Chiral high‐performance liquid and supercritical fluid chromatographic enantioseparations of limonene‐based bicyclic aminoalcohols and aminodiols on polysaccharide‐based chiral stationary phases

Abstract

Enantioseparation of limonene‐based bicyclic 1,3‐aminoalcohols and 1,3,5‐ and 1,3,6‐aminodiols was performed by normal‐phase high‐performance liquid chromatographic and supercritical fluid chromatographic (SFC) methods on polysaccharide‐based chiral stationary phases. The effects of the composition of the mobile phase, the column temperature and the structures of the analytes and chiral selectors on retention and selectivity were investigated by normal‐phase LC and SFC technique. Thermodynamic parameters derived from selectivity–temperature‐dependence studies were found to be dependent on the chromatographic method applied, the nature of the chiral selector and the structural details of the analytes. Enantiorecognition in most cases was enthalpically driven but an unusual temperature behavior was also observed: decreased retention times were accompanied by improved separation factors with increasing temperature, i.e. some entropically driven separations were also observed. The elution sequence was determined in all cases. The separation of the stereoisomers was optimized in both chromatographic modalities.

Subcritical Fluid Chromatography at Sub-Ambient Temperatures for the Chiral Resolution of Ketamine Metabolites with Rapid-Onset Antidepressant Effects

“…Although SFC separations on the latter CSP have been reported [35,36,37], to the best of our knowledge this is the first comparison involving i-Amylose-3. Our results suggest halogen- and hydrogen-bonding to be significant for chiral recognition of chlorinated analytes such as K and its metabolites on chlorinated polysaccharide-based CSPs, which is supported by previous observations concerning achiral chemo-selectivity of halogenated analytes on Amylose-2 [38].…”

“…Contrary to previous reports of peaks narrowing as temperature rises [22], we observed better peak shapes and chiral resolution as temperature declined with the best performance at sub-ambient temperatures (15 °C). Method development for SFC methods generally entails the screening of temperatures from 25–60 °C [39] and sometimes ambient temperatures [37,40], however, sub-ambient temperature working conditions, here tentatively termed SubFC, proved superior in the case of analytes that otherwise resisted chiral resolution (K). Indeed, while higher temperatures are known to affect the chiral recognition ability of polymeric CSPs through the induction of—often irreversible—conformational changes [41], lower temperatures may increase the rigidity of the polysaccharide back bone resulting in higher accessibility to the chiral ravines, within which enantio-selective hydrogen bonding is responsible for chiral recognition [42].…”

Polysaccharide- and β-Cyclodextrin-Based Chiral Selectors for Enantiomer Resolution: Recent Developments and Applications

“…A method for the ES of limonene-based bicyclic 1,3-aminoalcohols and 1,3,5- and 1,3,6-aminodiols was reported by Orosz et al [ 38 ]. Different types of commercial chiral columns were employed, namely, Lux ® Cellulose-2, Lux ® Cellulose-3, Lux ® Cellulose-4, Lux ® i-Cellulose-5 ( Table 1 ), Lux ® Amylose-1, Lux ® Amylose-2 (250 × 4.6 mm i.d., 5 μm silica gel for all the columns) ( Table 2 ) and Lux ® Cellulose-1 (250 × 4.6 mm i.d., 3 μm silica gel) ( Table 1 ), under normal-phase HPLC and SFC conditions.…”

Enantioselective Separations Based on High-performance Liquid Chromatography

“…hexane, heptane) and alcohol (e.g. propan-2-ol) in NP mode can be a good choice as starting mobile phase for a polysaccharide-based CSP [5]. Polysaccharide-based columns recently commercialized can also be applied under reversed phase conditions, but it is important to note that varying the chromatographic modes may result in extended equilibration times upon change of mobile phases and reduction of the observed efficiency.…”