College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China.
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310032, China.
J Chromatogr A. 2021 Jan 25;1637:461804. doi: 10.1016/j.chroma.2020.461804. Epub 2020 Dec 16.
2-(3-Methylphenyl)propanic acid and 2-(4-methylphenyl)propanoic acid were successfully enantioseparated by countercurrent chromatography using hydroxypropyl-β-cyclodextrin (HP-β-CD) as a chiral selector. 2-(2-Methylphenyl)propanoic acid was also studied to compare the enantioseparation ability of three isomeric 2-(methylphenyl)propanoic acids. Totally 20 mg of 2-(3-methylphenyl)propanic acid and 20mg of 2-(4-methylphenyl)propanic acid were enantioseparated individually by countercurrent chromatography. Recovery for the (±)-2-(3-methylphenyl)propanic acid enantiomer was in the range of 85%-90% with 98.0%-98.8% purity and recovery for the (±)-2-(4-methylphenyl)propanic acid enantiomer was in the range of 80%-83% with 97.0%-98.0% purity. The enantioseparation factor in countercurrent chromatography for 2-(4-methylphenyl)propanic acid and 2-(3-methylphenyl)propanic acid were 1.31 and 1.26, and the peak resolution in HPLC reached 2.2 and 1.4. However, no enantioseparation could be found for 2-(2-methylphenyl)propanic acid. In addition, the inclusion complexes were investigated by UV spectrophotometer. The inclusion formation constant of inclusion complex between 2-(4-methylphenyl)propanic acid, 2-(3-methylphenyl)propanic acid, 2-(2-methylphenyl)propanic acid and HP-β-CD were determined as 121.73 mol/L, 78.12 mol/L and 53.18 mol/L, respectively. The present results showed that enantiorecognition was greatly affected by substituted positions of methyl group on the benzene ring. Combined with our previous results, the steric hindrance had a significant effect on inclusion interaction between HP-β-CD and racemic 2-(substitutedphenyl)propanoic acids. No enantiorecognition could be achieved for 2-(substitutedphenyl)propanoic acids with ortho-substituent group on benzene, while the influence of meta- and para- group on enantiorecognition varies with different substituent groups on benzene ring.
2-(3-甲基苯基)丙酸和 2-(4-甲基苯基)丙酸成功地通过逆流色谱法用羟丙基-β-环糊精（HP-β-CD）作为手性选择剂进行对映体分离。还研究了 2-(2-甲基苯基)丙酸，以比较三种 2-(甲基苯基)丙酸的对映体分离能力。通过逆流色谱法分别对 20mg 2-(3-甲基苯基)丙酸和 20mg 2-(4-甲基苯基)丙酸进行对映体拆分。（±）-2-(3-甲基苯基)丙酸对映体的回收率在 85%-90%之间，纯度在 98.0%-98.8%之间，（±）-2-(4-甲基苯基)丙酸对映体的回收率在 80%-83%之间，纯度在 97.0%-98.0%之间。2-(4-甲基苯基)丙酸和 2-(3-甲基苯基)丙酸在逆流色谱中的对映体分离因子分别为 1.31 和 1.26，HPLC 中的峰分离度分别达到 2.2 和 1.4。然而，2-(2-甲基苯基)丙酸没有对映体分离。此外，还通过紫外分光光度计研究了包合物。2-(4-甲基苯基)丙酸、2-(3-甲基苯基)丙酸和 2-(2-甲基苯基)丙酸与 HP-β-CD 形成包合物的包合形成常数分别为 121.73、78.12 和 53.18mol/L。结果表明，对映体识别受苯环上甲基取代位置的影响很大。结合我们以前的结果，空间位阻对 HP-β-CD 与外消旋 2-(取代苯基)丙酸之间的包合相互作用有显著影响。苯环上邻位取代基的 2-(取代苯基)丙酸不能获得对映体识别，而间位和对位取代基对对映体识别的影响随苯环上不同取代基而变化。
