Oxalate Oxidase for In Situ H 2 O 2 -Generation in Unspecific Peroxygenase-Catalysed Drug Oxyfunctionalisations

• Published in: Angewandte Chemie International Edition Vol. 61; no. 39; p. e202207831
• Main Authors: Romero, Elvira, Johansson, Magnus J, Cartwright, Jared, Grogan, Gideon, Hayes, Martin A
• Format: Journal Article
• Language: English
• Published: Germany 26.09.2022
• Subjects: Biocatalysis; Carbon Dioxide; Drug Late-Stage Functionalisation; H2O2-Generation; High-Throughput Screening; Mixed Function Oxygenases; Oxalates; Oxidoreductases; Tolmetin; Drug Late-Stage Functionalisation; High-Throughput Screening; Biocatalysis; Oxidoreductases; H2O2-Generation
• ISSN: 1433-7851; 1521-3773; 1521-3773
• DOI: 10.1002/anie.202207831

H O -driven enzymes are of great interest for industrial biotransformations. Herein, we show for the first time that oxalate oxidase (OXO) is an efficient in situ source of H O for one of these biocatalysts, which is known as unspecific peroxygenase (UPO). OXO is reasonably robust, produces only CO as a by-product and uses oxalate as a cheap sacrificial electron donor. UPO has significant potential as an industrial catalyst for selective C-H oxyfunctionalisations, as we confirm herein by testing a diverse drug panel using miniaturised high-throughput assays and mass spectrometry. 33 out of 64 drugs were converted in 5 μL-scale reactions by the UPO with OXO (conversion >70 % for 11 drugs). Furthermore, oxidation of the drug tolmetin was achieved on a 50 mg scale (TON 25 664) with 84 % yield, which was further improved via enzyme immobilization. This one-pot approach ensures adequate H O levels, enabling rapid access to industrially relevant molecules that are difficult to obtain by other routes.