Improvement of N-benzoylation catalysis driven by an amyloid-substrate complex.

Abstract

Nucleophilic reactions of amines are important chemical transformations, but the reactions are incompatible with acidic buffer conditions. Azo-stilbene is a motif that binds to amyloids formed by accumulation of β-sheet peptides. We previously reported that the amino group attached to azo-stilbene is activated by proximity to an amyloid catalyst, promoting nucleophilic reactions in acidic buffers. Here, we show that we could improve the N-benzoylation yield for what was previously a difficult substrate by (1) derivatizing an amyloid catalyst, (2) modulating the amyloid morphology with His, and (3) adding thioflavin-T as a reaction additive. These results are predicted to accelerate the application of the amine modification catalysis system driven by the amyloid-substrate complex and to advance research on functional molecules containing an azo-stilbene motif.