Enantioseparation of Novel Chiral Tetrahedral Clusters on an Amylose Tris-(3,5-dimethylphenylcarbamate) Chiral Stationary Phase by Normal Phase HPLC

Introduction In recent years, chiral transition metal cluster has at-tracted a great deal of interests due to its potential ap-plication in asymmetric catalytic reaction.1-3 Producing catalysis for asymmetric induction using a rigid chiral framework would not only bring a basically conceptual breakthrough in the asymmetric catalysis, but also en-rich the methodology in the design of new chiral cata-lysts.4 So far, a lot of chiral clusters have been re-ported,5-9 but only a few of them have bee…     

Optically Active T-Butylphenylphosphinothioic Acid: Synthesis,Selected Structural Studies and Applications as a Chiral Solvating Agent

Abstract

Synthesis, structural studies and the use of the (?)-(S)- and (+)-(R) enantiomers of t-butylphenylphosphinothioic acid as a chiral solvating agent for the determination of enantiomeric purity is discussed. Systems that are the most extensively studied are emphasized.     

手性有机聚合物毛细管电色谱整体柱研究进展

毛细管电色谱具有高分离效率、多种保留机制和高选择性的优点。近年来,利用毛细管电色谱进行对映异构体的手性拆分受到了广泛关注。相对于传统的填充柱和开管柱,整体柱在手性拆分方面具有显著优势。与手性硅基整体柱相似,手性有机聚合物整体柱由于具有大孔,可产生较高的流速而压降较小。该文综述了近十年手性有机聚合物整体柱制备方法的研究进展,将手性有机聚合物整体柱的制备方法分为"原位聚合法"和"手性修饰法"两种,虽然前者制备简单并广泛应用于早期研究,但聚合混合液成分的微小改变即可引起最终聚合物的形态变化,并且大部分带丙烯基的手性选择剂较难从市场购买。因此,手性修饰法因作为手性选择剂基质的整体柱制备且优化只需进行一次的优势而受到普遍关注。亲核取代、杂环开环和点击化学是常用的修饰手段。该文总结了这两种制备方法的应用,同时对未来的研究方向提出参考性意见。     

Enantioseparation of Novel Chiral Tetrahedral Clusters on an Amylosoe Tris-（3,5-dimethylphenylcarbamate） Chiral Stationary Phase by Normal Phase HPLC

Amylose tris(3,5-dimethylphenylcarbamate) (ADMPC) coated on a kind of small particle silica gel was prepared. On this ADMPC chiral stationary phase (CSP), the direct enantiomeric separation of six novel chiral transition metal tetrahedral clusters has firstly been achieved using n-hexane as the mobile phase containing various alcohols as modifiers. The effect of mobile phase modifiers and the structural variation of the solutes on their retention factors (k‘) and resolutions (Rs) were investigated. The result suggests that not only the structure and concentration of alcohol in mobile phase, but also the structural differences in racemates can have a pronounced effect on enantiomeric separation. ADMPC-CSP is a suitable CSP for the optical resolution of chiral tetrahedral cluster by HPLC.     

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.     

Using the Chiral Organophosphorus Derivatizing Agents for Determination of the Enantiomeric Composition of Chiral Carboxylic Acids by ^31PNMR Spectroscopy

The use of chiral organophosphorus derivatizing agents prepared in situ from chiral tartrate or chiral diamine for the ^31PNMR determination of the enantiomeric composition of chiral carboxylic acids is described. The method is accurate, reliable and convenient.     

Applications of Cellulose-Based Chiral Stationary Phases in the Resolution of Some Beta-Adrenoceptor Antagonists

Abstract

Cellulose tris (3,5-dimethylphenyl carbamate) known as Chiralcel OD chiral stationary phase (CSP) is one of the most commonly used cellulosic CSPs which have been successfully used for separation, enantiomeric purity determination and analysis of several drug racemates including β-adrenoceptor antagonists.

Resolution of timolol, penbutolol, celiprolol and carazolol enantiomers are achieved using this CSP. A possible chiral recognition mechanism(s) for these β-adrenergic blockers and this chiral stationary phase is presented.     

(3,5-二甲基苯基氨基甲酸酯)衍生的纤维素手性固定相

纤维素三（3,5-二甲基苯基氨基甲酸酯）是液相色谱中使用最广泛的手性柱。该文详细地研究了不同程度衍生的纤维素（3,5-二甲基苯基氨基甲酸酯）以及不同硅胶（粗制硅胶、氨丙基粗制硅胶、精制硅胶、氨丙基精制硅胶、大孔硅胶、氨丙基大孔硅胶）作为支撑体对该柱手性分离能力的影响。自制了13根手性色谱柱,分别考察了其对16种外消旋体的拆分,分离结果显示：三取代纤维素柱 > 二取代纤维素柱 > 纤维素柱;精制硅胶和大孔硅胶优于粗制硅胶,大孔硅胶的柱压更低;硅胶的氨丙基化对手性选择性有一定的影响;这些手性柱之间具有一定的互补性,尤其是纤维素柱。该文有助于人们更深刻地理解和更好地把握高效液相色谱手性柱的制备。     

手性溶解剂在NMR法测定对映体比率和绝对构型的研究进展

综述了手性溶解剂在NMR法测定对映体比率及绝对构型的研究进展.按照手性溶解剂的结构类型,包括胺、酰胺、羧酸、醇、氨基醇、大环化合物,对手性溶解剂的结构特点与手性识别性能进行了详细的介绍.     

Chiral Capillary Electrokinetic Chromatography: Principle and Applications,Detection and Identification,Design of Experiment,and Exploration of Chiral Recognition Using Molecular Modeling

This work reviews the literature of chiral capillary electrokinetic chromatography from January 2016 to March 2021. This is done to explore the state-of-the-art approach and recent developments carried out in this field. The separation principle of the technique is described and supported with simple graphical illustrations, showing migration under normal and reversed polarity modes of the separation voltage. The most relevant applications of the technique for enantioseparation of drugs and other enantiomeric molecules in different fields using chiral selectors in single, dual, or multiple systems are highlighted. Measures to improve the detection sensitivity of chiral capillary electrokinetic chromatography with UV detector are discussed, and the alternative aspects are explored, besides special emphases to hyphenation compatibility to mass spectrometry. Partial filling and counter migration techniques are described. Indirect identification of the separated enantiomers and the determination of enantiomeric migration order are mentioned. The application of Quality by Design principles to facilitate method development, optimization, and validation is presented. The elucidation and explanation of chiral recognition in molecular bases are discussed with special focus on the role of molecular modeling.     

Polysaccharide- and β-Cyclodextrin-Based Chiral Selectors for Enantiomer Resolution: Recent Developments and Applications

Polysaccharides, oligosaccharides, and their derivatives, particularly of amylose, cellulose, chitosan, and β-cyclodextrin, are well-known chiral selectors (CSs) of chiral stationary phases (CSPs) in chromatography, because they can separate a wide range of enantiomers. Typically, such CSPs are prepared by physically coating, or chemically immobilizing the polysaccharide and β-cyclodextrin derivatives onto inert silica gel carriers as chromatographic support. Over the past few years, new chiral selectors have been introduced, and progressive methods to prepare CSPs have been exploited. Also, chiral recognition mechanisms, which play a crucial role in the investigation of chiral separations, have been better elucidated. Further insights into the broad functional performance of commercially available chiral column materials and/or the respective newly developed chiral phase materials on enantiomeric separation (ES) have been gained. This review summarizes the recent developments in CSs, CSP preparation, chiral recognition mechanisms, and enantiomeric separation methods, based on polysaccharides and β-cyclodextrins as CSs, with a focus on the years 2019–2020 of this rapidly developing field.     

Amylose-3,5-dimethylphenylcarbamate immobilized on monolithic silica stationary phases for chiral separations in capillary electrochromatography

Chiral monolithic silica capillary columns were prepared by immobilization of amylose-3,5-dimethylphenylcarbamate (ADMPC) bearing a small fraction of 3-(triethoxysilyl)propyl residues through intermolecular polycondensation of the triethoxysilyl groups. The obtained columns were used for chiral separations in capillary electrochromatography (CEC). The effects of the silica monolith nature and the used chiral selector concentration on the resulting enantiomeric separations were investigated. Fifteen chiral compounds, including acidic, neutral, and basic substances were evaluated and twelve showed partial or baseline separation at some of the different conditions tested. These results demonstrated the promising applicability of ADMPC-immobilized monolithic silica columns in CEC enantioseparations, but also revealed the need for further improvements on the level of baseline separations and efficiencies.     

手性镧系位移试剂核磁共振法测定芳氧丙酸酯类除草剂对映体纯度

以Eu(hfc)3和Pr(hfc)3为手性镧系位移试剂(CLSR),比较了两种CLSR对2,4-滴丙酸甲酯的1HNMR和13C NMR谱手性分离效果,结果表明:Pr(hfc)3比Eu(hfc)3对手性中心相连的甲基具有更好的手性分离效果。首次应用Pr(hfc)3测定了盖草能、稳杀得和喹禾灵3种手性芳氧丙酸酯类除草剂的1HNMR和13CNMR谱,其1HNMR谱分离度R约为1,盖草能和喹禾灵的13C NMR谱分离度R大于1.5,说明1H NMR和13CNMR谱手性分离效果适用于对映体纯度测定。与手性色谱法相比,CLSR-NMR法测定对映体纯度具有操作简便、分析速度快的显著优势。     

Determination of the enantiomeric purity of epinephrine by HPLC with circular dichroism detection

Several hundred drug substances approved by the U.S. Food and Drug Administration are chiral molecules. For the enantiomeric purity assessment, current practice is to develop separation techniques using chiral columns or mobile phase modifiers to separate enantiomers before detection. An alternative approach is to use currently accepted HPLC assay methods and use chiral-specific detectors to confirm whether the correct enantiomer is present. In this paper, adding a circular dichroism (CD) detector to an achiral HPLC method from the US Pharmacopeia (USP) is shown to be amenable for the determination of the enantiomeric purity of epinephrine, a substance used to treat anaphylaxis. This HPLC-UV-CD approach was able to detect the inactive D-(+) enantiomer at 1% of the total epinephrine composition. The linearity, accuracy, and precision of HPLC-UV-CD were evaluated and compared to analyses using a chiral HPLC method. Additionally, an epinephrine drug product was analyzed for assay (concentration) and enantiomeric purity. The results from achiral and chiral methods were identical within the experimental error. Overall, achiral chromatography performed using a USP method with CD detection may serve as a general means of determining chiral drug enantiomer purity and avoids the need for the development of additional chiral-specific methods for each individual drug.     

Changes in the Enantiomeric Composition of Chiral Mixtures Upon Adsorption on a Non‐Chiral Surface

The adsorption of propylene oxide, a chiral molecule, on a Pt(111) single‐crystal surface was studied as a function of enantiomeric composition by temperature programmed desorption (TPD) and molecular beams. Two opposing trends were observed leading to variations in the enantiomeric excess (ee) of the chemisorbed layers with respect to the composition of the gas‐phase mixtures: a kinetic effect dominant during the initial uptake, with a preference toward the formation of enantiopure layers, and a steady‐state effect seen after approximately monolayer half‐saturation, at which point the preference is toward racemization. These effects may account for important phenomena such as the bias toward one chirality in biological systems and the selective crystallization of some chiral compounds, and may also be used in practical applications for chemical separations and catalysis.     

测定手性有机酸对映体纯度的新试剂

用NMR技术测定微量手性化合物的对映体纯度,已有多种方法。其中,加手性镧化物位移试剂法适用面最广,但对有机酸,结果常不理想。另一种使用较广的方法是加手性试剂,将样品中两对映体转变成非对映异构体,然后比较非对映基因NMR信号的强度,确定原样品中对映体的组成比例。国外已出售的手性试     

Enantiomeric Discrimination by Surface‐Enhanced Raman Scattering–Chiral Anisotropy of Chiral Nanostructured Gold Films

A surface‐enhanced Raman scattering‐chiral anisotropy (SERS‐ChA) effect is reported that combines chiral discrimination and surface Raman scattering enhancement on chiral nanostructured Au films (CNAFs) equipped in the normal Raman scattering Spectrometer. The CNAFs provided remarkably higher enhancement factors of Raman scattering (EFs) for particular enantiomers, and the SERS intensity was proportional to the enantiomeric excesses (ee) values. Except for molecules with mesomeric species, all of the tested enantiomers exhibited high SERS‐ChA asymmetry factors (g), ranging between 1.34 and 1.99 regardless of polarities, sizes, chromophores, concentrations and ee. The effect might be attributed to selective resonance coupling between the induced electric and magnetic dipoles associated with enantiomers and chiral plasmonic modes of CNAFs.     

Enantiomeric Separation of Non-Protein Amino Acids by Chiral Ligand-Exchange High-Performance Liquid Chromatography

Abstract

The enantiomeric separation by high-performance liquid chromatography of underivatized non-protein amino acids was investigated by using a column packed with octadecylsilanized silica coated with N,S-dioctyl-D-penicillamine as a chiral ligand-exchange phase (Sumichiral OA-5000). Excellent to good separations of enantiomers were achieved with a variety of nonprotein amino acids carrying aliphatic or aromatic side-chains by optimizing the amount (0-20%, v/v) of the organic component (2-propanol) and the concentration (1-5 mM) of the complexing metal ion (Cu²⁺) in the hydro-organic eluent.     

Design of Selenium‐Based Chiral Chemical Probes for Simultaneous Enantio‐ and Chemosensing of Chiral Carboxylic Acids with Remote Stereogenic Centers by NMR Spectroscopy

Selenium‐based enantiopure chiral chemical probes have been designed in a modular way starting from available amino alcohols. The probes developed were found to be efficient in chemoselective interaction with carboxylic functions of chiral substrates leading to diastereomeric amide formation and in sensing α‐, β‐, and remote (up to seven bonds away from the carboxylic group) chiral centers by using ⁷⁷Se NMR spectroscopy. As a result, it was possible to determine the enantiomeric ratio of structurally diverse individual chiral acids including polyfunctional compounds and drugs with high accuracy. An approach to analyzing the crude reaction mixtures has been successfully developed by using bifunctional selenium‐ and fluorine‐containing chiral probes. More importantly, it was revealed that, based on the ⁷⁷Se NMR data obtained, it is possible to obtain primary information about the location and nature of the substituents at the chiral center (chemo‐ and enantiosensing), which can simplify the structural elucidation of complex compounds. The derivatization procedure takes as little as 5 min and can be performed directly in an NMR tube followed by NMR measurements without any isolation and purification steps.     

Preparation of monolithic silica columns for high-performance liquid chromatography

Preparation methods of monolithic silica columns for HPLC including the surface modification were reviewed. Chemical modification methods recently reported to obtain stationary phases for reversed-phase (RP), chiral, ion-exchange, and hydrophilic interaction chromatography (HILIC) separations were discussed. Recent results related to preparation methods of monolithic silica were also covered. The characteristics and properties of silica monoliths and some applications of monolithic silica columns for different analytical and bioanalytical fields will be commented.