Asymmetric Synthesis of α-Deuterated α-Amino Acids through Nonenzymatic Transamination Reaction and the Determination of Their Enantiomeric Excesses

Article abstract of DOI:10.1246/bcsj.56.3652

Optically active α-deuterated α-amino acids were prepared in methanol-d through Zn²⁺-catalyzed transamination reaction between the chiral pyridoxamine analogs, (R)- or (S)-15-aminomethyl-14-hydroxy-5,5-dimethyl-2,8-dithia<9>(2,5)pyridinophane and various α-keto acids with enantiomeric excesses ranging from 40 to 94percent.Aliphatic α-keto acids gave α-deuterated α-amino acids, whereas aromatic ones possessing a methylene group between the carbonyl group (ketone) and the aromatic ring underwent concomitant deuterium substitution at the active methylene group to give the amino acids deuterated at both α- and β-positions of the carbonyl group.The use of the (S)-pyridoxamine analog gave the (R)-deuterated α-amino acids in excess and vice versa.The enantiomeric excesses of the amino acids were determined through the analyses of 1H NMR spectra of the Schiff bases produced by the condensation of the amino acids with the chiral pyridoxal analog, (R)- or (S)-15-formyl-14-hydroxy-2,8-dithia<9>(2,5)pyridinophane.The azomethine protons of the diastereomeric Schiff bases were clearly resolved in the spectrum and their intensities well reflected the amount of the diastereomers.