Mimicking enzymatic transaminations: attempts to understand and develop a catalytic asymmetric approach to chiral alpha-amino acids.
Attempts are made to build a bridge between asymmetric catalysis and enzymatic reactions by mechanistic investigations and the development of a catalytic and enantioselective approach to amination of alpha-keto esters by primary amines catalyzed by chiral Lewis acids as a model for transamination enzymes. Different Lewis acids can catalyze the half-transamination of alpha-keto esters using primary amine nitrogen sources such as pyridoxamine and 4-picolylamine. The mechanistic studies of the Lewis-acid catalyzed half-transamination using deuterium-labelled compounds show the incorporation of deuterium atoms in several positions of the alpha-amino acid derivative, indicating that the enol of the alpha-keto ester plays an important role along the reaction path. The catalytic enantioselective reactions are dependent on the pKa-value of the solvent since enantioselectivities were only obtained in solvents with high pKa-values relative to methanol. However, stronger acidic conditions generally gave better yields, but poor enantioselectivities. A series of chiral Lewis acids were screened as catalysts for the enantioselective half-transamination reactions and moderate yields and enantioselectivities of up to 46% ee were obtained.
Bachmann
Stephan
S
Danish National Research Foundation: Center for Catalysis, Department of Chemistry, Aarhus University, DK-8000 Aarhus C, Denmark.
Knudsen
Kristian Rahbek
KR
Jorgensen
Karl Anker
KA
D000586:Amination; D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000138:chemical synthesis*; D032701:Biomimetics; D002384:Catalysis; D004798:Enzymes / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D013237:Stereoisomerism
D000588:Amines; D000596:Amino Acids; D004798:Enzymes; D004952:Esters