New synthesis of 3′- [formula omitted]-substituted nucleosides

Abstract

The base catalyzed addition reactions at C-3′ of 2′, 3′-dideoxy-3′-nitro-thymidine 1 or -uridine 2 with paraformaldehyde, methyl vinyl ketone, acrylonitrile and ethyl propiolate have produced various 1-(2′,3′-dideoxy-3′- C -substituted-3′-nitro-β-D-pentofuranosyl)pyrimidine nucleosides 3 – 26 [α-substitution (major); β-substitution (minor)]. The stereochemistry of products formed in the reaction clearly suggest that the incipient carbanion at C3′ preferentially attacks the electron-deficient reagent from the α-face of the sugar ring. Subsequently, the 3′-nitro group from 3, 14, 17, 22 and 25 was removed by the action of Bu 3SnH and AIBN to give 3′- C -substituted nucleosides 27 – 44 [threo (major) and erythro (minor)] which suggested that the intermediary 3′-carbon radical abstracted the hydrogen atom preferentially from the α-face. The stereochemistry of the products from the base-catalyzed addition reactions and free-radical promoted denitration reactions were ascertained by detailed structure analysis by NMR spectroscopy. The results presented in this paper is the first example of the preparation of C -branched nucleosides using the base catalyzed addition reaction at the α-carbon of a nitro function in the sugar moiety of nucleoside.