Synthesis of 2′,3′-Dideoxy-3′-nitro-2′,3′-didehydrothymidine. Its Use as a General Intermediate for the Preparation of Various 2′,3′-Substituted Nucleosides

Abstract

Abstract The first synthesis of 1-(2,3-dideoxy-3-nitro-β-D-glycero-pent-2-enofuranosyl)thymine (7), is reported starting directly from l-β-D-xylofuranosyl)thymine (1). We also report a stereospecific conversion of (6) to 3′-nitro-2′,3′-dideoxythymidine (9). Detailed NMR studies have shown that the solution conformation of 3′-nitro-2′,3′-dideoxythymidine (9) is very similar to 3′-fluoro-2′,3′-dideoxythymidine but the former is almost 100 fold less active than the later against HIV reverse transcriptase. Subsequently, the synthetic utilities of 1-(2,3-dideoxy-3-nitro-β-D-glycero-pent-2-enofuranosyl) thymine, (6) and (7), in the preparation of various 2′- and 3′-modified nucleosides have been established through Michael addition reactions with various oxygen, nitrogen and carbon nucleophiles.