Oxopiperazine capping: Formation of oxopiperazine-containing peptoids via C-terminal cyclization

Abstract

An unexpected side reaction was observed in peptoids containing a C-terminal carboxamide with a 2-aminoethyl side chain. The reaction proceeded via cyclization and release of NH3, resulting in C-terminal oxopiperazine formation, analogous to pyroglutamate formation from N-terminal glutamine in peptides. Reaction conditions that promote oxopiperazine formation were developed. In particular, the addition of organic bases accelerated the cyclization, thus providing a simple strategy for the post-synthetic C-terminal capping of peptoids. © 2018 Elsevier Ltd