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 diesters^1,2.