C-Terminal-Modified Oligourea Foldamers as a Result of Terminal Methyl Ester Reactions under Alkaline Conditions

Hybrids of short oligourea foldamers with residues of alpha, beta and gamma-amino acids esters at the C-terminus were obtained and subjected to a reaction with LiOH. There are two possible transformations under such conditions, one of which is ester hydrolysis and the formation of a carboxylic group and the other is the cyclization reaction after abstraction of a proton from urea by a base. We have investigated this reaction with difference C-terminal residue structures, as well as under different work-up conditions, especially for oligourea hybrids with alpha-amino acid esters. For these compounds, an oligourea-hydantoin combination is the product of cyclization. The stability of the hydantoin ring under alkaline conditions has been alsotested. Furthermore, this work reports data related to the structure of C-terminal-modified oligourea foldamers in solution and, for one compound, in the solid state. Helical folding is preserved both for cyclized and linear modifications, with oligourea-acid hybrids appearing to be more conformationally stable, as they are stabilized by an additional intramolecular hydrogen bond in comparison to cyclic derivatives.

Automated summary

In this study, hybrids of short oligourea foldamers with residues of different amino acids esters were synthesized and reacted with LiOH. Ester hydrolysis and cyclization reaction were observed as possible transformations under these conditions. The reaction was investigated using different C-terminal residue structures, as well as under different work-up conditions. The stability of the resulting products, including hydantoin rings, was also tested.