Biocatalytic Synthesis of Substituted Cinnamaldehydes

Abstract

Abstract Substituted cinnamaldehydes are valuable compounds, but current syntheses rely on expensive and toxic reagents. We report a biocatalytic synthesis of substituted cinnamaldehydes from the corresponding benzaldehydes via an aldolase, NahE, and benzoylformate decarboxylase. This is the first use of α,β-unsaturated 2-oxo acids as substrates for thiamine diphosphate-dependent 2-oxo acid decarboxylases. We found electron-donating substituents were better tolerated than electron-withdrawing substituents, but all showed good to excellent conversions. A preparative-scale reaction gave 4-methoxycinnamaldehyde in 77% isolated yield.