Synthesis of nucleoside thiophosphoanhydrides

A process for preparing a nucleoside thiophosphoanhydride having a thiotriphosphate moiety, comprising the steps of:

• reacting in a liquid solvent a first compound having a first moiety selected from phosphorodihalidate and thiophosphorodihalidate
• with a second compound having a second moiety selected from phosphate and thiophosphate
• said reaction creating a cyclic intermediate;
• the reaction prior to the formation of the cyclic intermediate being run at conditions suitable to keep the solvent in its liquid form;
• the selection of said first and second moieties being such that one of them is the thio variant;
• the selection of the first and second moieties being such that prior to the formation of the cyclic intermediate one is attached to a linking group selected from phosphate and thiophosphate that links it to a nucleoside moiety;
• and
• adding water to the cyclic intermediate whereby the nucleoside thiophosphoanhydride is formed.

A process for preparing a nucleoside thiophosphoan hydride having a thiotriphosphate moiety, comprising the steps of:

• reacting a first compound having a first moiety selected from phosphorodihalidate and thiophosphorodihalidate
• with a second compound having a second moiety selected from phosphate and thiophosphate
• said reaction creating a cyclic intermediate;
• the reaction prior to the formation of the cyclic intermediate being run at a temperature between 4.degree. C. and 30.degree. C. in an essentially aqueous free polar organic liquid solvent such that the cyclic intermediate is formed;
• the selection of said first and second moieties being such that one of them is the thio variant;
• the selection of the first and second moieties being such that prior to said formation of the cyclic intermediate one is attached to a linking group selected from phosphate and thiophosphate that links it to a nucleoside moiety;
• and
• adding water to the cyclic intermediate to form the nucleoside thiophosphoanhydride.