Additive Pummerer reaction of 3,5-O-(di-t-butylsilylene)-4-thiofuranoid glycal and stereoselective synthesis of beta-anomer of 4'-thioribonucleosides.
Upon reacting 3,5-O-(di-t-butylsilylene) (DTBS)-4-thiofuranoid glycal S-oxide (7) with Ac2O in the presence of TMSOAc and BF3.OEt2, additive Pummerer reaction proceeded to furnish 1,2-di-O-acetyl-3,5-O-DTBS-4-thioribofuranose (8) in 61% yield. When 8 was reacted with bis-O-TMS-uracil and TMSOTf, 2'-O-acetyl-3',5'-O-DTBS-4'-thiouridine (13a) was obtained along with it's beta-anomer (13b) in 93% yield (13a/13b = 22/1). This highly stereoselective glycosidation reaction was applicable to the synthesis of 14-17. The glycosyl donor 8 was also useful for the synthesis of 4'-thio-C-nucleoside 18 and 19. In contrast to the above results, treatment of 8 with TMSCN gave rise to the formation of the spiro derivative 20. To avoid this intramolecular cyclization, 2-O-TBDMS-protected 21 was prepared from 8. Bromination of 21 with TMSBr and substitution reaction of the resulting bromide 22 with Hg(CN)2 gave 1'-C-cyanide 23.
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
Matsui
Hiromitsu
H
Takami
Shin
S
Tanaka
Hiromichi
H
D006031:Glycosylation; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013872:Thionucleosides / Q000138:chemical synthesis* / Q000737:chemistry
D012263:Ribonucleosides; D013872:Thionucleosides