Synthesis of Nucleoside Selenophosphoramidates via H-Phosphonate Intermediates.

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.