Nucleoside H-Phosphonates. 18. Synthesis of Unprotected Nucleoside 5‘-H-Phosphonates and Nucleoside 5‘-H-Phosphonothioates and Their Conversion into the 5‘-Phosphorothioate and 5‘-Phosphorodithioate Monoesters

A simple and efficient protocol for the preparation of unprotected nucleoside 5‘-H-phosphonates and nucleoside 5‘-H-phosphonothioates via a one-step deprotection of suitable precursors with methylamine has been developed. The synthetic utility of the unprotected nucleotide derivatives was demonstrated by converting them under mild conditions to the corresponding nucleoside 5‘-phosphorothioate and nucleoside 5‘-phosphorodithioate monoesters. Factors affecting oxidation of H-phosphonate, H-phosphonothioate, and phosphite derivatives with elemental sulfur are also discussed.