An improved method for the synthesis of nucleoside triphosphate analogues

Nucleoside monophosphates, when activated by trifluoroacetic anhydride and N-methylimidazole, efficiently couple with a variety of electron-deficient diphosphonates in a reproducible and efficient manner (< 2 h, > 72% isolated yield). Unlike traditional methods for the preparation of nucleoside 5'-beta,gamma-methylenetriphosphate analogues, there is no requirement for predrying, or conversion to specific salt forms, of commercially available nucleoside monophosphate starting materials.