Enantiomer separation of drugs by micellar electrokinetic chromatography using chiral surfactants

A review surveying enantiomer separations by micellar electrokinetic chromatography (MEKC) using chiral surfactants is described. MEKC is one of the most popular techniques in capillary electrophoresis, where neutral compounds can be analyzed as well as charged ones, and the use of chiral micelles enable one to achieve the enantioseparation. The chiral MEKC systems are briefly reviewed according to the types of chiral surfactants along with typical applications. As chiral micelles or pseudostationary phases in MEKC, various natural and synthetic chiral surfactants are used, including several low-molecular-mass surfactants and polymerized surfactants or high-molecular-mass surfactants. Cyclodextrin modified MEKC using chiral micelles is also considered.     

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.     

超分子手性组装体的构建与应用

超分子手性组装体通常由多种非共价相互作用协同驱动形成,是一类具有独特手性限域微环境的软物质,对材料工程、生命科学、光学器件、催化合成等领域的发展具有重要作用.其主要构建方法分为三种;手性基元组装、手性因素诱导非手性基元组装、非手性基元对称性破缺组装.通过分析近年来的研究成果,归纳了利用这三种方法构建超分子手性组装体的一...     

Enantioselective reductions by chirally modified alumino- and borohydrides

Fifty years after the first report on the reduction of carbonyl compounds using chiral LiAlH₄-derived hydrides (Bothner-By, A. A. J. Am. Chem. Soc. 1951, 73, 846), the field of enantioselective aluminohydride and borohydride reagents modified by chiral additives is reviewed. The first section deals with the preparation, scope, limits, mechanism of action and synthetic applications of chiral aluminohydrides, classified according to the chemical nature of the stereogenic modifier. The second covers the field of chiral borohydrides, which have been further classified according to the boron sources, namely metal borohydrides (via reaction with chiral additives or in the presence of chiral catalysts), or chiral boranes (by reduction with alkyllithiums or metal hydrides).     

Scalemic and racemic imprinting with a chiral crosslinker

The development of molecularly imprinted chiral stationary phases has traditionally been limited by the need for a chiral pure template. Paradoxically, availability of a chiral pure template largely defeats the purpose of developing a chiral stationary phase. To solve this paradox, imprinting of scalemic and racemic template mixtures was investigated using both chiral (N-α-bismethacryloyl-l-alanine) and achiral (N,O-bisacrylamide ethanolamine) crosslinkers. Imprinting of scalemic mixtures provided polymers capable of partial separation of Boc-tyrosine enantiomers with virtually the same results when using either the chiral or achiral crosslinker. However, the chiral crosslinker was required for chiral differentiation by the racemic imprinted polymers which were evaluated in both batch rebinding and chromatographic modes. Batch rebinding analysis revealed intersecting binding isotherms for the L- and D-Boc-tyrosine, indicating bias for the D or L enantiomer is concentration dependent. Partial chromatographic separation was achieved by the racemic imprinted polymers providing variable D or L bias in equal probability over multiple replicates of polymer synthesis. Correlation of enantiomer bias with the batch rebinding results and optimization of HPLC parameters are discussed.     

Control of helix sense in protein-mimicking backbone by the noncovalent chiral effect

We have reviewed our previous work regarding induction or control of a peptide helix sense through chiral stimulus to the peptide chain terminus. An optically inactive 3(10)-helix designed mainly with unusual alpha-amino acid residues was commonly employed. Such an N-terminal-free peptide generates a preferred helix sense by chiral acid molecule. A helix sense pre-directed in chiral sequence is also influenced or controlled by the chiral sign of such external molecule. Here free amide groups in the 3(10)-helical N-terminus participate in the formation of a multipoint coordinated complex. The terminal asymmetry produces the noncovalent chiral domino effect (NCDE) to influence the whole helix sense. The NCDE-mediated control of helicity provides the underlying chiral nature of protein-mimicking helical backbones: notably, chiral recognition at the terminus and modulation of helical propensity through chiral stimulus. The above items from our previous reports have been outlined and reviewed together with their significance in biopolymer science and chiral chemistry.     

Chiral pillar[n]arenes: Conformation inversion,material preparation and applications

Chiral pillar[n]arenes have shown great research value and application prospect in construction of chiral materials and chiral applications, due to their inherent planar chiral configurations, chiral recognition ability, easy modification and highly symmetric hydrophobic cavity. This review systematically summarized the conformation inversion factors of planar chiral pillar[5]arenes (pR/pS), such as solvents, temperature, substituent size, alkyl chains, chiral and achiral guest molecules. We firstly introduced the applications of chiral pillar[n]arenes for constructing chiral materials and pointed out that planar conformation inversion showed a great potential role in constructing chiral materials. Then, we mainly concluded the chiral applications of chiral and planar chiral pillar[n]arenes like chiral enantiomer analysis by circular dichroism, electrochemistry or chiral fluorescence sensing. From this review, we found that the inherent planar chiral conformation of chiral pillar[n]arenes have played a very important role in chiral field in the future.     

16种手性化合物在不同自制手性固定相上的拆分比较

采用高效液相色谱法,在自制的纤维素-三(3,5-二甲基苯基氨基甲酸酯)(ATEO-OD)、纤维素-三(4-甲基苯基氨基甲酸酯)(ATEO-OG)和纤维素-三(4-甲基苯基甲酸酯)(ATEO-OJ)3种手性柱上对16种不同结构的手性化合物进行了拆分和比较.试验结果表明:16个手性样品在这3种手性固定相上分别获得了不同程度的拆分,A TEO-OD对所分析样品具有更好的手性识别能力,ATEO-OG和ATEO-OJ的手性识别能力相当.     

Comparative Enantiomer-Resolving Ability of Coated and Covalently Immobilized Versions of Two Polysaccharide-Based Chiral Selectors in High-Performance Liquid Chromatography

The separation of enantiomers of over 175 randomly selected chiral acidic, basic, and neutral compounds was studied on 4 polysaccharide-based chiral columns made by coating or covalent attachment of cellulose 3,5-dichlorophenylcarbamate or amylose 3,5-dimethylphenylcarbamate on the surface of silica. Triscarbamate derivatives of cellulose or amylose were used for the preparation of coated-type columns, while in the case of covalently immobilized chiral stationary phases, the respective polysaccharides were not completely carbamoylated but only close to triscarbamates. It was found that this minimal difference in the chemical composition of the polysaccharide derivatives resulted in significantly different enantiomer-resolving ability for certain groups of chiral compounds while only marginally different for other chiral analytes. This potential difference between coated- and covalently immobilized versions of the “same” chiral selector must be considered in method development with these columns, as well as in method transfer between them.     

Dress-up chiral columns for the enantioseparation of amino acids based on fluorous separation

In this paper, we report a new type of chiral high-performance liquid chromatography (HPLC) column—a so-called dress-up chiral column—featuring a chiral stationary phase adsorbed reversibly in a commercial fluorous HPLC column through fluorous interactions. We synthesized perfluroalkylated proline derivatives as chiral stationary phase compounds and then adsorbed them reversibly in the fluorous HPLC column through the pumping of their solutions. By using this dress-up chiral column and fluorophobic elution of an aqueous copper(II) sulfate/MeOH mixture, we could enantioseparate seven racemic amino acids within 40 min. When we washed the dress-up chiral column with fluorophilic tetrahydrofuran or MeOH, the adsorbed chiral stationary phase compounds desorbed from the column, completely destroying its enantioseparation ability. The relative standard deviation of the retention times, the number of theoretical plates, and the resolution for each of four preparations of the dress-up columns were all less than or equal to 9.53 % in 20-times repeated analysis, and were all less than or equal to 18.7 % in four different preparations, respectively.     

Enantioselective crystallization of histidine on chiral self-assembled films of cysteine

In this paper, the preparation and use of chiral surfaces derived from enantiomerically pure crystals of amino acids are described. For this purpose, a self-assembly process to grow thin chiral films of (+)-L- or (-)-D-cysteine on gold surfaces was chosen. These chiral films were utilized as crystallization catalysts in the crystallization of enantiomers from solutions. To demonstrate the chiral discrimination power of the chiral surfaces in crystallization processes, the crystallization of racemic histidine onto the chiral films was investigated. Our study demonstrates the potential application of chiral films to control chirality throughout crystallization, where one enantiomer crystallizes onto the chiral surfaces with relative high enantiomeric excess. In addition, crystallization of pure histidine enantiomers onto chiral films results in strong crystal morphology modification with preferred orientation.     

Chiral ionic liquids: synthesis, properties, and enantiomeric recognition

We have synthesized a series of structurally novel chiral ionic liquids which have a either chiral cation, chiral anion, or both. Cations are an imidazolium group, while anions are based on a borate ion with spiral structure and chiral substituents. Both (or all) stereoisomeric forms of each compound in the series can be readily synthesized in optically pure form by a simple one-step process from commercially available reagents. In addition to the ease of preparation, most of the chiral ILs in this series are liquid at room temperature with a solid to liquid transformation temperature as low as -70 degrees C and have relatively high thermal stability (up to at least 300 degrees C). Circular dichroism and X-ray crystallographic results confirm that the reaction to form the chiral spiral borate anion is stereospecific, namely, only one of two possible spiral stereoisomers was formed. Results of NMR studies including 1H{15N} heteronuclear single quantum coherence (HSQC) show that these chiral ILs exhibit intramolecular as well as intermolecular enantiomeric recognition. Intramolecularly, the chiral anion of an IL was found to exhibit chiral recognition toward the cation. Specifically, for a chiral IL composing with a chiral anion and a racemic cation, enantiomeric recognition of the chiral anion toward both enantiomers of the cation lead to pronounced differences in the NMR bands of the cation enantiomers. The chiral recognition was found to be dependent on solvent dielectric constant, concentration, and structure of the ILs. Stronger enantiomeric recognition was found in solvent with relatively lower dielectric constants (CDCl3 compared to CD3CN) and at higher concentration of ILs. Also, stronger chiral recognition was found for anions with a relatively larger substituent group (e.g., chiral anion with a phenylmethyl group exhibits stronger chiral recognition compared to that with a phenyl group, and an anion with an isobutyl group has the weakest chiral recognition). Chiral anions were also found to exhibit intermolecular chiral recognition. Enantiomeric discrimination was found for a chiral IL composed of a chiral anion and achiral cation toward another chiral molecule such as a quinine derivative.     

Synthesis of chiral azobenzene-based compounds for use in the photochemical tuning of the helical structure of liquid crystals

We have synthesized azobenzene-based molecules containing either one or two chiral groups. A cholesteric phase can be induced by adding the chiral azobenzene compounds to a host nematic liquid crystal. We investigated the effects of the trans - cis photoisomerization of the chiral azobenzene compounds on the properties of the cholesteric phase, such as the helical pitch length. This can be increased or decreased by the photoisomerization of the chiral azobenzene compounds. We discuss the photochemically driven change in the helical pitch of the cholesteric phase with respect to structural effects involving the chiral groups.     

Quantification of the chiral recognition in electrochemically driven ion transfer across the interface water/chiral liquid

The electrochemically driven transfer of the chiral anions of d- and l-tryptophan across the interface water/chiral liquid (d- or l-menthol) is stereoselective, and it can be used to determine quantitatively the difference in Gibbs energies for the solvation of chiral ions in chiral liquids. The ion transfer can be achieved in a three-phase arrangement where a droplet of the chiral liquid containing decamethylferrocene as the electroactive redox probe is attached to a graphite electrode immersed in the aqueous solution containing the chiral ions.     

Synthesis of chiral azobenzene-based compounds for use in the photochemical tuning of the helical structure of liquid crystals

We have synthesized azobenzene-based molecules containing either one or two chiral groups. A cholesteric phase can be induced by adding the chiral azobenzene compounds to a host nematic liquid crystal. We investigated the effects of the trans-cis photoisomerization of the chiral azobenzene compounds on the properties of the cholesteric phase, such as the helical pitch length. This can be increased or decreased by the photoisomerization of the chiral azobenzene compounds. We discuss the photochemically driven change in the helical pitch of the cholesteric phase with respect to structural effects involving the chiral groups.     

外消旋萘普生酯类在(S,S)-Whelk-O1与CDMPC手性柱上的对映体分离及手性识别机理的比较

在Pirkle型的(S,S)-Whelk-O 1与纤维素衍生物型的CDMPC两种手性柱上对六种 外消旋萘普生酯进行了对映体分离，通过研究烷氧基结构上的差异以及流动相中不 同的醇类添加剂对手性识别的影响，探讨和比较了外消旋萘普生酯在两种手性固定 相上手性识别的机理。对于 (S,S)-Whelk-O 1， 溶质与固定相之间的吸引作用于 手性识别的主要因素，而对于CDMPC，溶质在手性空腔中的空间适应性很可能是手 性识别的关键。     

Application of the ΔΛ isomerism of octahedral metal complexes as a chiral source in photochemistry

Photochemical studies on the use of chiral metal complexes in homogenous and heterogeneous systems are surveyed and commented on their significance. A main focus is laid on the utility of the ΔΛ isomerism of octahedral metal complexes as a chiral source. The reported works demonstrate that chiral metal complexes are effective as a molecular element in achieving varieties of functions such as chiral discrimination, chiral transfer, sensing and photoresponsive guests for biomolecules or liquid crystals.     

Last ten years (2008–2018) of chiral ligand‐exchange chromatography in HPLC: An updated review

Chiral ligand‐exchange chromatography is one of the elective strategies for the direct enantioresolution of small chelating compounds: amino acids, diamines, amino alcohols, diols, small peptides, etc. Unlike other methods, the interaction between chiral selector and analyte enantiomers is mediated by a cation, thus producing diastereomeric ternary complexes. Two main approaches are conventionally applied in chiral ligand‐exchange chromatography. The first relies upon chiral stationary phases where the chiral selector is either covalently immobilized or physically adsorbed onto suitable packing materials (coated phases). In the second approach, chiral molecules are added to the eluent, thus generating chiral eluent systems. Among the advantages of chiral ligand‐exchange chromatography, the generation of UV/vis‐active metal complexes, and the use of commercially available or easy‐to‐synthesize chiral selectors, in combination to rather inexpensive achiral columns for coated phases and chiral eluents, are noteworthy. Besides amino acids and amino alcohols, other species have proven suitable for chiral ligand‐exchange chromatography applications. Recently, the use of either chiral ionic liquids or micellar liquid chromatography systems as well as the successful off‐column formation of diastereomeric complexes have expanded the selectivity profiles and application fields. All of these issues are touched in the review, shedding light to the contributions appeared in the last decade.     

Chiral pool based synthesis of pyrrolidinium ionic liquids

Chiral ionic liquids show promising applications in various different fields. A series of pyrrolidinium-based chiral ionic liquids bearing a chiral cation, a chiral anion or both was prepared in good yields using an efficient, economic and simple pathway. The chirality was introduced using (l)-lactate and (l)-menthol derivatives. The resultant chiral compounds were characterized by both spectroscopy and polarimetry. We envision that these new chiral compounds can serve as effective reaction media and chiral catalysts for asymmetric reactions, which are presently being investigated in our lab.     

Chiral resolution of basic drugs by capillary electrophoresis with new glycosaminoglycans

New glycosaminoglycans, fucose-containing glycosaminoglycan (FGAG) and depolymerized holothurian glycosaminoglycan (DHG), were investigated as chiral additives for the separation of drug enantiomers by capillary electrophoresis. The average molecular masses of FGAG and DHG were estimated to be about 59,000 and 14,000, respectively. A variety of basic drug enantiomers were resolved using 10 mM phosphate buffer, pH 5.0, containing 3% FGAG or DHG. Since chiral recognition properties of FGAG and DHG are different, some drug enantiomers were only separated by using FGAG or DHG. With regard to comparison of chiral recognition abilities of FGAG and DHG with other chiral selectors, tolperisone and eperisone enantiomers were not separated with alpha- or beta-cyclodextrin, or heparin as the chiral additives, but were separated with FGAG and DHG. The results obtained reveal that FGAG and DHG are useful as the chiral selectors for separations of drug enantiomers by CE, and that they could be complementarily used with other chiral additives.