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Synthesis of 5′‐halo‐2′,3′‐ lyxo ‐epoxy and 2′,3′‐unsaturated thieno[3,2‐ d ]pyrimidine nucleosides
Author(s) -
Fossey Christine,
Ladurée Daniel,
Robba Max
Publication year - 1995
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570320243
Subject(s) - chemistry , pyrimidine , epoxide , derivative (finance) , medicinal chemistry , substituent , olefin fiber , silylation , moiety , palladium , stereochemistry , catalysis , organic chemistry , financial economics , economics
A series of thieno[3,2‐ d ]pyrimidine‐2,4‐dione nucleosides modified in the carbohydrate moiety has been synthesized. In the first part, synthetic routes are described for the replacement of 5′‐hydroxyl group in preformed 1‐(β‐D‐ribofuranosyl)thieno[3,2‐ d ]pyrimidine‐2,4‐dione I by fluoro, iodo or chloro atoms. Reduction of the 5′‐iodo substituent of VI was then carried out catalytically using palladium on carbon as catalyst to give the expected 5′‐deoxy derivative VIII. The lyxo ‐epoxide derivative XII was then synthesized by sequential treatment of the 5′‐deoxy‐5′‐chloro derivative X with methanesulfonyl chloride and with sodium hydroxide. In the second part, most of attention has been devoted to apply different methods reported in the literature that allow access to 2′,3′‐olefinic derivatives from the corresponding 2′,3′‐dihydroxy precursor. The 5′‐ O ‐silyl protected bisxanthate XIV either on reduction with tri‐ n ‐butyltin hydride or by reductive elimination of the haloacetate XVI afforded the free 2′,3′‐olefin nucleoside after removal of the 5′‐protecting group. However none of the compounds in this series exhibited significant antiviral activity against HIV at the doses tested.