Biocatalytic and Chemo-Enzymatic Synthesis of Quinolines and 2-Quinolones by Monoamine Oxidase (MAO-N) and Horseradish Peroxidase (HRP) Biocatalysts

Haoyue Xiang; Salvatore Ferla; Carmine Varricchio; Andrea Brancale; Nicola L Brown; Gary W Black; Nicholas J Turner; Daniele Castagnolo

doi:10.1021/acscatal.2c05902

Biocatalytic and Chemo-Enzymatic Synthesis of Quinolines and 2-Quinolones by Monoamine Oxidase (MAO-N) and Horseradish Peroxidase (HRP) Biocatalysts

ACS Catal. 2023 Feb 22;13(5):3370-3378. doi: 10.1021/acscatal.2c05902. eCollection 2023 Mar 3.

Authors

Haoyue Xiang¹, Salvatore Ferla², Carmine Varricchio³, Andrea Brancale^{3

4}, Nicola L Brown⁵, Gary W Black⁵, Nicholas J Turner⁶, Daniele Castagnolo¹

Affiliations

¹ Department of Chemistry, University College London, 20 Gordon Street, London WC1H 0AJ, U.K.
² Medical School, Faculty of Medicine, Health and Life Science, Swansea University, Swansea SA2 8PP, U.K.
³ School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff CF10 3NB, U.K.
⁴ University of Chemistry and Technology, Prague, 166 28 Prague 6, Czech Republic.
⁵ Department of Applied Sciences, Northumbria University, Newcastle upon Tyne NE1 8ST, U.K.
⁶ Department of Chemistry, University of Manchester, Manchester Institute of Biotechnology, 131 Princess Street, Manchester M1 7DN, U.K.

Abstract

The oxidative aromatization of aliphatic N-heterocycles is a fundamental organic transformation for the preparation of a diverse array of heteroaromatic compounds. Despite many attempts to improve the efficiency and practicality of this transformation, most synthetic methodologies still require toxic and expensive reagents as well as harsh conditions. Herein, we describe two enzymatic strategies for the oxidation of 1,2,3,4-tetrahydroquinolines (THQs) and N-cyclopropyl-N-alkylanilines into quinolines and 2-quinolones, respectively. Whole cells and purified monoamine oxidase (MAO-N) enzymes were used to effectively catalyze the biotransformation of THQs into the corresponding aromatic quinoline derivatives, while N-cyclopropyl-N-alkylanilines were converted into 2-quinolone compounds through a horseradish peroxidase (HRP)-catalyzed annulation/aromatization reaction followed by Fe-mediated oxidation.