removal of most alkaline-sensitive protective building blocks of peptidoglycans, mucopolysaccharides (hyalugroups and which also often results in an important decrease of ronic acids, keratan sulfate), glycoproteins (inner and outer the overall yield. core regions), oligosaccharides of human milk, and blood group The results described recently in the literature dealing with determinants (1). They are also often encountered in bacterial the versatile uses of the allyloxycarbonyl protective group antigens where they constitute part of the antigenic determinant (11, 12) prompted us to study its participating properties in (2). The teichoic acids of Staphylococcus aureus (3), for 1,2-trans-glucosylation reactions. In a continuation of our example, contain a P-D-GlcNAc-(I-+4)-D-ribitol repeating studies on the glucosylation reactions (4, 5 ) , we now report unit, the synthesis of which was realized recently in our two different efficient methods for 1,2- trans-glucosylation laboratory (4, 5). of D-glucosamine. Both Koenigs-Knorr type reactions and The usual procedures for the 1,2-trans-glucosylation of condensations catalyzed by Lewis acids are depicted and D-glucosamine are mainly the so-called oxazoline method (6) compared. and the phthalimido procedure (7). Despite their synthetic Results and discussion usefulness, these methods suffer some disadvantages. In the first method, the 2-methyl-(3,4,6-tri-0-acetyl- 1 ,2-dideoxy-DThe carbamate approach for the synthesis of 1,2-transglucopyrano)[2,1-dl-2-oxazoline(6) or a synthetic precursor (8) glucosides of D-glucosamine has already been mentioned in the is reacted with the alcohol (usually in refluxing nitromethaneliterature. Using a benzyl carbamate derivative, K. Heyns et al. toluene) in acidic medium. Yields are generally good with primary (13) did not succeed in obtaining the expected P-D-glucoside alcohols and still satisfactory. with reactive secondary alcohols whereas J. Lessard et al. (14) were able to prepare such (9), affording the P-D-glucosides of N-acetylated glucosamine P-D-glucosides in moderate yields using reactive alcohols only. directly. Nevertheless, the rather drastic conditions do not allow Most recently, S. Kusumoto et al. (15) described the synthesis the use of acid-sensitive protective groups in the glycosylating of a disaccharide from a trichloroethyl carbamate derivative of agent or the aglycon. D-glucosamine. In the phthalimido method, the alcohol is reacted with These rather divergent results induced us to undertake a 3,4,6-tri-O-acetyl-2-deoxy-2-phthalimido-~-glucopyranosyl systematic study on the glucosylation reactions of the N-allylbromide (usually at low temperature) in the presence of the oxycarbonyl derivatives of D-glucosamine. silver triflate - collidine complex. The yields are generally As previously reported (16), the reaction of 3,4,6-tri- 0excellent, even with weakly reactive alcohols, and this method acetyl-2-N-allyloxycarbonyl-2-amino-2-deoxy-ol-~-glucopyrais the most widely used for the preparation of complex nosy1 bromide (2) with alcohols promoted by mercury[Il] or oligosaccharides. The major disadvantage of the method is the silver[I] salts afforded the expected P-D-glucosides (4), together need of further steps for deprotection and reacetylation of the with various amounts of oxazolidinone (5) as a by-product. This reaction has been extended to 1,2-trans-glucosylations promoted by Lewis acids (17) and both methods were compared ' ~ u t h o to r whom correspondence may be addressed. with regard to the stability of the protective groups and the 'on leave from Fisheries and Oceans Canada, Science Branch, P.O. Box 5667, St. John's, Nfld., Canada A l C 5X 1. reactivity of the aglycons (Scheme 1). Pnntcd In Canada i lmpnmC au Canada

CAN. J . CHEM. VOL. 6 5 , 1987

1,2,3


AcO

D-gIucosamine, HCi

0R

- : cA AcO

NHAc

AcO

OR HNAOC

AcO

ACO AcO -

OAc

3 I . NaOMe, MeOH; 2. ClCOOAll, Et3N; 3. Ac20, pyr.; 4. HBr, AcOH, CH2CI2, 5. H ~ ( O A C )HOAc; ~, 6, Hg(CN)2, ROH; 7. TMS triflate, ROH; 8. Pd(PPh3)4, CH2(COOMe)2; 9. Ac20, pyr.

The glycosyl bromide (2) could be prepared with a 74% propylidene-a-D-glucofuranose,the glucoside (4d) was accomoverall yield from D-glucosamine hydrochloride, via the interpanied by important amounts of the oxazolidinone (5), the mediate 1,3,4,6-tetra-O-acetyl-2-N-allyloxycarbonyl-2-amino-formation of which was already reported by K. Heyns et al. 2-deoxy-a-~-glucopyranose (I), as a stable crystalline material, (13). contrary to its N-acetylated analog. This glucoside precursor The formation of both products (4a-g and 5) could be was synthesized by a very classical pathway and could, in turn, explained by the participation of the N-allyloxycarbonyl group be converted into another precursor, namely the corresponding giving rise to a strongly delocalized carbocationic species p-acetate (3), by means of mercury[II] acetate in acetic acid, (Scheme 1). This intermediate could react following pathway with an excellent yield. The preparation of compound 3 could be (a) (leading to the p-D-glucosides 4) or pathway (b) (forming the realized by shorter pathways, but the method described herein oxazolidinone 5) but the possible pathway (c) resulting from was the only one not requiring a chromatographic separation of an attack on the C-2 carbon atom of the oxazolidinium ion, a and p anomeric acetates at the final step of the synthesis. was never observed. Pathway (a) was very preponderant with The reaction of the glycosyl bromide (2) with one equivalent reactive alcohols (with regard to steric hindrance and (or) of alcohol and one equivalent of mercury[II] cyanide in nucleophilicity) while pathway (b) gained in importance with dichloromethane at room temperature resulted in the complete less reactive alcohols (see entry d in Table 1). It was, moreover, consumption of the starting material in less than 24h, depending observed that the oxazolidinone (5) was not reactive itself on the aglycon. With reactive alcohols, the expected P-Dtoward the alcohol under the experimental conditions, and glucosides (4a-c and 4e-g) were obtained in good yields, therefore cannot constitute an intermediate in the formation of whereas with unreactive aglycons, such as 1,2:5,6-di-0-isop-D-glucosides (4).

1345

BOULLANGER ET AL.

TABLE1. Glucosylation of alcohols from 3,4,6-tri-O-acetyl-2-N-allyloxycarbonyl-2-amino-2-deoxy-a-~-glucopyranosy1 bromide (2)' and 1,3,4,6-tetra-O-acetyl-2-N-allyloxycarbonyl-2-amino-2-deoxy--~-gucopyranose (31b Glucosylations from compound 3

Glucosylations from compound 2 Alcohol


a Methanol b Isopropanol

Glucoside 4a

4b

Glucoside yield (%)

Oxazolidinone(5) yield (%)

Reaction time (h)

Glucoside yield (%)

Reaction time (h)

91 76

Traces -5

2 6

85 95

12

86

Traces

5

82

16

35 81 63

-5 Traces -5

3

12

5 83 85

16 16 16

4

OH OBn

B~OO -R

e R = TBDMS f R = All g R = AOC

4e

4f 4g

-

-

- -

7 -

-

"Reactions performed with one equivalent of alcohol and one equivalent of mercury[II] cyanide with respect to 2, at room temperature in dichloromethane. bReactions performed with one equivalent of alcohol and one equivalent of trimethylsilyl triflate with respect to 3, at -35°C in dichloromethane. '(1+6)-P-D-glucoside resulting from a rearrangement of the isopropylidene protective group. dThe poor yield could be attributed to the cleavage of the tertiobutyldirnethylsilyl protective group during the reaction and (or) extraction and purification of the disaccharide.

Several experimental observations allowed us to conclude that, contrary to Heyns' results, the nucleophile (Nu-) involved in pathway (b) was not the alcohol but, probably, the bromide ion formed in the first step of the reaction, since no allylated alcohol (resulting from pathway (b) with Nu- = ROH) was detected in any condensations and since the addition of one equivalent of tetraethylammonium bromide to the reaction medium resulted in an increase of oxazolidinone formation. The results obtained with this Koenigs-Knorr type reaction are summarized in Table 1. The reaction of the p-D-acetate (3) with alcohols, on the other hand, could be conducted with various Lewis acids. Amongst those tested, the trimethylsilyl triflate gave the best results with regard to the yields of glucosides, ease of use, and lower amount of by-products. The reactions were conducted with one equivalent of the alcohol and one equivalent of the Lewis acid, with respect to the starting p-D-acetate at - 35OC in dichloromethane. The P-D-glucosides were obtained in good yields, even with the unreactive aglycon previously mentioned, and the oxazolidinone resulting from pathway (b) (Scheme 1) was not observed in that case. The results obtained with the Lewis acid promoted glucosylations are reported in Table 1. It should be noticed that the low yield of P-glucoside (4e) obtained by both methods could be attributed to undesired cleavage of the tertiobutyldimethylsilyl protective group during the reaction and (or) the purification of the product, rather than to an important formation of oxazolidinone (5).

As already reported in the literature (1 8), the Koenigs-Knorr reaction carried out on 1 ,2:5,6-di-0-isopropylidene-a-D-glucofuranose resulted in an acetal migration from the.5,6 to the 3,5 position of the aglycon and therefore afforded a 1-6 glycoside (4d) as attested mainly by 13C nmr (the chemical shifts of the quaternary carbons of the acetal protective groups, 112.53 ppm and 101.36 ppm, correspond to those of dioxolane and dioxane rings, respectively). The isopropylidene migration had been observed in a glycosylation promoted by trimethylsilyl triflate (19). The yields of glucosylations described in this paper can be compared favourably with those reported in the literature. The isopropyl glucoside, for example, was obtained in 85% yield only by the oxazoline method, using a 2-10 molar excess of the alcohol (20). The glucosides of 1,2:3,4-di-0-isopropylidenea-D-galactopyranose (c) were obtained, under the best conditions, in 81% yield by the oxazoline method (21) and in 86% yield by both phthalimido (22) and N-allyloxycarbonyl procedures (Table 1). On the other hand, the glucosylations of the ribitol derivatives (f and g ) were realized, in our laboratory, respectively in 71 (5) and 50% yields by the oxazoline method, in 79 and 7 1% yields by the phthalimido procedure, and in 83 and 85% yields by the N-allyloxycarbonyl procedure (Table 1). As can be seen from Table 1, the yields are slightly better starting from the bromide 2 than from the p-acetate 3 with primary alcohols but lower with secondary and hindered alcohols. These two methods are quite complementary since the


1346

CAN. J. CHEM.

VOL. 65, 1987

with basic aluminium oxide (Alumina Woelm B) before distillation lower reactivity of the bromide (2) is accompanied by a better over LiAIH4 and exhaustively flushed with argon just prior to use. selectivity towards primary alcohols and a better preservation of the acid-sensitive protective groups. The p-D-acetate (3), on I ,3,4,6-Tetra-0-acetyI-2N -allyloxycarbony-2 -amino-2-deoxy-a-D the other hand, seems to be much more reactive; these two glucopyranose ( 1) properties will be explored in the near future in the field of D-Glucosamine hydrochloride (21.6 g, 0.1 mol) was added to a complex carbohydrate synthesis involving selectivity and (or) sodium methylate solution, obtained by reaction of methanol (100 mL) with sodium (2.3 g, 0.1 mol), and then shaken at room temperature reactivity towards various alcohols. for 10 min. After filtration, triethylamine (I4 mL, 0.1 mol) and allylThe deprotection of the N-allyloxycarbonyl group could chloroformate (12.0 g, 0.104 mol) were added to the filtrate at a be realized by using the numerous methods reported in the temperature maintained below 30°C. The reaction was completed after literature; the reductive cleavage (23) and the deprotection 3 h at room temperature and the solvent was evaporated to dryness, promoted by nickel tetracarbonyl (24) have now been substifollowed by acetylation overnight (acetic anhydride: 100 mL, pyridine: tuted by newer methods based on homogeneous palladium 200 mL). After the usual extraction procedure, the title compound (1) catalysis. These methods are promoted by Pd(0) complexes, was recovered as a pink foamy material that could be used directly usually tetrakis(tripheny1phosphine) palladium, together with in the next step or recrystallized from ether (38.5 g, 89%): mp 119an allyl acceptor. Amongst these acceptors, the most widely 121°C; [ a ] t 3 $27.6 ( c 2.36, CHC13); 200-MHz IH nmr (CDCl,) 6: used are dimedone (25), 2-ethylhexanoic acid (26), or tributyl6.20 (d, IH, J = 3.6 Hz, H-I), 5.96-5.70 (m, IH, vinyl proton), tin hydride (27); these acceptors give rise to by-products of 5.32-5.11 (m, 4H), 4.97 (d, lH, J = 9.4 Hz, NH) 4.58-3.98 (m, 5H), 2.19, 2.12, 2.09, 2.04 (4s, 12H, 40Ac); "C nmr (CD3COCD3) low volatility, creating the need of further chromatographic 6: 156.37 (CO: allyloxycarbonyl), 133.87 (CH=CH2), 117.1 1 purification to recover the free amine after deprotection. The (CH=CH2), 90.96 (C-I), 71.33, 70.25 (C-5, C-3), 68.90 (C-4), Pd(0) catalyzed deprotection can also be realized by hydrogeno65.73 (CH2-CH=CH2), 62.24 (C-6), 53.48 (C-2). Anal. calcd. for lytic cleavage with formic acid (28) to afford the amine as a ClsHrsOllN(Mol. Wt. 431.39): C 50.1 1, H 5.84, N 3.25; found: quaternary salt, requiring an ion exchange to remove the free C 49.97, H 5.90, N 3.11. amine. The results of these different techniques have been 3,4,6-Tri-0-acetyl-2-N-allyloxycarbonyl-2 -amino-2 -deoxy - a - D recently reviewed in the field of nucleotide synthesis (12). glucopyranosyl bromide (2) To take advantage, in the field of carbohydrates, of the The above-mentioned derivative (1) (30 g, 0.07 mol) dissolved in remarkable selectivity of Pd(0) complexes, and to avoid the dry dichloromethane (200 mL) was treated at O°C with 33% hydroabove-mentioned inconveniences, we have used dimethyl bromic acid in acetic acid (50 mL) for 0.5 h. The mixture was then malonate as allyl acceptor to obtain volatile by-products after poured into cold water and the aqueous layer extracted with chloroallylation. After complete deprotection, the amino-free glycoform. The mixed organic extracts were then neutralized with an side could be reacetylated to prepare natural oligosaccharide aqueous solution of sodium carbonate, washed once with cold water, analogs (Scheme 1) or esterified with a fatty acid to obtain and dried over calcium chloride. After evaporation to dryness, analogs of glycolipids (15). compound 2 was recovered as a dark yellow foam. The pure derivative was recovered after two recrystallizations from ether (26 g, 82%): This new strategy for the synthesis of P-D-glucosides of mp 93-94°C; [a]',4 + 147 (c 1.9, CHC13);80-MHz 'H nmr (CDC13)6: glucosamine should, in our opinion, complete the panel of well-known and classical methods of 1,2-trans-glucosylations. 6.55 (d, IH, J = 3.6 Hz, H-1); "C nmr (CD3COCD3) 6: 155.95 (CO: allyloxycarbonyl), 133.63 (CH=CH?), 117.28 (CH=CH,), The N-allyloxycarbonyl approach is easy to use; the glucosyla93.55 (C-1), 73.43, 71.17 (C-5, C-3), 68.10 (C-4), 65.96 (CH2tion conditions are very smooth, and compatible with most CH=CH2), 6 1.77 (C-6), 55.85 (C-2). Anal. calcd. for C16H2209NBr hydroxyl protective groups stable in slightly acidic medium. (Mol. Wt. 452.25): C 42.49, H 4.90, N 3.10, Br 17.67; found: The choice between a glycosyl bromide and an anomeric C 42.64, H 5.09, N 2.92, Br 17.48. p-D-acetate as glucosylation precursor will permit selective I ,3,4,6-Tetra-0-acetyI-2-N -allyloxycarbonyl-2-amino-2-deoq-P-Dreactivities towards alcohols. The N-allyloxycarbonyl function glucopyranose (3) is quite stable in most of the conditions encountered in The glycosyl bromide 2 (20 g, 0.044 mol) dissolved in acetic acid saccharide chemistry and can survive the deprotection of many (100 mL), was treated for 45 min with mercury[II] acetate (16 g, other groups; its cleavage is, moreover, perfectly selective and 0.050 mol) at room temperature. After filtration on a bed of Celite, the compatible with most 0- and N-protkctive groups, which filter cake was washed three times with chloroform and the mixed represents a real advantage over the classical methods used in chloroformic extracts poured into cold water. After washing and that field. neutralization with an aqueous solution of sodium carbonate, the

Experimental Melting points were determined on a Buchi apparatus and were uncorrected. Optical rotations were measured using a Perkin Elmer 24 1 polarimeter in I-dm cells. The H nmr spectra were recorded on Varian EM-360, Brucker W.P. 80 CW, or Brucker A.C. 200 instruments. The I3Cnmr spectra were recorded on a Varian XL-100A (25.3 MHz) spectrometer operating in the Fourier transform mode. Chemical shifts are relative to internal Me&. In I3C nrnr spectra of the disaccharides, the primed carbon atom resonance signals are attributed to the carbohydrate moiety bound to P-D-glucosamine. The I3C nmr spectra always contain additional signals corresponding to acetates and aromatics in the case of benzylated ribitol derivatives. Microanalyses were carried out by the Laboratoire Central d'Analyse du CNRS (Solaise, France) and acceptable values are reported to a &0.4% tolerance. Chromatographic separations were performed on Merck silica gel (230-400 mesh). Dichloromethane was washed with water and dried on CaC12 before distillation over P2O5.Oxolane was treated

'

organic extracts were dried over calcium chloride and evaporated, to leave crude compound 3 as a yellowish crystalline material. Recrystallization from ether afforded the pure derivative (16.5 g, 87%): mp 109-1 10°C; [ a ] i 3 +25.9 (c2.14, CHC13);200-MHz 'H nmr (CDC13) 6: 5.87-5.76 (m, lH, vinyl proton), 5.37-5.12 (m, 4H), 4.95 (m, lH, NH), 4.58-3.81 (m, 6H), 2.15, 2.09, 2.08, 2.05 (4s, 12H, 40Ac); 13Cnmr (CD3COCD3) 6: 156.21 (CO: allyloxycarbonyl), 133.99 (CH=CHZ), 116.83 (CH=CH2), 92.88 (C-I), 73.13, 72.98 (C-5, 62.37 (C-6), 55.50 C-3), 69.08 (C-4), 65.54 (CHI-CH=CH2), (C-2). Anal. calcd. for C18H25011N (Mol. Wt. 431.39): C 50.11, H 5.84, N 3.25; found: C 50.35, H 5.91, N 3.20. General procedure for the Koenigs-Knorr glycosidatiorls starting from compound 2 The glycosyl bromide 2 (1.00 g, 2.21 mmol), the alcohol to be glucosylated (2.21 mmol), and dry mercury[II] cyanide (0.558 g, 2.21 mmol) were dissolved simultaneously in dry, alcohol-free dichloromethane (20 mL). The reaction, stirred at room tempeature, was monitored by tlc and stopped 1 h after completion (reaction times

;ER ET AL.


in Table 1). The reaction mixture was filtered on Celite, the filter cake washed twice with chloroform, and the mixed chloroformic extracts washed once with water. After drying over calcium chloride and evaporation, the product was purified by column chromatography (eluent: ethyl acetate/hexane from 1:2 to 2:l depending on the aglycon); yields are given in Table 1. General procedure for the Lewis acidpromoted glucosylarions starting from compound 3 The p-acetate 3 (1 .OO g, 2.3; mmol), the alcohol to be glucosylated (2.32 mmol), and powered 5 A molecular sieves (0.5 g) were added simultaneously in dry alcohol-free dichloromethane (50 mL). The reaction mixture was then flushed with argon while cooling to - 35°C. Trimethylsilyl triflate (0.516 g, 2.32 mmol) was then introduced through a syringe and the argon flush maintained for 0.5 h; the external temperature was kept near - 35 i 5°C all during the processing. The reaction times indicated in Table 1 are purely indicative, since the reactions were not monitored to avoid hydrolysis during the withdrawal of aliquots. The reaction was stopped by addition of triethylamine (0.5 g, 4.94 mmol) at -35OC; the mixture was then allowed to reach O°C, filtered on Celite, and the filtrate was collected into a cold, dilute aqueous solution of sodium carbonate. The same work-up and purification procedures as previously mentioned were then applied; yields are indicated in Table 1.

1347

obtained as a white crystalline material: mp 109- 1 1 1°C (ether/petroleum ether); [a];* + 15.5 ( c 2.3, CHC13); "C nmr (CD3COCD3) 6: 156.56 (CO: allyloxycarbonyl), 134.54 (CH=CH,), 1 17.03 (CH=CH2), 1 12.53 (quaternary C: 1,2-isopropylidene), 106.90 (C1-1), 102.60 (C-1), 101.36 (quaternary C: 3,5-isopropylidene), 84.87 (C'-2), 79.73 (C1-4), 75.85 (C'-3), 73.76, 72.54, 72.45 (C-5, C-3, C'-5), 7 1.03 (Cf-6), 70.04 (C-4), 65.62 (CH2--CH=CH2), 63.05 (C-6), 56.9 1 (C-2), 27.46,26.83,24.33 (CH,: isopropylidene). Anal. calcd. for C28H41015N (Mol. Wt. 631.63): C 53.24, H 6.54, N 2.22; found: C 53.29, H 6.75, N 2.21.

2,3,5-Tri-O-benzyl-I-O-tertiobutyldimethylsilyl-~-ribito (e) 2,3,5-Tri-0-benzyl-D-ribitol (30) (2.55 g, 6.04 mmol), dissolved in dry DMF (20 mL), was treated for 36 h at room temperature with imidazole (1.0 g, 14.7 mmol) and tertiobutyldimethylsilyl chloride (1.21 g, 7.93 mrnol). After concentration to 5 mL, the mixture was diluted with chloroform (20 mL) and washed with cold water. After drying (CaCl,) and evaporation, a clear syrup was obtained (3.17 g, 98%). This compound (e), homogeneous in tlc, was purified by column chromatography for analytical urposes, but could be used directly for further steps: syrup; [a]; +22.8 ( c 7.0, CHCl,); 13C nmr (CD3COCD3)6: 80.95,80.04 (C-2, C-3), 73.75,73.12,72.55,72.18 (C-5, 3CHz: benzyl), 70.82 (C-4), 63.33 (C-I), 26.06 (CH,: tertbutyl), 18.40 (quaternary C: tert-butyl), - 5.27 (CH3-Si). Anal. calcd. for C32H4405Si(Mol. Wt. 536.79): C 71.60, H 8.26, Si 5.23; Methyl 3,4,6-tri-0-acetyl-2-N-allyloxycarbonyl-2-amir10-2-deoq-~found: C 71.20, H 8.18, Si 5.27. D-glucopyranoside (4a) 4-0-(3,4,6-Tri-O-ace~l-2-N-allyloxycarbonyl-2-amino-2-deoq-~White crystalline material: mp 1 11- 1 12°C (ether); [ a ] i4 + 10.2 D-g[~~0pyran0~yl)-2,3,5-tri-O-ben~yl-l -tertiobutyldimethylsilyl(C1.9, CHCl,); 200-MHz 'H nmr(CDC13)6: 5.89 (m, lH, vinyl CH), D-ribitol (4e) 5.33-5.15 (m, 3H, vinyl CH2, H-3), 5.07 (t, 1 H, J = 9.5 Hz, H-4), 4.92 (m, lH, NH), 4.63-4.47 (m, 3H, allyl CH,, H-1), 4.22 (m, 2H, Waxy material: [a];' - 3.3 ( c 3.4, CHC1,); I3Cnmr (CD3COCD3) 6: 156.43 (CO: allyloxycarbonyl), 134.23 (CH=CH2), 116.97 J6.6' = 12.3 HZ, J5.6 = 4.7 HZ, J5.6' = 2.4 HZ, H-6, H-6'), 3.70 (CH=CH2), 101.54 (C-1), 80.76, 80.12 (Cf-2,C'-3), 79.38 (C1-4), (m, lH, H-5), 3.60 (m, lH, H-2), 3.52 (s, 3H, OCH,), 2.09, 2.04, 2.03 (3s, 9H, 30Ac); I3C nmr (CD3COCD3)6: 156.19 (CO: allyl74.40,73.65, 72.98 (3CHz: benzyl), 73.65, 72.32 (C-5, C-3), 71.23 (C1-5),69.99 (C-4), 65.58 (CH2-CH=CH,), 63.87, 62.99 (Cf-1, oxycarbonyl), 133.84 (CH=CH2), 116.74 (CH=CH2), 102.30 (C-1), 73.40,71.98 (C-5, C-3), 69.55 (C-4), 65.36 (CH2-CH=CH2), C-6), 57.26 (C-2), 26.46 (CH,: tert-butyl), 18.89 (quaternary C: 62.60 (C-6), 56.68 (OCH3), 56.33 (C-2). Anal. calcd. for C17H2sOloN tert-butyl), - 5.01 (CH3-Si). Anal. calcd. for C48H65014NSi (Mol. (Mol. Wt. 403.38): C 50.62, H 6.25, N 3.47; found: C 50.58, H 6.36, Wt. 908.13): C 63.49, H 7.21, N 1.54, Si 3.09; found: C 63.31, H7.22, N 1.51, Si 3.13. N 3.44.

4-0-(3,4,6-Tri-O-acetyl-2-N-allyloxycarbonyl-2-amino-2-deo.~y -P~-g~ucopyranosyl)-l-0-allyl-2,3,5-tri-0-ben-~-ribi101 (4f) The aglycon was prepared according to ref. 5. Syrup; [ a ] i 4 -2.3 (C 2.8, CHC13); 13C nmr (CD3COCD3) 6: 156.27 (CO: allyloxycarbonyl), 135.96 (CH=CH2: allyl), 134.03 (CH=CH2: allyloxycarbonyl), 116.76 (CH=CH2: allyloxycarbonyl), 116.01 (CH=CH2: allyl), 101.23 (C-1), 80.02, 79.03, 78.98 (Cf-2, C'-3, C'-4), 74.18, 73.49, 72.56 (3CH2: benzyl), 73.49, 72.29 (C-5, C-3), 72.10 (CH2-CH=CH2: allyl), 70.93, 70.72 (C'-1, C'-5), 69.76 (C-4), 65.39 (CHI-CH=CH2: allyloxycarbonyl), 62.81 (C-6), 57.03 6-0-(3,4,6-Tri-O-acetyl-2-N-allyloxycarbonyl-2-amino-2-deoxy-~((2-2). Anal. calcd. for C45H55014N(Mol. Wt. 833.93): C 64.81, ~ - g l ~ ~ o p y r a n o ~ y :3,4-di-0-(I-methylethy1idene)-CY-Dl)-l,2 H 6.65, N 1.68; found: C 64.92, H 6.65, N 1.68. galactopyranose (4c) The aglycon was prepared according to ref. 29. Compound 4c 4 -0-(3,4,6-Tri-O-acetyl-2-N-allyloxycarbonyl-2-amino-2-deoxy-~was obtained as a white crystalline material: mp 135-136°C (ether); ~-g~ucopyranosy~)-~-O-a~~y~oxycarbol1y~-2,3,~-tri-O-benz [a]i4 -41.3 ( c 1.4, CHC13); 200-MHz 'H nmr (CDCl,) 6: 5.89 ribitol (4g) (m, lH, vinyl CH), 5.52 (d, lH, J = 5.2Hz, H-1: galactose moiety), The aglycon was prepared according to ref. 31. Syrup; [ a ] ? -8.4 5.53-5.18 (m, 3H, vinyl CH2, H-3), 5.07 (t, lH, J = 9.7Hz, H-4), (c 4.4, CHC1,); I3cnmr (CD3COCD3) 6: 156.35 (CO, N-allyloxy4.92(m, lH,NH),2.09,2.02,2.01 (3s,9H,30Ac), 1.51, 1.44, 1.32 carbonyl), 155.54 (CO: 0-allyloxycarbonyl), 134.15 (CH=CH2: (3s, 12H, 2 isopropylidene); I3C nmr (CD3COCD3) 6: 156.19 (CO: N-allyloxycarbonyl), 132.95 (CH=CH2: 0-allyloxycarbonyl), 118.43 allyloxycarbonyl), 134.20(CH=CH2), 116.74 (CH=CH2), 109.29, (CH=CH2: 0-allyloxycarbonyl), 116.94 (CH=CH2: N-allyloxy108.78 (quaternary C: isopropylidene), 102.15 (C-1), 96.79 (C'-1), carbonyl), 101.15 (C-1), 79.14, 78.39, 77.97 (C1-4, C'-3, C'-2), 73.40, 72.18 (C-5, C-3), 71.56, 71.26, 71.11 (C'-2, C'-3, C'-5), 74.39, 73.78,72.64 (3CHz: benzyl), 73.49, 72.26 (C-5, C-3), 70.77 69.70 (C-4), 69.06 (C'-6), 67.70 (C'-4), 65.45 (CH2-CH=CH2), (C1-5),69.82 (C-4), 68.64 (C'-1), 67.52 (CH2-CH=CH2: O-allyl62.94 (C-6), 56.88 (C-2), 26.30,25.17,24.53 (CH,: isopropylidene). oxycarbonyl), 65.55 (CH2-CH=CH2: N-allyloxycarbonyl), 62.94 Anal. calcd. for C28H41015N (Mol. Wt. 631.63): C 53.24, H 6.54, (Mol. Wt. 863.91): (C-6), 57.08 (C-2). Anal. calcd. for C45H53016N N2.25;found:C53.29,H6.56, N2.16. C 62.56, H 6.18, N 1.62; found: C 62.20, H 6.35, N 1.59.

I-Methylethyl 3,4,6-rri-0-acetyl-2-N-allyloxycarbonyl-2 -amino-2deoxy-P-D-glucopyranoside(4b) White crystalline material: mp 148- 149°C (ether); [ a ];4 + 4.2 (C 1 .O, CHC13); I3C nmr (CD3COCD3)6: 156.27 (CO: allyloxycarbonyl), 134.12 (CH=CH2), 116.66 (CH=CH,), 100.29 (C-I), 73.45, 72.53, 71.96 (C-5, C-3, CH: isopropyl), 69.84 (C-4), 65.27 (CH2-CH=CH2), 62.85 (C-6), 56.81 (C-2), 23.59, 22.17 (CH,: isopropyl). Anal. calcd. for C19H29010N (Mol. Wt. 431.44): C 52.89, H 6.78, N 3.25; found: C 52.85, H 6.75, N 3.21.

6-0-(3,4,6-Tri-O-acetyI-2-N-allylo.rycarbonyl-2-arnino-2-deoxy-PGeneral procedure for the cleavage of the N -allyloxycarbonyl protec~-gl~copyran0~)1l)-l,2 :3,5-di-0-(I-tnethylethy1idene)-a-o-glurive group cofuranose (4d) Palladium bis(dibenzy1idene acetone) (20 mg, 0.035 mmol) was The aglycon was prepared according to ref. 29. Compound 4d was reacted with triphenylphosphine (50 mg, 0.191 mmol) in dry, oxygen-

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CAN. J. CHEM. VOL. 65, 1987

free oxolane (3.5 rnL) at room temperature for 10 min. The N-allyloxycarbonyl-P-D-glucosaminide (4a-f) (1.00 mmol) dissolved in oxygen-free oxolane (5 rnL) and dimethyl malonate (0.6 rnL, 7.0 mmol) was then added to the above solution and the mixture was stirred for 24 h at room temperature. After concentration to 1 mL, the mixture was applied at the top of a small silica gel column and eluted first with ethyl acetate, to remove the triphenylphosphine by-products, and then with methanol, to recover the expected amino-free derivative in almost auantitative vield.


Acknowledgements The authors are indebted to C.N.R.S. for the postdoctoral position of one of us (J.B.), to Professor S. Czernecki for valuable discussions and suggestions, and to the French SociCtt Nationale des Poudres et Explosifs (SNPE) for providing allylchloroformate.

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