Enantioselective resolution of methyl 2-chloromandelate by Candida antarctica lipase A in a solvent-free transesterification reaction

• Published in: Journal of Molecular Catalysis B: Enzymatic
• Main Authors: Uhm, KN Uhm, Ki-Nam, Lee, SJ Lee, Sang-Joon, Kim, HK Kim, Hyung-kwoun, Kang, HY Kang, Han-Young, Lee, YH Lee, Young-Hoon
• Format: Article in Journal/Newspaper
• Language: English
• Published: ELSEVIER SCIENCE BV 2007
• Subjects: CATALYZED TRANSESTERIFICATIONS; ORGANIC MEDIA; KLEBSIELLA-OXYTOCA; SECONDARY ALCOHOLS; MANDELIC-ACIDS; BIPHASIC MEDIA; BIOCATALYSIS; OPTIMIZATION; SELECTIVITY; HYDROLASE; Antarc*; Antarctica
• Online Access: http://hdl.handle.net/10203/16233; https://doi.org/10.1016/j.molcatb.2006.10.006

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.