Access to Optically Pure 4- and 5-Substituted Lactones:  A Case of Chemical−Biocatalytical Cooperation

• Published in: Journal of organic chemistry Vol. 68; no. 16; pp. 6222 - 6228
• Main Authors: Wang, Shaozhao, Kayser, Margaret M, Jurkauskas, Valdas
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08.08.2003
• Subjects: Catalysis; Chemistry; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Indicators and Reagents; Lactones - chemical synthesis; Lactones - chemistry; Magnetic Resonance Spectroscopy; Organic chemistry; Oxidation-Reduction; Preparations and properties; Catalytic reaction; Cyclohexane derivatives; Regioselectivity; Enzyme; Escherichia coli; Enzymatic catalysis; Lactone; Oxygen heterocycle; Ketone; Ring expansion; Oxygenase; Baeyer Villiger reaction; Chirality; Bacteria; Copper I; Oxidoreductases; Chemical synthesis; Enone; Cyclopentane derivatives; Enterobacteriaceae
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo026605q

Optically pure or highly enantiomerically enriched 4- and 5-substituted lactones are rather difficult to obtain. Chemical or enzymatic syntheses alone are not particularly successful. A combination of chemical catalysis and biocatalysis, however, provides a convenient route to a variety of these useful chiral compounds. In this paper we describe the synthesis of several optically pure 4- and 5-substituted lactones obtained via whole cell-catalyzed Baeyer−Villiger oxidations of highly enantiomerically enriched 3-alkyl cyclic ketones. Such chiral ketones are readily accessed by recently developed copper-catalyzed asymmetric conjugate reductions of the corresponding enones. A very high proximal regioselectivity and complete chirality transfer was obtained by employing biological Baeyer−Villiger oxidations, using recombinant E. coli strains that overexpress cyclopentanone monooxygenase (CPMO). A comparative study showed that CPMO gives superior results to those obtained with cyclohexanone monooxygenase (CHMO) catalyzed oxidations.