Stereoselective synthesis and biological evaluations of novel 3'-deoxy-4'-azaribonucleosides as inhibitors of hepatitis C virus RNA replication.

3'-Deoxy-4'-azaribonucleosides (15a-d) were synthesized starting from the commercially available (4R)-trans-4-hydroxy-l-proline 7. From biological evaluations, 15b and 15d emerged as potent inhibitors of HCV replication on a replicon assay. These findings demonstrate that synthesized pyrrolidine nucleosides represent a new template for antiviral or other biological studies and could be considered for novel combination therapy against HCV infection using nucleoside inhibitors and non-nucleoside inhibitors of HCV NS5B.