title: 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.
authors.affiliation: Department of Chemistry and Protein Research Center for Bio-Industry, Hankuk University of Foreign Studies, Yongin, Kyunggi-Do 449-719, Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Doo-Ha
authors.initials: DH
authors.lastname: Yoon
authors.forename: Philjun
authors.initials: P
authors.lastname: Kang
authors.forename: Won Koo
authors.initials: WK
authors.lastname: Lee
authors.forename: Heesung
authors.initials: H
authors.lastname: Eum
authors.forename: Hyun-Joon
authors.initials: HJ
authors.lastname: Ha
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry / Q000378:metabolism; D002175:Candida / Q000201:enzymology*; D004800:Enzymes, Immobilized / Q000378:metabolism*; D004952:Esters / Q000737:chemistry / Q000378:metabolism; D005656:Fungal Proteins / Q000378:metabolism*; D005977:Glutarates / Q000737:chemistry / Q000378:metabolism*; D008049:Lipase / Q000378:metabolism*; D056004:Molecular Dynamics Simulation; D000069583:Pregabalin; D013237:Stereoisomerism; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D004800:Enzymes, Immobilized; D004952:Esters; D005656:Fungal Proteins; D005977:Glutarates; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D008049:Lipase; C431349:lipase B, Candida antarctica; C035736:glutaric acid