Additive Pummerer reaction of 3,5-O-(di-t-butylsilylene)-4-thio-furanoid glycal and stereoselective synthesis of _ -anomer of 4’-thioribonucleosides

• Published in: Nucleic Acids Symposium Series Vol. 51; no. 1; pp. 143 - 144
• Main Authors: Haraguchi, Kazuhiro, Matsui, Hiromitsu, Takami, Shin, Tanaka, Hiromichi
• Format: Journal Article
• Language: English
• Published: Oxford University Press 01.11.2007
• ISSN: 0261-3166; 1746-8272
• DOI: 10.1093/nass/nrm072

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 _ -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.