Enantioselective resolution of methyl 2-chloromandelate by Candida antarctica lipase A in a solvent-free transesterification reaction
Enantiomerically pure 2-chloromandelic acid esters are important chiral building blocks for synthesis of a wide range of pharmaceutical products, such as an anti-thrombotic agent, (S)-clopidogrel. An efficient and novel process for resolution of methyl 2-chloromandelate was developed by using a lipa...
Published in: | Journal of Molecular Catalysis B: Enzymatic |
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Main Authors: | , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
ELSEVIER SCIENCE BV
2007
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Subjects: | |
Online Access: | http://hdl.handle.net/10203/16233 https://doi.org/10.1016/j.molcatb.2006.10.006 |
Summary: | Enantiomerically pure 2-chloromandelic acid esters are important chiral building blocks for synthesis of a wide range of pharmaceutical products, such as an anti-thrombotic agent, (S)-clopidogrel. An efficient and novel process for resolution of methyl 2-chloromandelate was developed by using a lipase-mediated transesterification. Among 11 hydrolytic enzymes examined, Candida antarctica lipase A (CAL-A) showed the highest enantioselectivity and reaction rate toward methyl (S)-2-chloromandelate. Methyl (R)-2-chloromandelate was obtained in enantiomerically pure form (> 99% ee) and 41% yield through the lipase-mediated resolution under a solvent-free condition. CAL-A maintained its catalytic activity during 13 cycles of repeated use without significant decrease in enantioselectivity, indicating that the method is economical and easy to scale-up for commercial production of methyl (R)-2-chloromandelate. (c) 2006 Elsevier B.V. All rights reserved. |
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