Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

›› 2009, Vol. 17 ›› Issue (3): 506-512.

Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

杨根生^1,2, 应黎², 欧志敏², 姚善泾¹

1. Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou 310027, China;
2. College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, China

收稿日期:2008-10-15 修回日期:2009-03-17 出版日期:2009-06-28 发布日期:2009-06-28
通讯作者: YAO Shanjing,E-mail:yaosj@che.zju.edu.cn
基金资助:
Supported by the Natural Science Foundation of Zhejiang Province (Y404353)

Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

YANG Gensheng^1,2, YING Li², OU Zhimin², YAO Shanjing¹

1. Department of Chemical and Biochemical Engineering, Zhejiang University, Hangzhou 310027, China;
2. College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310032, China

Received:2008-10-15 Revised:2009-03-17 Online:2009-06-28 Published:2009-06-28
Supported by:
Supported by the Natural Science Foundation of Zhejiang Province (Y404353)

摘要/Abstract

摘要： The asymmetric hydrolysis of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. In this work, a catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was obtained against an immunogen consisting of tetrahedral phosphonate hapten attached to bovine serum albumin (BSA). The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. With 6% DMF in the buffer solution (containing catalytic antibody 0.25 μmol, 0.2 mol·L^-1 phosphate buffer, pH 8) at 37℃ for 10 h, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached. The kinetic analysis of the catalytic antibody-catalyzed reaction showed that the hydrolysis in the water-miscible organic-solvent system with DMF in buffer solution followed the Michaelis-Menten kinetics. The catalytic efficiency (K_cat/K_m) was enhanced to 151.91 L·mmol^-1·min^-1, twice as large as that for the buffer solution only.

关键词: catalytic antibody, ibuprofen, enantioselective hydrolysis, water-miscible organic-solvent, conversion

Abstract: The asymmetric hydrolysis of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. In this work, a catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was obtained against an immunogen consisting of tetrahedral phosphonate hapten attached to bovine serum albumin (BSA). The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. With 6% DMF in the buffer solution (containing catalytic antibody 0.25 μmol, 0.2 mol·L^-1 phosphate buffer, pH 8) at 37℃ for 10 h, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached. The kinetic analysis of the catalytic antibody-catalyzed reaction showed that the hydrolysis in the water-miscible organic-solvent system with DMF in buffer solution followed the Michaelis-Menten kinetics. The catalytic efficiency (K_cat/K_m) was enhanced to 151.91 L·mmol^-1·min^-1, twice as large as that for the buffer solution only.

Key words: catalytic antibody, ibuprofen, enantioselective hydrolysis, water-miscible organic-solvent, conversion

杨根生, 应黎, 欧志敏, 姚善泾. Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents[J]. , 2009, 17(3): 506-512.

YANG Gensheng, YING Li, OU Zhimin, YAO Shanjing. Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents[J]. , 2009, 17(3): 506-512.

参考文献

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Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

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