Turn-Mimic Hydantoin-Based Loops Constructed by a Sequential Multicomponent Reaction

A collection of peptidomimetics characterized by having an aspartic acid motif embedded in a rigid hydantoin heterocycle are synthesized through a sequential multicomponent domino process followed by standard regioselective deprotection/coupling reactions based on acid-base liquid/liquid purification protocols. ¹H nuclear magnetic resonance experiments, molecular modeling, and X-ray analysis showed that the resulting hydantoin-based loops I (in particular) and II (to a lesser extent) can be considered novel β-turn inducer motifs being able to project two peptide-like strands in a U-shaped conformation driven by the formation of intermolecular hydrogen bonds.