The role of π‐acidic and π‐basic chiral stationary phases in the high‐performance liquid chromatographic enantioseparation of unusual β‐amino acids

Abstract

The application of 3,5-dimethylphenyl-carbamoylated-beta-cyclodextrin (Cyclobond I 2000 DMP) and 2,6-dinitro-4-trifluoromethylphenyl-ether-beta-cyclodextrin-based (Cyclobond DNP) chiral stationary phases for the high-performance liquid chromatographic enantioseparation of unusual beta-amino acids is reported. The investigated amino acids were saturated or unsaturated alicyclic beta-3-homo-amino acids and bicyclic beta-amino acids. Prior to chromatographic analyses, all amino acids were transformed to N-3,5-dinitrobenzoyl- or N-3,5-dimethylbenzoyl form to ensure a pi-acidic or pi-basic function and to enhance the pi-acidic-pi-basic interactions between analytes and chiral selectors. Chromatographic results are given as retention, separation and resolution factors. The chromatographic conditions were varied to achieve optimal separation. The sequence of elution of the enantiomers was determined in some cases.

Recent advances in the direct and indirect liquid chromatographic enantioseparation of amino acids and related compounds: A review

“…The application of 3,5-dimethylphenyl-carbamoylated-␤-cyclodextrin (Cyclobond I 2000 DMP) and 2,6-dinitro-4-trifluoromethylphenyl-ether-␤-cyclodextrin-based (Cyclobond DNP) as CSPs for the HPLC enantioseparation of unusual ␤-amino acids is reported by Ilisz et al [46]. Prior to chromatographic analyses, all amino acids were transformed to N-3,5-dinitrobenzoyl-or N-3,5-dimethylbenzoyl form to ensure a -acidic or -basic function and to enhance the -acidic--basic interactions between analytes and chiral selectors.…”

Chiral Recognition Mechanism: Practical Considerations for Pharmaceutical Analysis of Chiral Compounds

“…Underivatized CD CSPs are mainly used in reversed-phase and polar organic modes, but less likely in normal-phase mode. It is common for aromatic compounds with multiple H-bonding sites to be separated on CD CSPs in both RP and POM [73,79,82]. In these cases, the U-shaped retention behavior is typically observed, i.e., the analytes are more strongly retained under high aqueous content and high organic content mobile phases.…”

“…Unlike hydrocarbon component in normal phase, it is much easier for carbon dioxide molecule in the CD cavity to be displaced by solute molecule due to its smaller size [85]. Derivatized CD CSPs such as (R)-and (S)-naphthylethylcarbamoylated-β-cyclodextrins (R-NEC-CD and S-NEC-CD) have been shown to be as effective in SFC as in three LC modes [82]. Since both SFC and NPLC share similar chiral recognition mechanisms on NEC-CD CSPs, the chiral separations obtained in NPLC could be easily reproduced in SFC with the same elution order of enantiomers.…”

“…They predominate as CSPs in the applications of chiral GC [66] and in CE as chiral run buffer additives [67]. Covalently bonded CDs are important CSPs for HPLC [68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] and SFC [83][84][85]. They have been successfully used to separate many pharmaceutical chiral compounds [69,73].…”

“…To promote π−π interaction, derivatized CD CSPs with aromatic substituents have been developed [76][77][78]82]. The aromatic groups can be π-electron rich (i.e., π-basic), such as naphthylethyl in the case of 1-(1-naphthyl)ethyl carbamoylated β-CDs [76,77] and dimethylphenyl in the case of 3,5-dimethylphenyl carbamoylated β-CD [82], or π-electron deficient (i.e., π-acidic), such as dinitrophenyl in the case of 2,6-dinitro-4-trifluoromethylphenyl ether-substituted β-cyclodextrin [78,79]. Furthermore, carbamate linkage can provide additional sites for H-bonding and dipole-dipole interactions.…”