Enantioselective Synthesis of α-Amino Acids by Chiral Phase-Transfer Catalysis

Abstract

α-Amino acids are the most important naturally occurring amino acids assembling into polypeptides with a wide range of vital biological functions, and hence the development of an efficient and reliable method for the preparation of optically active α-amino acids and their derivatives with sufficient structural diversity has been a field of considerable interest. Main purpose of this review is to illustrate the range of asymmetric approaches available for the laboratory preparation of optically active α-amino acids by using chiral phase-transfer catalysts. The key process is revealed to be stereoselective functionalization (alkylation, Michael addition, aldol reaction) of the Schiff base of α-amino acid esters including glycine tert-butyl ester with either cinchona alkaloid-derived quaternary ammonium salts or purely synthetic chiral ammonium salts as catalyst, providing a practical route to a variety of optically active α-alkyl-α-amino acids, α, α-dialkyl-α-amino acids and β-hydroxy-α-amino acids. In addition, highly stereoselective N-terminal alkylation of Schiff base-activated peptides by chiral phase-transfer catalysis is also described.