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Stereochemical Control of Enzymatic Carbon–Carbon Bond‐Forming Michael‐Type Additions by “Substrate Engineering”
Author(s) -
Miao Yufeng,
Tepper Pieter G.,
Geertsema Edzard M.,
Poelarends Gerrit J.
Publication year - 2016
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201601126
Subject(s) - chemistry , michael reaction , enantioselective synthesis , acetaldehyde , substrate (aquarium) , catalysis , yield (engineering) , organic chemistry , biocatalysis , acceptor , stereoselectivity , combinatorial chemistry , stereochemistry , reaction mechanism , ethanol , materials science , oceanography , physics , condensed matter physics , metallurgy , geology
The enzyme 4‐oxalocrotonate tautomerase (4‐OT) promiscuously catalyzes the Michael‐type addition of acetaldehyde to β‐nitrostyrene derivatives to yield chiral γ‐nitroaldehydes, which are important precursors for pharmaceutically active γ‐aminobutyric acids. In this study, we investigated the effect of different substituents at the aromatic ring of the Michael acceptor on the catalytic efficiency and stereoselectivity of the 4‐OT‐catalyzed acetaldehyde addition reactions. Highly enantioenriched ( R )‐ and ( S )‐γ‐nitroaldehydes and 4‐substituted chroman‐2‐ol could be obtained in good to excellent yields by applying different substituents at appropriate positions of the aromatic substrate. Stereochemical control of these enzymatic Michael‐type additions by “substrate engineering” allowed the enantioselective synthesis of valuable γ‐aminobutyric acid precursors. In addition, the results suggest a novel enzymatic synthesis route towards precursors for chromans and derivatives, which are valuable scaffolds for preparing biologically active natural products.