One-Pot Biocatalytic Double Oxidation of [alpha]-Isophorone for the Synthesis of Ketoisophorone

The chemical synthesis of ketoisophorone, a valuable building block of vitamins and pharmaceuticals, suffers from several drawbacks in terms of reaction conditions and selectivity. Herein, the first biocatalytic one-pot double oxidation of the readily available [alpha]-isophorone to ketoisophorone i...

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Bibliographic Details
Published in:ChemCatChem 2017-09, Vol.9 (17), p.3338
Main Authors: Tavanti, Michele, Parmeggiani, Fabio, Castellanos, J Rubén Gómez, Mattevi, Andrea, Turner, Nicholas J
Format: Article
Language:English
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Summary:The chemical synthesis of ketoisophorone, a valuable building block of vitamins and pharmaceuticals, suffers from several drawbacks in terms of reaction conditions and selectivity. Herein, the first biocatalytic one-pot double oxidation of the readily available [alpha]-isophorone to ketoisophorone is described. Variants of the self-sufficient P450cam-RhFRed with improved activity have been identified to perform the first step of the designed cascade (regio- and enantioselective allylic oxidation of [alpha]-isophorone to 4-hydroxy-[alpha]-isophorone). For the second step, the screening of a broad panel of alcohol dehydrogenases (ADHs) led to the identification of Cm-ADH10 from Candida magnoliae. The crystal structure of Cm-ADH10 was solved and docking experiments confirmed the preferred position and geometry of the substrate for catalysis. The synthesis of ketoisophorone was demonstrated both as a one-pot two-step process and as a cascade process employing designer cells co-expressing the two biocatalysts, with a productivity of up to 1.4gL-1d-1.
ISSN:1867-3880
1867-3899
DOI:10.1002/cctc.201700620