Efficient Asymmetric Synthesis of Lamivudine and its enantiomer via Enzymatic Dynamic Kinetic Resolution

Efficient Asymmetric Synthesis of Lamivudine and its enantiomer via Enzymatic Dynamic Kinetic Resolution

Hu, Lei; Schaufelberger, Fredrik; Zhang, Yan; Ramström, Olof

Abstract:

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. Although there are many 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 main drawback of those methods is the great loss in yield, as no more than 50% yield could be obtained while maintaining high stereoselectivity, due to the nature of the kinetic resolution.

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. Although there are many 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 main drawback of those methods is the great loss in yield, as no more than 50% yield could be obtained while maintaining high stereoselectivity, due to the nature of the kinetic resolution.

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DOI: 10.5151/chempro-15bmos-BMOS2013_2013101412329

Referências bibliográficas

• [1] 1 Romeo, G.; Chiacchio, U.; Corsaro, A.; Merino, P. Chem. Rev.2010, 110, 3337.

Como citar:

Hu, Lei; Schaufelberger, Fredrik; Zhang, Yan; Ramström, Olof; "Efficient Asymmetric Synthesis of Lamivudine and its enantiomer via Enzymatic Dynamic Kinetic Resolution", p-128-128. In: In Blucher Chemistry Proceedings, São Paulo, v. 1, n. 2, Dezembro.2013. São Paulo: Blucher, 2013.
ISSN 23184043, DOI 10.5151/chempro-15bmos-BMOS2013_2013101412329