Highly diastereoselective Michael addition reactions between nucleophilic glycine equivalents and β-substituted-α,β-unsaturated carboxylic acid derivatives; a general approach to sterically χ-constrained α-amino acids

Michael addition reactions between nucleophilic glycine equivalents and alpha,beta-unsaturated carboxylic acid derivatives, represent the most methodologically concise and generalized approach to the family of chi-constrained five-carbon-atom amino acids. Such amino acids are of critical importance in the de novo peptide design and for elucidation of peptide/protein three-dimensional structure and its biological function/activity. This review summarizes all of the synthetically and methodologically important achievements in the field published to date. The review consists of two major parts summarizing the literature methods and the author's own results on the development of highly diastereoselective, organic base-catalyzed room temperature Michael addition reactions. Discussion on each particular method includes highlighting of the synthetic opportunities and limitations, practicality and efficiency of the procedures and mechanistic rational of the observed stereochemical preferences.