Synthesis and anti-HCV evaluation of 4'(alpha)-ethyl and 2'(beta)-methyl-carbodine analogues

Abstract

Novel 4'(alpha)-ethyl-2'(beta)-methyl carbocyclic nucleoside analogues have been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell culture. The construction of cyclopentene intermediate 12 beta was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM) starting from Weinreb amide 5. Selective dihydroxylation and desilylation gave the target carbodine analogues. The synthesized nucleoside analogues mentioned above 18 and 19 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line (LucNeo#2). However, the synthesized nucleosides neither showed any significant antiviral activity nor toxicity up to 50 microM.