Stereoselective synthesis of the beta-anomer of 4'-thionucleosides based on electrophilic glycosidation to 4-thiofuranoid glycals.
Three types of 4-thiofuranoid glycal with different 3,5-O-silyl protecting groups were prepared and their electrophilic glycosidation was investigated. The 3,5-bis-O-(tert-butyldimethylsilyl)-4-thiofuranoid glycal (5) was obtained through mesylation of 2-deoxy-4-thio-D-erythro-pentofuranose (4) and subsequent base-promoted elimination, while thermal elimination of sulfoxide derivatives was suitable for the preparation of 3,5-O-(tetraisopropyldisiloxane-1,3-diyl) (9) and 3,5-O-(di-tert-butylsilylene) (11) 4-thioglycals. The glycosidation reactions of these 4-thioglycals were carried out, in the presence of either PhSeCl or NIS, by using silylated derivatives of uracil, thymine, cytosine, and N(6)-benzoyladenine. Among the three 4-thioglycals, 11 was found to be an excellent glycosyl donor, forming the desired beta-anomer exclusively irrespective of the nucleobase employed.
Haraguchi
Kazuhiro
K
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. harakazu@pharm.showa-u.ac.jp
Takahashi
Haruhiko
H
Shiina
Noriaki
N
Horii
Chikafumi
C
Yoshimura
Yuichi
Y
Nishikawa
Ayako
A
Sasakura
Eiko
E
Nakamura
Kazuo T
KT
Tanaka
Hiromichi
H
D002384:Catalysis; D002625:Chemistry, Organic / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D003596:Cytosine / Q000031:analogs & derivatives / Q000737:chemistry; D006031:Glycosylation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry*; D014498:Uracil / Q000031:analogs & derivatives / Q000737:chemistry
D013872:Thionucleosides; D014498:Uracil; D003596:Cytosine