A Type 1 Aldolase, NahE, Catalyzes a Stereoselective Nitro-Michael Reaction: Synthesis ofβ-Aryl-γ-nitrobutyric Acids.

Abstract

Michael additions are highly useful in organic synthesis and are commonly accomplished using organocatalysts. However, the corresponding biocatalytic Michael additions are rare and typically lack synthetically useful substrate scopes and suffer from low stereoselectivity. Here 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-γnitrobutyric acids in up to 99% isolated 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 aldehydes as substrates for aldolases.