Stereoselective synthesis of whisky lactone isomers catalyzed by bacteria in the genus Rhodococcus

Abstract

Whisky lactone is a naturally occurring fragrance compound in oak wood and is widely used as a sensory additive in food products. However, safe and efficient methods for the production of its individual enantiomers for applications in the food industry are lacking. The aim of this study was to develop an efficient and highly stereoselective process for the synthesis of individual enantiomeric forms of whisky lactones. The proposed three-step method involves (1) column chromatography separation of a diastereoisomeric mixture of whisky lactone, (2) chemical reduction ofcis-and trans-whisky lactones to correspondingsyn-and anti-diols, and (3) microbial oxidation of racemic diols to individual enantiomers of whisky lactone. Among various bacteria in the generaDietzia,Gordonia,Micrococcus,Rhodococcus,andStreptomyces,R. erythropolisDSM44534 andR. erythropolisPCM2150 effectively oxidizedanti-and syn-3-methyl-octane-1,4-diols (1a-b) to corresponding enantiomerically purecis-and trans-whisky lactones, indicating high alcohol dehydrogenase activity. Bio-oxidation catalyzed by whole cells of these strains yielded enantiomerically pure isomers oftrans-(+)-(4S,5R) (2a),trans-(−)-(4R,5S) (2b), andcis-(+)-(4R,5R) (2d) whisky lactones. The optical density of bacterial cultures and the impact of the use of acetone powders as catalysts on the course of the reaction were also evaluated. Finally, the application ofR. erythropolisDSM44534 in the form of an acetone powder generated the enantiomerically enrichedcis-(−)-(4S,5S)-isomer (2c) from the correspondingsyn-diol (1b). The newly developed method provides an improved approach for the synthesis of chiral whisky lactones.