Lactones 42. Stereoselective enzymatic/microbial synthesis of optically active isomers of whisky lactone

• Published in: Food chemistry 2013-11, Vol.141 (1), p.419-427
• Main Authors: Boratyński, Filip, Smuga, Małgorzata, Wawrzeńczyk, Czesław
• Format: Article
• Language: English
• Subjects: Animals; Beauveria bassiana; Biocatalysis; Biological and medical sciences; Biotransformation; Biotransformations; Chaetomium; Enantioselectivity; Enzyme reactions; Escherichia coli; Food toxicology; Fungi - metabolism; Horses; Lactones - chemistry; Lactones - metabolism; Liver - enzymology; Medical sciences; Oak lactones; Oxidation-Reduction; Saccharomyces cerevisiae; Stereoisomerism; Sugar Alcohol Dehydrogenases - chemistry; Toxicology; Whisky lactones
• ISSN: 0308-8146; 1873-7072
• DOI: 10.1016/j.foodchem.2013.02.106

•We examine two methods for synthesis optically pure cis- and trans-whisky lactones.•Depending on the method opposite enantiomerically enriched isomers can be obtained.•Lactonization of γ-oxoacids by filamentous fungi leads to trans-(+)-(4S,5R)-whisky lactone (ee=99%).•In oxidation of diols trans-(−)-(4R,5S)- or cis-(+)-(4R,5R)-whisky lactones were formed preferentially.•We evaluate the diols oxidation pathway and step responsible for enantioselectivity. Two different methods, enzyme-mediated reactions and biotrasformations with microorganisms, were applied to obtain optically pure cis- and trans-isomers of whisky lactone 4a and 4b. In the first method, eight alcohol dehydrogenases were investigated as biocatalysts to enantioselective oxidation of racemic erythro- and threo-3-methyloctane-1,4-diols (1a and 1b). Oxidation processes with three of them, alcohol dehydrogenases isolated from horse liver (HLADH) as well as recombinant from Escherichia coli and primary alcohol dehydrogenase (PADH I), were characterized by the highest degree of conversion with moderate enantioselectivity (ee=27–82%) of the reaction. In all enzymatic reactions enantiomerically enriched not naturally occurring isomers of trans-(−)-(4R,5S)-4b or cis-(+)-(4R,5R)-4a were formed preferentially. In the second strategy, based on microbial lactonization of γ-oxoacids, naturally occurring opposite isomers of whisky lactones were obtained. Trans-(+)-(4S,5R)-isomer (ee=99%) of whisky lactone 4b was stereoselectively formed as the only product of biotransformations of 3-methyl-4-oxooctanoic acid (5) catalyzed by Didimospheria igniaria KCH6651, Laetiporus sulphurens AM525, Chaetomium sp.1 KCH6670 and Saccharomyces cerevisiae AM464. Biotransformation of γ-oxoacid 5, in the culture of Beauveria bassiana AM278 and Pycnidiella resinae KCH50 afforded a mixtures of trans-(+)-(4S,5R)-4b with enantiomeric excess ee=99% and cis-(−)-(4S,5S)-4a with enantiomeric excesses ee=77% and ee=45% respectively.