Design and Synthesis of Carbocyclic Versions of Furanoid Nucleoside Phosphonic Acid Analogues as Potential Anti-Hiv Agents

Abstract

Novel 5′-norcarbocyclic adenine and guanine phosphonic acid analogues with 6′,6′-difluorine moiety were designed and synthesized from commercially available epichlorohydrin 5. A regioselective Mitsunobu reaction successfully proceeded from an allylic functional group 16b at low reaction temperature in polar cosolvent to give purine phosphonate analogues 17 and 24, respectively. The purine nucleoside phosphonate and phosphonic acid analogues were subjected to antiviral screening against HIV-1. Adenine analogue 21 and its SATE prodrug 29 show significant anti-HIV activity in MT-4 cell lines.

Keywords:

• Anti-HIV agents
• 6′,6′-difluoro-5′-norcarbocyclic nucleoside
• Mitsunobu reaction

Acknowledgments

This work was supported by the National Research Foundation of Korea Grant, funded by the Korean Government (MEST) (20100009002).