Synthesis Of Chiral Selectors And Their Application In Capillary Zone Electrophoresis

In recent years, capillary electrophoresis (CE) has become one of the rapid development branch of chiral analysis due to its unique features, such as simplification, high efficiency, sensitiveness, trace consumption of sample, solvent and chiral selectors. CE has been widely used in life science, chemistry and pharmaceutical sciences, especially in chiral resolution and analysis of pharmaceutical and biomacromolecule. In CE chiral separation, the chiral selector is usually dissolved in the running buffer to provide chiral environment. The difference of the interactions between chiral selectors and enantiomers leads to the difference of electrophoretic mobilities, so the two enantiomers can be separated.In this thesis, four chiral selectors have been synthesized and used in CE for the resolution of chiral vicinal diols, chiral secondary aromatic alcohols and amino acids derivatives, respectively. Moreover, the mechanism of chiral resolution has been discussed.This thesis mainly focuses on four aspects as follows:1. A new access was improved to synthesis of 1,4-bis (9-O-quininyl) phthalazine [(QN)2PHAL], a very useful chiral ligand for catalytic asymmetric dihydroxyl- ation (AD), by using CaH₂ as acid-binding reagent in a high yield under mild conditions. The application of (QN)2PHAL to the AD reactions of eight olefins exhibited excellent enantioselectivity and activity with corresponding chiral vicinal diols. Furthermore, a capillary zone electrophoresis (CZE) method was developed to separate the synthetic chiral vicinal diols by using neutralβ-cyclodextrin(β-CD)as chiral selector and borate as running buffer. High resolution was achieved under the optimal conditions (β-CD 2.2% (w/v), pH 10, 200 mmol·L^-1 borate buffer at 15 kV and 20℃within 15 min). The relative standard deviations of the corrected peak areas and migration time were less than 3.9% and 1.3%, respectively. In addition, the developed method was successfully applied to the determination of the purity and the enantiomeric excesses value (%ee) of the AD reaction products.2. Two new kinds of cationic amino-β-cyclodextrin chiral selector (β-CDen andβ-CDdien) have been prepared via modification of C6-β-cyclodextrin. The synthetic method to prepare intermediate (6-OTs-β-CD) was also improved in higher yield and simpler procedure.β-CDen andβ-CDdien were obtained by the reaction of 6-OTs-β-CD and ethylenediamine or diethylenetriamine in the presence of trace ammount of DMAP, and the chemical yields was 50.3% and 51.6%, respectively. Furthermore, these new chiral selectors were successfully applied for capillary electrophoresis separations of enantiomers of eight vicinal diols. To our delight, these new chiral selectors have achieved good results in chiral separation. The chiral recognition ability is superior to the naturalβ-neutral cyclodextrin, especially for the terminal chiral vicinal diols, showing greater chiral recognition. High resolution was achieved under the optimized conditions ofβ-CDen 10mmol·L^-1, pH 10, 200 mmol·L^-1 borate buffer at 15 kV and 20℃. In addition, the established method was successfully applied to the determination of the enantiomeric excesses value (%ee) of the AD reaction products. It was also found that the results of the CE analysis was in accordance with that of HPLC, which indicates that the proposed method is suitable for the determination of %ee value of the vicinal diols samples.3. A new CE method was developed to efficiently separate seven chiral secondary aromatic alcohols by using S-β-CD as chiral selector. Under the optimal conditions, the baseline separation of the enantiomers of secondary aromatic alcohols was obtained. In addition, the established method was successfully applied to the determination of the enantiomeric excesses value (%ee) of products of asymmetric transfer hydrogenation reactions. It was found that the results of determination by the CE analysis were in accordance with that by GC and HPLC.4. (2S,3S)-(+)-2,3-O-isopropylidene-l,4-tetramethylenediamine was synthesized in six steps from (2R,3R)-tartaric acid via esterification, hydroxyl protection, reduction, and MsCl esterification, azide reaction, and catalytic hydrogenation. Furthermore, two kinds of new cationic chiral amine-β-cyclodextrin chiral selector, which was used to enantioseparate the anionic chiral compounds, were synthesized from (1R,2R)-(-)-1,2-diaminocyclohexane and (2S,3S)-(+)-2,3-O- isopropylidene-l,4-tetramethylenediamine by introducing two chiral centre in C6 ofβ-CD, respectively. Furthermore, a CE method was established to separate 10 Dns-amino acids and N-acetylphenylalanine by using above-mentioned synthetic aminoderivatives ofβ-CD as chiral selector and phosphate as running buffer. Excellent enantiomeric separation was obtained under the optimal conditions (chiral selector 10mmol·L^-1, pH 6.5, 20 mmol·L^-1 Na2HPO4-NaH₂PO4 buffer at 15 kV and 20℃). Moreover, satisfactory enantioseparation was also achieved for the mixed samples of four amino acids under the optimal conditions.