高效液相色谱法对二氢吡喃酮衍生物的手性拆分

介绍了利用手性chiralcel OD和chiralpak AD柱在高效液相色谱上对一系列二氢吡喃酮衍生物进行手性拆分，获得了良好的分离结果，考察了部分对映体在这两种柱上的色谱行为。实验表明手性化合物与手性柱之间存在着化学作用与空间作用，两者的共同作用决定了分离结果。     

联萘酚手性拆分方法及其用于实验室废水的检测

联萘酚是具有手性的药物中间体,其对映体的拆分和检测具有重要意义.建立一种反相液相色谱手性拆分方法,用于联萘酚对映体的拆分.考察了6种不同手性色谱柱的拆分效果,并进一步对流动相配比、柱温和流速等因素进行了优化.结果表明,CHIRALPAK?IA手性柱对联萘酚对映体有较好的拆分性能,在流动相为甲醇-1％ 乙酸(90:10,...     

1,2-二苯基乙二胺及与脱氢乙酸缩合生成的席夫碱化合物对映体的高效液相色谱法拆分

1,2-二苯基乙二胺（DPEN,见图1）是～种重要的具有C,一对称性的手性试剂。DPEN与脱氢乙酸缩合生成的席夫碱化合物（DPHS,结构见图1）是合成新型烯烃环氧化反应金属催化剂的手性配体”。虽然手性高效液相色谱拆分DPEN衍生物对映体已有文献报道”,但仍未见利用色谱法直接拆分DPEN和DPHS对映体的报道。本文考察了DPEN和DPHS对映体在Chiralcel OD—H和Chiralpak AD—H手性色谱柱上的拆分行为,建立了DPEN和DPHS对映体纯度的高效液相色谱测定方法。     

配体交换毛细管区带电泳拆分未衍生化氨基酸

以铜（Ⅱ）-L-谷氨酸络合物为手性分离选择剂，对苯丙氨酸、酪氨酸和色氨酸3种非衍生芳香族氨基酸的手性对映体拆分进行了研究，建立了一种快速、简便拆分未衍生化的氨基酸对映体的配体交换毛细管电泳方法。在使用10mmol／L NH4AC（pH5．0），5mmol／L CuSO4和10mmol／L L-谷氨酸的条件下，成功地拆分了苯丙氨酸、酪氨酸手性对映体；色氨酸手性对映体也得到部分分离；考察了电泳缓冲液组成、pH值等影响分离效果的因素。     

Chiralpak AD和Chiralcel OD-H手性固定相拆分3α-酰氧基-6β-乙酰氧基莨菪烷类化合物

采用高效液相色谱法,以不同配比的正己烷-异丙醇为流动相,在正相色谱条件下,考察了6个3α-酰氧基-6β-乙酰氧基莨菪烷对映体在淀粉型手性固定相Chiralpak AD、纤维素型手性固定相Chiralcel OD-H上的分离情况,以建立该类化合物的手性拆分方法。结果表明,在Chiralpak AD手性柱上,对映体6实现完全分离,而对映体1完全不能分离;在Chiralcel OD-H柱上,对映体1、4、3分别实现完全分离、基线分离和基本分离,对映体6只能实现部分分离;对映体5在两种手性柱上都完全不能被分离。说明固定相手性空腔的结构对化合物的拆分结果影响很大。研究发现,C-3α位取代基团的空间位阻效应主导手性固定相对对映体的选择性识别作用,而化合物与固定相之间的分子间作用力对手性拆分也产生重要影响。研究结果为其他莨菪烷类化合物的手性拆分提供了参考。     

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。     

L-脯氨酸手性键合固定相的制备和表征

采用气相色谱技术可用下述两种方法实现氨基酸对映体的拆分:一种是用手性试剂与样品反应生成非对映体后,在普通色谱柱上实现拆分,其缺点是:衍生反应费时,需要昂贵的手性试剂,衍生过程中还可能产生消旋化,影响测定结果;另一种是在手性固定相上实现拆分,例如Chirasil-Val就是一种     

非衍生芳香族蛋白氨基酸对映体的毛细管电泳手性拆分

以羟丙基—α—环糊精为手性选择剂，对苯丙氨酸、酪氨酸和色氨酸3种非衍生芳香族蛋白氨基酸的毛细管电泳分离和对映体手性拆分进行了研究；结果表明，背景电解质的pH值、手性选择剂的浓度和柱温对分离效果影响较大；经过一系列实验优化，在选定的条件下，3种未衍生氨基酸混合物，不仅达到了相互之间的完全分离，而且每种氨基酸对映体均达到了完全手性拆分。     

C18柱串联冠醚手性柱高效分离3种芳香族氨基酸对映体

将C18柱与手性冠醚柱串联,建立了一种反相高效液相色谱法用于3种芳香族氨基酸对映体同时拆分的方法.考察了反相色谱流动相的组成、pH值、柱温、流速对对映体拆分的影响.实验结果表明,当流动相为HClO4-乙睛溶液(86:14,V/V,pH 2.0)、柱温20℃、流速0.4 mL/min时,3种氨基酸对映体可获得基线分离.进一步对比了C18柱、冠醚手性柱和串联顺序不同的4种分离模式,结果表明,C18柱不能拆分氨基酸对映体,仅能分离不同种类氨基酸;冠醚手性柱可分离氨基酸映体,但不同种类氨基酸色谱峰出现重叠;串联模式能实现3种氨基酸对映体的基线分离,实现双柱优势互补,而串联顺序对分离影响不大,仅影响色谱峰的峰形.     

Chiralcel OD-RH直接拆分五味子乙素对映体

采用反相手性色谱柱Chiralcel OD-RH(纤维素3,5二甲基苯基氨基甲酸酯涂敷在5 μm硅胶上)建立了五味子乙素对映体的反相高效液相色谱拆分方法。考察了流动相组成、柱温和流速对五味子乙素手性对映体拆分的影响。以甲醇-水(90∶10)为流动相,流速0.5 mL/min,柱温20 ℃,检测波长254 nm,在Chiralcel OD-RH手性柱上成功拆分了五味子乙素对映体,其中R-构型先出峰。用lnk对1/T作图得到的Van-t Hoff曲线具有良好线性,相关系数（r）均大于0.99,计算了对映体与固定相相互作用的焓变以及焓变差值和熵变差值等热力学参数。结果显示,五味子乙素对映体的拆分过程为焓控过程,即氢键、π-π及偶极-偶极等作用方式对对映体的拆分起重要作用。     

Stereoselective effects in the separation of enantiomers of omeprazole and other substituted benzimidazoles on different chiral stationary phases

The enantioselective separation of omeprazole on different chiral stationary phases was investigated. The two enantiomers could be resolved on three different phases with immobilized protein, Chiral-AGP, Ultron ES-OVM and BSA-DSC, employing aqueous mobile phases with 2-propanol as organic modifier. On Chiralpak AD, an amylose-based chiral stationary phase, the enantiomers of omeprazole and three analogues could be separated using a non-polar hexane-ethanol mobile phase. For omeprazole the retention order was reversed when 2-propanol was replaced with ethanol or methanol as the modifier of hexane in the mobile phase.     

Enantiomers of New Synthetic Pyrrolylphenylethanoneamine Mono-Amino Oxidase Inhibitor Compounds: Analytical and Semipreparative HPLC Separations, and Chiroptical Characteristics

The polysaccharide chiral stationary phases (CSPs) Chiralcel OD and Chiralpak AD, and the brush-type (R,R)-Whelk-01 chiral stationary phases have been evaluated to separate new synthetic pyrrolylphenylethanoneamine racemic compounds, potentially monoamine oxidase (MAO) inhibitors, under various mobile phase compositions, using various temperatures. The enantioseparation was evaluated by comparing the (R,R)-Whelk-01 column performance with those of Chiralpak AD and Chiralcel OD. Significant differences were observed in their chiral recognition, as revealed from their retention, selectivity, resolution and elution order. Performances of the Chiralpak AD column were superior to those of the Chiralcel OD and (R,R)-Whelk-01 columns. Some of the racemic compounds were resolved by semipreparative chromatography on Chiralpak AD column in order to study the chiroptical proprieties of the single enantiomers.     

Application and comparison of derivatized cellulose and amylose chiral stationary phases for the separation of enantiomers of pharmaceutical compounds by high-performance liquid chromatography.

The direct high-performance liquid chromatographic separation of three pairs of structurally related enantiomers on derivatized cellulose and amylose chiral stationary phases (Chiralcel OD, Chiralpak AD and Chiralpak AS) was studied using hexane as the mobile phase with 2-propanol or ethanol as modifiers. The separation, retention and elution order of the enantiomers on the different columns using different alcohol modifiers were compared. The effect of structural variation of the solutes on their k' was noted. A reversal of elution order of one enantiomeric pair upon changing the mobile-phase modifier was observed. Chiralcel OD and Chiralpak AD columns provided different elution orders of the enantiomers, including a fourth pair of enantiomers that were not structurally related to the other three pairs.     

Enantioselective HPLC analysis of propafenone and of its main metabolites using polysaccharide and protein-based chiral stationary phases

HPLC on chiral stationary phases has been used for the enantioselective assay of propafenone (PPF), 5-hydroxypropafenone (PPF-50H) and N-despropylpropafenone (PPF-NOR) enantiomers. The results obtained on Chiralpak AD column showed that it is useful for the resolution of PPF and of its main metabolites, although the peaks obtained for PPF-NOR were not symmetrical under the conditions investigated. This column and circular dichroism-based detection system were used to determine the absolute configuration of the eluates. Furthermore, the influence of the mobile phase composition on the resolution of PPF and of its main metabolites was investigated on cellulose derivatives (Chiralcel OD-H and Chiralcel OD-R) and protein (Chiral AGP and Ultron ES-OVM)-based chiral stationary phases. The enantiomers of PPF were resolved on all the columns, except for the Ultron ES-OVM. This column, the Chiralpak AD and the Chiralcel OD-H columns were suitable for the resolution of the PPF-50H enantiomers. The PPF-NOR enantiomers were resolved on the Chiralpak AD, Chiral AGP and Chiralcel OD-R columns.     

Enantiomeric separation of chiral sulfoxides by supercritical fluid chromatography

The application of supercritical fluid chromatography (SFC) to the enantiomeric separation of several chiral sulfoxides belonging to the family of the substituted benzimidazoles, including omeprazole, lansoprazole, pantoprazole, rabeprazole, oxfendazole and ricobendazole, is presented in this work. The column employed was Chiralpak AD and the effect of different chromatographic conditions was studied. The results obtained showed that all the compounds can be enantiomerically resolved using SFC, with resolutions higher than 2 and analysis times that in most cases were lower than 10 min. Alcohol type modifiers provided the best results, with ricobendazole, oxfendazole, and omeprazole showing the highest retentions and resolutions. Study of the temperature effect revealed that, in general, the isoelution temperature was above the temperatures assayed, except in the cases of omeprazole, lansoprazole, and oxfendazole with ethanol as modifier and pantoprazole with acetonitrile. Enthalpy-entropy compensation could also be demonstrated for the retention of the first and second eluted enantiomers as well as for the selectivity, with compensation temperatures of 25 degrees C, 45 degrees C, and 83 degrees C, respectively. Reversal of elution on change of the organic modifier was only observed for omeprazole using 2-propanol.     

Application and comparison of immobilized and coated amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phases for the enantioselective separation of beta-blockers enantiomers by liquid chromatography

A direct liquid chromatographic enantioselective separation of a set of β-blocker enantiomers on the new immobilized and conventional coated amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phases (Chiralpak IA and Chiralpak AD, respectively) was studied using methanol as mobile phase and ethanolamine as an organic modifier (100:0.1, v/v). The separation, retention and elution order of the enantiomers on both columns under the same conditions were compared. The effect of the immobilization of the amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase on silica (Chiralpak IA) on the chiral recognition ability was noted when compared to the coated phase (Chiralpak AD) which possesses a higher resolving power than the immobilized one (Chiralpak IA). A few racemates, which were not or poorly resolved on the immobilized Chiralpak IA were most efficiently resolved on the coated Chiralpak AD. However, the immobilized phase withstand solvents like dichloromethane when used as an eluent or as a dissolving agent for the analyte. The versatility of the immobilized Chiralpak IA in monitoring reactions performed in dichloromethane using direct analysis techniques without further purification, workup or removal of dichloromethane was studied on a representative example consisting of the lipase-catalyzed irreversible transesterification of a β-blocker using either vinylacetate or isopropenyl acetate as acyl donor in dichloromethane as organic solvent.     

高效液相色谱的4种商品手性柱对38种手性化合物的拆分研究

采用纤维素-三(3,5-二甲基苯基氨基甲酸酯)涂敷型手性固定相(Chiralcel OD柱)、直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)涂敷型手性固定相(Chiralpak AD柱)、直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)键合型手性固定相(Chiralpak IA柱)和Pirkle型的(S,S)-Whelk-01手性固定相对38种外消旋体化合物进行手性拆分。实验结果表明,4种固定相的手性识别能力为:OD>AD>IA>(S,S)-Whelk-01,OD固定相的手性识别率达到60%,并且它们之间的手性识别性能还具有一定的互补性。本研究对4种常用手性固定相的拆分能力进行了对比,为拆分手性化合物时有的放矢地选择手性固定相提供了参考。     

Systematic enantiomeric separation of [60]fullerene bisadducts possessing an inherent chiral addition pattern

The optical resolution of trans-2 and trans-3 [60]fullerene bisadducts with an inherent chiral addition pattern, modified by Bingel reaction, cycloaddition by benzyne, Prato reaction, and cycloaddition by o-quinodimethane, was systematically investigated by using chiral HPLC columns (Chiralcel OD and Chiralpak AD). The chiroptical properties of enantiomers separated were also examined.     

Separation of the enantiomers of 4-aryl-7,7-dimethyl- and 1,7,7-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones by chiral HPLC

Summary Analytical HPLC methods using derivatized cellulose chiral stationary phases have been developed for separation of the enantiomers of 25 racemic 4-aryl-7,7-dimethyl- or 1,77-trimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-diones, condensed derivatives of dihydropyrimidines. The enantiomers of the compounds were resolved by normal-phase chromatography on silica-based cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD) and amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD) columns with mobile phases consisting of mixtures ofn-hexane and an alcohol (2-propanol, ethanol, or methanol) in different proportions. The mobile phase and the chiral stationary phase were varied to achieve the best resolution. The effect of the concentration of alcohol in the mobile phase was studied. The resolution obtained on the two columns was complementary.     

Chromatographic separation and enantiomeric resolution of flurbiprofen and its major metabolites

Summary The chromatographic separation and resolution of the enantiomers of flurbiprofen and its two major metabolites, 4′-hydroxyflurbiprofen and 3′-hydroxy-4′-methoxyflurbiprofen was investigated using four different approaches: reversed-phase HPLC after pre-column derivatization with (R)-1-(naphthen-1-yl)ethylamine; reversed-phase HPLC using hydroxypropyl-β-cyclodextrin as a chiral mobile phase additive; chiral-phase HPLC using either an α₁-acid glycoprotein CSP (Chiral-AGP) or an amylose tris(3,5-dimethylphenylcarbamate) CSP (Chiralpak AD). Of all the approaches, only the direct method using the Chiralpak AD CSP demonstrated separation and enantiomeric resolution of all three analytes within an acceptable run time of 45 minutes. Enantiomeric resolution values of 1.67,3.67 and 3.44 were obtained for flurbiprofen, 4′-hydroxyflurbiprofen and 3′-hydroxy-4′-methoxyflurbiprofen respectively. Semi-preparative isolation of the individual enantiomers of both metabolites, followed by CD analysis, revealed that the elution order on the AD CSP wasR-beforeS-enantiomer for both metabolites and the same as that observed for flurbiprofen. The metabolite elution order was subsequently confirmed on the analysis of urine samples obtained from a healthy volunteer following oral administration of the individual drug enantiomers.