Synthesis of γ-nitroaldehydes containing quaternary carbon in the α-position using a 4-oxalocrotonate tautomerase whole-cell biocatalyst

Abstract

Synthesis of γ-nitroaldehydes from branched chain aldehydes and a range of α,β-unsaturated nitroalkenes was achieved by a whole-cell biocatalytic reaction using 4-oxalocrotonate tautomerase as catalyst. Under mild conditions, cyclic and acyclic branched aldehydes were converted into synthetically valuable quaternary carbon containing γ-nitroaldehydes. The yields of the desired products were influenced by reaction condition parameters such as organic solvent, temperature and pH. The whole-cell biocatalytic approach to the generation of α,α-substituted γ-nitroaldehydes was compared to the organocatalytic approach involving the lithium salt of phenylalanine as a catalyst. As the resulting γ-nitroaldehydes exhibited moderate antifungal activity and mild in vitro cytotoxicity against human fibroblasts (0.2-0.4 mM) they could further be examined as potentially useful pharmaceutical synthons.