Design Of Chiral Dipyridoxine Catalyst And Its Application In Asymmetric Bionic

Amino acids are a class of very important organic compounds and exist widely in various natural products, drugs, and proteins. Although chemists have invented many methods for the synthesis of amino acids, development of new and efficient methodologies to access chiral α-amino acids are still highly desirable. Asymmetric transamination of α-keto acids, especially vitamin-B6-based biomimetic asymmetric transamination, not only may provide useful information for understanding the biological process, but also represents a highly attractive and straight strategy to synthesize optically active amino acids. In this thesis, we focused on chiral-pyridoxamine-catalyzed asymmetric biomimetic transamination of α-keto acids. The studies include the following several respects.(1) A series of axially chiral biaryl pyridoxamines bearing a lateral amine chain has been developed via multiple-step synthesis. The biaryl skeleton was chosen because the catalyst may adjust its configuration by rotating around the axial axis to meet the different structural requirements of the transition states involved in the transamination. The purpose for the introduction of the lateral amine chain is to imitate the function of the Lys residue in transaminases.(2) With the obtained chiral pyridoxamines as the catalyst, reaction parameters including solvent, the amount of water, concentration, additive, and temperature were systematically investigated to get the optimal conditions for the asymmetric transamination.(3) Under the established optimal conditions, reaction scope was then examined with the chiral pyridoxamines as the catalyst. A variety of α-keto acids were smoothly transaminated to give the corresponding α-amino acids in good yields with excellent ee’s.(4) A reasonable mechanism and a transition state mode have been proposed for understanding the transamination pathway and the origin of the chirality, respectively. A plausible explanation also has been provided for the interesting and remarkable impact of the lateral amine chain on the transamination.