Synthesis of a phosphoramidate pro-drug of 6-thio-7-deaza-2′-deoxyguanosine (TDG): a regioselective phosphorylation

Abstract

6-Thio-7-deaza-2′-deoxyguanosine-5′-triphosphate (TDG-TP) is a potent inhibitor of human telomerase. Regioselective synthesis of the 5′-phenyl methoxyalaninyl phosphate pro-drug of 6-thio-7-deaza-2′-deoxyguanosine (TDG) has been achieved in good yields by the reaction of TDG with phenyl methoxyalaninyl phosphochloridate in the presence of N-methylimidazole at −70°C. This pro-drug of TDG is effective in producing measurable levels of TDG-TP in A549 cells.