| Enantioseparation of a series of chiral compounds were investigated using chiral stationary phase (CSP) by high performance liquid chromatography (HPLC). The effects of composition of mobile phase, the structure of solute and the column temperature on chiral separation were extensively studied. The chiral recognition mechanism was discussed.In the chapter 1 and chapter 2, the literatures on chiral separation were briefly reviewed. The kinds of chiral stationary phase were introduced, especially Pirkle type CSPs, Cellulose derivation CSPs, tartaric acid CSPs and macrocyclic glycopeptide CSPs.In the chapter 3, the enantioseparation of 1-Phenyl-1-ethanol, 1-Phenyl propanol and 2-Phenyl-propionic acid methyl ester was studied on two different kinds of chiral columns—self-prepared cellulose CDMPC and Pirkle's type chiral stationary phase —(S,S)-Whelk-Ol, (R,R)-DNB-DPEDA chiral columns. There are no literatures searched about the enantioseparation of 1-Phenyl-1-ethano! and 1-Phenyl propanol on (S,S)-Whelk-Ol, (R,R)-DNB-DPEDA chiral columns. And as for 2-Phenyl-propionic acid methyl ester, it was enantioseparated for the first time on HPLC-CSP. The results indicated that on (S,S)-Whelk-Ol chiral column and (R,R)-DNB-DPEDA chiral column, the primary interaction is attraction between solute and stationary phase, while on CDMPC the inclusion is the dominant chiral recognition mechanism for the solutes, and the solute molecular volume size and its geometric shape must play a principle role in meeting the requirement for a stereoselective fit into the cellulose chiral cavity, which may be critical to the chiral recognition of these three solutes on CDMPC CSP. The hydrogen-bond interaction is not important for the chiral recognition. 1-Phenyl-1-ethanol and 1-Phenyl propanol gained best enantioseparation when the concentration of n-butanol was 0.39 mol L-1, while 2-Phenyl-propionic acid methyl ester could not be separated.In the chapter 4, the enantioseparation of a group of triazole fungicides and intermediate was studied: (1) The enantioseparation of hexaconazole, diniconazole, uniconazole, paclobutrazol and triadimenol on tartardiamide-DMB chiral stationary phase (CHI-DMB)was studied. The influence of the mobile phase composition including the type and concentration of the alcoholic modifier in hexane and the structures of the analytes on the chiral separation was studied. The chiral recognition mechanism between the analyte and CHI-DMB was also discussed. The resultsshowed the steric structure of solutes especially the environment of chiral carbon was the predominant factor for the enantioseparation. The mobile phase including the composition, the steric structure and the concentration of the alcoholic modifier also influenced the retention factor and the resolution greatly. Furthermore., the hydrogen-bonding, n-n interactions played an important role on enantioseparation on tartardiamide-DMB CSP. Among five triazole fungicides, diniconazole got best enantioseparation. The highest resolution was 3.04. That also indicated that solutes which connected with electron withdrawing group on aromatic ring or -O group on chiral carbon might be propitious to enantioseparation.(2)The enantioseparation of chloretherketone on (S,S)-Whelk-Ol. The effects of the column temperature, the type and concentration of the polar alcohol modifier on the chiral resolution were studied. Associated with the calculated thermodynamic parameters, the mechanism of chiral recognition was discussed . The results indicated that chloretherketone obtained good enantioseparation. The polarity alteration of mobile phase affects the nature of CSP discrimination. The stronger of the polarity of the mobile phase, the worse of enantioseparation. The temperature also influenced the chiral separation. And It was evident that the k'and the Rs decreased with the increase of the column temperature.In the chapter 5, it was reported the enantioseparation of Naproxen, Ketoprofen and Etodolac on tartardiamide-DMB chiral stationary phase ( CH1-DMB ) and (R,R) -DNB-DPEDA chiral stationary phase, using hexane as the mobile phase with various modifiers. The influence of the mobile phase composition including the type and concentration of the modifiers in hexane and the structures of the analytes on the chiral separation was studied. The results indicated that the steric structure of the solute, especially the environment of the chiral carbon, was the predominant factor for the chiral recognition. The type, the steric structure and the concentration of the modifiers also influenced the retention factor and the resolution. The chiral recognition mechanism of the analytes on CHI-DMB and (R,R) -DNB-DPEDA was also discussed. The hydrogen-bonding interaction played an important role on enantioseparation on CHI-DMB, so did the n-n interaction. On (R,R) -DNB-DPEDA the n-n interaction was the key for the solutes retention and enantioseparation, while hydrogen-bonding interaction was not important. Additionally, it has been demonstrated that enantioselectivity and retention was also dependentupon the nature and functional groups on the aromatic ring of solutes and CSP.In the chapter 6, the enantioseparation of propranolol, metoprolol, atenolol and bisoprolol fumarate was investigated on teicoplanin chiral stationary phase. Propranolol, metoprolol, atenolol, and bisoprolol fumarate all gained baseline enantioseparation on teicoplanin chiral stationary phase. The results showed the steric structure of solutes was the predominant factor for the enantioseparation. The mobile phase including the content of polar organic modifiers, the radio of acid and base, the type of polar organic and the temperature, the length of column also influenced the retention factor and the resolution greatly. Furthermore, the hydrogen-bonding, n-n interactions played an important role on enantioseparation on teicoplanin CSP. And It was evident that the separation factor decreased with the increase of the column temperature. The van't Hoff plots for a was linear (r1 > 0.99) for all P-blockers investigated from 20 to 50°C. That showed the enantioselective interactions did not change within the temperature range studied. Furthermore the values of AAH° and AAS° were both negative, which indicated an enthalpy-driven separation. In the chapter 7, direct enantiomeric resolution of ethofumesate has been achieved, using hexane as the mobile phase with various alcoholic modifiers on CDMPC CSP. The influence of the mobile phase composition and the column temperature on the chiral separation was studied. It was found that at a constant temperature and within a certain range of alcohol modifier concentration, the conformation of the polymeric phase, and the selective adsorption sites were not affected by alcohol modifier concentration, The type and the concentration of the alcoholic modifiers influenced the retention factor and the separation factor. Ethofumesate gained best enantioseparation using 2-butanol as alcoholic modifier at 25°C with a-value 1.70. And the separation factor decreased with the increase of the column temperature. The van't Hoff plots was linear (R2 > 0.96) for ethofumesate from 25 °C to 50 °C. That showed the enantioselective interactions do not change within the temperature range studied. Furthermore the values of A AH° and AAS° were both negative, which indicated an enthalpy-driven separation. And the possible chiral recognition mechanism of the analyte on CDMPC was discussed. It was found that the hydrogen-bonding played an important role on enantioseparation on CDMPC CSP. The inclusion and fitness of solute shape in the chiral cavity significantly contributed to the enantioseparation of solute. |
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