Synthesis and Anti-HIV Activity of 5′-Homo-2′,3′-dideoxy-2′,3′-didehydro-4′-selenonucleosides (5′-Homo-4′-Se-d4 Ns)

On the hypothesis that one carbon homologation of 4′‐selenonucleosides might relieve the steric repulsion between cellular kinases and bulky selenium, 5′‐homo‐4′‐Se‐d4Ns, 3 a–e, as anti‐HIV agents were designed and synthesized stereoselectively from d‐gulonic γ‐lactone, with the conversion of 2′,3′‐diol into the olefin as the key step. The anti‐HIV activity of all synthesized compounds, 5′‐homo‐4′‐Se‐d4Ns, was toxicity‐dependent, unlike normal 4′‐Se‐d4Ns, which were inactive against HIV‐1. This result indicates that 5′‐homo‐4′‐Se‐d4Ns might be phosphorylated by cellular kinases as per the hypothesis. Se you there: Stereoselective synthesis of 5′‐homo‐2′,3′‐dideoxy‐2′,3′‐didehydro‐4′‐selenopyrimidine and purine nucleosides (4′‐Se‐d4Ns) 3 a–e as anti‐HIV agents was accomplished from d‐gulonic γ‐lactone.