Liquid chromatographic enantioseparation of limonene‐based carbocyclic β‐amino acids on zwitterionic Cinchona alkaloid‐based chiral stationary phases

Abstract

The eight stereoisomers of limonene-based carbocyclic β-amino acids containing three chiral centers have been directly separated on chiral stationary phases containing Cinchona alkaloid-based zwitterionic selectors. The effects of bulk solvent composition of the mobile phase, the nature of base additives, counterion concentration, and the structure of selector on the enantiorecognition were studied. Experiments were performed at constant mobile phase composition in the temperature range 5-40°C to study the effect of temperature. Thermodynamic parameters were calculated on the basis of the plots of ln α versus 1/T curves. The enthalpically or entropically driven enantioseparations were found to depend strongly on the structures of analyte and selector. The eight stereoisomers of limonene-based carbocyclic β-amino acids could be differentiated as well-separated peaks in a traditional 1D chromatographic system in two runs by applying the two complementary ZWIX(+)™ and ZWIX(-)™ columns.

Liquid chromatographic enantiomer separations applying chiral ion-exchangers based on Cinchona alkaloids

“…According to the data in Table S3, Table S3, the decrease in k and the concomitant increase in α with increasing temperature were observed in most cases on QN-based ZWIX(+) CSP. However, a similar behavior was obtained on QD-based ZWIX(-) CSP for ß 2 -amino acids [104], 2-aminocyclopentanecarboxylic acid [105,108], a methyl-substituted isoxazoline-fused aminocyclopentanecarboxylic acid analog [103] and for two pairs of limonene-based carbocyclic β-amino acids [109]. should be noted that changes in elution sequence with temperature change are rarely observed for enantioseparation [130][131][132][133][134], especially in liquid chromatography applications.…”

“…No significant variation of the chromatographic parameters could be observed with the change of the acid type (AcOH or FA). Regarding the influence of acid and base additives on the elution strength, in general, quite similar results were obtained for secondary amino acids[98], tetrahydroisoquinoline analogs[88], ß 2 -amino acids[99], monoterpene-based 2-aminocarboxylic acids[101] and limonene-based carbocyclic ßamino acids[109]. NH3 exhibited the highest, while TEA the lowest elution strength, and the acid applied (AcOH or FA) had only a slight effect on retention.…”

“…log c gives a linear relationship, where the slope of the straight line is proportional to the effective charge involved in the ion-exchange process. Several articles discuss the validity of the simple displacement model for anion-exchangers[14,30,39,44,51,69,80] and for zwitterionic phases[42,52,53,80,97,[105][106][107][108][109][110][111]120]. The slope of log k vs. log c generally varies in the A C C E P T E D M A N U S C R I P T range (-0.3)-(-1.2) and (-0.1)-(-0.8) for anion-exchangers and zwitterionic CSPs, respectively.…”

Preparation and evaluation of a deoxycholic‐calix[4]arene hybrid‐type receptor as a chiral stationary phase for HPLC

“…The detection and separation of enantiomers in racemic mixtures is of great importance for scientists, as each enantiomer in a racemic mixture may show different toxicity, as well as different behavior in biological systems. Among various available analytical techniques for this purpose, HPLC seems to be the most popular and the most efficient technique to analyze racemic mixtures and to obtain enantiopure compounds . New HPLC chiral stationary phases (CSPs) with high chiral recognition for the separation of chiral molecules with varying structural properties are being introduced every day .…”

“…The detection and separation of enantiomers in racemic mixtures is of great importance for scientists, as each enantiomer in a racemic mixture may show different toxicity, as well as different behavior in biological systems. Among various available analytical techniques for this purpose, HPLC seems to be the most popular and the most efficient technique to analyze racemic mixtures and to obtain enantiopure compounds [1][2][3][4][5]. New HPLC chiral stationary phases (CSPs) with high chiral recognition for the separation of chiral molecules with varying structural properties are being introduced every Abbreviations: AIBN, Azobisisobutyronitrile; CSP, chiral stationary phase; DCM, dichloromethane; DEA, diethylamine; DNB-DL-leucine, N-(3,5-dinitrobenzoyl)-DL-leucine; DNB-DL-valine, N-(3,5-dinitrobenzoyl)-DL-valine; DNB, N- (3,5-dinitrobenzoyl); EtOH, ethanol; HOAc, acetic acid; IPA, 2-propanol; MeOH, methanol; TFA, trifluoroacetic acid; THF, tetrahydrofuran Conflict of interest: The authors have declared no conflict of interest.…”