2,3-di-O-methoxymethyl-6-O-tert-butyldimethylsilyl-gamma-cyclodextrin: a new class of cyclodextrin derivatives for gas chromatographic separation of enantiomers

Octakis(2,3-di-O-methoxymethyl-6-O-tert-butyldimethylsilyl)-gamma-cyclodextrin (2,3-MOM-6-TBDMS-gamma-CD) was employed as stationary phase for capillary gas chromatographic separation of enantiomers. Selective introduction of the acetal function at positions 2 and 3 of the glucose units was achieved by reaction of 6-O-TBDMS-gamma-cyclodextrin with methoxymethyl chloride. 2,3-MOM-6-TBDMS-gamma-CD was shown to be a chiral stationary phase suitable for enantiodifferentiation of a broad spectrum of chiral volatiles from various chemical classes. A total of 125 pairs of enantiomers could be separated. Structural influences of the analytes on the enantioseparation were demonstrated. High alpha values up to 1.8 were observed for the hydroxyketone acetoin and some methyl branched ketones. Pronounced enantioseparations were also determined for cyclic pentenolone and furanone derivatives.     

麦草伏甲酯对对映体的高效液相色谱分离

手性分离;麦草伏甲酯对对映体的高效液相色谱分离     

纤维素2,3-位和2,3,6-位苯基氨基甲酸酯手性固定相的选择性研究

合成了纤维素-2,3,6-三苯基氨基甲酸酯、纤维素-2,3-二苯基氨基甲酸酯、纤维素-2,3,6-三(3,5-二甲基苯基氨基甲酸酯)和纤维素-2,3-二(3,5-二甲基苯基氨基甲酸酯)4种纤维素衍生物手性固定相,用正己烷-异丙醇（体积比为9∶1）混合液作流动相,对9种手性化合物进行了高效液相色谱拆分。实验结果表明:对所测的9个样品,纤维素-2,3-二苯基氨基甲酸酯的手性选择性大大好于纤维素-2,3,6-三苯基氨基甲酸酯;而纤维素-2,3-二(3,5-二甲基苯基氨基甲酸酯)与纤维素-2,3,6-三(3,5-二甲基苯基氨基甲酸酯)的分离因子针对不同的对映体各有优点,但前者通常具有更小的保留因子,可以缩短一定的分析时间。     

High-performance liquid chromatographic enantioseparation of beta-3-homo-amino acid stereoisomers on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid-based chiral stationary phase

High-performance liquid chromatographic methods were developed for the separation of the enantiomers of thirteen unusual beta-3-homo-amino acids and three of its ethyl esters on a chiral stationary phase containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as chiral selector. The effects of the mobile phase composition and the acidic modifiers on the separation were investigated. The structures of the substituents in beta-position substantially influenced the retention and enantioseparation. The influence of ionic strength on the enantioseparation was established experimentally. The elution sequence was determined in all cases.     

高效液相色谱手性流动相添加法拆分奥昔布宁对映体

采用C18固定相,以羟丙基-β-环糊精为手性流动相添加剂,建立了奥昔布宁对映体的高效液相色谱拆分方法。考察了手性添加剂、有机极性调节剂、缓冲盐的种类和浓度以及流动相的pH值和流速及柱温等因素对对映体分离的影响。在最佳分离条件下,奥昔布宁对映体的分离度为1.54,检测限为1.0 ng。该方法简便,重复性好,比手性固定相法更加经济。     

新型键合纤维素手性固定相的制备及其拆分性能评价

键合型多糖手性固定相因具有化学稳定性高和溶剂耐受性好的特点而受到研究者的极大关注。采用施陶丁格（Staudinger）反应将6-叠氮-6-脱氧纤维素-3,5-二氯苯基氨基甲酸酯键合到氨丙基硅胶上得到一种新的键合型手性固定相（ImCel）,研究了其手性分离性能,并探讨了非常规流动相（如氯仿、四氢呋喃等）的影响。结果表明,在20对手性化合物中,17对在合适的流动相下得到基线分离。ImCel在正相条件下的分离性能优于反相条件,且在含氯仿的流动相中仍对手性化合物表现出良好的分离能力。在分离一系列芴甲氧羰基（fmoc）-氨基酸衍生物时,ImCel与键合6-叠氮-6-脱氧纤维素-3,5-二甲基苯基氨基甲酸酯的手性固定相表现出互补性,出现了固定相改变引起的对映体洗脱反转现象。本研究丰富了键合型多糖手性固定相的种类和合成方法,为开发新的键合型手性固定相提供了参考。     

High-performance liquid chromatographic enantioseparation of beta-amino acid stereoisomers on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid-based chiral stationary phase

Direct reversed-phase high-performance liquid chromatographic methods were developed for the separation of enantiomers of 14 unnatural beta-amino acids, including several beta-3-homo-amino acids on a chiral stationary phase containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid bonded to 3-aminopropyl silica gel as chiral selector. The effects of the organic and the acidic modifiers and the mobile phase composition on the separation were investigated. The natures and positions of the substituents on the aromatic ring substantially influenced the retention and enantioseparation. The elution sequence in most cases was determined and the R enantiomers were eluteted before the S enantiomers.     

Enantiomeric separation by capillary electrochromatography. II. Chiral separation of dansyl amino acids and phenoxy acid herbicides on sulfonated silica having surface-bound hydroxypropyl-beta-cyclodextrin

A chiral silica-based stationary phase having surface-bound hydroxypropyl-beta-cyclodextrin (HP-beta-CD) with a relatively strong electroosmotic flow (EOF) was introduced for enantioseparation by capillary electrochromatography (CEC). The stationary phase contained a hydrophilic sulfonated sublayer to which a chiral top layer of HP-beta-CD was immobilized. While the sulfonated sublayer was to provide a relatively strong EOF, the top HP-beta-CD was to confer the desired chiral recognition towards enantiomeric solutes. This HP-beta-CD sulfonated silica (CDSS) stationary phase proved useful for the rapid separation of anionic enantiomers such as dansyl amino acids and phenoxy acid herbicides. The effects of the organic modifier content, pH, and ionic strength of the mobile phase on enantioseparation were investigated. Under the optimized separation conditions, ten dansyl amino acids and six phenoxy acid herbicides were enantioseparated with a resolution greater than unity.     

万古霉素及其苯异氰酸酯衍生物手性固定相的制备与应用

采用"一锅法",以1,6-二异氰酸正己酯作间隔臂,制备了万古霉素及苯异氰酸酯衍生化的万古霉素手性固定相。对拉米夫定、拉米夫定的L-薄荷醇酯、酞胺哌啶酮和盐酸氟西汀进行了手性分离研究,在极性有机相模式下,研究了流动相甲醇中冰醋酸-三乙胺浓度和比例对手性分离的影响,观察到两种手性固定相具有不同的手性识别能力。在万古霉素手性固定相上4种溶质都获得了基线分离;在苯异氰酸酯衍生化的手性固定相上除盐酸氟西汀外也均获得基线分离。     

手性流动相添加剂法拆分西那卡塞原料及中间体

以自制1-萘万古霉素(Na-VAN)为手性固定相(CSP),D-酒石酸(D-Tar)、L-酒石酸二乙酯(L-TADE)、D-酒石酸二乙酯(D-TADE)分别为手性流动相添加剂(CMPA),建立了西那卡塞原料1-(1-萘基)乙胺(化合物1)及西那卡塞中间体(化合物2)的高效液相色谱手性拆分方法。考察了流动相中醇类改性剂、CMPA对对映体分离的影响,初步探讨了手性识别机理。以Na-VAN为CSP,正相模式下,添加不同种类的CMPA,化合物1、化合物2均可获得一定程度的分离,其中以D-TADE为CMPA时,化合物1、化合物2获得最佳分离。结果表明,醇的分子体积、CMPA的立体构型均对手性分离有影响。     

Enantioseparation and molecular modeling study of eight psychoactive drugs on a coated polysaccharide-based chiral stationary phase

The enantioseparation of eight psychoactive drugs has been firstly performed on a coated cellulose-based chiral stationary phase (Chiralcel OJ-H). To obtain optimum separation conditions, the influences of alcohol modifiers and basic/acidic additives have been studied. As a result, except for the partial separation of oxybutynin enantiomers, the other seven drug enantiomers, including mirtazapine, sulpiride, promethazine, citalopram, oxazepam, donepezil, and cyamemazine, have been completely separated. Additionally, for gaining a better insight into the chiral recognition mechanisms, molecular docking was carried out using the Autodock software. Herein, binding energy and conformations of the chiral stationary phase complexes were provided, and it was found that the distinction in enantiomeric conformation determined the number and strength of intermolecular interactions between analytes and chiral stationary phase which resulted in the difference in binding energies of two enantiomers, and ultimately led to the different migration. These modeling results were in accordance with the observed enantioseparation results in high performance liquid chromatography experiments. At last, chiral separation mechanisms have been discussed in detail, and it has been confirmed that hydrogen bond, π–π, hydrophobic interactions, and some special interactions synergistically contributed to the enantioseparation of psychoactive drugs.     

亚微米C18键合硅胶固定相加压毛细管电色谱法同时拆分3种手性三唑类农药

采用改良Stöber法制备420 nm亚微米单分散二氧化硅微球,采用C18硅烷化修饰后装填成毛细管色谱柱。采用该色谱柱,在加压毛细管电色谱平台上成功地实现了3对手性三唑类农药烯效唑、烯唑醇和丙环唑的同时拆分和分离。考察了各因素对手性分离效果的影响,优化后的色谱条件为：流动相为乙腈-20 mmol/L磷酸盐缓冲液（pH=6.8）（45：55,v/v）,其中缓冲液中含20 mmol/L羟丙基-γ-环糊精（HP-γ-CD）;泵流速为0.04 mL/min;施加电压-9.4 kV;检测波长220 nm。在上述条件下,烯效唑、烯唑醇和丙环唑3种对映体同时得到拆分和分离,相邻两峰之间的分离度依次为4.20、12.9、4.41、4.09、1.70,分离时间仅为12 min,柱效最高达到310000 plates/m。该研究为手性三唑类农药的同时分离提供了新的分离分析思路。     

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.     

手性离子液体和纤维素三(3,5-二甲基苯基氨基甲酸酯)混合气相色谱手性固定相研究

合成了手性离子液体[C7H17NO] [(CF3SO2)2]-和纤维素三(3,5-二甲基苯基氨基甲酸酯),将其混合作为气相色谱固定相。研究结果表明:该混合固定相麦氏常数的平均极性值为760;在容量因子大于2的前提下,新型柱的塔板数可达1680块/m;其对手性化合物、特别是对氨基酸类具有良好的分离效果。有10对氨基酸的分离因子大于1.10,展示了该类色谱柱良好的手性应用前景。     

Enantiomeric separation by capillary electrochromatography. I. Chiral separation of dansyl amino acids and organochlorine pesticides on a diol-silica dynamically coated with hydroxypropyl-beta-cyclodextrin

In this work, a commercially available diol-silica stationary phase was converted in situ to a chiral stationary phase by dynamically coating it with hydroxypropyl-beta-cyclodextrin (HP-beta-CD). This stationary phase was shown useful for the capillary electrochromatography (CEC) separation of neutral and anionic enantiomers such as some organochlorine pesticides and dansyl amino acids, respectively. The inclusion of HP-beta-CD in the mobile phase to produce the in situ chiral stationary phase allowed the rapid separation of the anionic dansyl amino acid enantiomers at relatively low electroosmotic flow (EOF). The formation of host-guest complexes between the dansyl amino acids and the neutral HP-beta-CD in the mobile phase lowered the actual charge-to-mass ratios of the anionic solutes, thus speeding up their transport by the EOF across the packed capillary column. Several parameters affecting enantioseparation were investigated, including the concentration of HP-beta-CD, ionic strength, pH, and organic modifier content of the mobile phase.     

The study of enantioseparation of zolmitriptan on vancomycin-bonded chiral stationary phase

In this study, the chiral stationary phase was prepared by bonding vancomycin to 5 microm spherical silica gel according to "one-pot" synthetic strategies, and used to separate the enantiomers of zolmitriptan under polar ionic mode. The influences of mobile phase composition, such as the concentration and ratio of glacial acetic acid (HOAc) and triethylamine (TEA), on the enantioseparation were investigated, and the chiral recognition mechanism is discussed. It was found experimentally that the retention factors were increased with the increase of the HOAc/TEA concentration in a certain extent, and the ionic interactions, hydrogen bondings, and steric interactions may play key role together. The method is suitable for baseline separation of zolmitriptan enantiomers.     

HPLC enantioseparation of β2‐homoamino acids using crown ether‐based chiral stationary phase

RP high‐performance liquid chromatographic methods were developed for the enantioseparation of eleven unusual β²‐homoamino acids. The underivatized analytes were separated on a chiral stationary phase containing (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid as chiral selector. The effects of organic (alcoholic) and acidic modifiers, the mobile phase composition and temperature on the separation were investigated. The structures of the substituents in the α‐position of the analytes substantially influenced the retention and resolution. The elution sequence was determined in some cases: the S enantiomers eluted before the R enantiomers.     

The Study of Separation and Thermodynamics of Adsorption of the Enantiomers of Ethofumasate on a Modified Cellulose

Abstract

Cellulose and cellulose derivatives are biopolymers that are often used as stationary phases for the separation of enantiomers. Describing the mechanism of such separations is a difficult task due to the complexity of these phases. In the present study, direct enantiomeric resolution of ethofumesate has been achieved, using hexane as the mobile phase with various alcoholic modifiers on cellulose tri(3,5‐dimethylphenylcarbamate) chiral stationary phase (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 the best enantioseparation using sec‐butanol as alcoholic modifier at 25°C with α‐value 1.70. And the separation factor decreased with the increase of the column temperature. The van't Hoff plots were linear (R ²>0.96) for ethofumesate from 25°C to 50°C. That showed the enantioselective interactions do not change over the temperature range studied. Furthermore the values of ΔH° and ΔS° were both negative, which indicated an enthalpy‐driven separation. And the possible chiral recognition mechanism of the analyte and CDMPC was discussed. It was found that hydrogen bonding plays an important role on enantioseparation of CDMPC CSP. The inclusion and fitness of solute shape in the chiral cavity significantly contributed to the enantioseparation of solute.     

Chiral metal-organic cages used as stationary phase for enantioseparations in capillary electrochromatography

Since some metal-organic cages (MOCs) have been synthesized in past several years, the applications of MOCs such as drug delivery, molecular recognition, separation, catalysis, and gas storage, etc. have been witnessed with a significant increase. However, to the best of our knowledge, so far no one has used MOCs as chiral stationary phase to separate chiral compounds in CEC. In this study, three MOCs were developed as the stationary phase for CEC separation of enantiomers. The MOCs coated capillary column showed good chiral recognition ability for some chiral compounds, including amine, alcohols, ketone, etc. The influence of buffer concentration, applied voltage, pH of buffer solution on the chiral separations was also investigated. The RSDs of run-to-run, day-to-day, and column-to-column for retention time were 2.1-4.67%, 1.2-4.36%, and 3.62-6.43%, respectively. This work reveals that the chiral MOCs material is feasible for the enantioseparation in CEC.     

Enantioseparation of vesamicol and novel vesamicol analogs by high-performance liquid chromatography on different chiral stationary phases

High-performance liquid chromatography enantioseparation of vesamicol and six novel azaspirovesamicols (amino alcohols) was accomplished on different chiral stationary phases (CSPs) by using an optical rotation based chiral detector for identification of the resolved enantiomers. The Pirkle-type column Reprosil Chiral-NR was found to be most suitable for chiral resolution in normal phase (NP) mode; all compounds could be enantioseparated successfully. Also the cellulose-based column Reprosil Chiral-OM showed appropriate separation properties by using NP conditions. The amylose-type column Reprosil Chiral-AM-RP was most suitable for enantioseparation in reversed phase (RP) mode; five out of seven compounds were resolved. This CSP showed a considerably higher capability for chiral recognition of vesamicol derivatives in RP mode than the corresponding cellulose-based column Reprosil Chiral-OM-RP. Enantioseparation with the teicoplanin aglycone-based column Reprosil Chiral-AA was successful under polar ionic mobile phase conditions.