A facile and effective synthesis of lamivudine 5'-diphosphate

Béatrice Roy (1) , Isabelle Lefebvre (1) , Jean-Yves Puy (1) , Christian Perigaud (1)

1 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]

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 oxydation by (-)-(8,8-dichlorocamphorylsulfonyl)oxaridine. 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.

Mots clés: Lamivudine; 3TC; Phosphorylation; Phosphonylation; LC/MS

Domaines: Chimie organique

Béatrice Roy, Isabelle Lefebvre, Jean-Yves Puy, Christian Perigaud. A facile and effective synthesis of lamivudine 5'-diphosphate. Tetrahedron Letters, 2011, 52, pp.1250-1252. ⟨10.1016/j.tetlet2010.12.105⟩. ⟨hal-00566611⟩