Stereoselective Synthesis of 4′-Selenonucleosides
via Seleno-Michael Reaction as Potent Antiviral Agents
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Abstract
Based on the hypothesis that the
bulky selenium atom, with 4p orbitals,
can sterically hinder the approach of a cellular kinase to 5′-OH
for phosphorylation, 4′-selenonucleosides with one-carbon homologation
were designed and synthesized via a novel seleno-Michael reaction,
with the stereoselectivity controlled by steric effects. 5′-Homo-4′-selenonucleosides
(<i>n</i> = 2) demonstrated potent antiherpes simplex virus
(HSV-1) activity, indicating that the bulky selenium atom might play
a key role in preventing phosphorylation by cellular kinases, resulting
in no antiviral activity