Synthesis and Evaluation of Novel 6′,6′-Difluoro 5′-Deoxycarbocyclic Phosphonic Acid Nucleosides as Antiviral Agents

Abstract

The authors describe highly efficient synthetic routes for the preparation of novel 6',6'-difluoro 5'-deoxycarbocyclic phosphonic acid nucleosides from 1,4-dihydroxy-2-butene. The discovery that the 6'-fluorinated carbocyclic nucleoside (2, EC₅₀ = 0.16 μM) is a potent anti-HSV-1 agent led to the syntheses and biological evaluations of 6'-modified 5'-deoxyversions of carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 15, 18, 22, and 25 were tested for anti-HIV activity and for cytotoxicity. However, none of them showed significant anti-HIV-1 activity or cytotoxicity at concentrations up to 100 μM.

Recent Progress for the Synthesis of Selected Carbocyclic Nucleosides

“…Hong et al [45] have also described a highly efficient synthetic route for the preparation of novel 6′,6′-difluoro-5′-deoxycarbocyclic phosphonic acid nucleosides from 1,4-dihydroxy-2-butene. However, none of them showed significant anti-HIV-1 activity or cytotoxicity at concentrations up to 100 μM.…”