Separation of α-cyclohexylmandelic acid enantiomers using biphasic chiral recognition high-speed counter-current chromatography

Abstract

This work concentrates on a novel chiral separation technology named biphasic recognition applied to resolution of α-cyclohexylmandelic acid enantiomers by high-speed counter-current chromatography (HSCCC). The biphasic chiral recognition HSCCC was performed by adding lipophilic (−)-2-ethylhexyl tartrate in the organic stationary phase and hydrophilic hydroxypropyl-β-cyclodextrin in the aqueous mobile phase, which preferentially recognized the (−)-enantiomer and (+)-enantiomer, respectively. The two-phase solvent system composed of n-hexane-methyl tert-butyl ether-water (9:1:10, v/v/v) with the above chiral selectors was selected according to the partition coefficient and separation factor of the target enantiomers. Various parameters involved in the chiral separation were investigated, namely the types of the chiral selector (CS); the concentration of each chiral selector; pH of the mobile phase; and the separation temperature. The mechanism involved in this biphasic recognition chiral separation by HSCCC was discussed. Langmuirian isotherm was employed to estimate the loading limits for each chiral selector. The overall experimental results show that the HSCCC separation of enantiomer based on biphasic recognition is much more efficient than the traditional monophasic recognition chiral separation, since it utilizes the cooperation of both lipophilic and hydrophilic chiral selectors.

Enantioseparation of phenylsuccinic acid by high speed counter-current chromatography using hydroxypropyl-β-cyclodextrin as chiral selector

“…(9). As for the same two-phase solvent systems with different elution mode and the same HSCCC apparatus, the separation factor, theoretical plates and retention of stationary phase would be almost identical.…”

“…Another reason is the difficulty of finding suitable chiral selectors that are highly selective in the liquid phase of the two-phase solvent system that does not affect their selectivity and retains the capacity to elute chiral isomers of interest. Literatures about chiral separation using counter-current chromatography (CCC) and centrifugal partition chromatography (CPC) before 2001 had been reviewed [3] and totally 14 papers about chiral separation by CCC and CPC have been reported after 2001 [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. So far the following nine chiral selectors had been successfully applied in chiral separation by CCC and CPC: cinchona alkaloid derivatives [4,5], N-dodecanoyl-l-proline derivatives [3,6], ␤-cyclodextrin derivatives [3,[7][8][9][10], vancomycin [3], cellulose and amylose derivatives [11,12], (+)-(18-crown-6)-tetracarboxylic acid [13], tartaric acid derivatives [3,9,14], (S)-naproxen derivatives [15,16] and fluorinated chiral selectors [17].…”

Enantiomeric separation of (R, S)-naproxen by recycling high speed counter-current chromatography with hydroxypropyl-β-cyclodextrin as chiral selector

“…So far the following nine chiral selectors had been successfully applied in chiral separation by CCC and CPC: cinchona alkaloid derivatives [14,15], N-dodecanoyl-lproline derivatives [16,17], ␤-cyclodextrin derivatives [18][19][20][21], vancomycin [22], cellulose and amylose derivatives [23,24], (+)-(18-crown-6)-tetracarboxylic acid [25], tartaric acid derivatives [20,26,27], (S)-naproxen derivatives [28,29] and fluorinated chiral selectors [30]. In the present study, hydroxypropyl-␤-cyclodextrin (HP-␤-CD) was used as chiral selector for HSCCC separation of (R, S)-naproxen using recycling elution mode.…”

Chiral separation of α-cyclohexylmandelic acid enantiomers using ionic liquid/salt aqueous two-phase system

“…Many researchers have reported that HP-β-CD mainly exhibited chiral recognition ability and affinity for molecular α-CHMA (Tang et al, 2007b;Tong et al, 2010). To create an appropriate acidic environment, (NH 4 ) 2 SO 4 was chosen as the salting-out agent.…”

“…When the pH becomes higher, the corresponding α-CHMA anions can form a strong hydrogen bond with water. Though the accounts in the literature showed that HP-β-CD mainly exhibited an affinity for molecular α-CHMA (Tang et al, 2007b;Tong et al, 2010), herein the hydrogen bond might be the dominant driving force and caused the α-CHMA to be distributed mainly in the salt-rich phase. In view of the enantioselectivity of ILATPS, the pH of 4.36 was chosen for the following experiments.…”