β-环糊精键合手性固定相分离苯并恶嗪类对映体

研究了在反相高效液相色谱模式下,基于点击化学的β-环糊精手性固定相对苯并恶嗪类对映体的手性分离情况。考察了流动相中有机改性剂的类型和比例、缓冲盐的浓度和pH值对分离的影响。考察结果表明: 乙腈作为有机改性剂比甲醇更有利于苯并恶嗪对映体的分离;乙酸三乙胺缓冲盐体积分数从0.1%增大到1.0%时,苯并恶嗪对映体的保留时间和分离度都随之减小,在pH 4.1时苯并恶嗪对映体具有最大分离度。因此确定乙腈和体积分数为0.1%的乙酸三乙胺缓冲盐流动相(pH 4.1)为最佳分离条件。分离机理研究结果表明,固定相和样品之间的包容络合相互作用以及样品和固定相之间的氢键作用,是样品得以分离的基础。本研究为进一步深入研究β-环糊精固定相提供了实验基础,同时也证明了点击化学在手性环糊精固定相制备中具有极大潜力。     

Green high‐performance liquid chromatography enantioseparation of lansoprazole using a cellulose‐based chiral stationary phase under ethanol/water mode

A simple and environmentally friendly reversed‐phase high‐performance liquid chromatography method for the separation of the enantiomers of lansoprazole has been developed. The chromatographic resolution was carried out on the cellulose‐based Chiralpak IC‐3 chiral stationary phase using a green and low‐toxicity ethanol‐aqueous mode. The effects of water content in the mobile phase and column temperature on the retention of the enantiomers of lansoprazole and its chiral and achiral related substances have been carefully investigated. A mixed‐mode hydrophilic interaction liquid chromatography and reversed‐phase retention mechanism operating on the IC‐3 chiral stationary phase allowed us to achieve simultaneous enantioselective and chemoselective separations in water‐rich conditions. The enantiomers of lansoprazole were baseline resolved with a mobile phase consisting of ethanol/water 50:50 without any interference coming from chiral and achiral impurities within 10 min.     

超临界流体色谱与高效液相色谱分离手性化合物的比较

超临界流体色谱(SFC)分离具有速度快、分离效率高、溶剂消耗少等优点,近年来在手性化合物的分离分析中得到诸多应用。本文对比研究了涂覆型多糖手性色谱柱在SFC和高效液相色谱(HPLC)上拆分24种手性化合物的差异。通过比较这些化合物在色谱柱上的保留时间和选择因子等发现多数化合物在SFC上的分离效率要高于其在HPLC上的分离效率,但HPLC对轴手性化合物的分离效率要优于SFC。SFC和HPLC的分离表现出一定的互补性,随着苯环侧链烷基的碳数增加,化合物在SFC上的保留逐渐增强,而在HPLC的保留却逐渐减弱。叶菌唑在使用SFC和HPLC分析时出现了洗脱顺序反转的现象。这些结果为SFC手性拆分提供了参考。     

同时烙印分子烙印手性固定相

对采用两种对本同时烙印的方法,制备的氨基酸衍生物分子烙印手性固定相进行了考察。研究表明,如果两种烙印分子单独烙印的分子烙印手性对固定相对两种烙印分子具有较强的手性交叉拆分能力,那么这两种烙印分子同时烙印制得的分子烙印手性固定相就可对两种烙印分子均具有很好的手性分离能力,从而使专一性强的分子烙印手性固定相能同时分离多种对映体。     

Separation of chiral furan derivatives by liquid chromatography using cyclodextrin-based chiral stationary phases

The enantiomeric separation of a set of 30 new chiral furan derivatives has been achieved on native and derivatized beta-cyclodextrin stationary phases using high performance liquid chromatography (HPLC). The hydroxypropyl-beta-cyclodextrin (Cyclobond RSP), the 2,3-dimethyl-beta-cyclodextrin (Cyclobond DM), and the acetyl-beta-cyclodextrin (Cyclobond AC) stationary phases are the most effective chiral stationary phases (CSPs) for the separation of these racemates in the reverse phase mode. No enantioseparations have been observed on the native beta-cyclodextrin chiral stationary phase (Cyclobond I 2000) and only a few separations have been attained on the S-naphthylethyl carbamate beta-cyclodextrin (Cyclobond SN) and 3,5-dimethylphenyl carbamate beta-cyclodextrin (Cyclobond DMP) chiral stationary phases in the reverse phase mode. The polar organic and the normal phase mode on these CSPs are not effective for separation of these compounds. The characteristics of the analytes, including steric bulk, hydrogen bonding ability, and geometry, play an important role in the chiral recognition process. The pH affects the enantioseparation of compounds with ionizable groups and the addition of 0.5% methyl tert-butyl ether to the mobile phase significantly enhances the separation efficiency for some highly retained compounds.     

Direct chiral high performance liquid chromatography separation of O-ethyl O-phenylN - isopropylphosphoroamidothioates

The enantiomers of thirty-nine O-ethyl O-phenyl N-isopropyl phosphoroamidothioates have been separated by high performance liquid chromatography on a Pirkle model chiral stationary phase using ten mobile phase. Chromatographic data are presented for the separation of these organic phosphorus enantiomers on the chiral phase. The influences of molecular structures and compositions of mobile phases have been described.     

聚甲基丙烯酸葡萄糖酯及聚甲基丙烯酸纤维二糖酯高效液相色谱手性固定相的性能测评

首先合成了甲基丙烯酸葡萄糖酯和甲基丙烯酸纤维二糖酯,然后通过甲基丙烯酸-3-(三甲氧基硅基)丙酯分别聚合在硅胶上,并将其作为高效液相色谱手性固定相。分别以正己烷-异丙醇(体积比为90:10)、正己烷-异丙醇-三乙胺(体积比为90:10:0.2)和正己烷-异丙醇-三氟乙酸(体积比为90:10:0.2)溶液作为流动相,对15种包含醇类、胺类、酰胺类和酮类的外消旋体化合物进行手性拆分。拆分结果表明,葡萄糖和纤维二糖聚合物固定相对大多数醇类和胺类以及部分酰胺类和酮类外消旋体化合物有较好的手性识别能力,并且二者的手性识别能力还具有一定的互补性。该研究表明,单糖和二糖聚合物固定相可成为一类新型的高效液相色谱手性固定相。     

高效液相色谱-串联质谱法结合多糖衍生物手性固定相拆分氰戊菊酯

建立了以多糖衍生物为手性固定相的高效液相色谱-串联质谱(HPLC-MS/MS)直接拆分氰戊菊酯对映体的方法。在反相液相色谱条件下,考察了手性固定相的种类、流动相组成、柱温、流速对氰戊菊酯4个立体异构体分离的影响。同时,利用热力学方法对氰戊菊酯的立体异构体与固定相之间的色谱保留和分离的热力学机理进行了探讨。结果表明:采用Lux Cellulose-3(纤维素-三(4-甲基苯甲酸酯))手性色谱柱,在以流动相为乙腈-水(5 mmol/L甲酸铵)=(55:45,V:V)流速0.4 mL/min,柱温30℃的条件下,可在14 mins内实现氰戊菊酯4个立体异构体的基线分离。拓展了HPLC-MS/MS在菊酯类手性农药对映体分离及检测上的应用。     

High‐performance liquid chromatographic and subcritical fluid chromatographic separation of α‐arylated ß‐carboline,N‐alkylated tetrahydroisoquinolines and their bioisosteres on polysaccharide‐based chiral stationary phases

New, pharmacologically interesting chiral amino compounds, namely, stereoisomers of α‐hydroxynaphthyl‐ß‐carboline, benz[d]azepine and benz[c]azepine analogs as well as N‐α‐hydroxynaphthylbenzyl‐substituted isoquinolines were enantioseparated by high‐performance liquid chromatographic and subcritical fluid chromatographic methods on polysaccharide‐based chiral stationary phases. Separation of the stereoisomers was optimized in both subcritical fluid chromatography and normal phase liquid chromatographic modes by investigating the effects of the composition of the bulk solvent, temperature, and the structures of the analytes and selectors. Both normal phase liquid chromatography and subcritical fluid chromatography exhibited satisfactory performance, albeit with somewhat different effectiveness in the separation of the stereoisomers studied. The optimized methods offer the possibility to apply preparative‐scale separations thereby enabling further pharmacological investigations of the enantiomers.     

Effect of different immobilization strategies on chiral recognition properties of Cinchona‐based anion exchangers

In the enantiomeric separation of highly polar compounds, a traditionally challenging task for high‐performance liquid chromatography, ion‐exchange chiral stationary phases have found the main field of application. In this contribution, we present a series of novel anion‐exchange‐type chiral stationary phases for enantiomer separation of protected amino phosphonates and N‐protected amino acids. Two of the prepared selectors possessed a double and triple bond within a single molecule. Thus, they were immobilized onto silica support employing either a thiol‐ene (radical) or an azide‐yne (copper(I)‐catalyzed) click reaction. We evaluated the selectivity and the effect of immobilization proceeding either by the double bond of the Cinchona alkaloid or a triple bond of the carbamoyl moiety on the chromatographic performance of the chiral stationary phases using analytes with protecting groups of different size, flexibility, and π‐acidity. The previously observed preference toward protecting groups possessing π‐acidic units, which is a typical feature of Cinchona‐based chiral stationary phases, was preserved. In addition, increasing the bulkiness of the selectors’ carbamoyl units leads to significantly reduced retention times, while very high selectivity toward the tested analytes is retained.     

Recent advances in metal‐organic frameworks and covalent organic frameworks for sample preparation and chromatographic analysis

In the field of analytical chemistry, sample preparation and chromatographic separation are two core procedures. The means by which to improve the sensitivity, selectivity and detection limit of a method have become a topic of great interest. Recently, porous organic frameworks, such as metal‐organic frameworks (MOFs) and covalent organic frameworks (COFs), have been widely used in this research area because of their special features, and different methods have been developed. This review summarizes the applications of MOFs and COFs in sample preparation and chromatographic stationary phases. The MOF‐ or COF‐based solid‐phase extraction (SPE), solid‐phase microextraction (SPME), gas chromatography (GC), high‐performance liquid chromatography (HPLC) and capillary electrochromatography (CEC) methods are described. The excellent properties of MOFs and COFs have resulted in intense interest in exploring their performance and mechanisms for sample preparation and chromatographic separation.     

大分子键合型手性固定相的研究进展

高效液相色谱（HPLC）被广泛认为是分离制备光学纯单一对映体最有效的方法。在高效液相色谱手性拆分中,手性固定相的性能直接影响到色谱柱的手性分离能力。在众多手性固定相中,键合型手性固定相具有溶剂耐受性好,分离模式灵活等优点,是很重要的一大类手性固定相。本文主要针对大分子键合型手性固定相,包括多糖衍生物键合型手性固定相、蛋...     

A new approach to the chiral separation of novel diazenes

Two new types of potential liquid‐crystalline azo compounds were synthesized in the form of racemic mixtures and as the individual S enantiomers. Both materials consisting of two substituted aromatic rings in the molecular core and one chiral center at the aliphatic moiety showed mesomorphic behavior. The separation of the R and S enantiomers by chiral high‐performance liquid chromatography was unsuccessful when the azo compounds were in their natural E state. However, the irradiation of the compounds in the solution by UV light led to an almost quantitative transition to their Z forms. The chromatographic behavior of the compounds in their Z forms was significantly different, and partial separation of the individual enantiomers on chiral polysaccharide‐based stationary phases was obtained. Thus, the proposed procedure represents a novel approach to the enantioseparation of chiral diazenes.     

Evaluation of silica from different vendors as the solid support of anion‐exchange chiral stationary phases by means of preferential sorption and liquid chromatography

Chromatographic performance of a chiral stationary phase is significantly influenced by the employed solid support. Properties of the most commonly used support, silica particles, such as size and size distribution, and pore size are of utmost importance for both superficially porous particles and fully porous particles. In this work, we have focused on evaluation of fully porous particles from three different vendors as solid supports for a brush‐type chiral stationary phase based on 9‐O‐tert‐butylcarbamoyl quinidine. We have prepared corresponding stationary phases under identical experimental conditions and determined the parameters of the modified silica by physisorption measurements and scanning electron microscopy. Enantiorecognition properties of the chiral stationary phases have been studied using preferential sorption experiments. The same material was slurry‐packed into chromatographic columns and the chromatographic properties have been evaluated in liquid chromatography. We show that preferential sorption can provide valuable information about the influence of the pore size and total pore volume on the interaction of analytes of different size with the chirally‐modified silica surface. The data can be used to understand differences observed in chromatographic evaluation of the chiral stationary phases. The combination of preferential sorption and liquid chromatography separation can provide detailed information on new chiral stationary phases.     

直链淀粉手性固定相高效液相色谱法拆分比索洛尔对映体

采用直链淀粉手性固定相高效液相色谱法在正相条件下直接拆分了比索洛尔对映异构体。分别以异丙醇、乙醇为有机改性剂,考察了流动相的组成与配比、流速及柱温等因素对比索洛尔对映体分离的影响。确定了比索洛尔对映体的最佳拆分条件:流动相正己烷-乙醇-二乙胺(体积比为88∶12∶0.1),流速0.6 mL/min,检测波长270 nm,柱温20 ℃。该方法可快捷、简便地拆分比索洛尔对映体。     

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.     

Liquid chromatographic resolution of proline and pipecolic acid derivatives on chiral stationary phases based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid

Two liquid chromatographic chiral stationary phases based on (+)‐(18‐crown‐6)‐2,3,11,12‐tetracarboxylic acid were applied to the resolution of the amide derivatives of cyclic α‐amino acids including proline and pipecolic acid. Among the five amide derivatives of proline, aniline amide was resolved best on the first chiral stationary phase, which contains two N–H tethering amide groups, with the separation factor of 1.31 and the resolution of 2.60, and on the second chiral stationary phase, which contains two N–CH₃ tethering amide groups, with the separation factor of 1.57 and the resolution of 5.50. Among the five amide derivatives of pipecolic acid, 2‐naphthyl amide was resolved best on the first chiral stationary phase with the separation factor of 1.30 and the resolution of 1.75, but 1‐naphthylmethyl amide was resolved best on the second chiral stationary phase with the separation factor of 1.30 and the resolution of 2.26. In general, the second chiral stationary phase was found to be better than the first chiral stationary phase in the resolution of the amide derivatives of cyclic α‐amino acids. In this study, the second chiral stationary phase was first demonstrated to be useful for the resolution of secondary amino compounds.     

Enantioselective Liquid Chromatographic Separations Using Macrocyclic Glycopeptide-Based Chiral Selectors

Numerous chemical compounds of high practical importance, such as drugs, fertilizers, and food additives are being commercialized as racemic mixtures, although in most cases only one of the isomers possesses the desirable properties. As our understanding of the biological actions of chiral compounds has improved, the investigation of the pharmacological and toxicological properties has become more and more important. Chirality has become a major issue in the pharmaceutical industry; therefore, there is a continuous demand to extend the available analytical methods for enantiomeric separations and enhance their efficiency. Direct liquid chromatography methods based on the application of chiral stationary phases have become a very sophisticated field of enantiomeric separations by now. Hundreds of chiral stationary phases have been commercialized so far. Among these, macrocyclic glycopeptide-based chiral selectors have proved to be an exceptionally useful class of chiral selectors for the separation of enantiomers of biological and pharmacological importance. This review focuses on direct liquid chromatography-based enantiomer separations, applying macrocyclic glycopeptide-based chiral selectors. Special attention is paid to the characterization of the physico-chemical properties of these macrocyclic glycopeptide antibiotics providing detailed information on their applications published recently.     

基于直链淀粉衍生物手性固定相的高效液相色谱-串联质谱法拆分4种β-受体阻滞剂对映体及其分离机制的探讨

建立了以直链淀粉衍生物为手性固定相的高效液相色谱-串联质谱(HPLC-MS/MS)直接拆分普萘洛尔、美托洛尔、阿罗洛尔和卡维地洛4种β-受体阻滞剂对映体的方法。考察了手性固定相的种类、流动相改性剂和添加剂的体积分数、柱温和流速等对4种药物对映体分离的影响。结果表明:在Chiralpak AD-H手性色谱柱上,在正己烷-乙醇-二乙胺(20∶80∶0.03,v/v/v)为流动相、流速0.550 mL/min、柱温40℃的条件下,普萘洛尔、美托洛尔、阿罗洛尔和卡维地洛对映体均达到基线分离,分离度分别为1.37、1.80、2.09和4.70。通过热力学研究及对映体结构分析对拆分机理进行了探讨,发现4种药物对映体的手性拆分均为焓驱动过程,而固定相的手性空腔对不同药物的拆分影响较大。研究结果为β-受体阻滞剂的深入研究提供了参考方法。