淀粉及纤维素三(3-三氟甲基苯基氨基甲酸酯)手性固定相的制备及其性能评价

为了扩展多糖类手性固定相的种类,制备了基于淀粉及纤维素三(3-三氟甲基苯基氨基甲酸酯)的涂敷型手性固定相,以正己烷-异丙醇混合液为流动相,对8种手性化合物进行了高效液相色谱拆分。研究表明: 虽然与应用最广泛的分别以淀粉及纤维素三(3,5-二甲基苯基氨基甲酸酯)为手性选择因子的商品化手性柱Chiralpak AD和Chiralcel OD相比,所制备的手性固定相的手性分离能力较低,但纤维素三(3-三氟甲基苯基氨基甲酸酯)手性固定相显示出特异的手性识别能力,一些手性化合物在此固定相上得到了比在Chiracel OD上更好的分离;所制备的手性固定相的手性识别能力随流动相中异丙醇含量的降低而变好,当流动相中正己烷与异丙醇的体积比为95:5时所制备的手性固定相显示出相对较高的手性识别能力;总体来说,淀粉三(3-三氟甲基苯基氨基甲酸酯)手性固定相的手性识别能力稍强于纤维素三(3-三氟甲基苯基氨基甲酸酯)手性固定相,同时两种手性固定相的手性识别能力具有一定的互补性。     

高效液相色谱的4种商品手性柱对38种手性化合物的拆分研究

采用纤维素-三(3,5-二甲基苯基氨基甲酸酯)涂敷型手性固定相(Chiralcel OD柱)、直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)涂敷型手性固定相(Chiralpak AD柱)、直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)键合型手性固定相(Chiralpak IA柱)和Pirkle型的(S,S)-Whelk-01手性固定相对38种外消旋体化合物进行手性拆分。实验结果表明,4种固定相的手性识别能力为:OD>AD>IA>(S,S)-Whelk-01,OD固定相的手性识别率达到60%,并且它们之间的手性识别性能还具有一定的互补性。本研究对4种常用手性固定相的拆分能力进行了对比,为拆分手性化合物时有的放矢地选择手性固定相提供了参考。     

纤维素2,3-位和2,3,6-位苯基氨基甲酸酯手性固定相的选择性研究

合成了纤维素-2,3,6-三苯基氨基甲酸酯、纤维素-2,3-二苯基氨基甲酸酯、纤维素-2,3,6-三(3,5-二甲基苯基氨基甲酸酯)和纤维素-2,3-二(3,5-二甲基苯基氨基甲酸酯)4种纤维素衍生物手性固定相,用正己烷-异丙醇（体积比为9∶1）混合液作流动相,对9种手性化合物进行了高效液相色谱拆分。实验结果表明:对所测的9个样品,纤维素-2,3-二苯基氨基甲酸酯的手性选择性大大好于纤维素-2,3,6-三苯基氨基甲酸酯;而纤维素-2,3-二(3,5-二甲基苯基氨基甲酸酯)与纤维素-2,3,6-三(3,5-二甲基苯基氨基甲酸酯)的分离因子针对不同的对映体各有优点,但前者通常具有更小的保留因子,可以缩短一定的分析时间。     

纤维素苯基氨基甲酸酯的均相合成及其手性拆分性能评价

认识多糖类手性拆分材料的结构性能关系对于构建新型高效手性固定相具有重要指导意义。该文中,以1-烯丙基-3-甲基咪唑氯离子液体为介质,合成了系列不同结构的纤维素苯基氨基甲酸酯,进而考察了取代度、取代基团种类和位置对产物手性拆分性能的影响。结果表明,随着取代度的增加,纤维素苯基氨基甲酸酯对于绝大部分手性分子的拆分效果提高;苯环上取代基团的种类和位置对纤维素苯基氨基甲酸酯手性拆分性能影响显著,弱吸电子基团氯基和给电子基团甲基在合适的位置能显著增强纤维素苯基氨基甲酸酯的手性拆分性能;纤维素3-甲基-4-氯苯基氨基甲酸酯、3,5-二氯苯基氨基甲酸酯和2-甲基-5-氯苯基氨基甲酸酯对一些手性分子的拆分效果优于纤维素3,5-二甲基苯基氨基甲酸酯。     

纤维素类手性固定相高效液相色谱法拆分三唑类手性化合物

采用纤维素-三(3,5-二甲基苯基氨基甲酸酯)手性固定相(Chiralcel OD)和纤维素-三(4-甲基苯基甲酸酯)手性固定相(Chiralcel OJ),在正相高效液相(N-HPLC)模式下,基线拆分了两个系列共13个结构类似的三唑类手性化合物,结果发现,当手性固定相(Chiral Stationary Phase,CSP)可以与溶质分子之间形成较强氢键时,Chiralcel OD的手性识别能力明显优于Chiraleel OJ,当手性固定相(CSP)与溶质分子之间不能或难于形成氢键时,两种CSP的手性拆分能力相似;提高流动相中极性改性剂的极性有利于手性化合物的拆分。在反相高效液相(R-HPLC)模式下,共基线拆分了8个三唑类手性化合物,实验发现,OJ-CSP的手性拆分能力明显优于OD-CSP．它们对对映体分子的选择性主要受CSP与溶质分子间的π-π相互作用的影响。     

多糖类氨基甲酸酯衍生物的区域选择性合成及其手性识别

通过糖单元6-位羟基的保护和去保护,运用区域选择性方法合成了6种新型多糖类氨基甲酸酯衍生物,分别为纤维素/直链淀粉-[2,3-二(3,5-二甲基苯基)-6-环己基]氨基甲酸酯、[2,3-二(3,5-二氯苯基)-6-环己基]氨基甲酸酯及[2,3-二(4-氯苯基)-6-环己基]氨基甲酸酯,并将其涂敷在氨丙基硅胶的表面制备HPLC手性固定相.利用1H-NMR与FTIR光谱技术对所合成衍生物进行结构表征和分析,并应用HPLC法评价其对于9种手性化合物的手性识别能力.通过与以手性识别能力高而著称且含有单一取代基的纤维素/直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)等手性固定相的对比分析表明,所合成新型手性固定相对于某些对映体显示出更优的手性识别能力.由进一步分析表明,糖单元2-、3-和6-位取代基的性能对于纤维素和直链淀粉氨基甲酸酯类衍生物的手性识别能力均具有较大影响.     

高效液相色谱的8种商品手性柱对52种手性化合物的拆分研究

用8种手性柱纤维素-三(3,5-二甲基苯基氨基甲酸酯)涂敷型固定相(Chiralcel OD)、纤维素-三(3,5-二甲基苯基氨基甲酸酯)键合型固定相(Chiralpak IB)、直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)涂敷型固定相(Chiralpak AD)、直链淀粉-三(3,5-二甲基苯基氨基甲酸酯)键合型固定相(Chiralpak IA)、直链淀粉-三((S)-α-甲基苄基氨基甲酸酯)涂敷型固定相(Chiralpak AS)、Pirkle型固定相((S,S)-Whelk-O1)、弱阴离子交换剂固定相(Chiralpak QN-AX)和替考拉宁固定相(Chirobitotic T柱)对52种外消旋体化合物进行了拆分,并讨论拆分条件对一些手性柱分离情况的影响。结果表明,这8根手性柱对这些对映体具有良好的手性识别效果和互补性。它们对这些样品手性拆分实验结果比较可得出其手性识别能力为:Chirobitotic TODADIAASIB(S,S)-Whelk-O1Chiralpak QN-AX。     

高效液相色谱手性固定相法直接拆分4种吲哚类衍生物

将纤维素-三(3,5-二甲基苯基氨基甲酸酯)(CDMPC)涂敷于自制的球形氨丙基硅胶上,制备成了纤维素-三(3,5-二甲基苯基氨基甲酸酯)手性固定相(CDMPC-CSP)。利用正相高效液相色谱,在该固定相上对新合成的4种吲哚类衍生物对映体进行了手性拆分。通过选择不同结构和浓度的醇类改性剂,优化了色谱分离条件,同时探讨了醇的结构和浓度对于对映体拆分和保留的影响。结果表明,适合Ⅱ~Ⅳ号样品拆分的醇类改性剂分别为正丁醇、乙醇和乙醇,而适合Ⅰ号样品的醇类改性剂为乙醇和正丙醇组成的混合体系。在优化的各流动相体系下,4种吲哚类衍生物的对映体都得到了很好的分离。在此基础上计算了它们的对映体过量值(e.e.值)。实验结果令人满意,表明高效液相色谱手性固定相法是拆分这类化合物的一种理想方法。     

非均匀取代淀粉衍生物手性固定相的制备及其手性识别能力

通过区域选择性方法制备了两种新型淀粉衍生物,分别为淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)和淀粉2-苯甲酸酯-3-(3,5-二氯苯基氨基甲酸酯)-6-(4-甲基苯基氨基甲酸酯),将二者分别涂覆于氨丙基硅胶后用作液相色谱手性固定相。研究表明:所制备的手性固定相显示出特异的手性识别能力,其手性识别能力明显高于均匀取代淀粉衍生物——淀粉三(3,5-二氯苯基氨基甲酸酯),取代基的性质及在葡萄糖单元上的位置对手性固定相的手性识别能力有较大的影响。一些未在商品化的手性柱Chiralpak AD上得到有效分离的手性化合物在所制备的固定相上得到了更好的分离。所测试的8对对映体在淀粉2-苯甲酸酯-3-(4-甲基苯基氨基甲酸酯)-6-(3,5-二氯苯基氨基甲酸酯)固定相上均得到了分离,因而此固定相的手性识别能力较强,具有潜在的应用价值。     

高效液相色谱手性固定相法分离取代环己酮及取代环己醇的对映体

在4种自制的涂敷型纤维素衍生物手性柱，即纤维素三苯甲酸酯(CTB)、纤维素三(4-甲基苯甲酸酯)(CTMB)、纤维素三苯基氨基甲酸酯(CTPC)和纤维素三(3，5-二甲基苯基氨基甲酸酯)(CDMPC)与小分子的Prikle型(S，S)-Whelk—O1手性柱上对取代环己酮及取代环己醇进行了对映体分离。研究了溶质的立体结构因素对手性分离的影响，并初步探讨、比较了溶质在这两种手性柱上的手性识别的机理。结果发现，在(S，S)-Whelk—O1柱上溶质与固定相之间的吸引作用是手性识别的主要原因，而对于纤维素衍生物手性柱，溶质的空间结构在手性空腔中的空间适应性可能是手性识别的关键。     

流动相组成对有机硒手性化合物拆分的影响

 在自制的涂敷型纤维素 三 (3,5 二甲基苯基氨基甲酸酯 ) (CDMPC)手性固定相上拆分了一些结构相似的有机硒手性化合物 ,详细考察了三元流动相对手性拆分的影响 ,并探讨了溶质分子与手性固定相相互作用的模式。实验结果表明 :在二元流动相中加入极少量的质子性改性剂 (醇 )或非质子性改性剂 (乙腈 ) ,可使溶质的保留和手性拆分发生较大的变化。     

外消旋硫代缩水甘油醚在多糖基质手性柱上的手性拆分

在自行合成的3种多糖基质的手性固定相上直接拆分了7种外消旋硫代缩水甘油醚，初步探讨了手性化合物结构在手性识别过程中对手性拆分的影响，并对手性固定相的手性识别能力进行了评价。     

Enantioseparation of some Racemic Compounds on Cellulose Tris (3,5-dimethylphenylcarbamate) Chiral Stationary Phase

During the last two decades, polysaccharide derivatives have been widely used in theresolution ofracemic compounds by HPLCI' 2. In this papeT, CDMPC, coated on APS gelprepared according to reference', was used to resolve racemic compounds in differentmobile phase systems. The separation was performed on LC-6A HPLC (Shimadzu,Japan) system with an SPD-6AV ultraviolet-visible detector and a C-R3Achromatographic data recorder. All solvents were of analytical grade (Tianjin SecondChem…     

Chiral covalent organic framework incorporated organic polymer monolithic capillary column for enantioseparations

A chiral covalent organic framework was synthesized, characterized, and incorporated into organic polymer monolithic capillary columns to provide chiral stationary phases for enantioseparations. The prepared monolithic capillary columns were characterized by scanning electron microscopy and elemental analysis. To obtain better enantioseparations, the columns’ preparation conditions, and enantioseparation conditions were optimized. Baseline resolutions of several chiral compounds were obtained with good reproducibility and stability. Furthermore, the mechanism of chiral recognition was investigated using molecular docking with AutoDock. Docking results showed that the enantioselectivity factor rather than resolution is correlated with the binding free energy difference between enantiomers with the chiral covalent organic framework. And abundant acetoxy and nitrile groups as well as benzene rings in the chiral covalent organic framework are responsible for the enantioseparation ability of the chiral monolithic capillary columns.     

纤维素衍生物手性固定相用于高效液相色谱对映体分离

纤维素衍生物是目前高效液相色谱 (HPLC)中应用最为广泛的手性固定相之一 ,对各种类型的外消旋体都表现出了很高的对映体选择性 ,因其负载量大特别适用于对映体制备分离。本文对纤维素衍生物手性固定相的种类、影响手性选择性的因素以及手性识别的机理进行了较为全面的评述 ,并展望了研究前景     

正反相模式下键合纤维素手性固定相对手性化合物的拆分

在自行合成的键合型纤维素-(3,5-二甲基苯基氨基甲酸酯)(CDMPC-CSP)手性固定相上,在正相模式下对苯偶姻和甲霜灵外消旋体进行了拆分,考察了流动相中醇以及温度在手性识别中对手性分离的影响。同时考察了反相模式下外消旋体的拆分。     

Evaluation of chlorine containing cellulose-based chiral stationary phases for the LC enantioseparation of basic pharmaceuticals using polar non-aqueous mobile phases

The discrimination ability of three cellulose-based chiral stationary phases (CSPs) was evaluated towards the enantiomers of basic drugs, using ACN as the main solvent in polar organic mobile phases. The study was focused on CSPs containing cellulose tris(3-chloro-4-methylphenylcarbamate) (3-Cl-4-MePC), cellulose tris(4-chloro-3-methylphenylcarbamate) (4-Cl-3-MePC) or cellulose tris(3,5-dichlorophenylcarbamate) (3,5-diClPC) as the chiral selector. The behaviour of these CSPs was studied systematically in order to investigate the influence of the presence and position of the chlorine substituents on the phenylcarbamate moieties on the retention and resolution of the enantiomers. The evaluation was made with three different generic mobile phases, namely ACN/0.1%DEA/0.1% TFA (DEA, diethylamine), ACN/0.1%DEA/0.2% FA and ACN/0.1%DEA/0.2%AcA, deduced from the previous study. The nature of the acidic additive and of the chiral selector was found to be particularly important for the retention and enantioresolution of these basic compounds. High-resolution values could be obtained for most studied enantiomers with these CSPs, clearly demonstrating the interest of using them in combination with polar organic mobile phases. However, significant differences in enantioresolution between the CSPs have been observed for many compounds, indicating that these phases seem to be quite complementary.     

Reversed-phase chiral HPLC and LC/MS analysis with tris(chloromethylphenylcarbamate) derivatives of cellulose and amylose as chiral stationary phases

Three polysaccharide-derived chiral stationary phases (CSP) were evaluated for the resolution of more than 200 racemic compounds of pharmaceutical interest in the reversed-phase (RP) separation mode. The population of test probes was carefully evaluated in order to insure that it covers as completely as possible all structural diversity of chiral pharmaceuticals. RP showed the highest potential for successful chiral resolution in HPLC and LC/MS analysis when compared to normal phase and polar organic separation modes. Method development consisted of optimizing mobile phase eluting strength, nature of organic modifier, nature of additive and column temperature. The newer CSPs, cellulose tris(3-chloro-4-methylphenylcarbamate) and amylose tris(2-chloro-5-methylphenylcarbamate), were compared to the commonly used cellulose tris(3,5-dimethylphenylcarbamate) in regards to their ability to provide baseline resolution. Comparable success rates were observed for these three CSPs of quite complimentary chiral recognition ability. The same method development strategy was evaluated for LC/MS analysis. Diethylamine as additive had a negative effect on analyte response with positive ion mode electrospray (ESI⁺) MS(/MS) detection, even at very low concentration levels (e.g., 0.025%). Decreasing the organic modifier (acetonitrile or methanol) content in the mobile phase often improved enantioselectivity. The column temperature had only a limited effect on chiral resolution, and this effect was compound dependent. Ammonium hydrogencarbonate was the preferred buffer salt for chiral LC with ESI⁺ MS detection for the successful separation and detection of most basic pharmaceutical racemic compounds. Ammonium acetate is a viable alternative to ammonium hydrogencarbonate. Aqueous formic acid with acetonitrile or methanol can be successfully used in the separation of acidic and neutral racemates. Cellulose tris(3-chloro-4-methylphenylcarbamate) and amylose tris(2-chloro-5-methylphenylcarbamate) emerge as CSPs of wide applicability in either commonly used separation modes rivaling such well established CSPs as cellulose tris(3,5-dimethylphenylcarbamate). Screening protocols including these two new CSPs in the preferentially screened set of chiral columns have higher success rates in achieving baseline resolution in shorter screening time.     

Comparison of Separation Performances of Cellulose-Based Chiral Stationary Phases in LC Enantioseparation of Aminonaphthol Analogues

The enantiomers of 1-(α-aminoarylmethyl)-2-naphthol, 1-(α-aminoalkyl)-2-naphthol and 2-(α-aminoarylmethyl)-1-naphthol analogues were separated on tris(3,5-dimethylphenyl)carbamoyl cellulose-based CelluCoat and Chiralcel OD-H chiral stationary phases, with n-heptane/alcohol or n-hexane/alcohol as mobile phase. The experimental data are utilised to discuss the effects of the mobile phase composition, the nature of the alcoholic modifier and the specific structural features of the analytes (1- or 2-naphthol analogues with aryl or alkyl substituents) on the retention and separation. The separation performances of CelluCoat and Chiralcel OD-H columns were compared. Due to its high resolution ability and its effectivity, CelluCoat proved to be a good choice for the enantiomeric separation of aminonaphthol analogues.