CAL-B catalyzed desymmetrization of 3-alkylglutarate: 'olefin effect' and asymmetric synthesis of pregabalin
| Autor: | Doo-Ha Yoon, Won Koo Lee, Heesung Eum, Hyun-Joon Ha, Philjun Kang, Jae-Hoon Jung |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Stereochemistry
Pregabalin Molecular Dynamics Simulation Biochemistry Desymmetrization Catalysis Fungal Proteins Glutarates Side chain Physical and Theoretical Chemistry Alkyl gamma-Aminobutyric Acid Candida chemistry.chemical_classification Olefin fiber biology Chemistry Organic Chemistry Enantioselective synthesis Active site Esters Stereoisomerism Lipase Enzymes Immobilized Allyl Compounds biology.protein Stereoselectivity |
| Zdroj: | Organicbiomolecular chemistry. 11(22) |
| ISSN: | 1477-0539 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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