键合型手性固定相拆分麻醉药JM-1232

使用Chiralpak IA色谱柱,实现了麻醉药JM-1232的对映体分离,并进一步考优化了流动相组成、柱温和流速等条件.得到最优色谱条件:流动相为正己烷:异丙醇= 65:35(V/V)、柱温301、流速1.0 mL/min,分离度达2.31.该方法显示出JM-1232对映体的足够分离度.     

Recent development trends for chiral stationary phases based on chitosan derivatives,cyclofructan derivatives and chiral porous materials in high performance liquid chromatography

The separation of enantiomers by chromatographic methods, such as gas chromatography, high‐performance liquid chromatography and capillary electrochromatography, has become an increasingly significant challenge over the past few decades due to the demand of pharmaceutical, agrochemical, and food analysis. Among these chromatographic resolution methods, high‐performance liquid chromatography based on chiral stationary phases has become the most popular and effective method used for the analytical and preparative separation of optically active compounds. This review mainly focuses on the recent development trends for novel chiral stationary phases based on chitosan derivatives, cyclofructan derivatives, and chiral porous materials that include metal‐organic frameworks and covalent organic frameworks in high‐performance liquid chromatography. The enantioseparation performance and chiral recognition mechanisms of these newly developed chiral selectors toward enantiomers are discussed in detail.     

手性固定相AD、AS和OD的拆分性能

手性固定相-高效液相色谱法在手性药物、手性农药等的分离分析中应用广泛。本文采用3种多糖衍生物的手性固定相(即EnantioPak AD、AS和OD)对20种手性化合物开展手性分离研究,进而探讨样品分子结构、多糖骨架和衍生基团对手性分离的影响。结果表明,除化合物13外,其余化合物在EnantioPak AD上均实现基线分离,分离度多在2.0以上,在正己烷-醇流动相中加入酸碱添加剂可改善和优化酸性或碱性化合物的分离效果;芳香醇(化合物13~16)随着侧链碳数增加在色谱柱上的保留减弱,其分离度呈现增加的趋势;对比8种化合物在3种手性固定相上的分离结果可知,EnantioPak AD表现出更优的分离性能。这为深入研究和了解多糖手性固定相、拓展其手性分离应用提供了参考。     

Enantioseparation of planar chiral ferrocenes on cellulose-based chiral stationary phases: Benzoate versus carbamate pendant groups

In this study, the enantioseparation of 14 planar chiral ferrocenes containing halogen atoms, and methyl, iodoethynyl, phenyl, and 2-naphthyl groups, as substituents, was explored with a cellulose tris(4-methylbenzoate) (CMB)-based chiral column under multimodal elution conditions. n-Hexane/2-propanol (2-PrOH) 95:5 v/v, pure methanol (MeOH), and MeOH/water 90:10 v/v were used as mobile phases (MPs). With CMB, baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.24 to 1.77, whereas only three analytes could be enantioseparated with 1.14 ≤ α ≤ 1.51 on a cellulose tris(3,5-dimethylphenylcarbamate) (CDMPC)-based column, used as a reference for comparison, under the same elution conditions. Pendant group–dependent reversal of the enantiomer elution order was observed in several cases by changing CMB to CDMPC. The impact of analyte and chiral stationary phase (CSP) structure, and MP polarity on the enantioseparation, was evaluated. The two cellulose-based CSPs featured by different pendant groups were also compared in terms of thermodynamics. For this purpose, enthalpy (ΔΔH°), entropy (ΔΔS°) and free energy (ΔΔG°) differences, isoenantioselective temperatures (T_iso), and enthalpy/entropy ratios (Q), associated with the enantioseparations, were derived from van ’t Hoff plots by using n-hexane/2-PrOH 95:5 v/v and methanol/water 90:10 v/v as MPs. With the aim to disclose the functions of the different substituents in mechanisms and noncovalent interactions underlying analyte–selector complex formation at molecular level, electrostatic potential (V) analysis and molecular dynamics simulations were used as computational techniques. On this basis, enantioseparations and related mechanisms were investigated by integrating theoretical and experimental data.     

双选择体手性固定相中选择体的构型对分离性能的影响

为研究选择体的构型对双选择体固定相手性识别的影响,以(1S,2S)-(~)-二苯基乙二胺及L-(~)-二苯甲酰酒石酸为手性源,合成了一种新的双选择体固定相,并用不同结构的手性样品测试了其手性分离能力。结果表明,这种固定相与以(1R,2R)-(+)-二苯基乙二胺及L(~)-二苯甲酰酒石酸为手性源制备的双选择体固定相有相当的手性分离能力,但这两种固定相所能分离的化合物不尽相同。对双选择体固定相中两个选择体的构型对固定相手性识别的影响进行了探讨。在手性识别中,以不同手性源制备的两个选择体的立体构型不能同时与一个手性样品的立体构型相匹配,从而导致相应的双选择体固定相手性分离能力的下降。     

新型直链淀粉类手性固定相的制备与手性拆分性能

通过对糖单元2-位进行选择性酯化以及6-位保护与去保护,运用区域选择性方法合成了5种新型直链淀粉类衍生物,分别为直链淀粉-2-苯甲酸酯-3-(4-氯苯基氨基甲酸酯)-6-(3,5-二甲基苯基氨基甲酸酯)、直链淀粉-2-苯甲酸酯-3-(4-氯苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)、直链淀粉-2-苯甲酸酯-3,6-二(4-氯苯基氨基甲酸酯)、直链淀粉-2-(4-氯苯甲酸酯)-3,6-二(3,5-二氯苯基氨基甲酸酯)和直链淀粉-2-(4-氯苯甲酸酯)-3,6-二(环己基氨基甲酸酯),并将其涂覆在氨丙基硅胶表面制备了HPLC手性固定相。利用核磁共振-氢谱(¹H-NMR)和傅里叶变换红外光谱(FT-IR)技术对所合成衍生物的结构进行了表征和分析,并用HPLC法评价所合成衍生物的手性识别能力。与具有单一取代基直链淀粉类手性固定相的对比分析表明,所合成的新型直链淀粉类手性固定相对于某些对映体具有更为优异的拆分结果。进一步分析表明,2-、3-和6-位取代基的性能和引入位置对直链淀粉衍生物的手性识别能力均有较大的影响。     

键合型手性固定相的研究进展

手性分离在生物医药等领域具有重要意义。高效液相色谱(HPLC)因其经济、快速、高效等特点被广泛应用于手性化合物的分离分析中。手性固定相(CSP)是HPLC实现手性分离的核心,而制备有效CSP的关键在于手性选择剂的筛选。近年来,大量文献报道了新型CSPs的制备,其中键合型CSPs因具有溶剂耐受性和较高稳定性等优点受到了广泛关注。该文对近年来以手性单分子、多糖、环糊精、大环抗生素、冠醚、杯芳烃及生物碱等为手性选择剂制备的新型键合型CSPs进行了归纳整理,并对其发展前景进行了展望。     

高效液相色谱中乙基纤维素手性固定相研究

对映异构现象广泛存在于自然界中,由于对映异构体分子之间具有不同的光学性能和生物活性,因而外消旋体的拆分在药学和生物学等领域具有十分重要的意义.在手性拆分中,高效液相色谱是最普遍使用的方法之一,而其中又以手性固定相法最为常用[1].在众多手性固定相中,各种多糖及其衍生物,特别是纤维素和直链淀粉的衍生物因具有很好的手性识别能力而得到了广泛研究[2-3].但到目前为止,我们还未见乙基纤维素手性固定相的报道.本文制备了乙基纤维素手性固定相,并在正相、反相以及极性有机溶剂的流动相条件下,对15种手性化合物的拆分情况进行了探究,其中9种得到了不同程度的分离,研究结果表明该手性固定相具有较好的手性拆分能力.     

键合型聚丙烯酰胺衍生物手性固定相的制备与手性识别性能

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的最有效方法。在高效液相色谱手性拆分中,手性固定相(CSP)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,已经发展成为一类重要的手性固定相。本文通过两步化学反应合成了新型的光学活性丙烯酰胺衍生物--(S)-1-丙烯酰-2-(N-苯基甲酰胺基)吡咯烷((S)-APACP),采用核磁共振氢谱表征了(S)-APACP的化学结构;通过3步化学反应制备了键合型聚丙烯酰胺衍生物手性固定相,采用热重分析法表征了聚合物的键合量,采用HPLC评价了键合型手性固定相的识别能力,分析了影响其手性识别能力的因素。研究结果表明,APACP聚合物成功地键合到硅胶表面制备了具有良好溶剂耐受性的键合型手性固定相,其聚合物键合量为10.2%~11.8%,该键合型手性固定相对若干种对映体显示了较好的手性识别能力。     

Chiralpak AD-H和Chiralcel OJ-H手性固定相拆分扁桃酸系列化合物

对比了商品化的淀粉型手性固定相Chiralcel OJ-H和纤维素型手性固定相Chiralpak AD-H柱在正相条件下对扁桃酸系列8个化合物的拆分,结果表明Chiralcel OJ-H柱对扁桃酸系列化合物具有更强的手性识别能力,8个外消旋扁桃酸化合物在36 min内都得到了基线分离。研究发现,扁桃酸苯环上的取代基对其拆分的难易程度影响很大,其电子诱导效应影响扁桃酸类化合物在固定相上的保留时间,其空间位阻效应是扁桃酸在固定相上被拆分成败的决定因素。通过对比分析扁桃酸和手性柱的结构,探讨了可能的手性拆分机理是基于Chiralpak AD-H(Chiralcel OJ-H)手性固定相和扁桃酸系列化合物之间的氢键-氢键、偶极-偶极、π-π电子相互作用以及空间适应性等诸多因素的综合影响,其中空间适应性起到至关重要的作用。本研究可为一些实际光学活性扁桃酸及其类似物的对映体纯度测定与拆分研究提供参考。     

衍生化β-环糊精手性固定相高效液相色谱法拆分米那普仑对映体及其分离机制

建立了新型抗抑郁药米那普仑在环糊精手性固定相上的高效液相色谱拆分方法。在反相色谱条件下采用未衍生化β-环糊精(Cyclobond I 2000)、乙酰基-β-环糊精(AC-β-CD)、2,3-二甲基-β-环糊精(DM-β-CD)、3,5-二甲基苯基氨基甲酸酯-β-环糊精(DMP-β-CD)4种手性柱分离米那普仑对映体。考察了固定相、流动相比例、pH、流速和柱温对拆分的影响。利用分子对接和结合能计算方法,研究米那普仑分子与AC-β-CD的对接过程,探讨其可能的分离机制。优化后的拆分条件如下:固定相为乙酰基-β-环糊精手性柱Astec CYCLOBONDTMI 2000 AC(25 cm×4.6 mm,5μm),流动相为乙腈-0.1%(体积分数)pH 5.0醋酸三乙胺溶液(TEAA)(5∶95,v/v),流速为0.4mL/min,柱温为25℃,检测波长为220 nm。在此条件下,米那普仑对映体获得快速拆分,分离度(Rs)为1.74,理论塔板数为10 125。分子模拟结果表明引起手性识别的作用力主要是环糊精衍生化的乙酰基导致的氢键作用差异。该方法快速、高效、重现性好。     

非均匀取代淀粉衍生物手性固定相的制备及其手性识别能力

通过区域选择性方法制备了两种新型淀粉衍生物,分别为淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)和淀粉2-苯甲酸酯-3-(3,5-二氯苯基氨基甲酸酯)-6-(4-甲基苯基氨基甲酸酯),将二者分别涂覆于氨丙基硅胶后用作液相色谱手性固定相。研究表明:所制备的手性固定相显示出特异的手性识别能力,其手性识别能力明显高于均匀取代淀粉衍生物——淀粉三(3,5-二氯苯基氨基甲酸酯),取代基的性质及在葡萄糖单元上的位置对手性固定相的手性识别能力有较大的影响。一些未在商品化的手性柱Chiralpak AD上得到有效分离的手性化合物在所制备的固定相上得到了更好的分离。所测试的8对对映体在淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)固定相上均得到了分离,因而此固定相的手性识别能力较强,具有潜在的应用价值。     

Supercritical fluid chromatography in chiral separations: Evaluation of equivalency of polysaccharide stationary phases

Nine different chiral columns based on covalently immobilized or coated tris(3,5‐dimethylphenylcarbamate) cellulose and amylose have been explored. We evaluated their respective enantioselective potential including the enantioseparation and qualitative characteristics of peaks. The generic screening conditions were using gradient elution from 5 to 40% organic modifier/CO₂ during 3 min with about 40 enantiomer pairs. Primary screening was carried out using ten different mobile phases varying in type of additives while using one representative amylose‐ and one cellulose‐based column. The complete evaluation of all nine columns was then carried out using three best performing organic modifiers: (1) methanol + 0.1% trifluoroacetic acid + 0.1% diethylamine, (2) isopropanol + 0.1% trifluoroacetic acid + 0.1% diethylamine, and (3) methanol + 0.1% ammonium hydroxide. Equivalency of different columns with the same chiral selector was not confirmed. Columns with the same stationary phase but different supports or manufacturing methods displayed differences in enantioselectivity and general performance. The similarity corresponded to 62 and 63% for the three cellulose‐coated columns taking CEL1 as the reference. The similarity was 67% for the pair of amylose‐based coated columns. For immobilized columns, the similarity was 69 and 59% for celluloses and amyloses pairs, respectively. The best performing column based on success rate of enantioseparation was Chiralcel OD‐3 when using methanol + 0.1% trifluoroacetic acid and 0.1% diethylamine combined additive.     

双手性选择单元手性固定相的研究进展

手性固定相（chiral stationary phase,CSP）作为手性色谱分离的核心技术,在手性化合物的识别和分离中得到广泛应用。以双手性选择单元结合作为CSP是近些年的研究热点,研究表明,两种手性选择单元相结合的CSP可增加手性识别位点,显著提高分离效果。本文介绍了近几年双手性选择单元手性固定相在手性分离中的研究进展,并对其发展前景进行了展望。     

高效液相色谱法手性分离联萘二酚苯甲酸酯对映体

采用Chirex(S)-LEU(S)-NEA、ChiralcelOD-H和ChiralpakAD-H手性色谱柱直接拆分了2′-羟基-1,1′-联萘-2-苯甲酸酯(HBNB)、1,1′-联萘-2,2′-二苯甲酸酯(BNDB)和2′-甲氧基-1,1′-联萘-2-苯甲酸酯(MBNB)对映体。分别考察了流动相组成、柱温和化合物结构对手性分离的影响。结果表明:3对联萘二酚苯甲酸酯对映体在ChiralpakAD-H柱上的拆分效果最好。当采用正己烷/异丙醇(40/60,v/v)为流动相时,HBNB、BNDB和MBNB对映体的分离因子(α)和分离度(Rs)分别为1.76、1.74、1.40和6.47、7.81、4.75。对比联萘二酚(BN)的分离,从联萘分子中2-位取代基、对映体出峰顺序和热力学参数等方面探讨了相关手性分离机理。     

Enantioseparation of Novel Chiral Tetrahedral Clusters on a Chiral Stationary Phase (CSP) by High Performance Liquid Chromatography

In recent years, the synthesis of chiral tetrahedral clusters has been studied extensively and various types are accessible , which are a kind of organometallic compounds with greatly growing interest due to their potential application to asymmetric reaction catalysts. As an efficient     

替考拉宁键合手性固定相的制备及其在反相条件下对手性化合物的拆分

以国产大环抗生素替考拉宁为手性选择剂制备了替考拉宁键合手性固定相(Tei-CSP),在反相条件下考察了键合相对华发令、西孟旦等手性药物、α-氨基酸(羟基酸)、衍生α-氨基酸的拆分效果。实验结果表明,在反相条件下,疏水(亲水)作用、静电作用对手性化合物在柱上的保留以及对映体的拆分起到了非常重要的作用;氨基酸在衍生前后,其在柱上的保留和手性识别机理发生了改变,衍生前,亲水作用参与保留机理,而衍生后,由于疏水作用增强,疏水作用参与保留,对映体在较低的有机改性剂条件下才能获得较好的分离。     

葡萄糖和N-乙酰-D-氨基葡萄糖作为手性固定相的研究

以3-氨基丙基三乙氧基硅烷、3-异氰酸丙基三乙氧基硅烷和3-缩水甘油醚氧基丙基三甲氧基硅烷作为键合臂,将葡萄糖和N-乙酰-D-氨基葡萄糖键合到硅胶上作为高效液相色谱手性固定相,对15种手性化合物进行拆分.研究结果表明:不同的键合臂对它们的手性分离能力有较大的影响,葡萄糖及其衍生物是一类具有良好实用前景的手性固定相.     

Evaluation of novel dendrimer chiral stationary phases using HPLC

Summary The reversed phase chromatographic properties of the [G1]-L-glutamic and ethyl ester-AC-silica (1), [G2]-L-glutamic acid ethyl ester-AC-silica (2) and the [G1]-L-glutamic acidt-butyl ester-AC-silica (3) dendrimer stationary phases were evaluated. Initial studies involved the comparison between these phases with a classic reversed phase (i.e. ODS1) by the separation of a standard reversed phase test mixture composed of dimethylphthalate, nitrobenzene, anisole, diphenylamine and fluorene. Separations were achieved with comparable performance to those obtained with the conventional reversed phase (ODS1). However, it was apparent that the chromatographic selectivity exhibited by the dendrimer stationary phases was different from that of the ODS1 phase. On a per mole basis, the dendrimers exhibited similar (and sometimes greater) affinity for these analytes compared with the ODS1 ligand. Subsequent chromatographic experiments were conducted upon the dendrimer chiral stationary phases using chiral analytes under reversed phase and normal phase conditions. Chiral resolution was not observed.     

Enantioseparation tuned by solvent polarity on a β‐cyclodextrin clicked chiral stationary phase

The efficient enantioseparation of 26 racemates has been achieved with the perphenylcarbamoylated cyclodextrin clicked chiral stationary phase by screening the optimum composition of mobile phase in high‐performance liquid chromatography. The chromatographic results indicate that both the retention and chiral resolution of racemates are closely related to the polarity of the mobile phases and the structures of analytes. The addition of alcohols can significantly tune the enantioseparation in normal‐phase high‐performance liquid chromatography. The addition of methanol and the ratio of ethanol/methanol or isopropanol/methanol played a key role on the resolution of flavonoids in ternary eluent systems. The chiral separation of flavonoids with pure organic solvent as mobile phase indicates the preferential order for chiral resolution is methanol>ethanol>isopropanol>n‐propanol>acetonitrile.