Chiral discrimination of α-hydroxy acids and N-Ts-α-amino acids induced by tetraaza macrocyclic chiral solvating agents by using¹H NMR spectroscopy

Abstract

In the field of chiral recognition, reported chiral discrimination by 1H NMR spectroscopy has mainly focused on various chiral analytes with a single chiral center, regarded as standard chiral substrates to evaluate chiral discriminating abilities of a chiral auxiliary. Among them, chiral α-hydroxy acids, α-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 α-hydroxy acids and N-Ts-α-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 α-hydroxy acids and N-Ts-α-amino acids were successfully discriminated in the presence of TAMCSAs 1a–1d by 1H NMR spectroscopy in most cases. Assignmnent of enantiomers of the α-hydroxy acids and N-Ts-α-amino acids were determined based on the change of integration of the 1H NMR signals of the corresponding protons. Enantiomeric excesses (ee) of N-Ts-α-amino acids 11 with different optical compositions were calculated based on the integration of the 1H NMR signals of the CH3 protons (Ts group) of 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 Job plots of (±)-2 with TAMCSAs 1b and proposed theoretical models of enantiomers of 2 and 6 with TAMCSA 1a, respectively.

The robust, readily available cobalt(iii) trication [Co(NH2CHPhCHPhNH2)3]3+ is a progenitor of broadly applicable chirality and prochirality sensing agents

“…Crystal structures have been reported for analyte adducts of only a few other CSAs. 22 , 24 Alternatively, insight can be gained by computational studies, 22 , 23 , 26 – 28 and a series of DFT investigations are currently underway.…”

“… 17 – 30 Many but not all of the CSAs are hydrogen bond donors, often with two-four NH or OH groups. 17 , 21 , 22 , 25 – 28 , 30 Some of these have been tailored to recognize a specific functional group, 19 , 23 , 24 , 26 – 28 while others have wider applicability. 17 , 20 – 22 , 25 , 29 , 30 …”

A New Chirally Organized Trifluoromethylanthrylmethanol Derivative and Its Application as Chiral Solvating Agent

“…The enantiomeric excess determination by NMR using a CSA is an easy, fast, and economically available methodology . Based on the formation of the corresponding diastereoisomeric complexes by addition of variable quantities of CSA to a chiral mixture, it allows determining the enantiomeric composition by the simple integration of the split signals.…”

Detection and Chiral Recognition of α‐Hydroxyl Acid through 1H and CEST NMR Spectroscopy Using a Ytterbium Macrocyclic Complex

“…As one of the most important chiral agents, α‐hydroxyl acids are frequently used in natural product synthesis and are also involved in asymmetrical synthetic steps . The present methods to recognize α‐hydroxyl acids are mostly through fluorescence, proton NMR spectroscopy and circular dichroism using a chiral solvent agent and all of them are performed in organic solvents . Until now, there is no report for α‐hydroxyl acid sensing in aqueous solution.…”