Synthesis and anti-HCV activity of ß-d-2'-deoxy-2'-α-chloro-2'-ß-fluoro and ß-d-2'-deoxy-2'-α-bromo-2'-ß-fluoro nucleosides and their phosphoramidate prodrugs.

ABSTRACT

We report herein the synthesis and evaluation of a series of ß-d-2'-deoxy-2'-α-chloro-2'-ß-fluoro and ß-d-2'-deoxy-2'-α-bromo-2'-ß-fluoro nucleosides along with their corresponding phosphoramidate prodrugs. Key intermediates, lactols 11 and 12, were obtained by a diastereoselective fluorination of protected 2-deoxy-2-chloro/bromo-ribonolactones 7 and 8. All synthesized nucleosides and prodrugs were evaluated with a hepatitis C virus (HCV) subgenomic replicon system.