A P(V)–N Activation Strategy for the Synthesis of Nucleoside Polyphosphates

Abstract

A general and high-yielding synthesis of nucleoside 5'-triphosphates (NTPs) and nucleoside 5'-diphosphates (NDPs) from protected nucleoside 5'-phosphoropiperidates promoted by 4,5-dicyanoimidazole (DCI) has been developed. (31)P NMR tracing experiments showed that the sequential deprotection and coupling reactions were exceptionally clean. The phosphoropiperidate exhibited superior reactivity to the conventional phosphoromorpholidate toward DCI-promoted NTP/NDP synthesis. The experimental results suggested that the mechanism of DCI activation could be distinctive for NTP and NDP synthesis, depending on the different nucleophilicity of pyrophosphate and phosphate.