Stereochemical Control of Enzymatic Carbon-Carbon Bond-Forming Michael-Type Additions by "Substrate Engineering".

ABSTRACT: The enzyme 4-oxalocrotonate tautomerase (4-OT) promiscuously catalyzes the Michael-type addition of acetaldehyde to ?-nitrostyrene derivatives to yield chiral ?-nitroaldehydes, which are important precursors for pharmaceutically active ?-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)-?-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 ?-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.

SUBMITTER: Miao Y 

PROVIDER: S-EPMC5113669 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature