Synthesis of Nucleoside-5′-O-Tetraphosphates from Activated Trimetaphosphate and Nucleoside-5′-O-Monophosphates

Abstract

This article describes a straight-forward chemical method for the synthesis of nucleoside-5′-O-tetraphosphates, such as cytosine-, guanosine-, adenosine-, and uridine-5′-O-tetraphosphates, starting from the corresponding nucleoside monophosphates and trimetaphosphate, a readily available and inexpensive starting material. The procedure involves reacting the tri(tetrabutylammonium) salt of trimetaphosphate with mesitylenesulfonyl chloride and N-methylimidazole. The resulting activated cyclic trimetaphosphate is reacted with the tetrabutylammonium salts of nucleoside monophosphates. After quenching the reaction with buffer and high-performance liquid chromatography purification, the desired nucleoside-5′-O-tetraphosphates were obtained in yields of 84% to 86%. © 2018 by John Wiley & Sons, Inc.