Commercially viable resolution of ibuprofen

被引：19

作者：

Department of Chemistry, University of Texas at El Paso, 500 W. University, El Paso, TX 79968, United States ^{[1
]}

机构：

[1] Department of Chemistry, University of Texas at El Paso, El Paso, TX 79968

来源：

Biotechnol. J. | 2009年 / 8卷 / 1222-1224期

关键词：

Enantiomeric excess; Enantiomeric ratio; Esterify; Hydrolysis;

D O I：

10.1002/biot.200900078

中图分类号：

学科分类号：

摘要：

Ibuprofen belongs to the non-steroidal anti-inflammatory drug (NSAID) family known as profens. Studies demonstrate that (S)-ibuprofen is 160 times more potent than (R)-ibuprofen in vitro, while the accumulation of (R)-ibuprofen can cause serious side effects such as gastrointestinal pain. Candida rugosa lipase was used to enantioselectively esterify racemic ibuprofen with decan-1-ol and butan-1-ol in cyclohexane with an enantiomeric ratio (E) of 130 and 46, respectively, in up to 46% conversion. Separation by bulb-to-bulb distillation of (R)-ibuprofen and unreacted alcohol from the corresponding (S)-alkyl ibuprofen ester was possible for the decyl but not the butyl case. The enantioselective hydrolysis of (S)-alkyl ibuprofen esters with the same biocatalyst in aqueous phosphate buffer was twice as slow for the decyl alcohol versus the butyl example. The combined environmentally friendly enantioselective esterification and hydrolysis of ibuprofen insured the isolation of (S)-ibuprofen with a greater than 99% enantiomeric excess. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

引用

页码：1222 / 1224

页数：2

共 17 条

[1]

Snell D., Colby J., Enantioselective hydrolysis of racemic ibuprofen amide to S-(+)-ibuprofen by Rhododcoccus AJ270, Enzyme Microb. Technol, 24, pp. 160-163, (1999)

[2]

Chang C.-S., Tsai S.-W., m A facile enzymatic process for the preparation of (S)-Naproxen ester prodrug in organic solvents, Enzyme Microb. Technol, 20, pp. 635-639, (1997)

[3]

Shen T.Y., Perspective in nonsteriodal antiinflamatory agents, Angew. Chem. Int. Edn. Engl, 11, pp. 460-472, (1972)

[4]

Adams S.S., Bresloff P., Manson G.C., Pharmacological difference between the optical isomers of ibuprofen: Evidence for metabolic inversion of the (-) isomer, J. Pharmacol, 28, pp. 156-157, (1976)

[5]

Fazlena H., Kamaruddin A.H., Zulkali M.M.D., Dynamic kinetic resolution: Alternative approach in optimizing S-ibuprofen production, Bioprocess. Biosyst. Eng, 28, pp. 227-233, (2006)

[6]

Mustranta A., Use of lipases in the resolution of racemic ibuprofen, Appl. Microbiol. Biotechnol, 38, pp. 61-66, (1992)

[7]

Chen C.-S., Sih C.J., General aspects and optimization of enantioselective biocatalysis in organic solvents, Angew. Chem. Int. Edn. Engl, 28, pp. 695-707, (1989)

[8]

Bornscheuer U.T., Kazlauskas R.J., Hydrolases in Organic Synthesis, (1999)

[9]

Xin J.-Y., Li S.-B., Xu Y., Chui J.-R., Xia C.-G., Dynamic enzymatic resolution of naproxen methyl ester in a membrane bioreactor, J. Chem. Technol. Biotechnol, 76, pp. 579-585, (2001)

[10]

Chang C.-S., Tsai S.-W., Lipase-catalyzed dynamic resolution of naproxen thioester by thiotransesterification in isooctane, Biochem. Eng. J, 3, pp. 239-242, (1999)

← 1 2 →