Résumé
Once inside the cells, nucleoside analogues must be phosphorylated to their corresponding 5′‐triphosphate forms, which interfere with nucleic acid biosynthesis as viral and/or cellular DNA and RNA polymerase inhibitors or as chain terminators. During this pharmacological process, few steps are considered to be limiting, such as the absorption of nucleoside analogues, and their phosphorylation by nucleoside kinases. This chapter focuses on prodrug approaches that allow the intracellular delivery of nucleoside 5′‐monophosphates (5′‐mononucleotides), also called pronucleotide approaches. It highlights recent synthetic pathways for pronucleotide preparation, primarily those reported during the past decade. These synthetic pathways may involve PIII and/or PV chemistry and are described according to the structure of the final pronucleotide. As some of these compounds are prepared and evaluated as a diastereomeric mixture, and because the two diastereomers have been shown to exhibit different biological activity, the chapter also reports recent attempts for the diastereoselective synthesis.