Synthesis and antiviral activity of cyclopropyl-spirocarbocyclic adenosine, (4R,5S,6R,7R)-4-(6-amino-9H-purin-9-yl)-7-(hydroxymethyl)spiro[2.4]heptane-5,6-diol against hepatitis C virus

An efficient method was developed for the synthesis of 6-exocyclic methylene carbocyclic intermediate 4. The Simmons–Smith cyclopropanation protocol was applied on the 6-exocyclic methylene of intermediate 4 and demonstrated its utility for the synthesis of novel class of a spiro-carbocyclic nucleoside analog 8. The titled compound 8 demonstrated a significant antiviral activity against HCV with EC50 values of 0.273 and 0.368 μM in genotypes 1A and 1B, respectively.

Graphical abstractCyclopropyl-spirocarbocyclic nucleoside 8 was synthesized and exhibited antiviral activity against HCV with EC50 values of 0.273 and 0.368 μM in genotypes 1A and 1B, respectively.Figure optionsDownload full-size imageDownload as PowerPoint slide