Design, synthesis and cellular metabolism study of 4′-selenonucleosides

Abstract

Background: 4′-seleno-homonucleosides were synthesized as next-generation nucleosides, and their cellular phosphorylation was studied to confirm the hypothesis that bulky selenium atom can sterically hinder the approach of cellular nucleoside kinase to the 5′-OH for phosphorylation. Results: 4′-seleno-homonucleosides (n = 2), with one-carbon homologation, were synthesized through a tandem seleno-Michael addition-SN2 ring cyclization. LC-MS analysis demonstrated that they were phosphorylated by cellular nucleoside kinases, resulting in anticancer activity. Conclusion: The bulky selenium atom played a key role in deciding the phosphorylation by cellular nucleoside kinases. [Formula: see text]