 In the last decade, lamivudine has been one of the most successful drugs for the treatment of HIV as well as chronic Hepatitis B. It inhibits both type 1 and 2 of the human HIV reverse transcriptase and also the reverse transcriptase of hepatitis B in vitro.1Although there are a lot of reported syntheses for the isomerically pure lamivudine, most of them introduce the chiral 1,3-oxathiolane motif by either crystallization of the correct isomer from a racemic mixture, or by enzymatic hydrolysis/acetylation of the other stereoisomers. The disadvantage of those methods is the yield limitation, as no more than 50% yield could be obtained while maintaining high stereoselectivity, due to the nature of the kinetic resolution.In this study, by using surfactant-treated subtilisin Carlsberg (STS) as a green catalyst, intermediate 1   could be obtained in good yield and ee, and later converted to lamivudine after Vorbr�ggen coupling and hydrolysis. The configuration of the intermediates could be easily controlled as enantiomer 2  was also accessed by changing STS to Candida antarctica lipase B (CAL B) under the same reaction conditions. Thus, this study describes an efficient methodology for the asymmetric synthesis of 1,3-oxathiolane-based nucleosides.

Efficient asymmetric synthesis of lamivudine through enzymatic dynamic kinetic resolution

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.