Phosphonate analogues of nucleoside polyphosphates

Abstract

This article provides an overview of the efforts toward the synthesis of nucleoside polyphosphate mimics featuring a P-CXY-P scaffold. The following synthetic approaches to these compounds are summarized: (i) nucleophilic displacement of 5′-O-tosyl nucleoside by the ammonium salts of methylenebisphosphonic acid; (ii) synthesis via activated phosphate/phosphonate substrates; (iii) Mitsunobu coupling between a nucleoside and methylenebisphosphonic acid; (iv) phosphorylation of a protected nucleoside under Yoshikawa's reaction conditions with methylenebis(phosphonic dichloride); (v) synthesis via nucleophilic cleavage of cyclic trimetaphosph(on)ates; (vi) enzyme-mediated reactions.