Synthesis of 13-16-Membered Cyclotetrapeptide Mimics by Ugi Reactions with Diacids and Diisonitriles

13-16-Membered cyclic tetraamides were synthesized by Ugi reactions using diisonitriles and dicarboxylic acids in 2,2,2-trifluoroethanol without (pseudo) high dilution conditions. Structures of these cyclic tetraamides were investigated by NMR and X-ray crystallography. Chemical libraries of 13-16-membered cyclic tetraamides were conveniently and quickly synthesized by multi-component Ugi reactions. The conformations of some cyclic tetraamides were studied by X-ray crystallography and NMR experiments.image