Zukic E,
Mokos D,
Weber M,
Stix N,
Ditrich K,
Ferrario V,
Müller H,
Willrodt C,
Gruber K,
Daniel B,
*,
Kroutil W.
*
University of Graz and BioTechMed Graz, Austria
Biocatalytic Heteroaromatic Amide Formation in Water Enabled by a Catalytic Tetrad
and Two Access Tunnels.
ACS Catal. 2024;
14: 8913-8921
DOI:
10.1021/acscatal.4c01268
Key words
amide synthesis - reactions in water - heterocyclic amides - preparative biocatalysis
Significance
Zukic et al. report a biocatalytic method that provides access to the variety of sterically
demanding, heteroaromatic amides. Lipase HXN-200 from Sphingomonas sp. is used as a catalyst that enables the formation of amide bonds by ester aminolysis.
The reaction proceeds in an aqueous medium, which is consistent with the principles
of green chemistry and yet competition of water as a nucleophile has been virtually
eliminated. High chemoselectivity of the process is possible due to the catalytic
tetrad in the enzyme active site.
Comment
Water – the optimal solvent for biocatalysts can act as a competing substrate in reactions
catalyzed by lipases. The authors succeeded in overcoming the hydrolysis of ester
starting material or product despite a considerable excess of water by utilizing the
selectivity of lipase from Sphingomonas sp. In addition, the enzyme can efficiently work with sterically bulky starting materials,
allowing access to pharmaceutically relevant molecules. The scalability of the method
shows how biocatalysis can be used in an industrially applicable synthesis protocol.
