The complete enantioseparations of eight aromatic amino acids and four alkyl esters of 2-phenylglycine were achieved by chiral capillary electrophoresis employing 20 mM Tris-citric acid background electrolyte (pH 2.50) containing 5.0 mM of (+)-18-crown-6-tetracarboxylic acid. The relative migration times (RMTs) to that of 6-aminonicotinic acid were characteristic of each enantiomer with good within-day precisions (% relative standard deviation (RSD) < or = 2.0). Quantitative structure-property relationship (QSPR) modeling based on comparative molecular field analysis (CoMFA) was performed to investigate the correlation between the molecular field descriptor values of each enantiomer studied as analyte and its RMT. The resulting CoMFA model allowed reliable prediction for the RMT values (q2= 0.406, r2 = 0.996), thus being expected to become a valuable tool to predict enantiomer migration orders (EMOs) of amino acids and amines whose pure enantiomers are unavailable. The CoMFA steric fields supported the well-established chiral recognition mechanism based on molecular interaction between chiral selector (+)-18-crown-6-tetracarboxylic acid and amino acid enantiomers.

This study describes the enantioseparation of three chiral amines as naphthaldimine derivatives, using normal phase HPLC with amylose and cellulose tris(3,5‐dimethylphenylcarbamate) chiral stationary phases (CSPs). Three chiral amines were derivatized using three structurally similar naphthaldehyde derivatizing agents, and the enantioselectivity of the CSPs toward the derivatives was examined. The degree of enantioseparation and resolution was affected by the amylose or cellulose‐derived CSPs and aromatic moieties as well as a kind of chiral amine. Especially, efficient enantiomer separation was observed for 2‐hydroxynapthaldimine derivatives on cellulose‐derived CSPs. Molecular docking studies of three naphthaldimine derivatives of leucinol on cellulose tris(3,5‐dimethylphenylcarbamate) were performed to estimate the binding energies and conformations of the CSP–analyte complexes. The obtained binding energies were in good agreement with the experimentally determined enantioseparation and elution order.

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Abstract:1) The chromatographic enantiomer separation of 9-anthraldimine derivatives of α-amino acid methyl and ethyl esters on four polysaccharide based chiral columns was performed. The 9-anthraldehyde Schiff base derivatives of α-amino acid esters were readily synthesized by stirring the α-amino acid ester hydrochloride salts with 9-anthraldehyde in the presence of 1,8-diazabicyclo [5.4.0]undec-7-ene as a base and anhydrous MgSO 4 . Chiralcel OD or Chiralcel OD-H showed the greatest enantiomer resolution of 9-anthraldimine derivatives of α-amino acid methyl and ethyl esters. The L-enantiomers of all the analytes were preferentially retained on Chiralcel OD or Chiralcel OD-H. This analytical method was applied in the determination of optical purities of several commercially available D-or L-α-amino acid methyl esters.

Simultaneous analysis of several β-blockers using a novel dual chiral selector system was achieved for their accurate chiral discrimination by chiral capillary electrophoresis (CE) in normal polarity mode. The CE system was operated using heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) dissolved in 100 mM phosphoric acid-triethanolamine buffer (pH 3) and (+)-or (−)-18-crown-6-tetracarboxylic acid (18-C-6-TA) as a co-chiral selector in DM-β-CD solution. All eight investigated analytes were resolved using (+)-18-C-6-TA as a co-chiral selector in the presence of DM-β-CD solution, whereas the other β-blockers, except propranolol, were resolved using (−)-18-C-6-TA as the second chiral selector in DM-β-CD solution. Also, DM-β-CD had a major effect on chiral discrimination compared with 18-C-6-TA as a co-chiral selector. Relative migration times to that of (S)-pindolol as an internal standard were characteristic of each enantiomer with good precision. The method showed good linearity with a correlation coefficient (r ≥ 0.993). The precision as a percentage of relative standard deviation (% RSD) and accuracy as a percentage of relative error (% RE) ranged from 0.5 to 9.6 and from −5.7 to 9.1, respectively. These were adequate for the chiral assay of the β-blockers investigated. Thus, the present chiral profiling method is expected to be useful for accurate chiral discrimination and optical purity tests of chiral β-blockers and their related drugs.