Enzymatic cascades for stereoselective and regioselective amide bond assembly
Author(s)
Type
Journal Article
Abstract
Amide bond formation is fundamental in nature and is widely used in the synthesis of pharmaceuticals and other valuable products. Current methods for amide synthesis are often step and atom inefficient, requiring the use of protecting groups, deleterious reagents and organic solvents that create significant waste. The development of cleaner and more efficient catalytic methods for amide synthesis remains an urgent unmet need. Herein, we present novel biocatalytic cascade reactions for synthesising various amides under mild aqueous conditions from readily available organic nitriles combining nitrile hydrolysing enzymes and amide bond synthetase enzymes. These cooperative biocatalytic cascades enable kinetic resolution of racemic nitriles and provide a highly enantioselective biocatalytic extension of the Strecker reaction. The regioselective non-directed C−H bond amidation of simple arenes was demonstrated through the incorporation of photoredox catalysis to the front end of the cascade. C−H bond amidation of simple aromatic precursors was also achieved via a CO2 fixation cascade combining enzymatic carboxylation and amide bond synthesis in one-pot.
Date Issued
2025-03-24
Date Acceptance
2025-01-01
Citation
Angewandte Chemie International Edition, 2025, 64 (13)
ISSN
1433-7851
Publisher
Wiley
Journal / Book Title
Angewandte Chemie International Edition
Volume
64
Issue
13
Copyright Statement
© 2025 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39792621
Subjects
amides
biocatalysis
cascades
green chemistry
ligases
Publication Status
Published
Coverage Spatial
Germany
Article Number
e202422185
Date Publish Online
2025-01-21