Synthesis of nucleoside 5'-O-(1,3-dithiotriphosphates) and 5'-O-(1,1-dithiotriphosphates)

2-Chloro-4H-1,3,2-benzodioxaphosphorin-4-one phosphitylates the 5'-hydroxy group of 3'-deoxy-3'-azidothymidine to form intermediate 1. Reaction of 1 with thiopyrophosphate (9) and sulfur results in the formation of an unseparable mixture of 3'-deoxy-3'-azidothymidine 5'-O-(1,3-dithiotriphosphate) (5) and 3'-deoxy-3'-azidothymidine 5'-O-(1,2-dithiotriphosphate) (3). An alternative route to nucleoside 5'-O-(1,3-dithiotriphosphates) consists of reacting a nucleoside 5'-O-(1-thiocyclotriphosphate) with Li 2 S. This reaction, when performed in pyridine/dioxane, leads to a mixture of the nucleoside 5'-O-(1,3-dithiotriphosphate) and the nucleoside 5'-O-(1,1-dithiotriphosphate). The latter is the only nucleotide product when the reaction is carried out in DMF