Chiral discrimination of α-hydroxy acids and N-Ts-α-amino acids induced by tetraaza macrocyclic chiral solvating agents by using 1H NMR spectroscopy

In the field of chiral recognition, reported chiral discrimination by H-1 NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate the chiral discriminating abilities of a chiral auxiliary. Among them, chiral alpha-hydroxy acids, a-amino acids and their derivatives are chiral organic molecules involved in a wide variety of biological processes, and also play an important role in the area of preparation of pharmaceuticals, as they are part of the synthetic process in the production of chiral drug intermediates and protein-based drugs. In this paper, several alpha-hydroxy acids and N-Ts-alpha-amino acids were used to evaluate the chiral discriminating abilities of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a-1d by 1H NMR spectroscopy. The results indicate that alpha-hydroxy acids and N-Ts-alpha-amino acids were successfully discriminated in the presence of TAMCSAs 1a-1d by H-1 NMR spectroscopy in most cases. The enantiomers of the alpha-hydroxy acids and N-Ts-alpha-amino acids were assigned based on the change of integration of the H-1 NMR signals of the corresponding protons. The enantiomeric excesses (ee) of N-Ts-alpha-amino acids 11 with different optical compositions were calculated based on the integration of the H-1 NMR signals of the CH3 protons (Ts group) of the enantiomers of (R)- and (S)-11 in the presence of TAMCSA 1b. At the same time, the possible chiral discriminating behaviors have been discussed by means of the Job plots of (+/-)-2 with TAMCSAs 1b and proposed theoretical models of the enantiomers of 2 and 6 with TAMCSA 1a, respectively.