脲衍生物型手性固定相分离α－氨基酸对映体的研究

 利用脲衍生物型手性色谱柱，作正相和反相液相色谱拆分Ｎ－３，５－二硝基苯甲酰化氨基酸丁酯衍生物。结果表明，正相色谱的手性分离效果比反相色谱要好得多，并且手性洗脱顺序完全相反。认为在固定相上对拆分起主要作用的可能是（Ｒ）－１－（α－萘基）乙胺部分的手性碳原子，而另外一个手性碳原子在拆分过程中起辅助作用。流动相在拆分过程中起着很重要的作用。     

高效液相色谱手性固定相法拆分α—氨基酸衍生物对映体

在纤维素－三（３，５－二甲基苯基氨基甲酸酯）（ＣＤＭＰＣ）手性柱上，凤正己烷－醇为流动相，对３种外消旋氨基酸衍生物（苯乙内酰脲）在正相模式下进行了拆分。考察了流动相中醇链长度、醇的立体结构、醇的含量对手性拆分的影响。首次用三元流动相体系对样品进行了拆分，发现利用三元流动相体系可达到最佳拆分效果。根据试验结果，对样品在ＣＤＭＰＣ－ＣＳＰ手性固定相上的正相手性识别机理进行了讨论。     

氟环唑外消旋体在纤维素-三(3,5-二甲基苯基氨基甲酸酯)手性固定相上的高效液相色谱法拆分

在纤维素-三(3,5-二甲基苯基氨基甲酸酯)（CDMPC）手性固定相上,分别采用正相、反相及极性有机相色谱模式对氟环唑外消旋体进行了拆分,并考察了流动相组成在手性识别中对手性分离的影响。氟环唑在Chiralcel OD-H手性色谱柱（填充CDMPC手性固定相）上采用反相色谱模式,以甲醇-水(体积比为80∶20)为流动相,获得了最佳的拆分,其两对对映异构体的分离度Rs分别为1.64和6.50。     

β-环糊精及其衍生物手性添加剂HPLC法拆分氯噻酮对映体过程热力学研究

以Me-β-环糊精为手性流动相添加剂,于Lichrospher C18反相柱上建立了氯噻酮对映体高效液相色谱拆分方法,同时改进了β-环糊精、HP-β-环糊精为手性流动相添加剂拆分氯噻酮对映体的色谱条件,并着重研究了在25-45℃范围内Me-β-CD、β-CD和HP-β-CD为手性流动相添加剂拆分氯噻酮对映体的过程热力学并结合手性药物氯噻酮所得的热力学数据对环糊精及其衍生物拆分能力的差异进行了比较和分析。结果表明都属于焓控过程,其拆分能力的不同主要是因为手性添加剂与对映体形成氢键作用、空间位阻效应和立体构象匹配程度存在差异。     

高效液相色谱中的纤维素衍生物手性固定相

评述了高效液相色谱中纤维素衍生物手性固定相直接拆分对映体的进展，介绍了纤维素衍生物的主要类型，纤维素衍生物作手性固定相三种不同方式的特点以及新的纤维素衍生物手性固定相应用，并结合色谱，NMR和分子模型设计和理论计算等方法讨论了纤维素衍生物手性固定的拆分机理。     

高效液相色谱手性固定相法直接拆分外消旋雷诺嗪

在反相以及正相争件下，利用自制的涂敷型纤维素-三（3，5-二甲基苯基氨基甲酸酯）手性固定相直接拆分了外消旋雷诺嗪，并考察了不同流动相对手性拆分的影响，特别是醇类物质对拆分影响。结果表明，醇的立体结构、极性对雷诺嗪的手性拆分均有影响。实验结果显示无论在正相条件下还是在反相条件下，涂敷型纤维素-三（3，5-二甲基苯基氨基甲酸酯）手性固定相均可以很好的拆分外消旋体雷诺嗪。     

手性固定相法拆分卟唑羧酸衍生物对映异构体

用直链淀粉－三（3，5－二甲基苯基氨基甲酸酯）手性固定相，在正相条件下首次拆分了6种卟唑羧酸衍生物对映异构体。考察了流动相中不同的酸性添加剂、不同的正丙醇浓度对样品和拆分的影响。     

2,6—O—二丁基—3—O—三氟乙酰基—γ—环糊精拆分一些氨基酸及分离机理探讨

用２，６－Ｏ－二丁基－３Ｏ－三氟乙酰基－γ－环糊精手性毛细管柱测定了一些氨基酸，羟基酸衍生物拆分过程的热力学数据△Ｈ°，△（△Ｓ°）。应用熵焓补偿关系对其进行了分析，认为构象诱导楔合及多点协同作用在手性拆分中可能起重要作用，对映体两构在同一固定相上拆分也可能不同，后流出构型可能与环糊精衍生物形成较稳定的包结物。     

薄层色谱用纤维素苯甲酸酯类手性固定相的制备及色谱性能

用超声方法合成了3种纤维素苯甲酸酯类手性固定相，三（苯甲酰基）纤维素（CTB）、三（4－甲基苯甲酰基）纤维素（CTMB）、三（4－硝基苯甲酰基）纤维素（CTPNB）；该类手性固定相（CSP）用于薄层色谱分离手性药物对映体，采用合适的展开剂系统，共有6对含氮手性药物获得了安全分离；比较了3种手性固定相的拆分性能，表明CTB和CTMB对手性药物显示出良好的拆分性能，而CTPNB的拆分性能较差。     

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.     

Enantiomeric separations of amino acids with inductively coupled plasma carbon emission detection

A chiral crown ether column with a pH 1.9 perchloric acid buffered aqueous mobile phase is used to separate amino acid enantiomers by high performance liquid chromatography. An inductively coupled plasma atomic emission spectrometer coupled to the chromatographic system is used as a detector by monitoring the carbon atomic emission line at 193.09 nm. Seven underivatized amino acids are separated and detected resulting in an average mass detection limit of 5 ng (2.5 ng carbon). The chiral crown ether column resolves compounds with a primary amino group near the chiral center by forming a complex between the crown ether and an ammonium ion moiety from the sample. The -form amino acid always elutes faster than its antipode. The carbon emission detector provides nearly identical sensitivities and similar detection limits for any compounds with comparable mass percents of carbon. Quantification is performed on unknown ratios of amino acids using an internal standard without the need for a calibration curve. Summing the calculated amounts of and amino acid and comparing to the known mixture quantity results in an average error of 1.0% for the seven amino acids separated.     

A study of chiral recognition for NBD-derivatives on a Pirkle-type chiral stationary phase.

A chiral stationary phase (CSP 1) derived from an (S)-N-3,5-dinitrobenzoyl-1-naphthylglycine showed excellent enantiomeric separation for amino acid derivatives with a fluorogenic reagent, 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F), in high-performance liquid chromatography (HPLC). We compared elution profiles (separation factor and elution order) of NBD-amino acids and their analogs on HPLC, to determine the diastereomeric complex between the chiral moiety of CSP 1 and NBD-amino acid, which is responsible for the chiral recognition. (1)H-NMR studies of a mixture of model compound of CSP 1 and NBD-Ala suggest that the diastereomeric complex is composed of two hydrogen bonding sites at the amino proton and oxygen atom, and a pi-pi interaction by the benzofurazan structure (2,1,3-benzoxadiazole) of NBD-amino acid. Furthermore CSP 1 was able to separate esters, amides and alpha-methyl amino acids derivatized with NBD-F.     

Design and synthesis of chiral alpha,alpha-disubstituted amino acids and conformational study of their oligopeptides

alpha,alpha-Disubstituted amino acids are alpha-amino acids in which the hydrogen atom at the alpha-position of the L-alpha-amino acid is replaced with an alkyl substituent. The introduction of an alpha-alkyl substituent changes the properties of amino acids, with the conformational freedom of the side chain in the amino acids and the secondary structure of their peptides being especially restricted. The author developed a synthetic route of optically active alpha-ethylated alpha,alpha-disubstituted amino acids using chiral cyclic 1,2-diol as a chiral auxiliary. It was found that the preferred secondary structure of peptides composed of chiral alpha-ethylated alpha,alpha-disubstituted amino acids is a fully extended C5-conformation, whereas that of peptides composed of chiral alpha-methylated alpha,alpha-disubstituted amino acids is a 3(10)-helical structure. Also, a new chiral cyclic amino acid; (3S,4S)-1-amino-3,4-di(methoxy)cyclopentanecarboxylic acid {(S,S)-Ac5c(dOM)}, and a bicyclic amino acid; (1R,6R)-8-aminobicyclo[4.3.0]non-3-ene-8-carboxylic acid {(R,R)-Ab5,6= c}, in which the alpha-carbon atom is not the chiral center but chiral centers exist at the side-chain cycloalkane skeleton, were designed and synthesized. The (S,S)-Ac5c(dOM) hexa- and octapeptides preferentially formed left-handed (M) helices, in which the helical-screw direction is exclusively controlled by the side-chain chiral centers. Contrary to the left-handed helices of (S,S)-Ac(5)c(dOM) peptides, the (R,R)-Ab5,6= c hexapeptide formed both diastereomeric right-handed (P) and left-handed (M) helices, and the twelve chiral centers at the side chain showed no preference for helical-screw direction. Thus, the chiral environment at the side chain is important for the control of helical-screw direction. Furthermore, the author designed a new class of chiral cyclic alpha,alpha-disubstituted amino acids that have pendant chiral centers at the substituent of the delta-nitrogen atom. The synthetic route would provide various optically-active cyclic alpha,alpha-disubstituted amino acids bearing a pendant chiral moiety.     

Individual (f,tA)‐ and (f,tC)‐Fullerene‐Based Nickel(II) Glycinates: Protected Chiral Amino Acids Directly Linked to a Chiral π‐Electron System

Stereoselective electrosynthesis of the first individual (^f,tA)‐ and (^f,tC)‐1,4‐fullerene derivatives with a non‐inherently chiral functionalization pattern is described, as well as the first example of an optically pure protected primary amino acid directly linked to the fullerene through only the chiral α‐amino‐acid carbon atom. An application of an auxiliary chiral nickel‐Schiff base moiety as derivatizing agent allowed separation of (^f,tA)‐ and (^f,tC)‐1,4‐fullerene derivatives using an achiral stationary phase, a separation which has never been done before.     

Reversed-phase high-performance liquid chromatographic separation of diastereomers of (R,S)-mexiletine prepared by microwave irradiation with four new chiral derivatizing reagents based on trichloro-s-triazine having amino acids as chiral auxiliaries and 10 others having amino acid amides

A new series of chiral derivatizing reagents (CDRs) consisting of four dichloro-s-triazine reagents was synthesized by nucleophilic substitution of one chlorine atom in trichloro-s-triazine with amino acids, namely L-Leu, D-Phg, L-Val and L-Ala as chiral auxiliaries. Two other sets of CDRs consisting of four dichloro-s-triazine (DCT) and six monochloro-s-triazine (MCT) reagents were also prepared by nucleophilic substitution of chlorine atom(s) with different amino acid amides as chiral auxiliaries in trichloro-s-triazine and its 6-methoxy derivative, respectively. These 14 CDRs were used for the synthesis of diastereomers of (R,S)-mexiletine under microwave irradiation (i.e. 60s and 90 s at 85% power (of 800 W) using DCT and MCT reagents, respectively), which were resolved by reversed-phase high-performance liquid chromatography using C18 column and gradient eluting mixtures of methanol with aqueous trifluoroacetic acid (TFA) with UV detection at 230 nm. The resolution (R(s)), difference between retention times of resolved diastereomers (Δt) and retention factors (k) obtained for the three sets of diastereomers were compared among themselves and among the three groups. Explanations have been offered for longer retention times and better resolution of diastereomers prepared with DCT reagents in comparison of their MCT counterparts and, for the influence of hydrophobicity of the side chain R of the amino acid in the CDRs on retention times and resolution. The newly synthesized CDRs were observed to be superior as compared to their amide counterparts in terms of providing better resolution and cost effectiveness. The method was validated for limit of detection, linearity, accuracy and precision.     

手性逆流色谱的研究进展

总结了手性逆流色谱的5个特点,系统地介绍了逆流色谱的手性分离以及高速逆流色谱手性分离中氨基酸衍生物、环糊精衍生物、手性有机酸、多糖衍生物、牛血清白蛋白等手性选择剂的应用。     

手性有机酸保留指数的手性指数及原子类型电拓扑指数模型

基于手性碳原子的取代基次序规则,提出分子手性指数(wj),结合原子类型电拓扑指数(En)研究18种手性羟基酸和氨基酸的薄层色谱保留指数(RM)的定量关系(QSRR).经最佳变量子集回归建立最佳四元数学模型,传统的相关系数(R2)为0.969,留一法(LOO)的交互验证系数(Q2)为0.943,结果证明具有良好的稳健性及预测能力.根据进入该模型的4个结构参数(wj,E13,E16,E17)可知,影响手性有机酸保留指数的主要因素是分子的二维结构特征(如襒O,—OH,—NH2)和分子的手性特征.综上所述,新建wj及En对手性有机酸的保留指数表征具有合理性与有效性,为预测手性有机酸的保留指数提供一种有效方法.     

Enantioseparation of 15 organic phosphonate esters on the cellulose tris(3,5-dimethylphenyl carbamate) chiral stationary phase by HPLC

A series of 15 organic phosphonate esters enatiomers containing a carbon atom as a chiral center have been separated on the cellulose tris(3,5-dimethylphenyl carbamate) chiral stationary phase (CSP) in the normal phase by high performance liquid chromatography (HPLC). Both the capacity factor (k) and separation factor () of all solutes are presented. The influence of the substitutional group on the benzene ring attached to the chiral carbon atom and the steric hindrance of alkoxyl of the phosphonate ester on the chiral separation are discussed. Based on and different structure parameters, good agreement between the predicted values and the experimental ones is obtained. The most characteristic parameter influencing the chromatographic separation is chosen from many structure parameters by linear regression method of QSAR software. The probable mechanism of the chiral recognition is proposed.     

Chromatographic determination of amino acid enantiomers in beers and raw materials used for their manufacture

Using gas chromatography (GC) on a chiral stationary phase, accompanied by high-performance liquid chromatography, beers and raw materials used for manufacturing (hops, barley grains, malts) were investigated for the pattern and quantities of amino acid enantiomers. Although L-amino acids were most abundant, certain D-amino acids were detected in all beers and most of the raw materials. Highest amounts of D-amino acids were detected in special beers such as Berliner Weisse that underwent bottle-conditioning with lactic cultures, and Belgian fruit beers produced by spontaneous fermentation. It is demonstrated that GC on chiral stationary phases is highly suitable for the quantitative determination of amino acid enantiomers in beers and raw materials used for their manufacture. Quantities, relative amounts and pattern of amino acid enantiomers can serve in particular as chiral markers for the authenticity of special beers.     

Structural scaffold of 18-crown-6 tetracarboxylic acid for optical resolution of chiral amino acid: X-ray crystal analyses and energy calculations of complexes of D- and L-isomers of tyrosine, isoleucine, methionine and phenylglycine

To clarify the structural scaffold of (+)-18-crown-6 tetracarboxylic acid ((+)-18C6H4) for the optical resolution of a chiral amino acid, the crystal structures of its equimolar complexes with L- and D-isomers of tyrosine (Tyr), isoleucine (Ile), methionine (Met) and phenylglycine (PheG) were analysed by X-ray diffraction methods. (+)-18C6H4 took very similar conformations for all complexes. Although the chemical structure of (+)-18C6H4 is C2-symmetric, it took a similar asymmetric ring conformation of radius ca. 6.0 A. In all complexes, the amino group of chiral amino acids was located near the center of the ring and formed three hydrogen bonds and five electrostatic interactions with eight oxygen atoms of the ether ring and carboxyl groups. Also, the Calpha atom of chiral amino acids participated in Calpha-H...O interaction with the oxygen atom of (+)-18C6H4. In contrast, the carboxyl group of chiral amino acids did not directly interact with (+)-18C6H4. These results indicate that the structural scaffold of (+)-18C6H4 for the optical resolution of chiral amino acids is mainly based on the mode of interaction of (+)-18C6H4 with the amino and Calpha-H groups of chiral amino acids. The differences in interaction pattern and binding energy between the L- and D-isomers of each amino acid are discussed in relation to the chiral recognition of (+)-18C6H4.