MICROBIOLOGICAL TRANSFORMATIONS .13. A DIRECT SYNTHESIS OF BOTH S-ENANTIOMER AND R-ENANTIOMER OF 5-HEXADECANOLIDE VIA AN ENANTIOSELECTIVE MICROBIOLOGICAL BAEYER-VILLIGER REACTION

The conversion of ketones to esters or lactones, i.e., the Baeyer-Villiger reaction,1is obviously one of the very important reactions in organic synthesis. However, the corresponding asymmetric Baeyer-Villiger reaction seems, up to now, to be unknown in the chemical literature. On the other hand, various studies have shown that “biological Baeyer-Villiger” reactions are involved in the oxidative degradation of a wide variety of organic compounds,2e.g., acyclic3and cyclic ketones4–6or diketones7like camphor,8fenchone,9and steroids.10However, only a few examples have been described showing that such enzymatic reactions may lead to optically active lactones.4a,7,11,12In the course of our work on the biological oxidation of various substrates, 13 we decided to explore the possibilities of asymmetric synthesis offered by this type of enzyme. The pioneering work of Trudgill et al.5 and Walsh et al.2,6has shown that Acinetobacter strains are able to perform “biological Baeyer-Villiger” reactions using a protein monooxygenase (cyclohexanone oxygenase EC 1.14.13.-) which has been isolated and characterized. Very recently, Taschner et al. also described some very interesting results on prochiral substrates using this purified enzyme and a NADPH recycling system. However, no indication about the scale of the reaction is given in this paper.12We here describe the use of these enzymes in order to perform a preparative enantioselective synthesis from racemic material which allows direct access to both (S)- and (R)-5- hexadecanolide, a pheromone isolated from the oriental hornet Vespa orientalis.14,15. © 1990, American Chemical Society. All rights reserved.