An efficient protection-free chemical synthesis of inosine 5'-nucleotides

A facile, straightforward, reliable, and efficient chemical synthesis of inosine nucleotides such as inosine-5'-monophosphate, inosine-5'-diphosphate, and inosine-5'-triphosphate, starting from inosine is delineated. The inosine-5'-monophosphate is achieved by the highly regioselective monophosphorylation of inosine using the Yoshikawa procedure. The inosine-5'-diphosphate is obtained by the coupling reaction of tributylammonium phosphate with an activated inosine-5'-monophosphate using zinc chloride as a catalyst. The inosine-5'-triphosphate is efficiently achieved by the improved "one-pot, three-step" Ludwig synthetic strategy. In all the cases, the resulting final product is isolated in good yields with high purity (>99.5%).