A Novel Method for Large-Scale Synthesis of Lamivudine through Cocrystal Formation of Racemic Lamivudine with (S)-(-)-1,1'-Bi(2-naphthol) [(S)-(BiNOL)]

摘要

A large-scale synthesis of (-)-[2R,5S]-4-amino-l- [2-(hydroxym-ethyl)-1,3-oxathiolan-5-yl]-2(1H)-pyrimidin-2-one (lamivudine) through resolution of racemic lamivudine by cocrystal formation with (S)- BINOL has been demonstrated. Lamivudine of very high purity with an enantiomeric excess of more than 99.9% was obtained. All four isomers of lamivudine have also been separated and characterized. Interestingly, cis-(-)- and trans-(-)-enanti-omers form cocrystals with (S)-BINOL.