Issue 22, 2013

CAL-B catalyzed desymmetrization of 3-alkylglutarate: “olefin effect” and asymmetric synthesis of pregabalin

Abstract

CAL-B catalyzed desymmetrization of prochiral 3-alkylglutaric acid diesters was performed to prepare optically active 3-alkylglutaric acid monoesters bearing various alkyl substituents, including methyl, ethyl, propyl and allyl groups. Allyl esters showed far better stereoselectivity among the alkyl esters, suggesting possible π–π interactions between the olefin of the substrate and the Trp104 or His224 side chains at the enzyme active site. Based on this reaction, the synthesis of (S)-(+)-3-aminomethyl-5-methylhexanoic acid (pregabalin) was achieved with a 70% overall yield.

Graphical abstract: CAL-B catalyzed desymmetrization of 3-alkylglutarate: “olefin effect” and asymmetric synthesis of pregabalin

Supplementary files

Article information

Article type
Paper
Submitted
12 Feb 2013
Accepted
28 Feb 2013
First published
01 Mar 2013

Org. Biomol. Chem., 2013,11, 3635-3641

CAL-B catalyzed desymmetrization of 3-alkylglutarate: “olefin effect” and asymmetric synthesis of pregabalin

J. Jung, D. Yoon, P. Kang, W. K. Lee, H. Eum and H. Ha, Org. Biomol. Chem., 2013, 11, 3635 DOI: 10.1039/C3OB40311D

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