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

Abstract

Synthesis of g-nitroaldehydes from branched chain aldehydes and a range of a,b-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 g-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 a,a-substituted g-nitroaldehydes was compared to the organocatalytic approach involving the lithium salt of phenylalanine as a catalyst. As the resulting g-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.Scheme 2 Tautomerase based whole-cell catalyzed Michael addition of isobutanal to b-nitrostyrene. Fig. 1 Structures of (A) branched donors and (B) g-nitroaldehyde products of Michael-type additions catalyzed by 4-OT.This journal is

Enabling protein-hosted organocatalytic transformations

“…4-OT and its variants have been used for a range of applications including enzymatic 115 and chemoenzymatic cascades, 116 alongside whole cell catalytic systems. 117 – 119 The anti-anxiety drug pregabalin and three of its analogues were synthesised by coupling the 4-OT reaction with catalysis by aldehyde dehydrogenase (ALDH, Fig. 8 ).…”