Synthesis and conformational studies of dipeptides constrained by disubstituted 3-(aminoethoxy)propionic acid linkers

A series of cyclic compounds with dimethyl-substituted 3-(aminoethoxy)propionic acid linkers have been prepared as potential beta-turn mimics. The desired linkers were prepared from disubstituted pyrones, which were coupled with dipeptides and then subjected to macrocyclization using diethylcyanophosphonate to furnish cyclic compounds 1-5. Conformational analysis was carried out using NMR and X-ray crystallography. All of the five cyclic compounds were found to exist in type I or type II beta-turn conformations.