Nucleosides. Part 6. New chemical modification of the ribosyl moiety in uridines; synthesis of 2,2′-anhydro-1-[5-deoxy-5-(substituted thio)-β-D-arabinofuranosyl]uracil derivatives and their conversion into 3′,5′-epithiopyrimidine nucleosides

Abstract

Treatment of 5-substituted 2′,5′-dichloro-2′,5′-dideoxyuridines (1) with thiols such as thiophenol, thioacetic S-acid, thiobenzoic S-acid, toluene-α-thiol, and ethanethiol in the presence of triethylamine or 1,1,3,3-tetramethylguanidine in N,N-dimethylformamide (DMF) gave the corresponding 2,2′-anhydro-1-[5-deoxy-5-(substituted thio)-β-D-arabinofuranosyl]uracils (2a–f) in good yield. Treatment of 5-substituted 2,2′-anhydro-1-(5-acetylthio-5-deoxy-β-D-arabinofuranosyl)uracils (2b) and (2f), prepared with ease by the reaction of (1) with thioacetic S-acid, with methanolic sodium methoxide gave the corresponding 1-(3,5-dideoxy-3,5-epithio-β-D-xylofuranosyl)uracils (9a) and (9c) fused with a thietane ring in the sugar moiety. None of the newly synthesized nucleosides displayed appreciable cytotoxicity or antiviral activity in primary rabbit cell cultures.