Studies on Nucleoside H-Phosphonothioates as Synthons in the Synthesis of Oligonucleotide Analogues

Abstract

Recently, we have reported that H-phosphonothioate diesters1 are versatile synthetic intermediates for the preparation of phosphorothioates, phosphorodithioates, or other phosphodiester analogues. The most suitable coupling agents to produce Hphosphonothioate diesters were found to be various chlorophosphates1 [e.g., 2-chloro-5,5-dimethyl-2-oxo-2λ5-1,3,2-dioxaphosphinane (NEP), diphenyl phosphorochloridate]. These reagents secure the required chemoselectivity during the condensation and are unreactive towards the P-H function in H-phosphonothioate diesters1,2.