X-Ray Analysis. Crystal and Molecular Structures of 2'-Deoxy-2'-(R)-phenylsulfinyl- uridine. Tadashi HATA*, Akira MATSUDA**t and Tadashi MIYASAKA**.
ANALYTICAL
SCIENCES
DECEMBER
1991,
VOL.
7
987
Instrumental
Achievements X-Ray Analysis
Crystal and Molecular Structures of 2'-Deoxy-2'-(R)-phenylsulfinyluridine Tadashi HATA*, Akira MATSUDA**t and Tadashi MIYASAKA** *Analytical and Metabolic Research Laboratories , Sankyo Co. Ltd., Hiromachi, Shinagawa, Tokyo 140, Japan **School of Pharmaceutical Sciences, Showa University, Hatanodai, Shinagawa, Tokyo 142, Japan
The modification of the sugar moiety of nucleosides, especially at the 2'-position, is becoming of increasing importance for the rational design of biochemically and pharmacologically interesting nucleoside analogs. The oxidation of 2'-phenylsulfide prepared from 3',5'-di-0acetyl-02,2'-cyclouridine furnished two diastereoisomers; the melting points are 243 - 245° C (dec) for the major one and 258-259°C (dec) for the minor one.l This paper presents the results of an X-ray analysis of the minor sulfoxide. Colorless prisms were grown by slow evaporation of an aqueous solution. Intensity data were measured with the w-28 scan mode on a diffractometer using graphite monochromated Cu Ka radiation. The size of the crystal used was 0.3X0.4X0.5 mm, but no correction was carried out regarding absorption. The 0(5')H hydroxyl group is disordered in the two orientations with a weight of 0.5. The positions of the hydrogen atoms were determined from a difference Fourier synthesis and refined isotropically. Both crystal and experimental
Table
1
Present Hokkaido
Crystal
and experimental
address: University,
Faculty Sapporo
of
data are given in Table 1. The molecular structure
is shown
with
scheme;
Table
an atomic
2
numbering
Pharmaceutical
distances
Final coordinates (X104)of non-H atoms
data
060, Japan.
in Fig. 2, together the bond
Sciences,
Beq=(4/3)iI;Bi;ai•a;.
ANALYTICAL
988
Table
3
SCIENCES
DECEMBER
1991, VOL.
7
Bond distances (A) and angles (°)
from the plane containing the remaining atoms (0(1'), C(1'), C(2') and C(3')) by 0.44(2) A. The glycosidic torsional angle, which describes the relative orientation of the base with respect to the sugar, is in the syn region with the torsional angle (0(1')-C(1')-N(1)-C(6) equal to -123 .7(4)°. The torsional angles (0(5')-C(5')-C(4')0(1') and 0(5')-C(5')-C(4')-C(3')) are -58.6(7) and 59.0(8)°, indicating a gauche-gauche conformation about the C(4')-C(5') bond. For the other disordered atom (0(51')), the conformation of the C(4')-C(5') bond is gauchetrans with two torsional angles of 69.6(7) and -172.8(5)°, respectively.
Reference
Fig.
2
Perspective
view with atom
numbering.
and angles are listed in Table 3. The configuration of sulfoxide is R relative to 2'-deoxyribose. The puckering of the sugar ring is C4'-exo. The C(4') atom is displaced
1. A. Matsuda, T. Miyasaka, T. Hata and C. Tamura, Abstracts of Papers, 104th Annual Meeting of The Pharmaceutical Society of Japan, Sendai, March 1984, p. 222. (Received July 27, 1991) (Accepted September 25, 1991)
