Diisopropyl Malonate as Acylating Agent in Kinetic Resolution of Chiral Amines with Lipase B from Candida antarctica
Authors
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József Szemes
Affiliation
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
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Ágnes Malta-Lakó
Affiliation
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
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Regina Eszter Tóth
Affiliation
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
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László Poppe
AffiliationDepartment of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Műegyetem rkp. 3, H-1111 Budapest, Hungary
Enzymology and Applied Biocatalysis Research Center, Faculty of Chemistry and Chemical Engineering, Babeş-Bolyai University, Arany János Str. 11, RO-400028 Cluj-Napoca, Romania
SynBiocat Ltd., Szilasliget u. 3, H-1172 Budapest, Hungary
Abstract
Activity of diisopropyl malonate (2) as a novel acylating agent was investigated in kinetic resolution (KR) of various racemic amines [(±)-1a-d] catalyzed by lipase B from Candida antarctica. Diisopropyl malonate (2) proved to be effective acylating agent with four racemic amines [(±)-2-aminoheptane, (±)-1-methoxy-2-propylamine, (±)-1-phenylethylamine and (±)-4-phenylbutan-2-amine; (±)-1a-d, respectively] selected for this study. The lipase-catalyzed acylation of the amines (±)-1a-d with 2 proceeded with good conversions (44.9–52.1%) and provided the expected (R)-amides [(R)-3a-d] in moderate to excellent yields (51–98%) with high enantiomeric excess (ee(R)-3a-d 92.0–99.9%) after 4 h reaction time under mild reaction conditions in batch mode. The best conversion (50%) combined with high enantiomeric purity (ee(R)-2d > 99%ee) was achieved in the KR from racemic 2-aminoheptane (±)-1a. The four novel (R)-amides [(R)-3a-d] were isolated and properly characterized.
