2022/12/09 by Douglas J. Fansher, David R. J. Palmer · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · #Asymmetric Synthesis and Catalysis #Chemical Synthesis and Analysis #Enzyme Catalysis and Immobilization
paper · doi:10.1002/anie.202214539
openalex publication_date 2022/12/09 · openalex created_date 2025/10/10 · openalex updated_date 2026/06/12
Michael addition reactions are highly useful in organic synthesis and are commonly accomplished using organocatalysts. However, the corresponding biocatalytic Michael additions are rare, typically lack synthetically useful substrate scope, and suffer from low stereoselectivity. Herein we report a biocatalytic nitro-Michael addition, catalyzed by NahE, that proceeds with low catalyst loading at room temperature in moderate to excellent enantioselectivity and high yields. A series of β-nitrostyrenes reacted with pyruvate in the presence of NahE to give, after oxidative decarboxylation, β-aryl-γ-nitrobutyric acids in up to 99 % yield without need for chromatography, providing a simple preparative-scale route to chiral GABA analogues. This reaction represents the first example of an aldolase displaying promiscuous Michaelase activity and opens the use of nitroalkenes in place of aldehydes as substrates for aldolases.