Synthesis and Evaluation of Optically Pure Dioxolanes as Inhibitors of Hepatitis C Virus RNA Replication.

A series of optically pure 1,3-dioxolane nucleoside mimics was synthesized by a synthetic route that allowed incorporation of a 5R-methyl substituent from commercially available starting materials. The pyrrolo[2,3-d]pyrimidine heterocycle was chosen as a substitute for the purine derivative. Coupling of the pyrrolo[2,3-d]pyrimidine and the dioxolane was performed under solid-liquid phase transfer conditions. The ability to inhibit HCV RNA replication was assessed in a cell based subgenomic replicon assay. None of the described compounds displayed significant anti-HCV activity.