键合偶联双奎宁手性固定相的制备和手性拆分性能

键合偶联双奎宁手性固定相的制备和手性拆分性能;手性固定相;奎宁;高效液相色谱;拆分     

手性胺酰胺型液相色谱手性固定相的制备及几种氨基酸衍生物的拆分

用(R)-1-苯基2-对甲基苯基乙基胺(PTE)与L-异亮氨酸制得含两个手性中心的手性选择剂,以琥珀酸酐作为连接臂,将手性选择剂键合到氨基丙基硅胶上制得手性固定相。以正己烷-异丙醇为流动相,利用该固定相对氨基酸衍生物进行高效液相色谱手性拆分,并考察了流动相中异丙醇含量对手性拆分的影响。结果表明,该手性固定相对所分析的氨基酸衍生物大部分都具有一定的拆分能力。当异丙醇含量为1%时,亮氨酸与苯丙氨酸的苯甲酰甲酯衍生物获得基线分离。当异丙醇含量为20%时,亮氨酸、缬氨酸、丙氨酸、谷氨酸的3,5-二硝基苯甲酰甲酯衍生物获得基线分离。     

新型氨基酸衍生物手性固定相的制备及应用

氨基酸是手性小分子,其选择和固定化的方法,有助于开发新的“刷型”手性固定相(CSP)。 分别以L-缬氨酸和L-丙氨酸为原料制备了10种新型氨基酸衍生物手性固定相(CSPs),包括8种氨基酸三嗪衍生物CSPs(CSP-1~CSP-8)和两种对甲基苯甲酰氨基酸CSPs(CSP-9~CSP-10),在正相色谱条件下,考察了所合成的CSPs对邻、间和对硝基苯酚位置异构体以及萘普生乙酯、丙环唑、苯醚甲环唑、戊唑醇、己唑醇和联萘酚6种外消旋样品的分离能力。 结果表明,硝基苯酚的3种位置异构体在CSP-1~CSP-3和CSP-6~CSP-8上获得较好分离。 相同条件下,由丙氨酸制得的CSPs对外消旋样品表现出更好的手性识别能力,萘普生乙酯在CSP-6上获得基线分离。 由化学软件Gaussian 09计算出的L-丙氨酸三取代三嗪衍生物CSP-Ⅵ与萘普生乙酯的两个光学异构体之间相互作用的结合能分别为52.51和133.9 kJ/mol,也说明了手性选择子与R、S形成的非对映配合物的稳定性不同,Gaussian 09所给出的结合构型图显示手性选择子与样品之间有明显的氢键作用。 Gaussian 09的计算结果有助于认识CSPs的手性识别机理。     

同时烙印分子烙印手性固定相

对采用两种对本同时烙印的方法,制备的氨基酸衍生物分子烙印手性固定相进行了考察。研究表明,如果两种烙印分子单独烙印的分子烙印手性对固定相对两种烙印分子具有较强的手性交叉拆分能力,那么这两种烙印分子同时烙印制得的分子烙印手性固定相就可对两种烙印分子均具有很好的手性分离能力,从而使专一性强的分子烙印手性固定相能同时分离多种对映体。     

酰胺型手性固定相直接拆分克仑特罗对映体

 将酰胺型手性固定相用于正相高效液相直接拆分 β2 受体兴奋剂克仑特罗。讨论了三元流动相中正己烷、1,2 二氯乙烷和甲醇含量的变化以及柱温和流速对分离的影响 ;优化了实验条件 :流动相为V(正己烷 )∶V(二氯乙烷 )∶V(甲醇 ) =5 4∶38∶8,柱温为 17℃ ,流速为 1 0mL/min ;并对拆分的机理加以探讨。方法简单、快速。     

氨基酸聚合物作为高效液相色谱手性固定相的研究

将L-丙氨酸、L-缬氨酸、L-色氨酸、L-苯甘氨酸和L-苯丙氨酸5种氨基酸的手性单体与甲基丙烯酸-3-(三甲氧基硅基)丙酯共聚到硅胶表面制备了5种氨基酸聚合物手性固定相,并用作高效液相色谱手性固定相。考察了它们的手性识别能力,L-丙氨酸、L-缬氨酸和L-色氨酸聚合物手性固定相具有较好的手性拆分效果,并且它们之间的手性识别能力还具有一定的互补性。     

改性环糊精手性固定相性能及对映体拆分研究

比较了合成的４种戊基化环糊精手性固定相对Ｇｒｏｂ试剂的保留性能。对２０种对映体进行拆分并研究了其可能的拆分机理。     

温度对蛋白和β-环糊精手性固定相拆分对映体的影响

 采用三聚氯氰为活化剂分别合成了牛血清白蛋白 (BSA)、人血清白蛋白 (HSA)和 β 环糊精手性固定相 ,研究了温度在色氨酸 ,华法令 ,酮基布洛芬和丹酰化苏氨酸手性拆分中的影响。结果表明 ,在蛋白手性固定相上对映体间的熵变对色氨酸 ,华法令和酮基布洛芬的拆分有很大的影响 ,而丹酰化苏氨酸对映体在 β 环糊精手性固定相上的拆分为典型的焓控过程 ,与蛋白柱有着不同的热力学特性。由于键合方式不同 ,色氨酸在我们合成的BSA手性固定相上的最佳分离温度为 35℃左右 ,而不是文献报道的以戊二醛为活化剂的 2 4℃。     

酰胺型手性固定相反相拆分布洛芬药物对映体

利用酰胺型手性固定相反相拆分了布洛芬对映异构体,用有０．０１ｍｏｌ／Ｌ ＮＨ４Ａｃ的甲醇和水作流动相。在优化分离条件的同时,研究了不同的有机调节和对分离的影响,并探讨了分离的机理。     

乳酸烷基酯在接枝聚硅氧烷β-环糊精固定相的手性拆分

采用新合成的手性接枝聚硅氧烷β－环糊精（二环「２，６－二－０－戊基－３－０－已烯基（－５）」五环「２，６－二－０－戊基－３－０－甲基」－β－ＣＤ－聚硅氧烷）固定相制备了毛细管气相色谱柱，对合成的不对称化合物乳酸烷基进行了有效的手性拆分，结果表明该固定相具有良好的手性分离能力。     

Zwitterionic chiral stationary phases based on cinchona and chiral sulfonic acids for the direct stereoselective separation of amino acids and other amphoteric compounds

An extensive series of free amino acids and analogs were directly resolved into enantiomers (and stereoisomers where appropriate) by HPLC on zwitterionic chiral stationary phases (Chiralpak ZWIX(+) and Chiralpak ZWIX(?)). The interaction and chiral recognition mechanisms were based on the synergistic double ion‐paring process between the analyte and the chiral selectors. The chiral separation and elution order were found to be predictable for primary α‐amino acids with apolar aliphatic side chains. A systematic investigation was undertaken to gain an insight into the influence of the structural features on the enantiorecognition. The presence of polar and/or aromatic groups in the analyte structure is believed to tune the double ion‐paring equilibrium by the involvement of the secondary interaction forces such as hydrogen bonding, Van der Waals forces and π–π stacking in concert with steric parameters. The ZWIX chiral columns were able to separate enantiomers and stereoisomers of various amphoteric compounds with no need for precolumn derivatization. Column switching between ZWIX(+) and ZWIX(?) is believed to be an instrumental tool to reverse or control the enantiomers elution order, due to the complementarity of the applied chiral selectors.     

冠醚固定相的制备及手性拆分

以R-联萘酚为原料合成了R-(1,1′-二萘基)-20-冠-6,并将其涂敷于C18硅胶(平均粒径5μm,孔径120nm)上制成了可用于高效液相色谱手性拆分的R-(1,1′-二萘基)-20-冠-6冠醚固定相(CSP).在以pH=2的高氯酸溶液为流动相,流速为0.1mL·min-1,柱温为25℃的条件下,研究了CSP对9种α-氨基酸对映体的拆分能力.实验结果表明,有5种手性氨基酸(缬氨酸、苯甘氨酸、对羟基苯甘氨酸、谷氨酸、色氨酸)得到不同程度的拆分,说明CSP能对手性氨基酸进行一定的拆分.     

Preparation and evaluation of novel chiral stationary phases based on quinine derivatives comprising crown ether moieties

The C9‐position of quinine was modified by meta‐ or para‐substituted benzo‐18‐crown‐6, and immobilized on 3‐mercaptopropyl‐modified silica gel through the radical thiol‐ene addition reaction. These two chiral stationary phases were evaluated by chiral acids, amino acids, and chiral primary amines. The crown ether moiety on the quinine anion exchanger provided a ligand‐exchange site for primary amino groups, which played an important role in the retention and enantioselectivity for chiral compounds containing primary amine groups. These two stationary phases showed good selectivity for some amino acids. The complex interaction between crown ether and protonated primary amino group was investigated by the addition of inorganic salts such as LiCl, NH₄Cl, NaCl, and KCl to the mobile phase. The resolution results showed that the simultaneous interactions between two function moieties (quinine and crown ether) and amino acids were important for the chiral separation.     

Liquid chromatographic separation of the enantiomers of beta-amino acids on a ligand exchange chiral stationary phase

A liquid chromatographic ligand exchange chiral stationary phase (CSP) derived from (S)-leucinol was applied in the separation of the enantiomers of 12 beta-amino acids. The resolution was quite successful especially for the enantiomers of beta-amino acids containing aromatic functional group in the side chain. The chromatographic resolution behaviors were dependent on the organic modifier and Cu(II) concentration in aqueous mobile phase and the column temperature.     

The effect of analyte lipophilicity on the resolution of α-amino acids on a HPLC chiral stationary phase based on crown ether

The effect of analyte lipophilicity on the resolution of α-amino acids on a chiral stationary phase based on chiral crown ether has been examined by the chromatographic resolution trends for the resolution of a homologous series of five α-amino acids with an alkyl group of different length at the chiral center. The retention factors (k₁ and k₂) for the two enantiomers and the separation factors (α) were found to depend on the lipophilicity of the α-amino acid. In general, the retention factors increased as the organic modifier content in the mobile phase increased, the degree of the enhancement of retention factors being dependent on the analyte lipophilicity. The separation factors also increased as the analyte lipophilicity and the organic modifier content in the mobile phase increased. Possible rationales for these behaviors have been proposed.     

Preparation of a new crown ether-based chiral stationary phase containing thioester linkage for the liquid chromatographic separation of enantiomers

A new chiral stationary phase (CSP) containing thioester linkages was prepared by bonding (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid to mercaptopropylsilica gel. The chiral recognition ability of the new CSP was found to be greater than that of the previously reported CSP containing amide linkages in the resolution of the various α-amino acids that were tested, except for that of Met, Ser and Thr. In the resolution of racemic amines and amino alcohols, the new CSP was always better than the one containing amide linkages in terms of the separation factors (α) and the resolutions (R_S). Given the identical elution orders on the two CSPs, it was concluded that the chiral recognition mechanism is not affected by the change of the linkage type. In addition, the new CSP was found to be quite stable under the acidic mobile phase conditions that were utilized, indicating that the thioester linkage is useful as a tethering group.     

Thermodynamic enantioseparation behavior of phenylthiohydantoin‐amino acid derivatives in supercritical fluid chromatography on polysaccharide chiral stationary phases

Thirteen pairs of enantiomers belonging to the same structural family (phenylthiohydantoin‐amino acids) were analyzed on two polysaccharide chiral stationary phases, namely, tris‐(3,5‐dimethylphenylcarbamate) of amylose (Chiralpak AD‐H) or cellulose (Chiralcel OD‐H) in supercritical fluid chromatography with a carbon dioxide/methanol mobile phase (90:10 v/v). Five different temperatures (5, 10, 20, 30, 40°C) were applied to evaluate the thermodynamic behavior of these enantioseparations. On the cellulose stationary phase, the retention, and separation trends were most similar among the set of probe analytes, suggesting that the chiral cavities in this stationary phase have little diversity, or that all analytes accessed the same cavities. Conversely, the retention and separation trends on the amylose phase were much more diverse, and could be related to structural differences among the set of probe analytes (carbon chain length in the amino acid residue, secondary amine in proline, existence of covalent rings, or formation of pseudo‐rings via intramolecular hydrogen bonds). The large variability of behaviors on the amylose phase suggests that the chiral‐binding sites in this chiral stationary phase have more variety than on the cellulose phase, and that the analytes did access different cavities.     

Preparation and characteristics of two new GC stationary phases-dihydroxy crown ether containing polysiloxane

Summary Two new kinds of crown ethers: 3,5-dibutyl-unsymmetrydibenzo-14-crown-4-dihydroxy (cis-, and trans-) with the OH-terminal silicone oil in different proportion were coated on glass capillary columns, and immobilized by condensation using a coupling agent of alkyltrimethoxysilane. Chromatographic characteristics, including column efficiency, polarity, selectivity, phase transition temperature and thermal stability were studied. The columns were compared with PEG-20M in terms of polarity and selectivity. The immobilization and retention mechanisms are also discussed.     

β-环糊精键合手性固定相分离苯并恶嗪类对映体

研究了在反相高效液相色谱模式下,基于点击化学的β-环糊精手性固定相对苯并恶嗪类对映体的手性分离情况。考察了流动相中有机改性剂的类型和比例、缓冲盐的浓度和pH值对分离的影响。考察结果表明: 乙腈作为有机改性剂比甲醇更有利于苯并恶嗪对映体的分离;乙酸三乙胺缓冲盐体积分数从0.1%增大到1.0%时,苯并恶嗪对映体的保留时间和分离度都随之减小,在pH 4.1时苯并恶嗪对映体具有最大分离度。因此确定乙腈和体积分数为0.1%的乙酸三乙胺缓冲盐流动相(pH 4.1)为最佳分离条件。分离机理研究结果表明,固定相和样品之间的包容络合相互作用以及样品和固定相之间的氢键作用,是样品得以分离的基础。本研究为进一步深入研究β-环糊精固定相提供了实验基础,同时也证明了点击化学在手性环糊精固定相制备中具有极大潜力。     

Complexation and transport of amino acid esters and their salts with synthesised chiral novel aza crown ether derivatives

The syntheses of four aza-15-crown-5 ethers bearing phenyl and phenoxymethyl moieties attached to a stereogenic centre on the crown ring were achieved. Macrocycles have exhibited strong binding ability (K_a = 5364–12,969 M^? 1) and modest enantiomeric discrimination towards the enantiomers of amino acid methyl ester salts by UV titration method in CHCl₃ at 25°C. Computer modelling results supported experimental data providing a detailed understanding of the molecular recognition mode between hosts and guests and the likely binding sites involved. Macrocycles were used for chiral discrimination of amino acids in their zwitterionic forms or as potassium and sodium salts in transport experiments across a bulk chloroform membrane with satisfactory selectivity.