Brønsted Acid-Catalyzed Dipeptides Functionalization through Azlactones

Abstract

Azlactones are useful building blocks in the synthesis of functional amino acid derivatives, heterocycles and bioactive molecules. In this work, a protocol for the organocatalytic functionalization of dipeptides has been presented. 2-Alkyl-substituted azlactone intermediates in the presence of different amines and alcohols were combined in a ring opening reaction approach. The products were synthesized in moderate to excellent isolated yields, providing new insights in peptide transformations involving carbodiimide activation.

Brønsted Acid-Catalyzed Epimerization-Free Preparation of Dual-Protected Amino Acid Derivatives

“…This problem is particularly important in transformations involving azlactones (also known as oxazolones). − These heterocycles are basically protected and cyclic amino acids bearing a very acidic hydrogen (p K a ≈ 9) in their scaffolds, which leads to fast racemization. Our research group has been extensively studying the reactivity of azlactones in various transformations − including racemic amide formation through the azlactone ring-opening reaction, and recently we have been interested in the development of an epimerization-free methodology to synthesize these cycles.…”

Theoretical Study on the Epimerization of Azlactone Rings: Keto–Enol Tautomerism or Base-Mediated Racemization?

“…Recently, our research group has been studying the reactivity of oxazolones in various transformations, − including alternatives for amino acid derivative formation, avoiding an azlactone intermediate and thereby the racemization process . Nevertheless, we have been curious about the epimerization process.…”