An Efficient Synthesis of 4'-Vinylated Carbocyclic Nucleoside Analogues via Two Directional Ring-closing Metathesis

Abstract

Two directional ring-closing metathesis (RCM) was applied successfully to the synthesis of 4'-vinylated carbocyclic nucleoside analogues from the trivinyl intermediate 12, which was readily made using a sequential Claisen rearrangement and ring-closing metathesis (RCM) starting from Weinreb amide 5. An antiviral evaluation of the synthesized compounds against various viruses such as HIV, HSV-1, HSV-2 and HCMV revealed that the guanine analogue 20 have moderate anti-HIV activity in the MT-4 cell line (<TEX>$EC_{50}$</TEX> = 10.2 <TEX>$\mu$</TEX> M).