异噁唑啉及异噁唑烷类化合物在多糖衍生物类柱上的手性拆分

在ＣｈｉｒａｌｃｅｌＯＤ，ＣｈｉｒａｌｃｅｌＯＪ及ＣｈｉｒａｌｐａｋＡＤ等３种多糖类手性固定相上，以各种配比的正己烷－异丙醇为洗脱剂，对７种异口恶唑啉及异口恶唑烷类化合物的对映体进行了手性拆分。考察了这些外消旋物在这些手性柱上的色谱行为。实验结果表明，手性固定相上葡萄糖片段构型的差异和它们高级结构的不同以及手性固定相上的二甲基苯基氨基甲酸酯或对甲基苯甲酸酯等功能团与样品的极性基团之间的相互作用，可能是支配手性拆分的主要原因。方法已用于不对称１，３－偶极环加成反应产物的光学纯度鉴定。     

高效液相色谱法对反式-1,2-二取代环丙烷类化合物的手性拆分

在ＣｈｉｒａｌｃｅｌＯＤ和ＣｈｉｒａｌｃｅｌＯＪ柱上,以各种配比的正己烷／异丙醇为洗脱剂,对１３种反式－１,２－二取代环丙烷类化合物的对映体进行了手性拆分。考察了这些外消旋物在这两种柱上的色谱行为。实验表明带芳环的反式－１,２－二取代环丙烷类化合物在ＯＤ及ＯＪ柱上的拆分能力明显地与芳环上取代基的性质和位置有关。另一方面,一些带有脂族取代基的反式－１,２－二取代环丙烷类化合物也能在这两种柱上得到拆分。     

9-蒽醛衍生化-高效液相色谱法拆分α-氨基酸甲酯和几种脂肪胺对映体

采用高效液相色谱法,以9-蒽醛为衍生试剂,在5种多糖衍生物的手性固定相(CSPs)上对几种α-氨基酸甲酯对映体进行了手性分离。色谱条件如下: 流动相为含3%～10%(v/v)异丙醇的正己烷溶液,流速为1.0 mL/min,检测波长为254 nm。结果表明,α-氨基酸甲酯-9-蒽醛亚胺衍生物在Chiralcel OD柱或Chiralcel OD-H柱上的手性分离结果优于其他CSPs,而且在Chiralcel OD柱或Chiralcel OD-H柱上全部得到了基线拆分(α=1.24～5.47, Rs=2.56～13.90), L-对映体在这两种色谱柱上的保留强于D-对映体。同时还考察了几种脂肪胺在5种多糖衍生物手性固定相上的对映体拆分效果,结果表明脂肪胺的9-蒽醛亚胺衍生物在Chiralcel OD柱或Chiralcel OD-H柱上的分离效果良好。该法可用于其他α-氨基酸酯和胺类化合物对映体的分析。     

Direct chromatographic resolution of racemic aminoglutethimide and its acetylated metabolite using different cellulose based chiral stationary phases

Summary Two improved methods for the enantiomeric separation of racemic aminoglutethimide (±AG) and its acetylated metabolite (±AAG) have been developed. Direct liquid chromatographic resolution of the enantiomers of aminoglutethimide and its acetylated metabolite was accomplished using Chiralcel OD and Chiralcel OJ columns without any derivatization. Maximum resolution of 8.87 and 2.23 was obtained for the enantiomers of aminoglutethimide and its acetylated metabolite using a Chiralcel OD column, while maximum resolution of 10.34 and 7.01 was obtained for the enantiomers using a Chiralcel OJ column. Optimization of separation was obtained using different concentration of 2-propanol in hexane as a mobile phase.     

Liquid Chromatorgraphic Separation of the Enantiomers of Phenylthiohydantoin α-Amino Acids Derivatives on Polysaccharide-Based Chiral Stationary Phases

ABSTRACT

The liquid chromatographic enantioseparation of the phenylthiohydantoin (PTH) derivatives of various amino acids on four commercial polysaccharide-derived chiral stationary phases (CSPs) is described. Chiralcel OF and Chiralpak AS showed better performance than the other CSPs for resolution of the enantiomers of PTH amino acid derivatives. The enantiomers of all amino acids as their PTH derivatives were well separated on Chiralcel OF and/or Chiralpak AS. The (-)(L) or (-)-enantiomers of all analytes examined were preferentially retained on Chiralpak AS, whereas the (+)(D) or (+)-enantiomers of most of analytes were preferentially retained on Chiralcel OF.     

The solute molecule—Rigid or partially flexible? calculation of benzodiazepineR F values as an example

Summary The liquid-chromatographic separation of the enantiomers of amino acid esters as benzophenone Schiff-base derivatives on polysaccharide-derived chiral stationary phases (CSPs) is described. The performance of Chiralcel OF was superior to that of the other CSPs for resolution of benzophenone imine derivatives of amino acid ethyl and methyl esters. The enantiomers of most of the amino acid esters examined as their benzophenone imine derivatives were resolved to baseline on Chiralcel OF. The L-(−) enantiomers of all the analytes were preferentially retained on Chiralcel OF. The resolution of several imine derivatives of amino acid esters was investigated, as was the effect of eluent composition on the resolution of amino acid ethyl esters as their benzophenone imine derivatives.     

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.     

Liquid chromatographic enantiomer resolution of N-fluorenylmethoxycarbonyl alpha-amino acids and their ester derivatives on polysaccharide-derived chiral stationary phases

The liquid chromatographic enantiomer separation of N-fluorenylmethoxycarbonyl (FMOC) protected alpha-amino acids and their ethyl ester derivatives was performed on polysaccharide-derived chiral stationary phases, Chiralcel OD, Chiralpak AD, and Chiralpak AS. In general, Chiralcel OD and Chiralpak AD showed good performance for resolution of N-FMOC alpha-amino acids and their ethyl esters, respectively. All investigated N-FMOC alpha-amino acid enantiomers were baseline separated on Chiralcel OD or Chiralpak AD, whereas N-FMOC alpha-amino acid ethyl ester enantiomers were baseline resolved (alpha = 1.15-3.03) on Chiralpak AD, except for two analytes. The L-enantiomers of all examined FMOC alpha-amino acid ethyl ester derivatives are preferentially retained on Chiralpak AD, while the elution orders of the other enantiomer separations are not consistent.     

Comparative study between the polysaccharide-based chiralcel OJ and chiralcel OD CSPSs in chromatographic enantioseparation of imidazole analogues of fluoxetine and miconazole

The enantiomeric separation of a series of imidazole analogues of Fluoxetine and Miconazole endowed with potent antifungal activity was performed using cellulose tris(4-methylbenzoate) (Chiralcel OJ) and cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD) as chiral stationary phases. Binary mixtures of n-hexane and alcohol as well as pure alcohols (ethanol or 2-propanol) were used as eluents. The enantiomer elution order was monitored by chiroptical detectors based on on-line optical rotation and circular dichroism measurements. For some of the compounds studied very high enantioseparation factor values (alpha > 7) on Chiralcel OJ CSP were observed. In order to study the chiroptical characteristics of the two most biologically active compounds, chromatographic resolutions were carried out on a semipreparative scale. Assignment of the absolute configuration was empirically established by comparing the CD spectra of the separated enantiomers with those obtained from the enantiomers of Miconazole.     

Chiral Separation of Organic Phosphonate Compounds on Polysaccharide-Based Chiral Stationary Phases

Four polysaccharide-based chiral stationary phases have been used to separate the enantiomers of fourteen O,O-dialkyl-1-benzyloxycarbonyl-aminoarylmethyl phosphonates. These polysaccharide-based chiral stationary phases are Chiralpak AD, Chiralpak AS, Chiralcel OG and Chiralcel OJ. The data obtained indicate that the chiral separation ability for these organophosphonate compounds are in the order Chiralpak AD > Chiralcel OG > Chiralcel OJ > Chiralpak AS. With Chiralpak AD, all of the studied compounds could be easily baseline separated. Those two polysaccharides possess different chiral discrimination mechanism due to of the difference of the conformational structures of amylose and cellulose. The chiral discrimination of derivatized amylose chiral stationary phases were based on the stereogenic fit of the analytes in the helical structures of amylose and the transient diastereomeric complex formation between the analyte and the amylose CSP through π–π interaction H-bond interactions and induced dipole interactions exerted by the substituents on the analyte molecules. The chiral discrimination, in case of derivatized cellulose chiral stationary phase is based on the stereogenic fit of the analytes in the grooves of cellulose followed by interactions mentioned above between the analytes and the cellulose CSP.     

三唑农药的手性拆分及对映体的转化

利用Chiralcel OJ-H和Chiralcel OD-H手性柱对烯唑醇、三唑酮和三唑醇的手性拆分进行了研究,进一步测定了烯唑醇和三唑酮对映体的旋光性质,据此确定了两种农药对映体的绝对构型,在此基础上结合三唑酮转化为三唑醇的还原实验确定了三唑醇4个对映异构体的绝对构型。考察了几种三唑农药在有机溶剂和缓冲溶液中的手性稳定性,其中三唑酮在甲醇、乙醇和水中存在明显的对映体转化行为,而烯唑醇和三唑醇则是手性稳定的,升高温度及碱性环境会加快三唑酮的对映体转化。     

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.     

Direct separation of the enantiomers of cetirizine and related compounds by reversed-phase chiral HPLC

Summary Direct separations of the enantiomers of cetirizine and related compounds have been achieved by reversed-phase HPLC on the Chiralcel OD-R, a polysaccharide-derived chiral stationary phase; the mobile phase was usually perchlorate solution supplemented with acetonitrile. Resolution of the enantiomers of cetirizine and related compounds was good. The effect of the acetonitrile content of the mobile phase was investigated, and the effect of the structure of the chiral compounds on their behavior on the Chiralcel OD-R column is discussed.     

Evaluation of polysaccharide-based chiral stationary phases in quality control of (S)-mirtazapine

High-performance liquid chromatographic methods were developed for separation of the enantiomers of mirtazapine and its four process-related substances. The direct separations were achieved on chiral stationary phases containing amylose tris(3,5-dimethylphenylcarbamate) (Chiralpak AD-H), cellulose tris(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and cellulose tris(4-methylbenzoate) (Chiralcel OJ-H ). The experimental data were utilized to discuss the effects of the mobile phase composition, the nature of the alcoholic modifier and the specific structural features of the analytes on retention and separation. The elution sequence was determined under the optimized separation conditions.     

乙炔基氮杂环丙烷类化合物在Chiralcel OD柱上的高效液相手性拆分

用HPLC方法考察了11种乙炔基氮杂环丙烷类化合物在手性固定相Chiralcel OD柱上的色谱拆分行为。五种芳环上带有卤素，硝基和吡啶基的乙炔基氮杂环丙烷化合物的外消旋混合物在Chiralcel OD柱上能被很好地拆分。实验结果表明，手性固定相上的二甲基苯基氨基甲酸酯与外消旋样品上的极性基团之间的氢键作用，偶极-偶极作用和π-π作用可能是进行手性识别的主要原因。此方法已用于不对称氮杂环丙烷化反应产物光学纯度的鉴定。     

High-performance liquid chromatographic separation of imidazolinone herbicide enantiomers and their methyl derivatives on polysaccharide-coated chiral stationary phases

Many chiral pesticides exhibit enantioselectivity in biotransformation and ecotoxicity in the environment. A significant class of chiral pesticides is imidazolinone herbicides, of which enantioselectivity has not been well studied. Development of efficient chiral separation methods is the first step for allowing characterization of enantioselectivity in environmental processes. In this study, we attempted to resolve enantiomers of imidazolinone herbicides using reversed-phase and normal-phase high-performance liquid chromatography with polysaccharide-type chiral columns. Enantiomers of imazethapyr, imazaquin, and imazamox were separated on a Chiralcel OD-R column using 50mM phosphate buffer-acetonitrile as mobile phase. Enantiomers of imazapyr, imazapic, imazethapyr, imazamox and imazaquin were resolved on a Chiralcel OJ column using n-hexane (0.1% trifluoroacetic acid)-alcohol as mobile phase. The enantiomers of five methyl derivatives of imidazolinone herbicides were also resolved on the Chiralcel OJ column. The Deltak' values revealed a structure-enantioselectivity relationship for the separation behaviors of the enantiomers on the OJ column. The described method was successfully applied for chiral analysis of two imidazolinone herbicides (imazapyr and imazaquin) in spiked soil samples.     

Determination of the enantiomeric purity of nucleoside analogs related to d4T and acyclovir,new potential antiviral agents,using liquid chromatography on cellulose chiral stationary phases

We reported a method of determination of enantiomeric purity of the new potential antiviral agents by direct analytical HPLC. Those agents are nucleoside analogs, having one chiral center. They are synthesized as a single enantiomer (R or S) by an asymmetric pathway. The chiral stationary phases chosen are silica-based cellulose tris-3,5-dimethylphenylcarbamate (Chiralcel OD-H), or tris-methylbenzoate (Chiralcel OJ). Resolution was achieved using normal-phase chromatography with a mobile phase consisting of n-hexane-alcohol (ethanol or 2-propanol) in various percentages. Furthermore the effects of structural features on retention, selectivity and resolution, as well as on the elution order were thoroughly studied. Differences in the lipophilicity of the compounds were also examined.     

Supercritical fluid chromatography tandem-column method development in pharmaceutical sciences for a mixture of four stereoisomers

A tandem-column method using Chiralpak AD-H and Chiralcel OD-H columns was achieved for baseline separation of a mixture of chiral pharmaceutical compounds (i.e., four stereoisomers) via supercritical fluid chromatography (SFC) with a mobile phase consisting of 90% liquid carbon dioxide and 10% ethanol:isopropanol (50:50 v/v). On the contrary, this mixture (mixture A) could not be baseline separated by SFC conditions explored with individual Chiralpak AD-H and Chiralcel OD-H columns. The effects of various mobile phases on elution order, capacity factor, selectivity, and resolution were determined with mixture A on the individual aforementioned columns to develop the tandem-column method.     

Chiralcel OD-RH手性柱拆分安息香对映体的热力学研究

利用Chiralcel OD-H手性柱拆分外消旋安息香化合物制备单一对映体标样,并对其进行圆二色光谱表征。在此基础上,采用甲醇、乙醇、乙腈为流动相考察了安息香在Chiralcel OD-RH柱上的色谱拆分行为和热力学特性。结果表明:以纯甲醇为洗脱液时,(S)-构型先出峰,安息香的拆分过程为焓控;以纯乙醇为洗脱液时,(R)-构型先出峰,拆分过程为熵控;而以纯乙腈为洗脱液时,虽然也是(R)-构型先出峰,但熵和焓对拆分均有贡献。文中还对比了安息香在Chiralcel OD-H柱的拆分性能。     

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。