Paper
ADH-Catalyzed Biooxidation of (Hetero)aromatic sec-Alcohols to Ketones Employing Vinyl Acetate as Acetaldehyde Surrogate
A. Rudzka, T. Reiter, W. Kroutil, P. Borowiecki
ChemCatChem 2024, e202400803 (10 pages)
The oxidation of sec-alcohols is a common reaction in organic chemistry. We report a biocatalytic approach for oxidizing racemic (hetero)aromatic sec-alcohols to the corresponding ketones. The reaction relies on employing freeze-dried E. coli cells containing a recombinant variant of an alcohol dehydrogenase deduced from Lactobacillus kefir (E. coli/Lk-ADH Prince) and vinyl acetate as an in situ acetaldehyde surrogate as oxidant. Biooxidations of a set of 20 racemic (hetero)aromatic alcohols were carried out in the presence of a catalytic amount of NADP+ cofactor, the biocatalyst, and vinyl acetate in an aqueous medium to generate the corresponding ketones with up to >99 % conv. Preparative scale (1.0 mmol; 100 mM in 10 mL) reactions led to obtaining ketones in the 56–83 % isolated yield range.
![Graphical Abstract](../images/publications/pub-431.jpg)
Herein, we show that an engineered variant of an alcohol dehydrogenase deduced from Lactobacillus kefir (Lk-ADH Prince) serves as an efficient biocatalyst for biooxidation of sec-alcohols under mild conditions employing vinyl acetate as an acetaldehyde surrogate, which takes up the hydride, allowing the synthesis of variously functionalized ketones quantitively. The merger of the Lk-ADH Prince-catalyzed biooxidation with transaminase-catalyzed amination in a one-pot, two-step sequential manner led to optically active amines. This work should provide useful input to the field of redox biotransformations.