Synthesis of Pharmaceutically Relevant Arylamines Enabled by a Nitroreductase from Bacillus tequilensis.

Autor: Russo S; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.; Molecular Enzymology Group, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands., Luján AP; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands., Fraaije MW; Molecular Enzymology Group, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands., Poelarends GJ; Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.
Jazyk: angličtina
Zdroj: Chembiochem : a European journal of chemical biology [Chembiochem] 2024 May 17; Vol. 25 (10), pp. e202300846. Date of Electronic Publication: 2024 Apr 19.
DOI: 10.1002/cbic.202300846
Abstrakt: Arylamines are essential building blocks for the manufacture of valuable pharmaceuticals, pigments and dyes. However, their current industrial production involves the use of chemocatalytic procedures with a significant environmental impact. As a result, flavin-dependent nitroreductases (NRs) have received increasing attention as sustainable catalysts for more ecofriendly synthesis of arylamines. In this study, we assessed a novel NR from Bacillus tequilensis, named BtNR, for the synthesis of pharmaceutically relevant arylamines, including valuable synthons used in the manufacture of blockbuster drugs such as vismodegib, sonidegib, linezolid and sildenafil. After optimizing the enzymatic reaction conditions, high conversion of nitroaromatics to arylamines (up to 97 %) and good product yields (up to 56 %) were achieved. Our results indicate that BtNR has a broad substrate scope, including bulky nitro benzenes, nitro pyrazoles and nitro pyridines. Hence, BtNR is an interesting biocatalyst for the synthesis of pharmaceutically relevant amine-functionalized aromatics, providing an attractive alternative to traditional chemical synthesis methodologies.
(© 2024 The Authors. ChemBioChem published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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