衍生化环糊精键合固定相对N-苄氧甲酰基-α-氨基膦 酸酯化合物色谱保留和手 性识别机理的研究

正相条件下,一系列N-苄氧甲酰基-α-氨基膦酸二苯酯化合物首次在苯基氨基甲酸酯衍生化β环糊精键合硅胶固定相上实现了高效液相色谱手性拆分,结合热力学模型,对手性分离过程的热力学行为进行了讨论。探索运用定量结构-对映异构体选择性保留关系的方法,将对映异构体的色谱保留和溶质分子描述参数相关性闻系建立定量方程,从超热力学模型的角度研究了色谱保留和手性识别机理。     

Separation of chiral phosphorus compounds on the substituted β‐cyclodextrin stationary phase in normal‐phase liquid chromatography

The separation of enantiomers of a series of eighteen novel nitrogen mustard linked phosphoryl diamide derivatives was investigated on the prepared phenyl carbamate derivative β‐cyclodextrin bonded phase in normal‐phase HPLC. Some of the enantiomers could be separated in baseline. The chiral recognition mechanism was also suggested for the separation of chiral phosphorus organic compounds.     

A convenient synthesis of a permethyl-substituted β-cyclodextrin-containing polysiloxane stationary phase using an amide linking group

A novel amide-linked permethyl-substituted β-cyclodextrin-bound polysiloxane stationary phase was prepared in only four steps. First, mono(6-O-toluenesulfonyl)-β-cyclodextrin was treated with sodium azide. Second, the resulting azide derivative was treated with methyl iodide and base followed by reduction with hydrogen to give amine-substituted permethylcyclodextrin 3 . Third, cyclodextrin 3 was treated with p-(allyloxy)benzoyl chloride to form 6^A-(p-allyloxybenzamido)-substituted permethyl-β-cyclodextrin 4 . Lastly, β-cyclodextrin 4 was hydrosilylated onto a polysiloxane backbone containing hydrogen, methyl, and p-tolyl substituents. This new phase separated the enantiomers of certain chiral lactones and alcohols in capillary supercritical fluid chromatography.     

Stereoisomeric flavor compounds. Part LXV: Preparative resolution of the enantiomers of chiral dihydrofuranones by recycling chromatography

Preparative resolution of the enantiomers of several chiral dihydrofuranones, known to be important flavor compounds, has been achieved by combining the use of bonded β-cyclo-dextrin as chiral stationary phase with closed-loop recycling chromatography. The purity of the separated enantiomers has been determined by chirospecific capillary GC analysis, using heptakis(2,3-di-O-methyl-6-TBDMS)-β-cyclodextrin as the chiral stationary phase.     

Stereoisomeric flavor compounds,part LXI: Enantioselective analysis of aroma-relevant dihydrofuranones

The odor impression of the pure enantiomers of various chiral dihydrofuranones which are important flavor compounds has been evaluated by sniffing the well separated optical antipodes in the GC eluate from heptakis(2,3-di-O-methyl-6-TBDMS)-β-cyclodextrin as the chiral phase for capillary gas chromato-graphic separation. Liquid chromatographic separation has been achieved by the use of bonded β-cyclodextrin as the chiral stationary phase and methanol–water as eluent. Enantiomer separation in the latter was improved by addition of triethylammonium acetate to the eluent.     

Enantioselective resolution of chiral aromatic acids by biphasic recognition chiral extraction

This paper reports a new chiral separation technology—biphasic recognition chiral extraction for the separation of aromatic acid enantiomers such as α-cyclohexyl-mandelic acid (CHMA) and naproxen (NAP). The biphasic recognition chiral extraction system was established by adding hydrophobic d(l)-isobutyl tartrate in 1,2-dichloroethane organic phase and hydrophilic β-cyclodextrin (β-CD) derivative in aqueous phase, which preferentially recognize the (R)-enantiomer and (S)-enantiomer, respectively. These studies involve an enantioselective extraction in a biphasic system, where aromatic acid enantiomers form complexes with the β-cyclodextrin derivative in the aqueous phase and d(l)-isobutyl tartrate in the organic phase, respectively. Factors affecting the extraction mechanism are analyzed, namely the influence of the concentrations of the extractants and aromatic acid enantiomers, the types of the extractants, pH, and temperature. The experimental results show that the biphasic recognition chiral extraction is of much stronger chiral separation ability than the monophasic recognition chiral extraction, which utilizes the cooperations of the forces of the tartrate and the β-CD derivative. Hydroxypropyl-β-cyclodextrin (HP-β-CD), hydroxyethyl-β-cyclodextrin (HE-β-CD), and methyl-β-cyclodextrin (ME-β-CD) have stronger recognition abilities for the (S)-aromatic acid enantiomers than those for (R)-aromatic acid enantiomers, among which HP-β-CD has the strongest ability. d-Isobutyl tartrate preferentially recognizes (R)-CHMA and (S)-NAP, while l-isobutyl tartrate preferentially recognizes (S)-CHMA and (R)-NAP. The maximum enantioselectivities of CHMA and NAP are 2.49 and 1.65, under conditions at which the pH values of the aqueous phases are 2.7 and 2.5, at the ratio of 2:1 of [isobutyl tartrate] to [HP-β-CD].     

Cyclodextrins as chiral stationary phases in capillary gas chromatography. Part IV: Heptakis(2,3,6-tri-O-pentyl)-β-cyclodextrin

O-Perpentylated β-cyclodextrin has been evaluated as chiral stationary phase in capillary gas chromatography. Enantioselectivity is observed towards many chiral hydroxy compounds, including cyanohydrins and carbohydrates. Most importantly, the enantiomers of many olefins and alkyl halides can be resolved on this chiral phase. The thermal stability of the cyclodextrin derivative exceeds 200°C.     

Chromatographic properties in normal-mode HPLC of chiral stationary phases based on substituted β-cyclodextrins

Summary Substituted β-cyclodextrin chiral stationary phases having different types of phenyl carbamate substituents have been prepared and evaluated (retention, selectivity, resolution) for the liquid chromatographic separation of several series of enantiomers. The influence on separations of the degree of substitution and the structure of the substituent are discussed. Different mechanisms are suggested to explain separations in normal mode conditions.     

Gas chromatographic separation of chiral organochlorines on modified cyclodextrin phases and results of marine biota samples

Four chiral stationary phases containing modified cyclodextrines diluted in or chemically bonded to a non-chiral phase were used to resolve chiral organochlorine compounds such as α-hexachlorocyclohexane (α-HCH), perdeuterated α-HCH (α-PDHCH), β-and γ-pentachlorocyclohexene (PCCH), oxychlordane, cis-and trans-chlor- dane, cis- and trans-heptachlorepoxide, PCB 95, PCB 132, PCB 149, and Chiral tozaphenes. The elution order was determined by analyzing standards with known enantiomeric excesses. Furthermore, an internal standard was used to even out slight variations in the ratio of peak hights of enantiomers which were determined from injection to injection. None of the chiral stationary phases resolved all chiral organochlorine compounds. However, the β-TBDM(35% heptakis (6-O-t-butyldimethylsilyl-2,3-di-O-methyl)-β-cyclodextrin in OV 1701) column allowed the separation of all compounds under investigation except for PCB 95 and chiral toxaphenes. Emphasis was placed on the separation of as many as possible enantiomers on a chiral phase by application of one temperature program and with respect to unambiguous quantitation of biological samples such as bludder and liver of marine and terrestrial mammals.     

新型噻吩杂环衍生化β-环糊精手性固定相合成及其气相色谱分离性能

设计合成了新的噻吩杂环衍生化β-环糊精手性固定相2,6-二-O-戊基-3-O-[(2-甲酰基)-噻吩基]-β-CD, 研究了色谱分离性能. 结果表明, 该固定相对各类有机化合物, 特别是芳香族位置异构体及对映异构体有较好的分离能力, 并对含多手性中心的菊酸衍生物具有一定的分离效果, 显示了较强的立体选择能力.     

Cyclodextrins as chiral stationary phases in capillary gas chromatography. Part III: Hexakis(3-O-acetyl-2,6-di-O-pentyl)-α-cyclodextrin

The properties of hexakis(3-O-acetyl-2,6-di-O-pentyl)-α-cyclodextrin as a chiral stationary phase for capillary gas chromatography are described. For the first time the enantiomers of a series of different lactones are separated and their order of elution is assigned. Moreover, the enantiomers of trifluoroacetylated aldols and amino alcohols, the cyclic carbonates of 1,2-diols, 1,3-diols, O-alkylated glycerols, and some chiral pharmaceuticals are also separated on the new chiral phase. The modified α-cyclodextrin is stable above 200°C.     

正相条件下温度和流速对衍生化环糊精键合手性高效液相色谱固定相立体异构体选择性的影响

合成了苯基氨基甲酸酯衍生化的β-环糊精键合固定相,9个α-氨基膦酸酯类化合物首次在环糊精类固定相上进行了有效拆分,研究了温度和流速对异构体选择性的影响,讨论了可能的手性识别机理.     

The separation of the enantiomers of diquats by capillary electrophoresis using randomly sulfated cyclodextrins as chiral selectors

Diquats, derivatives of the widely used herbicide diquat, represent a new class of functional organic molecules. A combination of their special electrochemical properties and axial chirality could potentially result in their important applications in supramolecular chemistry, chiral catalysis, and chiral analysis. However, prior to their practical applications, the diquats have to be prepared in enantiomerically pure forms and the enantiomeric purity of their P- and M-isomers has to be checked. Hence, a chiral capillary electrophoresis (CE) method has been developed and applied for separation of P- and M-enantiomers of 11 new diquats. Fast and better than baseline CE separations of enantiomers of all 11 diquats within a short time 5–7 min were achieved using acidic buffer, 22 mM NaOH, 35 mM H₃PO₄, pH 2.5, as a background electrolyte, and 6 mM randomly sulfated α-, β-, and γ-cyclodextrins as chiral selectors. The most successful selector was sulfated γ-cyclodextrin, which baseline separated the enantiomers of all 11 diquats, followed by sulfated β-cyclodextrin and sulfated α-cyclodextrin, which baseline separated enantiomers of 10 and nine diquats, respectively. Using this method, a high enantiopurity degree of the isolated P- and M-enantiomers of three diquats with a defined absolute configuration was confirmed and their migration order was identified.     

Cyclodextrin carbamates as novel chiral stationary phases for capillary gas chromatography

The following carbamate derivatives of cyclodextrins (CDs) were prepared as novel chiral stationary phases for capillary gas chromatography: hexakis(2,6-di-O-pentyl)-α-cyclodextrin hexa(3-n-propyl, 3-isopropyl, and 3-phenylcarbamate), heptakis-(2,6-di-O-pentyl)-β-cyclodextrin hepta(3-n-propyl, 3-isopropyl, and 3-phenylcarbamate), and octakis(2,6-di-O-pentyl)-γ-cyclodextrin octa(3-n-propyl, 3-isopropyl, and 3-isopropyl, and 3-phenylcarbamate). Metal capillary columns coated with these stationary phases resolved many kinds of racemic mixture. In general, they were especially effective towards polar compounds such as free alcohols, amines, and epoxides. The types of sample which were effectively resolved depended on the cavity size of the CD: α-CD derivatives were specifically effective toward compounds having linear alkyl chains, and β-CD derivatives toward compounds with phenyl groups. The results indicate that chiral separation with the cyclodextrin carbamates depends on the formation of inclusion complexes and also on the hydrogen-bonding interactions between the samples and the CD carbamates.     

Novel β-cyclodextrin derivative functionalized polymethacrylate-based monolithic columns for enantioselective separation of ibuprofen and naproxen enantiomers in capillary electrochromatography

A novel enantioselective polymethacrylate-based monolithic column for capillary electrochromatography was prepared by ring-opening reaction of epoxy groups from poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith with a novel β-cyclodextrin derivative bearing 4-dimethylamino-1,8-naphthalimide functionalities. Conditions for the ring-opening reaction with respect to different reaction parameters were thoroughly optimized to obtain high electroosmotic flow, separation efficiency and enantioselectivity for the analytes. The nonaqueous mobile phase composition regarding acetonitrile–methanol ratio and the concentration of electrolyte were examined to manipulate the hydrophobic inclusion and anion-exchange interaction between the analytes and chiral stationary phase. It was observed that in addition to β-cyclodextrin cavity, the electrostatic interaction exhibited pronounced influence on the enantioseparation of acidic analytes. Acidic enantiomers (ibuprofen and naproxen) could be separated with separation factor (α) values up to 1.08 and a maximum separation efficiency of 86 000 plates/m could be achieved.     

七-(2,6-二-O-甲基)-β-环糊精对1,1'-联萘酚对映体手性识别的电喷雾质谱研究

利用电喷雾质谱研究了β-环糊精、七-(2,6-二-O-甲基)-β-环糊精作为手性识别试剂对1,1'-联萘酚对映体的手性识别效应. 实验结果表明, 在气相中, β-环糊精与七-(2,6-二-O-甲基)-β-环糊精都可以与联萘酚形成非共价复合物. 对形成的复合物的串联质谱研究表明, β-环糊精不能识别联萘酚对映体, 而七-(2,6-二-O-甲基)-β-环糊精对联萘酚对映体有较强的手性识别效应. 进一步研究表明七-(2,6-二-O-甲基)-β-环糊精与联萘酚对映体混合比例以及CID能量对于手性识别并无影响.     

High Performance Liquid Chromatographic Enantioresolution of Benzoyl Amino Acid,Dipeptides and Tripeptide on β-Cyclodextrin Bonded Stationary Phase Using Polar-Organic Acetonitrile as the Mobile Phase

The enantiomeric resolution of several dipeptides, amino acid (i.e., isoleucine) and tripeptide (i.e., Leu-Gly-Phe) with two stereogenic centers on β-cyclodextrin bonded chiral stationary phase (β-CD CSP) using polar-organic acetonitrile as the mobile phase is examined through pre-column chemical derivatization with a series of tagging reagents such as benzoyl chloride, benzenesulfonyl chloride and 1-naphthalenesulfonyl chloride. These tagging reagents are similar in structure; however, the enantioselectivity for the same analyte derivatized with these tagging reagents is quite different and found to be the best with benzoyl chloride. In the reversed-phase mode or on the γ-CD CSP under the same chromatographic conditions, the enantioresolution diminishes for all tagged enantiomers that were examined in this study. Dipeptides derivatized by benzoyl chloride appear to be better resolved than by dansyl chloride as reported previously. Interestingly, no enantioresolution for most derivatized amino acids with single stereogenic center was observed. Finally, enantioresolution can be enhanced by replacing the basic additive such as triethylamine with tripropylamine in the polar-organic mobile phase.     

New,selectively substituted cyclodextrins as stationary phases for the analysis of chiral constituents of essential oils

New β- and γ-cyclodextrin derivatives, selectively substituted with n-pentyl and methyl groups, e.g. heptakis(2,6-di-O-methyl-3-O-pentyl)-β-cyclodextrin, octakis(2-O-methyl-3,6-di-O-pentyl)-γ-cyclodextrin, and octakis(2,6-di-O-methyl-3-O-pentyl)-γ-cyclodextrin, have been prepared from specifically protected intermediates. The new cyclodextrin derivatives exhibit unique enantioselectivity towards important chiral constituents of essential oils. The enantiomers of lavandulol, α-bisabolol, nerolidol, and other terpenoid alcohols could be resolved and their presence in different essential oils could be proved. Methyl jasmonate and epi-methyl jasmonate could, in addition, be detected in jasmine concrete by two-dimensional gas chromatography. The enantiomers of the macrocyclic ketone muscone have been separated for the first time.     

Chiral stationary phase design: A study in optimization

A π-basic, brush-type chiral stationary phase (CSP) derived from (S)-N-(1-naphthyl)leucine undecenyl ester has been shown to effectively separate the enantiomers of a broad array of π-acidic analytes. Armed with a mechanistic hypothesis as to how this CSP differentiates between the enantiomers of π-acidic derivatives of α-amino acids, the structure of this CSP was modified in a series of steps, each intended to enhance the enantioselectivity of the CSP. Specifically, brush-type CSPs were prepared from N-(5-naphthyl)leucine di-n-propyl amide and from N-(5-acenaphthyl)leucine di-n-propyl amide. The latter selector was also incorporated into a polysiloxane, then coated and bonded to silica. The rationale for each of the structural changes, and its effect on the enantioselectivity of the resulting CSP is described.     

Development of a capillary electrophoretic method for determination of ketorolac enantiomers in human plasma using cationic β-cyclodextrin derivative as a chiral selector

A novel approach for the separation of ketorolac enantiomers by capillary electrophoresis is presented. A cationic β-cyclodextrin derivative based on imidazole was synthesized and used as a chiral selector in the background electrolyte. The influence of pH and ionic strength of background electrolyte, as well as cationic β-cyclodextrin derivative concentration on the resolution of ketorolac enantiomers, was investigated. The highest value of the resolution for ketorolac enantiomers was 1.46 when the background electrolyte consisted of 25 mM NaH₂PO₄ (pH 6.4) with 1 mM 1-butyl-3-β-cyclodextrinimidazolium tosylate. Additionally, the possibilities of cationic derivatives for the separation of ketoprofen enantiomers were shown (peak resolution 1.06). The two-step preconcentration mode was developed to reduce the limit of detection of individual enantiomers. The proposed approach was successfully applied to determine ketorolac enantiomers in tablet “Ketorol express” and human plasma. The calibration range of ketorolac enantiomers for plasma samples was 0.25–2.50 μg/ml with coefficients of determination ≥ 0.99. The relative standard deviation both of the peak area and migration time was less than 15%, as well as the accuracy ranged from 90.1% to 110.2% for both analytes. The limits of detection were 44 and 55 ng/ml for R- and S-ketorolac. The quantity of ketorolac in plasma was verified with high-performance liquid chromatography.