高效液相色谱法分离2-(4-羟基苯氧基)丙酸酯的对映体

采用高效液相色谱法在手性柱上分离芳氧基苯氧基丙酸类除草剂中间体(±)-2-(4-羟基苯氧基)丙酸酯的对映体。实验结果表明,在三苯甲酸纤维素酯的手性柱上,以无水乙醇为流动相能较好地分离(±)-2-(4-羟基苯氧基)丙酸乙酯和甲酯,其分离因子α值分别为1.44和1.29;同时还发现在三苯甲酸纤维素酯的手性柱上2-取代芳氧基或芳基丙酸酯结构中的酯基团的大小对其对映体的分离有明显的影响,其中以乙基为最佳。并通过对照试验证实了2-(4-羟基苯氧基)丙酸乙酯的右旋体先流出,其左旋体后流出。     

纤维素-三(4-甲基苯甲酸酯)手性固定相的制备及其在拆分叔丁基亚磺酰胺对映体中的应用

分别在自制的纤维素-三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)和纤维素-三(4-甲基苯甲酸酯)(CTMB)涂覆型固定相上对叔丁基亚磺酰胺对映体进行手性拆分,并考察了流动相中异丙醇的含量对手性拆分的影响。结果表明,叔丁基亚磺酰胺在CTMB固定相上的分离效果更佳。随着异丙醇含量的减少,叔丁基亚磺酰胺对映体在两根色谱柱上的分离度和保留时间均随之增加。对CTMB固定相进一步探究柱温的影响,结果表明较低的温度有利于对映体保持稳定的手性构型,更易于与固定相反应。     

纤维素-三(3,5-二甲基苯基氨基甲酸酯)涂敷氧化锆手性固定相的制备和色谱评价

制备并表征了涂敷纤维素-三(3，5-二甲基苯基氨基甲酸醋)-ZrO2手性固定相。以正己烷／异丙醇为流动相，研究了正相色谱条件下手性固定相对几类光学异构体的手性拆分能力。实验结果表明：氧化锆载体表面的碱性性质对光学对映体的手性拆分有很大影响；在常用流动相条件下，酸性对映体被完全滞留；纤维素-三(3，5-二甲基苯基氨基甲酸醋)-ZrO2手性固定相对于中性及碱性对映异构体的分离呈现出较好的手性拆分能力。     

纤维素-三(4-甲基苯甲酸酯)涂覆型手性固定相的制备研究与分离应用

以C_8硅烷修饰的大孔硅胶作基质,涂覆制备了纤维素-三(4-甲基苯甲酸酯)手性固定相,研究了涂覆溶剂体系对固定相选择性的影响。实验选择氯仿或二氯甲烷作溶剂,分别添加N,N’-二甲基甲酰胺、苯酚、硝基苯、苯甲酸甲酯、苯乙酮涂覆制备了多个手性固定相,并以7种不同结构的手性化合物对固定相进行评价。结果表明,添加剂的种类与添加量对固定相的装柱柱效、保留以及选择性均会产生一定的影响。添加与纤维素酯等质量的苯甲酸甲酯制得的固定相性能较佳,其对于西孟坦中间体和酮咯酸消旋体具有良好的对映体拆分能力,具备工业制备分离的应用潜力。     

扁桃酸及其类似物在全甲基环糊精固定相上的手性拆分

在全甲基β－环糊精（ＰＭＢＣＤ）和全甲基γ－环糊精（ＰＭＧＣＤ）手性固定相上,考察了扁桃酸酯、α－甲氧基扁桃酸酯、２－羟基－３－苯基丙酸酯和２－羟基－４－苯基丁酸乙酯的气相色谱手性分离行为。结果表明,所有研究的羟基羟基羧酸酯均可以在ＰＭＣＤ手性固定相上得到很好的手性分离,而ＰＭＧＣＤ对所研究的对映体没有任何手性拆分能力。结合和学参数,探讨了手性诉分机理。     

禾草灵对映异构体在高效液相色谱手性固定相上的拆分

合成了手性纤维素-三(4-甲基苯甲酸酯)(CTMB)，并涂敷于氨丙基硅胶上，制备成手性固定相(CSP)；用高效液相色谱法在该手性固定相上对农药禾草灵外消旋体进行了拆分；考察了流动相组成、温度、醇效应对禾草灵对映体拆分及保留的影响，由实验结果对禾草灵对映体之间的-(ΔG^￠)π,s、（ΔH^￠）π,s、（ΔS^￠）π,s进行了计算，并对其在柱上保留机理进行了讨论。     

七(2,3,6-三-O-甲氧甲基)-β-环糊精的合成及其在气相色谱分离中的应用

将甲氧甲基引入β-环糊精的2,3,6-位合成了新的气相色谱手性固定相七(2,3,6-三-O-甲氧甲基)-β-环糊精,并采用静态法将其涂渍在毛细管内壁制备毛细管气相色谱柱。考察了毛细管柱的柱性能和分离性能。结果表明该固定相对Grob试剂、苯的二取代位置异构体(硝基甲苯、溴甲苯、二氯苯和二甲苯)及手性化合物(2-羟基丙酸甲酯、2-羟基丙酸乙酯和2-甲磺酰基丙酸甲酯)都具有良好的分离效果。与固定相2,3,6-三-O-甲基-β-环糊精的手性分离效果对比,结果显示两种手性固定相的分离能力各异,对一些手性脂类化合物对映体的分离存在互补性。     

纤维素-三(4-甲基苯甲酸酯)手性固定相的制备及对映异构体拆分

以微晶纤维素和对甲基苯甲酰氯为原料,合成了纤维素-三(4-甲基苯甲酸酯),并以3-氨丙基-三乙氧基硅烷修饰的硅胶为载体,制备了涂敷型纤维素-三(4-甲基苯甲酸酯)液相色谱固定相,对该固定相进行了表征,并在正相条件下对13种对映异构体进行了拆分,其中9种得到了分离,该柱表现出良好的手性分离性能.     

高效液相色谱纤维素衍生物类手性固定相拆分泮托拉唑对映体

泮托拉唑（pantoprazole,简称为PAN）是一种选择性的长效质子泵抑制剂。PAN分子由苯并咪唑通过亚砜基连接吡啶环组成,内含手性硫原子,故存在S-（-）型和R-（＋）型对映异构体,临床以消旋体给药。文献已有用牛血清白蛋白、卵粘蛋白、多糖衍生物和α1-糖蛋白、酒石酸衍生物等手性固定相拆分泮托拉唑对映体的报道。纤维素-三-（4-甲基苯甲酰酯）手性固定相稳定性好,柱效高,对羰基化合物、内酯、内酰胺、亚砜等化合物有较好的拆分能力,硫巴比妥衍生物、痛力克等药物都在该固定相上得到了完全分离。本文使用纤维素-三-（4-甲基苯甲酰酯）手性固定相实现了泮托拉唑对映体的拆分,并计算了对映体的光学纯度。     

2，6-二-O-乙氧乙基-3-O-三氟乙酰基-β-环糊精气相色谱手性固定相的制备及应用

将β-环糊精的2,6-位引入乙氧乙基,3-位引入三氟乙酰基,合成了新的环糊精衍生物2,6-二-O-乙氧乙基-3-O-三氟乙酰基-β-环糊精,并采用静态法涂渍毛细管气相色谱柱,考察了毛细管柱的柱性能和分离性能。结果表明,该固定相对G rob试剂、苯的二取代位置异构体氯甲苯、硝基甲苯和溴甲苯以及10种手性化合物如α-取代丙酸酯化合物、1-(2′-硝基苯基)-乙醇、α-甲基-对氯苯乙腈和丙炔醇酮乙酸酯等具有良好的分离效果。其中,对α-甲磺酰基丙酸酯对映体的拆分效果最好;对α-取代丙酸的甲酯衍生物的分离效果优于乙酯衍生物;对α-羟基取代丙酸酯的分离效果优于α-卤代丙酸酯。     

Separation of the enantiomers of pyrethroic acids and their esters by high-performance liquid chromatography on a polysaccharide-derived chiral stationary phase

Summary The liquid-chromatographic separation of the enantiomers of pyrethroic acids and their esters has been investigated on a polysaccharide-derived chiral stationary phase (CSP), Chiralpak AS. Good separation of the enantiomers of underivatized pyrethroic acids was achieved on the column, and the enantiomers of pyrethroic acid methyl and ethyl ester derivatives were also resolved.     

在纤维素衍生物类手性柱上分离托品酸对映体

以乙醇-水为流动相,用纤维素-三(苯甲酯)(CTB)作为手性固定相对外消旋体托体品酸进行了高效液相色谱手性分离,考察了不同比例的乙醇-水流动相,不同流速以及用不同醇类酯对托品酸酯在手性色谱柱上的色谱行为,实验表明,流动相中水的比例,流速以及酯化所用醇类均对托品酸酯衍生物分离有很大影响,以动相为乙醇-水(95:5)流速为0.1mL/min的色谱体系,使托品酸乙酯在CTB柱上得到基线分离,对托品酸乙酯在CTB手性固定相上反相手性识别机理进行了讨论.     

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.     

Direct Enantioselective HPLC Monitoring of Lipase-Catalyzed Kinetic Resolution of 2-Phenoxy Propionic Acid in Non-Standard Organic Solvents

In this work, a direct enantioselective HPLC monitoring system is developed. The system consists of an HPLC equipped with an immobilized cellulose-based chiral stationary phase Chiralpak IB, UV and a polarimetric detector in series. The developed system is used in the direct monitoring of the enantioselectivity of lipase-catalyzed enantioselective esterification of 2-phenoxy propionic acid of which the (R)-enantiomer is a precursor of the (R)-2-(p-hydroxyphenoxy)propionic acid known as an important intermediate in synthesizing aryloxyphenoxypropionic acid based agrochemicals. The versatility of the biocatalyzed reaction in chiral separation to access to both enantiomers of racemic 2-phenoxy propionic acid is demonstrated. The solvent versatility of the immobilized chiral stationary phase used in the direct monitoring of such reaction in non-standard HPLC solvent is shown.     

Chiral recognition: design and preparation of chiral stationary phases using selectors derived from ugi multicomponent condensation reactions and a combinatorial approach

Combinatorial approaches together with high-throughput screening have been used to develop highly selective stationary phases for chiral recognition. Libraries of potential chiral selectors have been prepared by the Ugi multicomponent condensation reactions and screened for their enantioselectivity using the reciprocal approach involving a chiral stationary phase with immobilized model target compound N-(3,5-dinitrobenzoyl)-alpha-l-leucine. The best candidates were identified from the library of phenyl amides of 2-oxo-azetidineacetic acid derivatives. This screening also enabled specification of the functionalities of the selector desired to achieve the highest level of chiral recognition. The substituents of the phenyl ring adjacent to the chiral center of the selector candidates exhibited the most profound effect on the chiral recognition. The best candidate was then synthesized on a larger scale, resolved into single enantiomers using preparative enantioselective HPLC, and attached to porous poly(2-hydroxyethyl methacrylate-co-ethylene dimethacrylate) beads via an ester linkage to afford the desired stationary phase. Selectivities alpha as high as 3.2 were found for the separation of a variety of amino acid derivatives.     

High-performance liquid chromatographic enantioseparation of beta-3-homo-amino acid stereoisomers on a (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid-based chiral stationary phase

High-performance liquid chromatographic methods were developed for the separation of the enantiomers of thirteen unusual beta-3-homo-amino acids and three of its ethyl esters on a chiral stationary phase containing (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid as chiral selector. The effects of the mobile phase composition and the acidic modifiers on the separation were investigated. The structures of the substituents in beta-position substantially influenced the retention and enantioseparation. The influence of ionic strength on the enantioseparation was established experimentally. The elution sequence was determined in all cases.     

万古霉素及其苯异氰酸酯衍生物手性固定相的制备与应用

采用"一锅法",以1,6-二异氰酸正己酯作间隔臂,制备了万古霉素及苯异氰酸酯衍生化的万古霉素手性固定相。对拉米夫定、拉米夫定的L-薄荷醇酯、酞胺哌啶酮和盐酸氟西汀进行了手性分离研究,在极性有机相模式下,研究了流动相甲醇中冰醋酸-三乙胺浓度和比例对手性分离的影响,观察到两种手性固定相具有不同的手性识别能力。在万古霉素手性固定相上4种溶质都获得了基线分离;在苯异氰酸酯衍生化的手性固定相上除盐酸氟西汀外也均获得基线分离。