Synthesis and antiviral evaluation of novel 2',2'-difluoro 5'-norcarbocyclic phosphonic acid nucleosides as antiviral agents

Abstract

A very efficient synthetic route to novel 2',2'-difluoro 5'-norcarbocyclic phosphonic acid nucleosides from but-3-en-1-ol 5 is described. The discovery of 2'-fluorinated furanose nucleoside 1 as a potent anti-HIV-1 agent has led to the synthesis and biological evaluation of 2'-modified 5'-norversions of the carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 18, 19, 23a, 23b, and 24 were tested for anti-HIV activity as well as cytotoxicity. Adenine analogue 19 shows significant anti-HIV-1 activity (EC(50) = 13 μM).