Hydrazinopeptide Motifs Synthesized via the Ugi Reaction: An Insight into the Secondary Structure

Abstract

A number of Na-alkyl,N߭acylhydrazines have been synthesized via the Ugi reaction of N-acylhydrazones with an isocyanide and trifluoroacetic acid. The trifluoroacetic acid acted as a 'silent partner' and becomes removed upon basic workup of the reaction. These compounds have been efficiently modified further via reductive alkylation to produce Na,Na-dialkyl,N߭acylhydrazines. The two groups of novel hydrazinopeptide motifs have been shown by simple 鈠NMR spectroscopic experiments to display two different secondary structure patterns. These observations were confirmed by X-ray crystallographic analysis. Combining the hydrazone and carboxylic acid moieties in one reaction precursor offers the opportunity for an 'intramolecular' hydrazino-Ugi reaction, which was also demonstrated.