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. 2024 May 17;25(10):e202300846.
doi: 10.1002/cbic.202300846. Epub 2024 Apr 19.

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

Sara Russo  1   2 , Alejandro Prats Luján  1 , Marco W Fraaije  2 , Gerrit J Poelarends  1
Affiliations

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

Sara Russo et al. Chembiochem. .

Abstract

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.

Keywords: arylamine; biocatalysis; flavoprotein; nitroreductase.

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References

    1. M. Hoogenraad, J. B. van der Linden, A. A. Smith, B. Hughes, A. M. Derrick, L. J. Harris, P. D. Higginson, A. J. Pettman, Org. Process Res. Dev. 2004, 8, 469–476.
    1. R. Angelaud, M. Reynolds, C. Venkatramani, S. Savage, H. Trafelet, T. Landmesser, P. Demel, M. Levis, O. Ruha, B. Rueckert, H. Jaeggi, Org. Process Res. Dev. 2016, 20, 1509–1519.
    1. B. S. Takale, R. R. Thakore, F. Y. Kong, B. H. Lipshutz, Green Chem. 2019, 21, 6258–6262.
    1. D. J. Dale, P. J. Dunn, C. Golightly, M. L. Hughes, P. C. Levett, A. K. Pearce, P. M. Searle, G. Ward, A. S. Wood, Org. Process Res. Dev. 2000, 4, 17–22.
    1. S. J. Brickner, D. K. Hutchinson, M. R. Barbachyn, P. R. Manninen, D. A. Ulanowicz, S. A. Garmon, K. C. Grega, S. K. Hendges, D. S. Toops, C. W. Ford, G. E. Zurenko, J. Med. Chem. 1996, 39, 673–679.