Click Preparation Of Functional Phenylcarbamoylated β-cyclodextrin Chiral Stationary Phase And Their Application For Enantiomer Separations

With humanbeing’s ever-increasing understanding on the effect of chirality of drugs on their pharmacological behaviors, chiral drugs separation have attracted great attention. High performance liquid chromatography (HPLC) has been widely used in the purity analysis and preparation of chiral drugs, due to its fast analysis, high loading and sensitivity. By taking advantage of the recognition ability of cyclodextrins (CDs), a large library of CD-based chiral stationary phases (CSPs) has been developed, which have exhibited great potential application in chromatography. In this dissertation, two perphenylcarbamoylated β-CD-based CSPs have been prepared via click reaction, the enantioseparation ability of the CSPs has been further evaluated with their packed columns. The column performance and enantiomeric separation ability of these CSPs were explored in HPLC under different modes.By varying the position of electron-withdrawing group (chloro) and electron-donating group (methyl) on phenyl ring, two perphenylcarbamoylated CDs were developed from 6A-azido-β-CD, their subsequent clicking onto alknyl silica gel has afforded the CSPs, namely, per-4-chloro-3-methylphenylcarbamoylated β-CD clicked CSP (CSP1) and per-5-chloro-2-methylphenylcarbamoylated β-CD clicked CSP (CSP2).The accuracy, precision and linear relationship of chromatographic columns with 3’-hydroxyflavanone as model compound was evaluated under both reversed-phase (RP) and normal-phase (NP) mode HPLC. The enantioseparation of 29 aryl alcohols and aromatic amine, flavanoids, adrenergic drugs and FMOC-amino acids were conducted under both modes. The results revealed that enantioseparations ability in RP-HPLC was better than NP-HPLC, and CSP1 could afford better chiral separations than CSP2. CSP1 can baseline separate 16 racemates, with chiral resolutions (Rs) over 4.0 obtained for 5 flavonoids in RP-HPLC, the Rs of 3’-hydroxyflavanone can reach 8.69, and 4 flavonoids can obtain Rs of 4.0 in NP-HPLC. However, CSP2 can only resolve 5 flavonoids and 1 FMOC-amino acids, with the Rs of only 2.8 achieved for 3’-hydroxyflavanone.Based on chromatographic results, the separation mechanisms of CSPs were revealed. The enantioseparation was achieved by the intermolecular interaction between functionalities of β-CD and racemate on the basis of inclusion complexes under RP-HPLC. But under NP-HPLC, inclusion complexation was absent due to the prevailing inclusion of weak polar solvent inside β-CD’s cavity, the intermolecular interaction was considered as the main driving force for enantioseparation. FMOC-amino acids can not be resolved in two CSPs under NP-HPLC, but it can be resolved in RP-HPLC. The position of substitutes of perphenylcarbamoylated CDs can make great effect on the chiral separation ability. The meta-and para-disubstituted on phenyl ring were found to enhance enantiomeric separation ability of CSP1, while ortho-and meto -disubstituted on phenyl ring would weaken this ability of CSP2.