Novel cyclodextrin chiral stationary phases for high performance liquid chromatography enantioseparation: Effect of cyclodextrin type

Three novel chiral stationary phases (CSPs) were prepared by regioselective chemical immobilization of mono(6^A-N-allylamino-6^A-deoxy)perphenylcarbamoylated (PICD) α-, β-, and γ-cyclodextrins (CDs) onto silica support via hydrosilylation. Their enantioseparation properties in high performance liquid chromatography (HPLC) were evaluated with a large spectrum of racemates including flavanone compounds, β-adrenergic blockers, amines and non-protolytic compounds. The effect of CD's cavity size on enantioseparation abilities was studied and discussed. The results indicated that CD's surface loading at silica support played an important role in the enantioseparation on these CSPs under normal-phase conditions while inclusion phenomena contributed the major driving force under reverse-phase conditions. As expected, α-PICD demonstrated the best resolutions towards flavonone and most aromatic alcohols under normal-phase conditions with the highest surface loading; while Fujimura's competitive inclusion model can be applied to explain the better enantioseparations towards β-adrenergic blockers, amines and non-protolytic compounds with α- and β-PICD CSPs. γ-PICD CSP showed superior enantioseparation ability for sterically encumbered analytes like flavanone compounds under both normal-phase and reversed phase conditions.     

Click regulation of cyclodextrin primary face for the preparation of novel chiral stationary phases

In this study, a series of novel CD chiral stationary phases were fabricated by immobilization of mono‐6^A‐deoxy‐N₃‐cyclodextrin onto silica surfaces followed by click regulation of CD primary face with 4‐pentynoic acid (acidic moiety), 2‐propynylamine (alkaline moiety) and L‐propargylglycine (chiral amino acid moiety), respectively. Enantioseparations of various kinds of racemates including dansyl‐amino acids, chiral lactides and diketones were conducted in reversed phase modes on these chiral stationary phases, where nearly forty diketones and chiral lactides were firstly separated on cyclodextrin stationary phases. 4‐Pentynoic acid moiety can make the retention ability decline while amine moiety significantly enhanced the retention ability of the stationary phases. For most of the studied analytes, the chiral amino acid moiety had the most positive effects on both the retention time and the resolution. The inclusion complexation between chiral analytes and cyclodextrins were also investigated by fluorescence method.     

新型糖基聚合物的合成及其作为高效液相色谱手性固定相的应用(英文)

Two novel polymers containing glucose units as the main-chain that only differ in terms of their regioregularity were synthesized to evaluate their chiral recognition abilities as chiral stationary phases(CSPs)for high performance liquid chromatography(HPLC).The regioregular polymer(poly-5)shows clear resolution ability for the racemate of cobalt(Ⅲ)acetylacetonate(Co(acac)3),whereas the corresponding regioirregular polymer(poly-3)does not show any chiral recognition for Co(acac)3.The regioregular polymer main-chain seems to play an important role not only in providing an efficient interaction with the racemate but also in expressing the chiral recognition ability as a CSP for HPLC.     

Use of native and derivatized cyclodextrin chiral stationary phases for the enantioseparation of aromatic and aliphatic sulfoxides by high performance liquid chromatography

Summary The enantioselectivity of native and derivatized cyclodextrin stationary phases for aromatic and aliphatic chiral sulfoxides was evaluated using high performance liquid chromatography (HPLC). Many sulfoxide enantiomers could be baseline resolved using the derivatized cyclodextrin stationary phases in the reverse phase mode. The most important factor influencing enantioselectivity is the presence of steric bulk alpha to the chiral center. However, substituents on an aromatic ring bonded to the sulfoxide have less pronounced effects on enantioselectivity. The 2,3-dimethyl β-cyclodextrin exhibits the broadest anantioselectivity for neutral chiral sulfoxides. Native cyclodextrins and hydroxypropyl-β-cyclodextrins were much less effective in separating this class of molecules. The hydrogen bonding ability of the organic modifier does not significantly affect enantioselectivity.     

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。     

Enantiomer separation by gas chromatography on cyclodextrin chiral stationary phases

Fused silica capillary columns coated with several alkyl or acyl cyclodextrin derivatives, especially those of α- and β-cyclodextrins, are suitable for the enantiomer separation of a wide variety of volatile compounds of different molecular size and functionality. Positional isomers and more than 250 pairs of optical isomers have been resolved, including chiral hydrocarbons, acetals, ethers, epoxides, carbonates, lactones, esters, acids, ketones, aldehydes, alcohols, halocarbons, and also nitrogen-and sulfur-containing compounds. The physical properties of the cyclodextrin derivatives, even those obtained as viscous fluids, could be improved by dissolving them in polysiloxane liquid phases commonly used for GLC.     

Imprinted chiral stationary phases in high-performance liquid chromatography

Polymers imprinted with chiral templates offer a new generation of tailor-made chiral stationary phases (CSPs) with predictable selectivities. This review summarizes the present state of the art of molecular imprinting to generate tailor-made CSPs and provides an overview of the main factors involved in the manufacturing process that are crucial to the chromatographic performance of the phases.     

Advances in enantiomeric resolution on monolithic chiral stationary phases in liquid chromatography and electrochromatography

During the last decade, chiral monolithic stationary phases have been prepared and used for rapid enantioseparations in CEC and HPLC. Various chiral selectors are used to prepare these CSPs. The preparation, properties, and applications of these CSPs are discussed in this paper. Attempts have been made to describe optimization strategies and the chiral recognition mechanisms. A comparison of chiral separations in CEC and HPLC is described. Efforts have also been made to predict the future perspectives and challenges of chiral monolithic stationary phases. The most effective chiral selectors include polysaccharides, cyclodextrins, and macrocyclic glycopeptide antibiotics. These chiral phases produced acceptable analytical enantiomeric separation of a variety of racemates. However, the development of these CSPs for preparative‐scale separations is needed.     

利用“网包法”制备高效液相色谱大环抗生素类手性固定相

万古霉素和替考拉宁都属于糖肽类的大环抗生素，具有立体的环状结构和多个手性中心，是两种常见的手性识别材料，广泛应用于对映体的色谱手性分离分析。该文以万古霉素和替考拉宁为手性选择剂，哌嗪为单体，4，4'-二苯基甲烷二异氰酸酯（MDI）、1，6-己二异氰酸酯（HDI）和2，4-甲苯二异氰酸酯（TDI）为交联剂，通过界面聚合反应形成网状层包裹硅胶载体的方法制得6种高效液相色谱手性固定相，用于分离外消旋化合物，并与MDI直接交联万古霉素和替考拉宁在硅胶表面所得固定相进行了比较。结果表明，利用"网包法"和直接交联法制备的手性柱与商品万古霉素和替考拉宁柱之间具有互补性，均对不同的外消旋体有不同程度的拆分。     

Chemically bonded stationary phases for gas and high performance liquid chromatography

Summary This review is intended to summarize current knowledge on chemically bonded stationary phases. Their preparation and effect on chromatographic processes in GC and HPLC are described and the complex separation mechanism on these phases is discussed.     

Enantiomeric resolution of new aromatase inhibitors by liquid chromatography on cellulose chiral stationary phases

Analytical HPLC methods using derivatized cellulose chiral stationary phases were developed for the direct enantioseparation of substituted [1-(imidazo-1-yl)-1-phenylmethyl)]-benzothiazolinone and benzoxazolinone derivatives with one chiral center. Those analogues of fadrozole constitute new potent nonsteroidal inhibitors of aromatase (P450 arom). The separations were made using normal phase methodology with a mobile phase consisting of n-hexane-alcohol (ethanol, 1-propanol, or 2-propanol) in various proportions, and a silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ). The effects of concentration of various aliphatic alcohols in the mobile phase were studied. A better separation was achieved on cellulose carbamate phase compared with the cellulose ester phase. The effects of structural features of the solutes along with the temperature of the column on the discrimination between the enantiomers were examined. Baseline separation (Rs > 1.5) was easily obtained in many cases.     

Analytical and semipreparative resolution of ranolazine enantiomers by liquid chromatography using polysaccharide chiral stationary phases

Novel HPLC methods were developed for the analytical and semipreparative resolution of new antianginal drug ranolazine enantiomers. Good baseline enantioseparation was achieved using cellulose tris (3,5-dimethylphenylcarbamate) (CDMPC) chiral stationary phases (CSPs) under both normal-phase and polar organic modes. The validation of the analytical methods including linearity, LODs, recovery, and precision, and the semipreparative resolution of ranolazine racemate were carried out using methanol as mobile phase without any basic and acidic additives under polar organic mode, using CDMPC CSPs. At analytical scale, the elution times of both enantiomers were less than 7.5 min at 20 degrees C and 1.0 mL/min, with the separation factor (a) 1.88 and the resolution factor (R(s)) 2.95. At semipreparative scale, about 14.3 mg/h enantiomers could be isolated and elution times of both enantiomers were less than 13 min at 2.0 mL/min. To increase the throughput, the technique of overlapping injections was used. The first eluted enantiomer was isolated with a purity of 99.6% enantiomer excess (e.e.) and > 99.0% yield. The second enantiomer was isolated with a purity of 98.8% e.e. and > 99.0% yield. In addition, optical rotation and circular dichroism spectroscopy of both ranolazine enantiomers isolated were also investigated.     

“Click” immobilized perphenylcarbamated and permethylated cyclodextrin stationary phases for chiral high-performance liquid chromatography application

Two cyclodextrin-based chiral stationary phases have been prepared by immobilization of functionalized mono-6-azido-β-CD derivatives to alkynyl modified silica via “click” chemistry and applied to the HPLC enantioseparation of various chiral compounds. The perphenylcarbamated CD CSP (CCP-CSP) exhibited excellent chiral recognition of a wide range of analytes including racemic aryl alcohols, flavonoids, bendroflumethiazide, atropine and some β-blockers. Methanol proved to be a better organic modifier than acetonitrile for most of the analytes with the exception of bendroflumethiazide. The “click” chemistry immobilized permethylated CD CSP (CCM-CSP) afforded poor chiral recognition for most analytes, but could resolve non-aromatic ionone derivatives which were not separated on CCP-CSP. These results suggest that resolution with cyclodextrin derived CSPs depend on a complex interplay of ‘host’–‘guest’ inclusion, hydrogen bonding, π–π and hydrophobic interactions.     

含极性基团的硅质高效液相色谱固定相

介绍了含极性基团硅质高效液相色谱固定相的研究进展,对反相固定相的合成、极性基团作用机理和色谱性质方面作了评述,对手性分离固定相和高效离子色谱固定相方面的进展也作了简单综述。     

Protein-based chiral stationary phases for high-performance liquid chromatography enantioseparations

The enantioseparations of various compounds using proteins as the chiral selectors in high-performance liquid chromatography (HPLC) are considered in this review. The proteins used include albumins such as bovine serum albumin and human serum albumin, glycoproteins such as alpha1-acid glycoprotein, ovomucoid, ovoglycoprotein, avidin and riboflavin binding protein, enzymes such as trypsin, alpha-chymotrypsin, cellobiohydrolase I, lysozyme, pepsin and amyloglucosidase, and other proteins such as ovotransferrin and beta-lactoglobulin. This review deals with the properties of HPLC chiral stationary phases based on proteins, and the enantioselective properties and chiral recognition mechanisms of these stationary phases.     

基于环糊精本征识别能力的手性色谱介质点击制备及应用

目前环糊精（CD）手性固定相（CSP）的研究大多集中于对CD或桥联臂进行功能衍生引入更多作用位点以提升手性拆分能力,鲜有能够反映天然CD本征识别能力的CSP的研究报道,该文通过"巯基-烯"点击化学反应合成了结构明确可控的单（6-巯基-6-去氧）-β -环糊精手性固定相（CSP1）,其最大限度地保留了天然CD的本征结构,且桥联臂无识别作用位点,固体核磁共振（¹³ C SSNMR）和红外光谱（FTIR）的表征结果证明了CSP1的成功制备,元素分析结果表明,与双键功能化硅胶相比,CSP1的C、H、N的百分含量均得到了提高,计算得出CSP1的表面CD固载量为0.82 μmol/m²。采用高效液相色谱反相模式对50多种手性对映体包括异（口恶）唑啉、手性交酯、手性酮、黄烷酮以及丹磺酰氨基酸等进行了手性拆分,充分考察了天然CD的本征手性识别能力,结果表明CD的本征识别能力比较有利于异（口恶）唑啉类样品中含有两个疏水苯环基团Ph-Ph类样品的分离,对于其他几类样品仅利于部分样品的分离。同时与前期制备的功能三唑桥联CD-CSP及咪唑嗡桥联CD-CSP在同一色谱条件下进行了结果比对,结果证明样品的分离过程除了与手性介质的结构有关外,还与样品分子的结构有很大关系,对桥联臂进行功能改性可提升对部分对映体的选择性,但同时会小幅损失CD的本征手性识别能力。对于环糊精本征识别能力易于分离的样品,在设计手性介质时,其桥联臂不需要任何官能团,这为CD固定相结构的设计提供了有益参考。