Solid-Supported Synthesis of Putative Peptide β-Turn Mimetics via Ugi Reaction for Diketopiperazine Formation

Abstract
The scope and limitations of the solid-supported synthesis of a bicyclic diketopiperazine, an internal, putative peptide β-turn mimetic, are presented. The 4CC multicomponent Ugi reaction of α-N-Boc-diaminopropionic acid resin ester (an amine input), optically active α-bromoacid, aldehyde, and isocyanide is the key step in the proposed synthetic protocol. Application of cyclitive cleavage as the final step led to desired products in high purity.