Synthesis and Some Properties of 4'-Phenyl-5'-Norcarbocyclic Adenosine Phosphonic Acid Analogues

Abstract

Steric and electronic parameters of 4'-substituents play significant roles in steering the conformation of nucleoside analogues. In order to investigate the relationship of 4'-substituent with antiviral enhancement, novel 4'-phenyl-5'-norcarbocyclic adenosine phosphonic acid analogues were racemically synthesized via de novo acyclic stereoselective route from propionaldehyde 5. The phenyl substituted cyclopentenols 15a and 15b as key intermediates were successfully constructed via reiterative carbonyl addition of Grignard reagents and ring-closing metathesis of corresponding divinyl 14. The synthesized nucleoside phosphonic acids analogues 19, 20, 21, and 23 were subjected to antiviral screening against HIV-1.

Chemical Approaches to Carbocyclic Nucleosides

“…Hong's group reported a series of racemic 5'norcarbanucleosides [74][75][76] including a phosphonate analog of 2'-modified 5'-norcarbocyclic adenine. [77] But-3-en-1-ol 201 was transformed into three steps to (�)À 202, (Scheme 31).…”