High-Performance Liquid Chromatographic Enantioseparation of Cyclic ß-Amino Acids on Zwitterionic Chiral Stationary Phases Based on Cinchona Alkaloids.

Stereoselective high-performance liquid chromatographic separations of eight sterically constrained cyclic ß-amino acid enantiomer pairs were carried out using the newly developed Cinchona alkaloid-based zwitterionic chiral stationary phases Chiralpak ZWIX(+) and ZWIX(-). The effects of the mobile phase composition, the nature and concentrations of the acid and base additives, the counterions and temperature on the separations were investigated. The changes in standard enthalpy, Δ(ΔH°), entropy, Δ(ΔS°), and free energy, Δ(ΔG°), were calculated from the linear van't Hoff plots derived from the ln α vs. 1/T curves in the studied temperature range (10-50°C). The values of the thermodynamic parameters depended on the nature of the selectors and the structures of the analytes. Unusual temperature behavior was observed on the ZWIX(-) column: decreased retention times were accompanied by increased separation factors with increasing temperature. On the ZWIX(+) column only enthalpically, whereas on the ZWIX(-) column both enthalpically and entropically driven separations were observed. The elution sequence was determined in all cases and was observed to be the opposite on ZWIX(+) and on ZWIX(-).

Investigation of the structure-selectivity relationships and van't Hoff analysis of chromatographic stereoisomer separations of unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids on Cinchona alkaloid-based chiral stationary phases.

The enantiomers of four unusual, rather rigid isoxazoline-fused 2-aminocyclopentanecarboxylic acids were directly separated on a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector. The effects of the mobile phase composition, the structures of the analytes and temperature on the separations were investigated. Experiments were performed at constant mobile phase composition in the temperature range 10-50°C to study the effects of temperature, and thermodynamic parameters were calculated from plots of ln α versus 1/T. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. It was found that the enantiomer separations were in most cases predominantly enthalpy-driven, but entropically-driven separations were also observed. The sequence of elution of the enantiomers was determined in all cases.

High-performance liquid chromatographic enantioseparation of amino alcohol analogues possessing 1,2,3,4-tetrahydroisoquinoline skeleton on polysaccharide-based chiral stationary phases.

The stereoisomers of 1,2,3,4-tetrahydroisoquinoline amino alcohol analogues and derivatives thereof were separated in normal-phase mode on chiral stationary phases based on preprepared silica coated with cellulose tris-(3,5-dimethylphenyl carbamate), cellulose tris-(3-chloro-4-methylphenyl carbamate), cellulose tris-(4-methylbenzoate) or cellulose tris-(4-chloro-3-methylphenyl carbamate). On all the investigated chiral columns, the retention and the enantioseparation were influenced by the nature and the concentrations of the mobile phase components and additives, and also the temperature. Experiments were performed in the temperature range 10-50°C. Thermodynamic parameters were calculated from plots of lnα vs 1/T. On these polysaccharide-based chiral columns, both enthalpy-driven separations and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. The sequence of elution of the stereoisomers was determined in all cases.

Direct high-performance liquid chromatographic enantioseparation of secondary amino acids on Cinchona alkaloid-based chiral zwitterionic stationary phases. Unusual temperature behavior.

Two chiral stationary phases containing a quinine- or a quinidine-based zwitterionic ion-exchanger as chiral selector were applied for the enantioseparation of 27 unusual cyclic secondary α-amino acids. The effects of the nature and concentration of the bulk solvent, the acid and base additives, the structures of the analytes and temperature on the enantioresolution were investigated. To study the effects of temperature and to obtain thermodynamic parameters, experiments were carried out at constant mobile phase compositions in the temperature range -5 to 55 °C. The thermodynamic parameters indicated that in most cases the separations were enthalpy-driven, but some entropy-driven separations were also observed. The sequence of elution of the enantiomers was determined in most cases.

Unusual temperature-induced retention behavior of constrained ß-amino acid enantiomers on the zwitterionic chiral stationary phases ZWIX(+) and ZWIX(-).

The effects of temperature on the chiral recognition of cyclic ß-amino acid enantiomers on zwitterionic [Chiralpak ZWIX(+) and ZWIX(-)] chiral stationary phases were investigated. Experiments were performed at different mobile phase compositions and under 10°C column temperature increments in the temperature range 10-50°C. Apparent thermodynamic parameters and T(iso) values were calculated from plots of ln k and ln α versus 1/T, respectively. Unusual temperature behavior was observed, especially on the ZWIX(-) column, where the application of MeOH/MeCN (50/50 v/v) containing 25 mM triethylamine and 50 mM formic acid as mobile phase led to nonlinear van't Hoff plots and increasing retention time with increasing temperature. On both columns, both enthalpically and entropically driven separations were observed.

Effect of mobile phase composition on the liquid chromatographic enantioseparation of bulky monoterpene-based ß-amino acids by applying chiral stationary phases based on Cinchona alkaloid.

Stereoselective HPLC separations of five sterically constrained monoterpene-based 2-aminocarboxylic acid enantiomers were carried out by using the newly developed zwitterionic chiral stationary phases Chiralpak ZWIX(+)™ and ZWIX(-)™ based on Cinchona alkaloid. In order to optimize the retention and enantioselectivity parameters, the ratio of the different organic solvents in the mobile phase and the nature of the acid and base additives (counter- and co-ions) were systematically varied. The effects of structure variants of the analytes on the resolution were investigated. The elution sequence was determined in all cases and observed to be opposite on ZWIX(+)™ and ZWIX(-)™.

High-performance liquid chromatographic enantioseparation of naphthol-substituted tetrahydroisoquinolines on polysaccharide-based chiral stationary phases.

The stereoisomers of 15 naphthol-substituted tetrahydroisoquinoline analogs were separated on chiral stationary phases containing the chiral selectors cellulose tris-(3,5-dimethylphenyl carbamate) (Cellulose 1), cellulose tris-(3-chloro-4-methylphenyl carbamate) (Cellulose 2), cellulose tris-(4-methylbenzoate) (Cellulose 3) and cellulose tris-(4-chloro-3-methylphenyl carbamate) (Cellulose 4). Experiments were performed in normal-phase mode with n-heptane(n-hexane)-alcohol-diethylamine mobile phases in the temperature range 5-40 °C. Thermodynamic parameters were calculated from plots of lnk or lnα vs 1/T. On the Cellulose 1 column, Δ(ΔH°) ranged from -6.8 to 5.9 kJ/mol, Δ(ΔS°) from -16.7 to 21.0 J/mol/K and the Gibbs energy, -Δ(ΔG°) from 0.2 to 1.5 kJ/mol; on the Cellulose 2 column, Δ(ΔH°) ranged from -7.8 to 2.5 kJ/mol, Δ(ΔS°) from -16.1 to 13.2 J/mol/K and - Δ(ΔG°) from 0.7 to 3.0 kJ/mol. Both enthalpy- and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature.

High-performance liquid chromatographic enantioseparation of isoxazoline-fused 2-aminocyclopentanecarboxylic acids on a chiral ligand-exchange stationary phase.

The application of a chiral ligand-exchange column for the direct high-performance liquid chromatographic enantioseparation of unusual ß-amino acids with a sodium N-((R)-2-hydroxy-1-phenylethyl)-N-undecylaminoacetate-Cu(II) complex as chiral selector is reported. The investigated amino acids were isoxazoline-fused 2-aminocyclopentanecarboxylic acid analogs. The chromatographic conditions were varied to achieve optimal separation. The effects of temperature were studied at constant mobile phase compositions in the temperature range 5-45°C, and thermodynamic parameters were calculated from plots of lnk or lnα versus 1/T. Δ(ΔH°) ranged from -2.3 to 2.2 kJ/mol, Δ(ΔS°) from -3.0 to 7.8 J mol(-1) K(-1) and -Δ(ΔG°) from 0.1 to 1.7 kJ/mol, and both enthalpy- and entropy-controlled enantioseparations were observed. The latter was advantageous with regard to the shorter retention and greater selectivity at high temperature. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes. The sequence of elution of the enantiomers was determined in all cases.

High-performance liquid chromatographic enantioseparation of unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid-based chiral stationary phases.

The enantiomers of four unusual isoxazoline-fused 2-aminocyclopentanecarboxylic acids were directly separated on chiral stationary phases containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as chiral selector. The nature of the alcoholic modifier (MeOH, EtOH, IPA) exerted a great effect on the retention, whereas the selectivity and resolution did not change substantially. Two types of dependence of retention on alcohol content were detected: k(1) increased continuously with increasing alcohol content or a U-shaped retention curve was observed. A comparison of the chromatographic data obtained with HCOOH, AcOH, TFA, HClO(4), H(2)SO(4), or H(3)PO(4) as acidic modifier at a constant concentration demonstrated that in most cases, larger k values were obtained on the application of AcOH or HCOOH, and an increase of the acid content resulted in a decrease of retention. Some mechanistic aspects of the chiral recognition process are discussed with respect to the structures of the analytes and selector. The sequence of elution of the enantiomers was determined in all cases.