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

Ki Nam Uhm; Sang Joon Lee; Hyung kwoun Kim; Han Young Kang; Younghoon Lee

doi:10.1016/j.molcatb.2006.10.006

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

Ki Nam Uhm
, Sang Joon Lee
, Hyung kwoun Kim
, Han Young Kang
, Younghoon Lee

Biotechnology

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

Abstract

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.

Original language	English
Pages (from-to)	34-38
Number of pages	5
Journal	Journal of Molecular Catalysis - B Enzymatic
Volume	45
Issue number	1-2
DOIs	https://doi.org/10.1016/j.molcatb.2006.10.006
State	Published - 1 Apr 2007

Bibliographical note

Funding Information:
We are grateful to Roche Diagnostics, Novozymes A/S and Meito Sangyo Co., Ltd., for the generous gift of enzymes used in this study. This work was supported by the Center for Molecular Design and Synthesis at KAIST. This work was supported by the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Science and Technology (Grant MG05-0304-1-0), Republic of Korea.

Keywords

Candida antarctica lipase A
Methyl (R)-2-chloromandelate
Solvent-free reaction
Transesterification
Vinyl propionate

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10.1016/j.molcatb.2006.10.006

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

abstract = "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.",

keywords = "Candida antarctica lipase A, Methyl (R)-2-chloromandelate, Solvent-free reaction, Transesterification, Vinyl propionate",

author = "Uhm, \{Ki Nam\} and Lee, \{Sang Joon\} and Kim, \{Hyung kwoun\} and Kang, \{Han Young\} and Younghoon Lee",

note = "Funding Information: We are grateful to Roche Diagnostics, Novozymes A/S and Meito Sangyo Co., Ltd., for the generous gift of enzymes used in this study. This work was supported by the Center for Molecular Design and Synthesis at KAIST. This work was supported by the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Science and Technology (Grant MG05-0304-1-0), Republic of Korea.",

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T1 - Enantioselective resolution of methyl 2-chloromandelate by Candida antarctica lipase A in a solvent-free transesterification reaction

AU - Uhm, Ki Nam

AU - Lee, Sang Joon

AU - Kim, Hyung kwoun

AU - Kang, Han Young

AU - Lee, Younghoon

N1 - Funding Information: We are grateful to Roche Diagnostics, Novozymes A/S and Meito Sangyo Co., Ltd., for the generous gift of enzymes used in this study. This work was supported by the Center for Molecular Design and Synthesis at KAIST. This work was supported by the 21C Frontier Microbial Genomics and Applications Center Program, Ministry of Science and Technology (Grant MG05-0304-1-0), Republic of Korea.

PY - 2007/4/1

Y1 - 2007/4/1

N2 - 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.

AB - 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.

KW - Candida antarctica lipase A

KW - Methyl (R)-2-chloromandelate

KW - Solvent-free reaction

KW - Transesterification

KW - Vinyl propionate

UR - https://www.scopus.com/pages/publications/33847273257

U2 - 10.1016/j.molcatb.2006.10.006

DO - 10.1016/j.molcatb.2006.10.006

M3 - Article

AN - SCOPUS:33847273257

SN - 1381-1177

VL - 45

SP - 34

EP - 38

JO - Journal of Molecular Catalysis - B Enzymatic

JF - Journal of Molecular Catalysis - B Enzymatic

IS - 1-2

ER -

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

Abstract

Bibliographical note

Keywords

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