The Application Of Capillary Electrophoresis In The Separation And Analysis Of Chiral Aromatic Alcohols And Benzopyran Compounds

Research purposes: This study selected simple and efficient CZE methods, used CDs as chiral selectors, and the CZE experimental conditions were optimized, finally established 8 kinds of neutral CDs-CZE models for separation and analysis of enantiomers of 11 neutral cis-1,2-diols, then chiral recognition mechanism was explored, which may be the foundation of the study of CZE analysis method of cis-1,2-diols enantiomers. The subject also established charged CDs-CZE models to separate and analyze enantiomers of 6 neutral diaryl methanols which are the products of the RCAA reaction and 7 neutral 3-nitro-2H-benzopyrans which are the products of the domino oxa-Michael-Henry reaction, and then CDs-CZE models were appiled to determine ee % values of these chiral compounds. This research may help lay a foundation for the analysis of optical purity about the above chiral compounds, and provide reliable reference for evaluating stereoselectivity of chiral ligands in asymmetric catalytic reactions.Methods: In the research of chiral recognition mechanism of cis-1,2-diol, the procedures were carried out in uncoated fused silica capillary column(48.7 cm × 75 μm i.d., the effective length: 38.5 cm), and used CZE model with diode array detector. Under the CZE conditions: p H 10.0, 200 mmol·L-1 borate buffer as the background electrolyte, 15 k V voltage, and 20 ?C temperature, 8 neutral CDs as chiral selectors, including netural CDs(α-CD, β-CD, γ-CD) or netural β-CD derivatives(HP-β-CD, HE-β-CD, M-β-CD, DM-β-CD and TM-β-CD). Migration behavior of enantiomers of 11 neutral chiral cis-1,2-diols under these 8 CDs-CZE models was explored in depth, and summarized the parameters which impact on the migration behavior, subsequently discussed the possible chiral recognition mechanism. In addition, the CZE conditions were optimized when α-CD or HE-β-CD used as chiral selectors respectively.In the separation and analysis of chiral diaryl methanols, using boric acid buffer as the background electrolyte, CM-β-CD as chiral selector. The CM-β-CD-CZE method was established by optimizing of p H and concentration of boric acid buffer, CM-β-CD concentration, operating voltage and column temperature, and the enantiomers optical purity(ee % values) were tested under the CZE conditions, then compared the data with results detected by HPLC to evaluate the accuracy of the estblished CM-β-CD-CZE method.In the separation and analysis of chiral 3-nitro-2H-benzopyrans, using phosphate buffer as the background electrolyte, HS-β-CD as chiral selector. The efficient HS-β-CD-CZE method was established by optimizing CZE conditions of p H and concentration of phosphate buffer, HS-β-CD concentration, operating voltage and column temperature, and the ee % values were tested, then compared the ee % values with results detected by HPLC to evaluate the accuracy of the established HS-β-CD-CZE method.Results and conclusions: In the research of chiral recognition mechanism of cis-1,2-diol, from the structural analysis of CDs, CDs size and its free hydroxyls are approved to play an important role in separating enantiomers of cis-1,2-diol. If CDs molecules cavity structure matched the cis-1,2-diol molecular size, host-guest inclusion compounds would be formed more easily; CDs cavity edge has free hydroxyl, and their chiral separation ability would be improved with the increased number of free hydroxyl. From the structural analysis of cis-1,2-diol, with more numbers of the chiral centre and substituted group on di-hydroxyls chain in the cis-1,2-diol molecules, the opportunity of them entering into the CD hydrophobic cavity to form CD-1,2-diol complex compounds were increases, enantiomers are separated more easily, and the values of Rs are higher. Besides that, through optimizing CZE conditions, α-CD and HE-β-CD were shown to be the good candidates for the separation of the tested 1,2-diols. Enantiomers of cis-1,2-diol(Ⅰ-Ⅵ) and(Ⅰ-Ⅷ) reached the baseline separation(Rs>1.5) by using the two CDs as chiral selector respectively, enlarging the selection range of netural CDs when CZE model was used to separate enantiomers of cis-1,2-diol.In the established CD-CZE analysis method of chiral diaryl methanols, the CZE conditions were determined: using p H 10.0, 150 mmol·L-1 borate buffer as BGE, 14 mg·m L-1 CM-β-CD as chiral selector, capillary temperature 20 ?C, applied voltage 15 k V. The enantiomers of 6 diaryl methanols reached baseline separation under the optimum CZE conditions. The method can be used for determination of ee % values, which were consistent with the results tested by HPLC, showed that established CM-β-CD-CZE method to dectect optical purity of chiral diaryl methanols is accurate and reliable. Therefore, the CM-β-CD-CZE method can provide some references for evaluating the stereoselectivity of the chiral ligands in the RCAA reaction.In the established CD-CZE analysis method of chiral 3-nitro-2H-benzopyrans, employing the reverse voltage mode, under the conditions of p H 2.8, 30 mmol·L-1 phosphate buffer, 7 mg·m L-1 HS-β-CD capillary temperature 20 ?C, applied voltage-15 k V, enantiomers of 7 chiral 3-nitro-2H-benzopyrans were separated. Under the established CZE method, the determination of ee % values of samples, which agree with the results tested by HPLC, showed that established HS-β-CD-CZE method to dectect optical purity of chiral 3-nitro-2H-benzopyrans is accurate and reliable. Therefore, the HS-β-CD-CZE method can provide some references for evaluating the stereoselectivity of the chiral ligands in domino oxa-Michael–Henry reaction.