Synthesis of medium-ring lactams and macrocyclic peptide mimetics via conjugate addition/ring expansion cascade reactions.

Abstract

A novel conjugate addition/ring expansion (CARE) cascade reaction sequence is reported that enables medium-sized ring and macrocyclic bis-lactams to be prepared from primary amines and cyclic imides. The reactions are simple to perform, generally high yielding, and very broad in scope, especially with respect to the primary amine component. CARE reactions can also be performed iteratively, enabling β-peptoid-based macrocyclic peptide mimetics to be ‘grown’ via well controlled, sequential 4-atom ring expansion reactions, with the incorporation of varied functionalised amines during each iteration.