Synthesis of Nucleoside Selenophosphoramidates via H-Phosphonate Intermediates.

Abstract

Two synthetic routes for the preparation of nucleoside selenophosphoramidates have been developed by using H-phosphonate derivatives as key substrates. The first method is a one-pot synthesis, which involves the condensation of an amine with H-phosphonate monoesters, mediated by a coupling agent, followed by oxidation with elemental selenium (A). The second approach makes use of the oxidative condensation reaction of H-phosphonoselenoate monoesters with amines promoted by iodine as an oxidizing agent (B). Both methods are efficient and experimentally simple, but the second method (B) seems to be more suited for the synthesis of selenophosphoramidates with bulky or sterically hindered amine residues. It has been shown that both methods also provide a convenient way to produce sulfurized counterparts, i.e., the corresponding thiophosphoramidate derivatives.