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3.4.2.5.2 Enzymatic Oxidation of 4-Substituted Cyclohexanones

DOI: 10.1055/sos-SD-216-00079

de Gonzalo, G.; van Berkel, W. J. H.; Fraaije, M. W.Science of Synthesis: Biocatalysis in Organic Synthesis, (20153195.

Prochiral 4-substituted cyclohexanones are converted into the corresponding optically active ε-caprolactones 13 in Baeyer–Villiger reactions catalyzed by Baeyer–Villiger monooxygenases (BVMOs) expressed in E. coli cells. Cyclohexanones bearing various substituents have been employed for these syntheses, including halides, hydroxy groups, esters, and alkyl chains (Scheme 9). The biocatalysts most employed for the preparation of the lactones are cyclohexanone monooxygenase from Acinetobacter calcoaceticus (CHMOAcineto) and cyclopentanone monooxygenase from Comanonas sp. NCIMB 9872 (CPMOComa). For some compounds, depending on the Baeyer–Villiger monooxygenase used, a different enantiopreference is achieved, and both enantiomers of the final lactone are accessible. Cyclopentanone monooxygenase is able to oxidize substrates with ether O-substituents bigger than methyl with good results. This is in contrast to CHMOAcineto, which only accepts 4-methoxycyclohexanone. The biooxidation of those ketones substituted with bulky groups (R1 = t-Bu, Ph) is more efficient using a cyclohexanone monooxygenase from Xanthobacter sp. ZL5 (CHMOXantho), furnishing the corresponding (−)-lactones 13 with high yields and excellent enantioselectivities.

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