Rui-Qi Gao's research while affiliated with South China Normal University and other places

Menthol has been widely used in pharmaceuticals, food industry, oral health care products, cosmetic industry, and tobacco products, and its HPLC chiral separation has been less reported till now. Herein, a simple and direct method has been developed for separation of menthol by normal-phase HPLC coupled with refractive index detector and/or optical rotation detector, in which special sample pretreatment and derivatization were not required. The effects of chiral stationary phases, alcoholic modifiers, column temperature, and injection amount were studied in detail. The amylose tris(3,5-dimethylphenylcarbamate)-coated chiral stationary phase showed the best separation performance for menthol with the resolution of 2.84. Through the optical rotation detector, (+)-menthol was first eluted on the amylose-based chiral stationary phase in the hexane-2-propanol mixture, but later eluted on the cellulose-derived chiral stationary phases in the same mobile phase. In addition, retention and resolution of menthol displayed an upward trend along with the content of 2-propanol and column temperature reduction. Chiral separation of menthol could be attributed to an enthalpically driven process, since ΔΔH (− 3.04 kJ mol− 1) and ΔΔS* (− 8.57 J mol− 1 K− 1) for two enantiomers were negative in the experimental temperature range. Moreover, the limits of detection and quantitation for the menthol enantiomers with the refractive index detector were similar to the optical rotation detector. These results would provide useful information for direct resolution for chiral compounds without typical chromophoric groups. Graphical abstract Open image in new window

Resolution of chiral compounds has played an important role in the pharmaceutical field, involving detailed studies of pharmacokinetics, physiological, toxicological, and metabolic activities of enantiomers. Herein, a reliable method by high-performance liquid chromatography (HPLC) coupled with an optical rotation detector was developed to separate isoborneol enantiomers. A cellulose tris(3, 5-dimethylphenylcarbamate)-coated chiral stationary phase showed the best separation performance for isoborneol enantiomers in the normal phase among four polysaccharide chiral packings. The effects of alcoholic modifiers and column temperature were studied in detail. Resolution of the isoborneol racemate displayed a downward trend along with an increase in the content of ethanol and column temperature, indicating that less ethanol in the mobile phase and lower temperature were favorable to this process. Moreover, two isoborneol enantiomers were obtained via a semipreparative chiral HPLC technique under optimum conditions, and further characterized by analytical HPLC, and experimental and calculated vibrational circular dichroism (VCD) spectroscopy, respectively. The solution VCD spectrum of the first-eluted component was consistent with the Density Functional Theory (DFT) calculated pattern based on the SSS configuration, indicating that this enantiomer should be (1S, 2S, 4S)-(+)-isoborneol. Briefly, these results have provided reliable information to establish a method for analysis, preparative separation, and absolute configuration of chiral compounds without typical chromophoric groups.