Ultrasound-assisted green one-pot synthesis of linked bis-heterocycle peptidomimetics via IMCR/post-transformation/tandem strategy

Abstract

The sequential aligning of two eco-friendly and powerful tools for the synthesis of peptidomimetics resulted in the rapid generation of molecular complexity in target molecules. We herein report a versatile IMCR/post-transformation/tandem synthetic strategy that emphasizes the special role of orthogonal bifunctional reagents in isocyanide based multicomponent reactions (IMCR) to generate a synthetic platform for subsequent heterocyclization reactions. This is the first one-pot synthesis of a 2,5-diketopiperazine linked to a 1,4-disubstituted 1,2,3-triazole. The Ugi-4CR/lactamization/click sequence is facile, mild, atom-economical, and green. The present work contributes to the green and one-pot synthesis of bis-heterocycle peptidomimetics and design of new bioactive molecules.