A review on the chemical synthesis of pyrophosphate bonds in bioactive nucleoside diphosphate analogs

Currently, there is an ongoing interest in the synthesis of nucleoside diphosphate analogs as important regulators in catabolism/anabolism, and their potential applications as mechanistic probes and chemical tools for bioassays. However, the pyrophosphate bond formation step remains as the bottleneck. In this Digest, the chemical synthesis of the pyrophosphate bonds of representative bioactive nucleoside diphosphate analogs, i.e. phosphorus-modified analogs, nucleoside cyclic diphosphates, and nucleoside diphosphate conjugates, will be described.