Water‐Medium Synthesis of Nucleoside 5′‐Polyphosphates

This unit describes a one‐pot, two step synthesis of ribonucleoside 5′‐di‐ and 5′‐triphosphates, as well as their purification. The first step of the synthesis involves the activation of an unprotected ribonucleoside 5′‐monophosphate with 2‐chloro‐1,3‐dimethylimidazolinium hexafluorophosphate and imidazole, in a mixture of water/acetonitrile. The resulting phosphorimidazolate intermediate is then treated with inorganic phosphate or pyrophosphate to afford the corresponding nucleoside 5′‐di‐ or 5′‐triphosphates. The attractive features of this strategy include the absence of protecting groups on the starting material and convenient set up (i.e., use of water, non‐dry solvents and reagents, commercially available sodium salts). © 2017 by John Wiley & Sons, Inc.