Catalytic Synthesis of β~3-Amino Acid Derivatives from α-Amino Acids

摘要

The synthesis of β-amino acids and their derivatives has garnered considerable interest over the past decades. These one-carbon homologues of α-amino acids are vital components of several pharmaceutics and have important roles in medicinal chemistry and biochemistry. Pioneering work by Seebach et al. and Gellman et al. has revealed that incorporating β-amino acids into peptide chains induces new secondary and tertiary structures and leads to biological activity in select cases,. Central to all of these applications is the use of stereochemically pure β-amino acids, and recently reported enantioselective routes include Mannich reactions, Kowalsky rearrangements, radical reactions, isoxazoline intermediates, organocatalysis, and enzymatic hydrolysis of β-lactams. The use of transition-metal catalysis shows promise for the generation of enantiomerically pure β-amino acid derivatives and current research focuses on asymmetric hydrogenation reactions using Rh catalysts, Classic synthetic methods such as the Arndt-Eistert protocol work well for the β-amino acids, but the hazardous nature of diazomethane and high cost of silver render it undesirable for large-scale synthesis.