A facile and effective synthesis of lamivudine 5'-diphosphate

Abstract We report on the first solution synthesis of lamivudine 5′-diphosphate in both high yield and purity. Efficient synthesis of lamivudine 5′-monophosphate was obtained through lamivudine H -phosphonate oxidation by (−)-(8,8-dichlorocamphorylsulfonyl)oxaziridine. Diphosphorylation was performed by nucleophilic substitution of the phosphorimidazolate derivative of lamivudine. HPLC coupled with UV or MS detection was found to be an invaluable tool for the follow-up of phosphorylation reactions.