1. Enantiomeric resolution, thermodynamic parameters, and modeling of clausenamidone and neoclausenamidone on polysaccharide-based chiral stationary phases
- Author
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Xuna Luo, Fang Chengqiao, Jingzi Xu, Hansen Lin, and Junru Mi
- Subjects
Pharmacology ,Detection limit ,010405 organic chemistry ,Chemistry ,Elution ,Hydrogen bond ,Organic Chemistry ,Analytical chemistry ,010402 general chemistry ,01 natural sciences ,High-performance liquid chromatography ,Catalysis ,0104 chemical sciences ,Analytical Chemistry ,Chiral column chromatography ,Docking (molecular) ,Drug Discovery ,Enantiomer ,Enantiomeric excess ,Spectroscopy - Abstract
The aim of the paper is to describe a new synthesis route to obtain synthetic optically active clausenamidone and neoclausenamidone and then use high-performance liquid chromatography (HPLC) to determine the optical purities of these isomers. In the process, we investigated the different chromatographic conditions so as to provide the best separation method. At the same time, a thermodynamic study and molecular simulations were also carried out to validate the experimental results; a brief probe into the separation mechanism was also performed. Two chiral stationary phases (CSPs) were compared with separate the enantiomers. Elution was conducted in the organic mode with n-hexane and iso-propanol (IPA) (80/20 v/v) as the mobile phases; the enantiomeric excess (ee) values of the synthetic R-clausenamidone and S-clausenamidone and R-neoclausenamidone and S- neoclausenamidone were higher than 99.9%, and the enantiomeric ratio (er) values of these isomers were 100:0. Enantioselectivity and resolution (α and Rs, respectively) levels with values ranging from 1.03 to 1.99 and from 1.54 to 17.51, respectively, were achieved. The limits of detection and quantitation were 3.6 to 12.0 and 12.0 to 40.0 ug/mL, respectively. In addition, the thermodynamics study showed that the result of the mechanism of chiral separation was enthalpically controlled at a temperature ranging from 288.15 to 308.15 K. Furthermore, docking modeling showed that the hydrogen bonds and π-π interactions were the major forces for chiral separation. The present chiral HPLC method will be used for the enantiomeric resolution of the clausenamidone derivatives.
- Published
- 2018