ASYMMETRIC SYNTHESIS OF CHI-CONSTRAINED GLUTAMIC ACIDS AND RELATED COMPOUNDS VIA MICHAEL ADDITION REACTIONS

Michael addition reactions involving nucleophilic glycine equivalents and α,β-unsaturated carboxylic acid derivatives offer a concise and generalized methodological approach to synthesizing a family of χ-constrained five-carbon-atom amino acids. These amino acids play a crucial role in de novo peptide design and the elucidation of peptide/protein three-dimensional structures and their biological functions/activities. This review encapsulates the signi­ficant synthetic and methodological advancements in the field to date. Each method discussed includes an evaluation of synthetic opportunities and limitations, practicality and efficiency of the procedures, and mechanistic rationale behind the observed stereochemical preferences.