Novel cinchona alkaloid carbamate C9-dimers as chiral anion-exchange type selectors for high-performance liquid chromatography

Nine new quinine (QN) carbamate C9-dimers (QN-X-QN), with different aliphatic and cyclic spacers (X), have been synthesized and immobilized onto porous silica gel for HPLC. The chiral discriminating behavior of these "dimeric" anion-exchange type chiral stationary phases (CSPs) has been investigated in detail, to elucidate the role of the presence of a second QN subunit on the chiral selector (SO), as well as the influence of the structure and length of the spacer, on the overall chiral recognition of a set of N-derivatized amino acids and other acidic drugs. The bulkiness of the intermediate spacer tuned the chiral recognition abilities of these SOs, with the 1,3-adamantylen-derived CSP being the one that led to the best separations. Shorter spacers reduced the chiral discrimination abilities of the "dimeric" selectors, with the n-hexylen bridge being the most favorable distance to allow a nearly independent interaction of the two QN subunits with the racemic analytes. The comparison to five "monomeric" CSPs showed that the "dimeric" ones usually retain the chiral analytes more strongly, though the enantioseparation is not improved. Nevertheless, the exceptional resolution abilities of dimeric SOs with a trans- 1,2-diaminocyclohexylen-bridge for the separation of DNP-derivatives of amino acids and certain acidic drugs of therapeutical interest (e.g., profens) seemed to be superior to most of the other CSPs.     

Asymmetric Transformation Driven by Confinement and Self-Release in Single-Layered Porous Nanosheets

Reported here is the use of single-layered, chiral porous sheets with induced pore chirality for repeatable asymmetric transformations and self-separation without the need for chiral catalysts or chiral auxiliaries. The asymmetric induction is driven by chiral fixation of absorbed achiral substrates inside the chiral pores for transformation into enantiopure products with enantioselectivities of greater than 99 % ee. When the conversion is completed, the products are spontaneously separated out of the pores, enabling the porous sheets to perform repeated cycles of converting achiral substrates into chiral products for release without compromising pore performance. Confinement of achiral substrates into two-dimensional chiral porous materials provides access to a highly efficient alternative to current asymmetric synthesis methodologies.     

Comparison of core-shell versus fully porous particle packings for chiral liquid chromatography productivity

A loading and productivity study was done using three racemates on vancomycin and teicoplanin-bonded chiral stationary phases of different particle formats. Two columns were packed with 2.7 μm superficially porous particles and two columns were packed with identically bonded 5 μm fully porous particles. The last two columns were packed with specially synthesized 4.5 μm vancomycin and teicoplanin superficially porous particles. The loading of different chiral compounds showed that the columns filled with 2.7-μm chiral stationary phases were inappropriate for preparative separations due to their very low permeability which precluded high flow rates. However, columns containing 4.5 μm superficially porous (core-shell) particles were as effective for small-scale preparative chiral separations as columns filled with classical 5 μm fully porous particles. Comparing the 4.5 μm superficially porous particles and 5 μm fully porous particles teicoplanin columns, the observed respective productivities of 270 and 265 mg/g chiral phase/h for 5-methyl-5-phenyl hydantoin enantiomers were obtained. Particular attention was given to the peculiar case of the mianserin enantiomeric separation on vancomycin columns that gave observed productivities of 200 and 205 mg/g chiral phase/h on the 4.5 μm superficially porous particles and 5 μm fully porous particles, respectively.     

手性多孔材料在色谱分离分析中的应用

手性多孔有机骨架材料(Chiral porous organic frameworks,CPOFs)具有孔性质优异、比表面积高、稳定性好以及易功能化等诸多优点,已经在手性催化、识别和分离等领域中得到应用。手性多孔有机骨架材料主要有手性金属-有机骨架材料(Chiral metal-organic frameworks,CMOFs)和手性共价有机骨架材料(Chiral covalent organic frameworks,CCOFs)及其他材料,这类材料具有特殊的手性识别、吸附作用,在色谱分离分析领域中已成为研究热点之一。该文综述了手性多孔材料的合成及其在色谱分离和选择性吸附中的应用,展望了未来CPOFs材料可能的应用与发展方向。     

Chiral proline-substituted porous organic cages in asymmetric organocatalysis

The efficient preparation of chiral porous organic cages (POCs) with specific functions is challenging, and their application in asymmetric catalysis has not previously been explored. In this work, we have achieved the construction of chiral POCs based on a supramolecular tetraformyl-resorcin[4]arene scaffold with different chiral proline-modified diamine ligands and utilizing dynamic imine chemistry. The incorporation of V-shaped or linear chiral diamines affords the [4 + 8] square prism and [6 + 12] octahedral POCs respectively. The appended chiral proline moieties in such POCs make them highly active supramolecular nanoreactors for asymmetric aldol reactions, delivering up to 92% ee. The spatial distribution of chiral catalytic sites in these two types of POCs greatly affects their catalytic activities and enantioselectivities. This work not only lays a foundation for the asymmetric catalytic application of chiral POCs, but also contributes to our understanding of the catalytic function of biomimetic supramolecular systems.

Two calix[4]resorcinarene-based chiral POCs with different self-assembly forms were constructed. The difference in the spatial distribution of chiral organocatalytic sites leads to the two chiral POCs exhibiting distinct stereoselectivities.     

Chiral crown ether pillared lamellar lanthanide phosphonates

A new chiral bridging ligand, 2,2'-pentaethylene glycol-1,1'-binaphthyl-6,6'-bis(phosphonic acid), was synthesized in 40.7% overall yield in five steps and used to generate single crystals of the first porous lanthanide phosphonates with chiral crown ether pillars. Single-crystal and powder X-ray crystallography established that these chiral crown ether decorated lamellar solids retain their framework structures after the removal of their included guest molecules and serve as structural models for porous solids that are exploitable for bulk chiral separations.     

Application of a chiral metal-organic framework in enantioselective separation

A modular approach for the synthesis of highly ordered porous and chiral auxiliary (Evans auxiliary) decorated metal-organic frameworks is developed. Our synthesis strategy, which uses known porous structures as model materials for incorporation of chirality via linker modification, can provide access to a wide range of porous materials suitable for enantioselective separation and catalysis. Chiral analogues of UMCM-1 have been synthesized and investigated for the enantioseparation of chiral compounds in the liquid phase and first promising results are reported.     

Templating mesoporous silica with chiral block copolymers and its application for enantioselective separation

In this paper we describe the synthesis of chiral mesoporous silica based on chiral block copolymers of poly(ethylene oxide) and of d-phenylalanine (PEO-b-D-Phe) as a surfactant template. The resulting porous structures are characterized by nitrogen sorption experiments, transmission electron microscopy, and small-angle XRD. It is shown that chiral block copolymers of PEO-b-D-Phe are effective as a surfactant template for the preparation of silica materials with highly ordered periodic mesoporous structures of hexagonal symmetry with a pore size of ca. 5 nm and high surface areas of ca. 700 m2/g. The enantioselectivity feature of this porous silica, after the extraction of the chiral copolymers, was examined by selective adsorption of enantiomers and racemic solutions of valine. The selective adsorption was measured by circular dichroism (CD) spectroscopy. A chiral selectivity factor of 2.34 was found with the D enantiomer of valine adsorbed preferably.     

Solvent-generated HPLC systems with β-cyclodextrin derivatives as chiral additives

It is shown that enantioselective solvent-generated liquid-liquid and liquid-solid Chromatographic systems with -cyclodextrin derivatives can be realized. The liquid-liquid systems are based on ternary solvent systems of limited miscibility, containing chiral additives; the chiral stationary phase is spontaneously generated on the porous microparticulate silica used as a solid support. In the solvent-generated adsorption systems a very small proportion of -cyclodextrin derivatives is added to the mobile phase. These components act as column activators, since they are strongly adsorbed on the RP solid support where they form new stereoselective adsorption sites. It is demonstrated that dynamically generated systems with -cyclodextrin derivatives as chiral agents are powerful and versatile tools for enantioseparation of different types of compounds. This technique creates not only a new type of selectivity but also leads to very stable and reproducible Chromatographic columns.Dedicated to Professor J. F. K. Huber on the occasion of his 65th birthday     

Direct synthesis of porous organosilicas containing chiral organic groups within their framework and a new analytical method for enantiomeric purity of organosilicas

Organosilica porous solids containing chiral organic moieties in the framework with an enantiomeric purity of 95% ee, estimated by eluting organic constituent units from chiral organosilicas, were synthesized from a newly designed chiral (R)-(+)-1,2-bis(trimethoxysilyl)phenylethane precursor via a surfactant-mediated self-assembly approach.     

Chiral ligand-exchange chromatography of amino acids using porous graphitic carbon coated with a dinaphthyl derivative of neamine

In this paper, we describe the preparation and the evaluation of a porous graphitic carbon (PGC) column coated with a new dinaphthyl derivative of neamine for chiral ligand-exchange (LE) chromatography. It was shown that the graphitic surface/dinaphthyl anchor system efficiently (1.15 μmol/m²) and stably (three months of intensive use) adsorbs the neamine template onto the chromatographic support. The resulting coated PGC stationary phase showed appreciable LE-based enantioselective properties towards several native amino acids. Chromatographic separation of methionine enantiomers using a dinaphtyl neamine-based ligand-exchange chiral stationary phase     

A homochiral porous metal-organic framework for highly enantioselective heterogeneous asymmetric catalysis

A homochiral porous noninterpenetrating metal-organic framework (MOF), 1, was constructed by linking infinite 1D [Cd(mu-Cl)2]n zigzag chains with axially chiral bipyridine bridging ligands containing orthogonal secondary functional groups. The secondary chiral dihydroxy groups accessible via the large open channels in 1 were utilized to generate a heterogeneous asymmetric catalyst for the addition of diethyzinc to aromatic aldehydes to afford chiral secondary alcohols at up to 93% enantiomeric excess (ee). Control experiments with dendritic aromatic aldehydes of different sizes indicate that the heterogeneous asymmetric catalyst derived from 1 is both highly active and enantioselective as a result of the creation of readily accessible, uniform active catalyst sites inside the porous MOF.     

Reversing the Handedness of Self‐Assembled Porous Molecular Networks through the Number of Identical Chiral Centres

Scanning tunnelling microscope observations at the 1‐phenyloctane/graphite interface reveal how chiral structural information at the molecular level is transferred and expressed structurally at the 2D supramolecular level for a porous system. The chirality of self‐assembled molecular networks formed by chiral dehydrobenzo[12]annulene (cDBA) derivatives having three chiral chains and three achiral chains, alternatingly, is compared with those of cDBAs having six chiral chains reported previously. While for all cDBAs homochiral surfaces are formed, their handedness is not simply a reflection of the absolute configuration of the stereogenic centres. Both the number of stereogenic centres as well as the length of the achiral chains determine the supramolecular handedness, providing a deep insight into the supramolecular chirality induction mechanisms at play. Moreover, these cDBAs act to induce chirality in porous networks formed by achiral DBAs.     

Preparation and evaluation of monodispersed,submicron, non‐porous silica particles functionalized with β‐CD derivatives for chiral‐pressurized capillary electrochromatography

Submicron, non‐porous, chiral silica stationary phase has been prepared by the immobilization of functionalized β‐CD derivatives to isocyanate‐modified silica via chemical reaction and applied to the pressurized capillary electrochromatography (pCEC) enantio‐separation of various chiral compounds. The submicron, non‐porous, cyclodextrin‐based chiral stationary phases (sub_μm‐CSP2) exhibited excellent chiral recognition of a wide range of analytes including clenbuterol hydrochloride, mexiletine hydrochloride, chlorpheniramine maleate, esmolol hydrochloride, and metoprolol tartrate. The synthesized submicron particles were regularly spherical and uniformly non‐porous with an average diameter of around 800 nm and a mean pore size of less than 2 nm. The synthesized chiral stationary phase was packed into 10 cm × 100 μm id capillary columns. The sub_μm‐CSP2 column used in the pCEC system showed better separation of the racemates and at a higher rate compared to those used in the capillary liquid chromatography mode (cLC) system. The sub_μm‐CSP2 possessed high mechanical strength, high stereoselectivity, and long lifespan, demonstrating rapid enantio‐separation and good resolution of samples. The column provided an efficiency of up to 170 000 plates/m for n‐propylbenzene.     

Evaluation of silica from different vendors as the solid support of anion‐exchange chiral stationary phases by means of preferential sorption and liquid chromatography

Chromatographic performance of a chiral stationary phase is significantly influenced by the employed solid support. Properties of the most commonly used support, silica particles, such as size and size distribution, and pore size are of utmost importance for both superficially porous particles and fully porous particles. In this work, we have focused on evaluation of fully porous particles from three different vendors as solid supports for a brush‐type chiral stationary phase based on 9‐O‐tert‐butylcarbamoyl quinidine. We have prepared corresponding stationary phases under identical experimental conditions and determined the parameters of the modified silica by physisorption measurements and scanning electron microscopy. Enantiorecognition properties of the chiral stationary phases have been studied using preferential sorption experiments. The same material was slurry‐packed into chromatographic columns and the chromatographic properties have been evaluated in liquid chromatography. We show that preferential sorption can provide valuable information about the influence of the pore size and total pore volume on the interaction of analytes of different size with the chirally‐modified silica surface. The data can be used to understand differences observed in chromatographic evaluation of the chiral stationary phases. The combination of preferential sorption and liquid chromatography separation can provide detailed information on new chiral stationary phases.     

多孔金属有机框架的组装与性能研究进展

对多孔金属有机框架的组装及其对气体的吸附性能的研究进展进行了评述,并对磁性和手性多孔金属有机框架进行了介绍.     

Chiral chromatography of amino- and hydroxy-acids on surface modified porous graphite

Summary A new type of chiral stationary phase has been prepared by coating porous graphite with a near-monolayer of an adsorbed enantiomeric modifier which then acts as an adsorbed stationary phase. The most effective modifiers are L- or D-isomers of N-(2-naphthalene-sulphonyl)-phenylalanine (NS-Phe). Conveniently 80% of monolayer coverages, corresponding to 1.2 mol m^–2, are achieved by adsorption of NS-Phe from methanolic solution. Enantiomeric separations by complexation with cupric ion show base-line resolution of -amino and -hydroxy acids with separation factors up to 2. Identical separations are achieved with chiral phases made from the L- and D-isomers of NS-Phe except that the elution orders of enantiomers are inverted. Reduced plate heights are around 5 and the adsorbed chiral phases are extremely stable, retention ratios being unchanged after passage of 7000 column volumes of eluent. A mechanism of retention is proposed, which fits the experimental observations.     

Chiral supercritical fluid chromatography on porous graphitic carbon using commercial dimethyl beta-cyclodextrins as mobile phase additive

Using dimethylated-beta-cyclodextrin mixtures (MeCD) as chiral selectors in CO2-polar modifier mobile phase and porous graphitic carbon as solid-phase, chiral supercritical (or subcritical) fluid chromatography was performed. The adsorbed quantity of MeCD onto the porous graphitic carbon (Hypercarb) was measured for various chiral selector concentrations using the breakthrough method with evaporative light scattering detector. The effects of MeCD concentration in the mobile phase, the nature of the polar modifier, the outlet pressure, the column temperature and the nature of the commercial MeCD mixture on the retention and the enantioselectivities were studied. For a given solute, the enantioselectivity is greatly dependent on the commercial MeCD mixture used. The retention mechanism was also studied. From the data, we find that the dominant mechanism for the chiral discrimination is the diastereoisomeric complexation in the mobile phase.     

A Facile Method for Preparing Porous,Optically Active,Magnetic Fe3O4@poly(N‐acryloyl‐leucine) Inverse Core/Shell Composite Microspheres

The first synthesis of porous, optically active, magnetic Fe₃O₄@poly(N‐acryloyl‐leucine) inverse core/shell composite microspheres is reported, in which the core is constructed of chiral polymer and the shell is constructed of Fe₃O₄ NPs. The microspheres integrate three significant concepts, “porosity”, “chirality”, and “magneticity”, in one single microspheric entity. The microspheres consist of Fe₃O₄ nanoparticles and porous optically active microspheres, and thus combine the advantages of both magnetic nanoparticles and porous optically active microspheres. The pore size and specific surface area of the microspheres are characterized by N₂ adsorption, from which it is found that the composite microspheres possess a desirable porous structure. Circular dichroism and UV‐vis absorption spectroscopy measurements demonstrate that the microspheres exhibit the expected optical activity. The microspheres also have high saturation magnetization of 14.7 emu g^–1 and rapid magnetic responsivity. After further optimization, these novel microspheres may potentially find applications in areas such as asymmetric catalysis, chiral adsorption, etc.

     

Chiral Monolithic Absorbent Constructed by Optically Active Helical‐Substituted Polyacetylene and Graphene Oxide: Preparation and Chiral Absorption Capacity

Chiral monolithic absorbent is successfully constructed for the first time by using optically active helical‐substituted polyacetylene and graphene oxide (GO). The preparative strategy is facile and straightforward, in which chiral‐substituted acetylene monomer (Ma), cross‐linker (Mb), and alkynylated GO (Mc) undergo copolymerization to form the desired monolithic absorbent in quantitative yield. The resulting monoliths are characterized by circular dichroism, UV–vis absorption, scanning electron microscopy (SEM), FT‐IR, Raman, energy‐dispersive spectrometer (EDS), X‐ray diffraction (XRD), Brunauer–Emmett–Teller (BET), XPS, and thermogravimetric analysis (TGA) techniques. The polymer chains derived from Ma form chiral helical structures and thus provide optical activity to the monoliths, while GO sheets contribute to the formation of porous structures. The porous structure enables the monolithic absorbents to demonstrate a large swelling ratio in organic solvents, and more remarkably, the helical polymer chains provide optical activity and further enantio‐differentiating absorption ability. The present study establishes an efficient and versatile methodology for preparing novel functional materials, in particular monolithic chiral materials based on substituted polyacetylene and GO.