Investigation of the donor and acceptor range for chiral carboligation catalyzed by the E1 component of the 2-oxoglutarate dehydrogenase complex

•Synthesis of chiral compounds using E1 of 2-oxoglutarate dehydrogenase is reported.•Chiral 2-hydroxyketones are synthesized varying donor and acceptor substrates.•Chiral products with (R) or (S) enantiomers were produced with 60–95% ee.•Use of an ester and a 2-oxoaldehyde as acceptors for the enamine is accomplished.•2-Oxovalerate and 2-oxoisovalerate are also accepted in carboligation as donors.

The potential of thiamin diphosphate (ThDP)-dependent enzymes to catalyze CC bond forming (carboligase) reactions with high enantiomeric excess has been recognized for many years. Here we report the application of the E1 component of the Escherichia coli 2-oxoglutarate dehydrogenase multienzyme complex in the synthesis of chiral compounds with multiple functional groups in good yield and high enantiomeric excess, by varying both the donor substrate (different 2-oxo acids) and the acceptor substrate (glyoxylate, ethyl glyoxylate and methyl glyoxal). Major findings include the demonstration that the enzyme can accept 2-oxovalerate and 2-oxoisovalerate in addition to its natural substrate 2-oxoglutarate, and that the tested acceptors are also acceptable in the carboligation reaction, thereby very much expanding the repertory of the enzyme in chiral synthesis.

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