CAL-B catalyzed desymmetrization of 3-alkylglutarate: olefin effect and asymmetric synthesis of pregabalinElectronic supplementary information (ESI) available: Preparation of substrates. NMR spectra. HPLC data for ee values. Further results of molecular dynamics simulation. See DOI: 10.1039/c3ob40311d

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...

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Main Authors: Jung, Jae-Hoon, Yoon, Doo-Ha, Kang, Philjun, Lee, Won Koo, Eum, Heesung, Ha, Hyun-Joon
Format: Article
Language:English
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Summary: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 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. 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.
ISSN:1477-0520
1477-0539
DOI:10.1039/c3ob40311d