Chemistry of bisSATE Mononucleotide Prodrugs

AbstractOn the basis of AZT as a nucleosidic model, the protocols herein describe the synthesis of various bis(S‐acyl‐2‐thioethyl) phosphotriester derivatives. These compounds, bearing transient phosphate‐protecting groups, were designed to liberate the corresponding 5′‐mononucleotide inside the cell through an esterase‐mediated activation process. Two synthetic approaches are presented using either phosphoramidite intermediates or esterification of a nucleoside 5′‐monophosphate.