Influence of Fluorination of the Sugar Moiety on the Anti-HIV-1 Activity of 2',3'-Dideoxynucleosides

Abstract The advent of AIDS has prompted the search for effective anti-HIV-1 agents, and, in view of the efficacy of azidothymidine in the treatment of AIDS, 2′,3′-dideoxynucleosides and analogues thereof have been considered as the most obvious candidates for AIDS chemotherapy. Various substituents have been introduced at the 3′-position, but only the 3′-azido and 3′-fluoro derivatives were found active against HIV-1. Introduction of a fluorine in organic compounds frequently causes a dramatic change in their biological activity. The stability of the carbon-fluorine bond and the strong electronegative character of fluorine, altering the electronic properties of the substituted molecule, led us to synthesize dideoxynucleosides with a fluorine substituent at different positions. The synthe-