3种芳氧苯氧丙酸类除草剂在CDMPC与万古霉素手性固定相上的对映体分离

在纤维素三（3,5-二甲基苯基氨基甲酸酯）（CDMPC）手性柱上成功分离了3种高效芳氧苯氧丙酸类除草剂——稳杀得、千金和禾草灵。正相系统下,分别考察了流动相醇类添加剂的种类、浓度以及溶质结构对手性分离的影响,3种溶质中千金的保留最强而禾草灵的分离效果最好。并在万古霉素手性固定相上对3种芳氧苯氧丙酸类除草剂进行了手性拆分。在正相流动相中,它们在万古霉素手性固定相上的手性分离效果明显不如在CDMPC上的好。探讨了2种手性固定相对3种溶质的手性识别机理。     

去甲万古霉素键合手性固定相的制备及其对磷酸苯并哌啉对映异构体的拆分

制备了去甲万古霉素键合手性固定相以及由苯基异氰酸酯衍生化去甲万古霉素键合手性固定相,并在极性有机相模式下对磷酸苯并哌啉进行了手性拆分的研究。发现在此模式下,衍生化去甲万古霉素键合手性固定相对磷酸苯并哌啉的手性选择性要优于没有衍生的去甲万古霉素键合手性固定相;在衍生化去甲万古霉素键合手性固定相上详细考察了流动相组成、酸碱添加剂用量、温度以及流速对分离的影响,优化了分离的条件。在优化的实验条件下,磷酸苯并哌啉可获得基线分离。     

万古霉素手性固定相分离几种药物对映体

采用高效液相色谱极性有机分离模式，在万古霉素手性固定相上，对阿替洛尔、噻利洛尔、卡替洛尔、沙丁胺醇、尼卡地平、异丙嗪6种药物对映体进行了手性分离；选用甲醇和不同比例的冰醋酸—三乙胺为洗脱剂，6种药物均达到基线分离；研究了流动相组成、比例及流速对分离的影响。     

氟西汀衍生物对映体在纤维素手性固定相上的拆分

用纤维素-三(3,5-二甲苯基氨基甲酸酯)(Chiraleel OD)手性固定相拆分了两种氟西汀衍生物对映体。使用15cm长色谱柱分离NBD-氟西汀衍生物的流动相为四氢呋喃／正己烷(25：75),分离DBD-氟西汀衍生物的流动相为四氢呋喃／正己烷(20：80);流速为1．0mL/min,荧光检测,柱温为室温。醇类改性剂作流动相甚至不能部分拆分氟西汀衍生物。实验考察了四氢呋喃含量和柱长对手性分离的影响,探讨了手性拆分氟西汀衍生物的机理。     

六种氨基醇药物在1-萘万古霉素手性固定相上的对映体分离

在1-萘万古霉素手性固定相上分离了6种氨基醇类药物的对映体。考察了流动相中的酸、碱添加剂种类和浓度、溶质的化学结构对对映体分离的影响,同时探讨了手性识别机理。结果表明:普萘洛尔、比索洛尔、阿替洛尔、美托洛尔、索他洛尔和沙丁胺醇等6种药物的对映体在1-萘万古霉素手性柱上得到了完全分离,当甲醇流动相中冰乙酸和三乙胺添加剂量均为0.001%(体积分数)时,6种氨基醇的选择因子依次是1.16,1.36,1.15,1.10,1.18,1.16。     

万古霉素手性固定相分离克伦特罗对映体

应用万古霉素手性固定相对克伦特罗对映体进行了分离,考察了洗脱模式、流动相组成、柱温等因素对分离的影响,并对其分离机制进行了探讨.最佳色谱条件为:甲醇-冰醋酸-三乙胺(体积比100:0.01:0.01),流速1.0mL/min,柱温20℃.在此条件下,克伦特罗对映体可实现基线分离,最大分离度可达2.67.克伦特罗对映体与固定相之间的离子相互作用是实现对映体分离的最主要分离机制.     

3，5-二甲基苯基异氰酸酯替考拉宁和苯基异氰酸酯替考拉宁手性固定相的评价与比较

用大环抗生素替考拉宁手性固定相(TE CSP)分别与3,5-二甲基苯基异氰酸酯和苯基异氰酸酯反应得到了两种新型的高效液相色谱手性固定相----3,5-二甲基苯基异氰酸酯替考拉宁手性固定相(DMP-TE CSP)和苯基异氰酸酯替考拉宁手性固定相(Ph-TE CSP)。用十八个手性化合物在反相及极性流动相模式对这两种CSP的对映体分离能力进行了评价和比较。在反相流动相中,十二个化合物（包括八个氨基酸和四个非氨基酸化合物----对羟基苯甘氨酸,拉米夫定,醇酸和去甲羟安定）的对映体在这两种手性固定相上都获得了分离,大部分的溶质在DMP-TE上获得了更强的保留和稍好的手性分离效果。在极性流动相中,六个氨基醇类化合物在DMP-TE上获得了更强的保留,但它们在两种CSP上的选择因子几乎没有区别。对自制的替考拉宁衍生物手性固定相进行评价和比较,将有助于大环糖肽类抗生素手性固定相手性识别机理的研究。     

新型L-羟脯氨酸聚合物键合手性固定相的制备及对手性化合物的拆分

以单分散亲水性交联聚甲基丙烯酸环氧丙酯-甲基丙烯酸乙二醇双酯(PGMA/EDMA)树脂为载体,制备新型L-羟脯氨酸聚合物键合高效手性配体交换固定相。该固定相在配体交换分离模式下,以0.2mol/LNaAc和0.1mmol/LCu(Ac)2水溶液(pH5.2)为流动相,柱温为30℃～50℃,对衍生和非衍生的D,L-氨基酸和α-羟基酸等9种手性化合物进行了高效液相色谱拆分。详细考察了流动相pH值、温度、流速和进样量对手性分离的影响,选择了合适的色谱分离条件。结果表明,所拆分的9种手性化合物,有5种手性化合物能得到基线分离,最好的分离因子α=2.32。     

全衍生化羟丙基-β-环糊精固定相的制备及应用

研究了3, 5-二甲基苯基异氰酸酯对羟丙基-β-环糊精固定相的手性识别影响.通过异氰酸丙基三乙氧基硅烷作偶联剂,将羟丙基-β-环糊精键合到3-氨丙基硅烷化硅胶上,再用3, 5-二甲基苯基异氰酸酯对β-环糊精和硅胶其余羟基进行衍生化,制得一种新型的3, 5-二甲基苯基氨基甲酸酯全衍生化羟丙基-β-环糊精键合硅胶手性固定相.在反相色谱条件下,对9种手性药物进行了拆分,结果表明,3, 5-二甲基苯基氨基全衍生化固定相较之羟丙基-β-环糊精固定相有更好的分离效果.     

万古霉素手性固定相分离曼尼希碱类化合物对映体

采用大环抗生素类万古霉素手性固定相高效液相色谱法研究了一系列曼尼希碱类化合物的手性分离情况,并讨论了流动相中有机相的种类和比例、缓冲盐的种类和浓度、pH和柱温对该类化合物手性分离的影响。最佳实验条件为:乙腈:硝酸铵(35mmol/L,pH3.8)=15∶85(V/V),柱温15℃,流速0.6mL/min,检测波长300nm;四氢呋喃:硝酸铵(20mmol/L,pH4)=15∶85(V/V),柱温15℃,流速0.6mL/min,检测波长350nm。通过对比研究8种曼尼希碱类化合物的色谱行为,从结构上讨论了化合物中各种官能团对手性分离的影响,并探讨了手性分离的内在机制。     

大环抗生素手性固定相拆分盐酸马布特罗对映体

基于三种大环抗生素类手性固定相Chirobiotic V,T和R,利用高效液相色谱法对盐酸马布特罗对映体进行了拆分;考察了洗脱模式、流动相组成、柱温等因素对分离的影响,对分离结果进行了比较,对分离机制进行了探讨.结果表明,盐酸马布特罗对映体在Chirobiotic R手性固定相上不能实现分离,在Chirobiotic V和T手性固定相上均可实现较好的基线分离.最佳色谱条件为:新极性有机相模式,流动相甲醇-冰醋酸-三乙胺(100∶0.01∶0.01,V/V/V),流速1.0mL/min,柱温20℃;相应的分离度分别可达3.08和3.73.与此同时,盐酸马布特罗对映体与大环抗生素类固定相之间的离子相互作用是实现对映体分离的最主要分离机制.     

Evaluation and Comparison of a 3,5‐Dimethylphenyl Isocyanate Teicoplanin with Phenyl Isocyanate Teicoplanin Chiral Stationary Phase Using RP‐HPLC

HPLC enantiomeric separations of 8 α‐amino acids were achieved using two self‐made chiral stationary phases (CSP)–phenyl isocyanate teicoplanin (Phe‐TE) and 3,5‐dimethylphenyl isocyanate teicoplanin (DMP‐TE), using reversed phase mobile phases. The Phe‐TE or the DMP‐TE CSP was prepared from the TE using derivative agents, phenyl isocyanate or 3,5‐dimethylphenyl isocyanate, respectively. The chromatographic results were given as the retention, selectivity, resolution factor and the enantioselective free energy difference corresponding to the separation of the two enantiomers. The effect of pH, organic modifier type and amount were discussed, and the stereoselectivities for two TE‐based CSPs were compared. The chiral selectivity factor for six α‐amino acids on DMP‐TE is somewhat bigger than that on Phe‐TE CSP under reversed phase (RP) mode. Comparison of the enantiomeric separations using self‐made Phe‐TE and DMP‐TE was conducted to gain a better understanding of the chiral recognition mechanism of the macrocyclic glycopeptide CSP.     

Comparison of enantioseparation of selected benzodiazepine and phenothiazine derivatives on chiral stationary phases based on β‐cyclodextrin and macrocyclic antibiotics

Enantioselective separation of some phenothiazine and benzodiazepine derivatives was studied on six different chiral stationary phases (CSPs) in HPLC. Selected CSPs, with respect to the structure of the separated compounds, were either based on β‐cyclodextrin chiral selectors – underivatized β‐cyclodextrin and hydroxypropyl ether β‐cyclodextrin, or on macrocyclic antibiotics – vancomycin, teicoplanin, teicoplanin aglycone, and ristocetin A. Measurements were carried out in a reversed‐phase separation mode. The influence of mobile phase composition on retention and enantioseparation was studied. Benzodiazepines could be enantioresolved with almost all the chiral stationary phases used, except for the vancomycin‐bonded CSP. Peak coalescence of oxazepam and lorazepam was observed if separation was carried out at laboratory temperature. Reduced temperature was required in some instances in order to avoid the on‐column racemization. Separation systems composed of teicoplanin‐bonded CSP and buffer‐methanolic or pure methanolic mobile phases were shown to be suitable even for preparative purposes due to high resolution values of the enantiomers. Enantioseparation of phenothiazine derivatives was more difficult to achieve but it was successful, at least partly, also with both types of the CSPs used (except for levomepromazine).     

Comparative Enantioseparation of Seven Amino Alcohols on Teicoplanin‐Based Chiral Stationary Phases

Abstract

The macrocyclic antibiotics represent a relatively new class of chiral selectors in separation science and teicoplanin‐based chiral stationary phases (CSP) have been used successfully in a number of applications in high‐performance liquid chromatography. In the present studies, we self‐prepared two bonded CSPs–teicoplanin (TE) and teicoplanin phenyl isocyanate (TE‐Phe). Seven amino alcohols, propranolol, bisoprolol fumarate, atenolol, salbutamol, isoproterenol, metoprolol, and labetalol were enantioseparated on both self‐made CSPs using methanol as mobile phase and acetic acid (HOAc) and triethylamine (TEA) as mobile phase additives. On both CSPs, the different enantioseparation behavior of analytes with different structure was compared. The influence of the concentration of mobile phase additives (HOAc and TEA) on the enantioseparation was investigated. In all conditions, the retention factors (k′) of seven analytes on TE‐Phe CSP were larger than that on TE CSP. However, the separation factors (α) and resolutions (Rs) on TE‐Phe CSP were smaller than that on TE CSP. The results indicated that the derivatized TE‐Phe CSP is not efficient as original teicoplanin CSP. Our observations also suggested that, for teicoplanin‐based CSPs, π‐π interactions and dipole‐dipole between solutes and CSPs mainly contribute to the retention of solutes on CSPs while hydrogen bonding and steric interactions play important roles in the chiral recognition for teicoplanin‐based CSPs.     

The Resolution of Enantiomeric Ibuprofen on Chiral Stationary Phases Containing N-Arylcarbamoyl Derivatives of Phenylglycine

A series of fourteen anilide derivatives of ibuprofen were resolved on six chiral stationary phases (CSPs) derived from N-arylcarbamoyl derivatives of (S)-phenylglycine. Excellent chiral resolutions were achieved on these CSPs. The ionic-type CSPs showed better chiral recognition abilities than the corresponding covalent-type CSPs, and the CSP bearing two chiral centers has better performance than the CSPs bearing only one chiral center. The highest separation factor was achieved using the ionic-type CSP bearing two chiral centers for the resolution of the 3,5-dinitroanilide derivative of ibuprofen. This result is better than those reported in literature for the resolution of ibuprofen on the CSPs derived from amino acids, According to the chromatographic behaviors, the hydrogen bonding interaction, the π-π interactions provided by the phenyl groups in CSPs bearing one chiral center, and the phenylethylcarbamoyl moiety in CSPs bearing two chiral centers dominate the chiral recognition.     

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。     

Preparation of two new liquid chromatographic chiral stationary phases based on diastereomeric chiral crown ethers incorporating two different chiral units and their applications

Two new liquid chromatographic chiral stationary phases based on diastereomeric chiral crown ethers incorporating two different chiral units such as optically active 3,3'-diphenyl-1,1'-binaphthyl and tartaric acid unit were prepared. Between the two CSPs, one was much superior to the other especially in the resolution of tocainide and its analogues (for example, in the resolution of tocainide the separation factor, alpha, was 4.26 vs. 1.00 on the two CSPs). From these results, the two chiral units composing the two diastereomeric chiral crown ether moieties of the stationary phases were expected to show "matched" or "mismatched" effect on the chiral recognition according to their stereochemistry. The different chiral recognition abilities of the two CSPs were rationalized by the different three-dimensional structures of the two diastereomeric chiral crown ethers.     

Preparation and characterization of phenyl carbamate derivative β-cyclodextrin bonded phase for chiral HPLC

A partially substituted β-cyclodextrin chiral stationary phase was prepared by the reaction of phenyl isocyanate. The enantiomers of a series of O,O-diethyl(p-methylbenzenesulfonamido)-aryl(or alkyl)-methylphosphonates were studied on the prepared phenyl carbamate derivative β-cyclodextrin bonded phase and a commercial (S)-(+)-1–(1-naphthyl) ethylcarbamate derivative β-cyclodextrin bonded phase on normal phase chromatographic condition. Results show that the prepared phenyl carbamate derivative β-cyclodextrin bonded phase has better enantiomeric selectivity to the series of compounds. A chiral recognition mechanism was suggested for the separation of these novel organic phosphorus enantiomers.     

Simultaneous separation and enantioseparation of thalidomide and its hydroxylated metabolites using high-performance liquid chromatography in common-size columns, capillary liquid chromatography and nonaqueous capillary electrochromatography

The separation of thalidomide (TD) and its hydroxylated metabolites including their simultaneous enantioseparation was studied using three different polysaccharide-type chiral stationary phases (CSPs) in combination with polar organic mobile phases. Three different techniques, high-performance liquid chromatography in common-size columns, capillary LC and nonaqueous capillary electrochromatography were compared in terms of separation. As this study illustrates, polar organic mobile phases represent a valuable extension for less polar and polar aqueous-organic mobile phases in combination with polysaccharide CSPs. Chiralpak AD consisting of 25% of amylose-tris(3,5-dimethylphenylcarbamate) coated on wide-pore aminopropylsilanized silica gel exhibited higher resolving ability compared to the similar cellulose derivative (Chiralcel OD) as well as to cellulose-tris(4-methylbenzoate) (Chiralcel OJ) CSPs for this particular set of chiral analytes. Baseline separation and simultaneous enantioseparation of all three compounds could be achieved under optimized separation conditions.     

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...