Synthesis and anti-HIV activity of l-β-3′- C-cyano-2′,3′-unsaturated nucleosides and l-3′- C-cyano-3′-deoxyribonucleosides

Abstract

An efficient synthetic method was developed for l-β-3′- C-cyano-2′,3′-unsaturated nucleosides and l-3′- C-cyano-3′-deoxyribonucleosides. The key intermediate 11 was obtained from l-xylose, from which a series of pyrimidine and purine nucleosides were prepared in high yield by the coupling of 11 and various silyl-protected bases in the presence of TMSOTf. These nucleosides were eliminated, followed by deprotecting to give l-β-3′- C-cyano-2′,3′-unsaturated nucleosides. When selectively deprotected by hydrazine hydrate in buffered acetic acid–pyridine followed by treatment with potassium carbonate in methanol, l-3′- C-cyano-3′-deoxyribonucleosides were obtained. The synthesized nucleosides were tested for anti-HIV activity.