Chloromethylphenylcarbamate derivatives of cellulose as chiral stationary phases for high-performance liquid chromatography

A new class of eight chloromethylphenylcarbamate derivatives of cellulose was prepared by introducing both an electron-donating methyl group and an electron-withdrawing chloro group on to the phenyl moieties and their chiral recognition abilities were evaluated as chiral stationary phases (CSPs) for high-performance liquid chromatography. The superiority of these derivatives over dichloro- and dimethylphenylcarbamates of cellulose as CSPs was demonstrated for some racemic compounds. The elution order and enantioselectivity were greatly dependent on the positions of the substituents. Meta- and para-disubstituted derivatives showed higher chiral recognition than ortho- and meta- or para- disubstituted derivatives. The correlation between the chemical shifts of the N---H protons of the carbamate moieties and the enantiomer-resolving abilities of the derivatives is discussed. Some of the derivatives were effective CSPs in both normal- and reversed- phase conditions and could efficiently separate some chiral drug enantiomers.     

Synthesis of novel chiral stationary phases for high-performance liquid chromatography

Three novel chiral selectors 4a-c were synthesized from(S)-amino acids and(R)-1-phenyl-2-(4-methylphenyl)ethylamine.4a-cwere connected to 3-aminopropylsilanized silica gel to be used as the chiral stationary phase for HPLC.Five amino acid derivativesand two pyrethroid insecticides were fairly resolved on these three new chiral stationary phases under normal phase condition.     

Regioselectively modified polysaccharide derivatives as chiral stationary phases in high-performance liquid chromatography

This review summarizes several regioselectively modified polysaccharide derivatives which have been prepared in order to be used for chiral separations chromatography. The goal was to combine the effects of the known tris-arylcarbamate and tris-arylesters of polysaccharides. The use of new materials as chiral stationary phases (CSPs) in liquid chromatography for enantiomeric discrimination was investigated and compared to the homogeneously substituted polysaccharide derivatives. The different works describing the preparations, the performances and the applications of regioselectively modified polysaccharide derivatives have been resumed.     

Covalently bonded polysaccharide derivatives as chiral stationary phases in high-performance liquid chromatography

Polysaccharide derivatives have been extensively used as chromatographic chiral selectors in chiral stationary phases (CSPs) for the separation of enantiomers by HPLC. When coated onto a silica matrix, they represent nowadays one of the most popular type of CSPs. However, they are only compatible with a limited choice of solvents. The main drawback of these CSPs is related to the solubility of the chiral selector in a number of solvents, which limits their applicability. The different attempts which have been described up to now to overcome this problem by covalently fixing the chiral selector to a matrix are reviewed in this paper.     

新型糖基聚合物的合成及其作为高效液相色谱手性固定相的应用(英文)

Two novel polymers containing glucose units as the main-chain that only differ in terms of their regioregularity were synthesized to evaluate their chiral recognition abilities as chiral stationary phases(CSPs)for high performance liquid chromatography(HPLC).The regioregular polymer(poly-5)shows clear resolution ability for the racemate of cobalt(Ⅲ)acetylacetonate(Co(acac)3),whereas the corresponding regioirregular polymer(poly-3)does not show any chiral recognition for Co(acac)3.The regioregular polymer main-chain seems to play an important role not only in providing an efficient interaction with the racemate but also in expressing the chiral recognition ability as a CSP for HPLC.     

Protein-based chiral stationary phases for high-performance liquid chromatography enantioseparations

The enantioseparations of various compounds using proteins as the chiral selectors in high-performance liquid chromatography (HPLC) are considered in this review. The proteins used include albumins such as bovine serum albumin and human serum albumin, glycoproteins such as alpha1-acid glycoprotein, ovomucoid, ovoglycoprotein, avidin and riboflavin binding protein, enzymes such as trypsin, alpha-chymotrypsin, cellobiohydrolase I, lysozyme, pepsin and amyloglucosidase, and other proteins such as ovotransferrin and beta-lactoglobulin. This review deals with the properties of HPLC chiral stationary phases based on proteins, and the enantioselective properties and chiral recognition mechanisms of these stationary phases.     

Imprinted chiral stationary phases in high-performance liquid chromatography

Polymers imprinted with chiral templates offer a new generation of tailor-made chiral stationary phases (CSPs) with predictable selectivities. This review summarizes the present state of the art of molecular imprinting to generate tailor-made CSPs and provides an overview of the main factors involved in the manufacturing process that are crucial to the chromatographic performance of the phases.     

Synthesis of novel chiral imidazolium stationary phases and their enantioseparation evaluation by high-performance liquid chromatography

Two novel chiral stationary phases (CSPs) were prepared by bonding chiral imidazoliums on the surface of silica gel. The chiral imidazoles were derivatized from chiral amines, 1-phenylethylamine and 1-(1-naphthyl)ethylamine. The obtained CSPs were characterized by Fourier Transform Infrared (FT-IR) spectroscopy and elemental analysis (EA), demonstrating the bonding densities of CSP 1 and CSP 2 were 0.43 mmol g⁻¹ and 0.40 mmol g⁻¹, respectively. These two CSPs could be used to availably separate 8 pharmaceuticals, 7 mandelic acid/its derivatives, 2 1-phenylethylamine derivatives, 1 1,1′-bi-2-naphthol, and 1 camphorsulfonic acid in high-performance liquid chromatography (HPLC). It is found that CSP 1 could effectively enantioseparate most chiral analytes, especially the acidic components, while CSP 2 could enantiorecognize all chiral analytes, although a number of components did not achieve baseline separation. Additionally, the effects of mobile phase composition, mobile phase pH and salt content, chiral selector structures, and analyte structures on the enantiorecognitions of the two CSPs were investigated. It is found that high acetonitrile content in mobile phases was conducive to enantiorecognition. Mobile phase pH and salt content could alter the retention behaviors of different enantiomers of the same chiral compound, resulting in better enantioresolution. Moreover, both chiral selector structures and substituted groups of analytes played a significant role in the separation of chiral solutes.     

Synthesis and application of mono-2A-azido-2A-deoxyperphenylcarbamoylated beta-cyclodextrin and mono-2A-azido-2A-deoxyperacetylated beta-cyclodextrin as chiral stationary phases for high-performance liquid chromatography

Two novel chiral stationary phases (CSPs) were prepared based upon the regioselective immobilizations of beta-cyclodextrin (beta-CD) at its C2 position to the silica support. The mono-2A-azido-2A-deoxyperphenylcarbamoylated beta-cyclodextrin and mono-2A-azido-2A-deoxyperacetylated beta-cyclodextrin were synthesized by selective tosylation and azidolysis followed by perfunctionalisation. The derivatised cyclodextrins were then immobilized onto the aminised silica gel via the Staudinger reaction to provide new chiral stationary phases. Their application to high-performance liquid chromatography (HPLC) enantioseparation of racemic compounds was demonstrated using beta-adrenergic blockers, flavonone compounds, benzodiazepinones, antihistamines and weakly protolytic compounds, of which good separations were achieved for some racemic compounds, for instance, bendroflumethiazide (Rs 6.26), oxazepam (Rs 5.99), temazepam (Rs 2.85) and althiazide (Rs 1.13) when compared with the corresponding CSPs where the beta-CD molecule was regioselectively immobilized at the C6 position. The enantiodiscriminatory properties of these CSPs were found to be affected by the orientation of the CD cavity under reversed-phase conditions, and also by the derivitising groups of the CD. The HPLC results inferred that the mono-6A-azido-6A-deoxyperphenylcarbamoylated CD CSP (CD bonded at C6 position to silica) exhibited slightly better chiral recognition ability than mono-2A-azido-2A-deoxyperphenylcarbamoylated CD CSP under the normal-phase and reversed-phase modes on the separation of 31 different racemic compounds and drugs. On the contrary, higher chiral recognition abilities were observed on the mono-2(A)-azido-2A-deoxyperacetylated CD CSP compared to mono-6A-azido-6A-deoxyperacetylated CD CSP.     

Synthesis and application of mono-6-(3-methylimidazolium)-6-deoxyperphenylcarbamoyl-beta-cyclodextrin chloride as chiral stationary phases for high-performance liquid chromatography and supercritical fluid chromatography

The synthesis of mono-6-(3-methylimidazolium)-6-deoxyperphenylcarbamoyl-beta-cyclodextrin chloride (MPCCD) and its application in chiral stationary phases (CSPs) for high-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) are being reported. This chiral selector is coated onto silica gel in different weight percentages (15, 20 and 35%, w/w) to obtain CSPs having different loading content. These new chiral stationary phases are tested using normal-phase HPLC for enantioseparation of racemic aromatic alcohols. Indeed, the enantiodiscrimination abilities of these CSPs are found to be influenced by the loading content of the chiral selector. Among the three columns (MPCCD-C15, MPCCD-C20 and MPCCD-C35), the best enantioseparation results are obtained using a column containing 20% (w/w) of MPCCD (MPCCD-C20). The resolution (R(s)) obtained for p-fluorophenylethanol, p-chlorophenylethanol, p-bromophenylethanol, p-iodophenylethanol and p-fluorophenyl-3-buten-1-ol using MPCCD-C20 ranges from 3.83 to 5.65. Good enantioseparation results are obtained for these analytes under SFC separation conditions using the MPCCD-C20 column.     

Cationic cyclodextrins chemically-bonded chiral stationary phases for high-performance liquid chromatography

Two covalently bonded cationic β-CD chiral stationary phases (CSPs) prepared by graft polymerization of 6^A-(3-vinylimidazolium)-6-deoxyperphenylcarbamate-β-cyclodextrin chloride or 6^A-(N,N-allylmethylammonium)-6-deoxyperphenylcarbamoyl-β-cyclodextrin chloride onto silica gel were successfully applied in high-performance liquid chromatography (HPLC). Their enantioseparation capability was examined with 12 racemic pharmaceuticals and 6 carboxylic acids. The results indicated that imidazolium-containing β-CD CSP afforded more favorable enantioseparations than that containing ammonium moiety under normal-phase HPLC. The cationic moiety on β-CD CSPs could form strong hydrogen bonding with analytes in normal-phase liquid chromatography (NPLC) to enhance the analytes’ retention and enantioseparations. In reversed-phase liquid chromatography (RPLC), the analytes exhibited their maximum retention when the pH of mobile phase was close to their pK_a value. Inclusion complexation with CD cavity and columbic/ionic interactions with cationic substituent on the CD rim would afford accentuated retention and enantioseparations of the analytes.     

Phenylcarbamate derivatives of cellulose and amylose immobilized onto silica gel as chiral stationary phases for high-performance liquid chromatography

Three polysaccharide phenylcarbamate derivatives [cellulose 2,3-bis(3,5-dimethylphenylcarbamate)-6-(3,5-dimethylphenylcarbamate)/(2-methacryloyloxyethylcarbamate), cellulose 2,3-bis(3,5-dichlorophenylcarbamate)-6-(3,5-dichlorophenylcarbamate)/(2-methacryloyloxyethylcarbamate), and amylose 2,3-bis(3, 5-dimethylphenylcarbamate)-6-(3,5-dimethylphenylcarbamate)/(2-methacryloyloxyethylcarbamate)] with vinyl groups were prepared and coated onto silica gel to immobilize them via radical copolymerization with 2,3-dimethylbutadiene. The copolymerization efficiently proceeded, and the coated polysaccharide derivatives were mostly immobilized on the surface of the silica gel. The immobilized polysaccharide derivatives showed high chiral recognition abilities similar to those of the corresponding coated polysaccharide derivatives. They could be used with an eluent containing chloroform, which dissolved the polysaccharide derivatives. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 4704–4710, 2004     

Enantioselective supercritical fluid chromatography using ristocetin A chiral stationary phases

Racemic mixtures of five acidic drugs have been successfully separated by supercritical fluid chromatography (SFC) using macrocyclic antibiotic chiral stationary phases (CSPs). A ristocetin A CSP has been prepared 'in-house' and effectively applied in packed capillary SFC to separate the enantiomers of dichlorprop (R(s) = 1.4), ketoprofen (R(s) = 0.9) and warfarin (R(s) = 0.9). The commercial ristocetin A CSP (Chirobiotic R) was subsequently studied in packed column SFC with similar results where the enantiomers of warfarin (R(s) = 2.2), coumachlor (R(s) = 2.5) and thalidomide (R(s) = 0.6) were separated. Interestingly, differences were observed between the two differently immobilised CSPs where the enantiomers of dichlorprop and ketoprofen, which were separated on the 'in-house' CSP, could not be separated on the commercial phase.     

Synthesis of siloxane stationary phases for capillary gas chromatography and supercritical fluid chromatography

A comparison is made between dichlorosilanes and cyclic siloxanes as starting materials in the synthesis of stationary phases for capillary gas chromatography (CGC) and supercritical fluid chromatography (SFC). Siloxanes containing one or more of the side groups methyl, vinyl, phenyl, and cyanoethyl in various ratios were synthesized and compared. These phases were characterized by chromatographic (gel permeation, GPC), spectroscopic (IR, ¹H NMR, ²⁹Si NMR), and thermal (DSC) methods. Coated fused silica columns were evaluated with respect to polarity, crosslinkability with several free-radical initiators, and thermal stability. A new liquid phase, 7% cyanoethyl, 7% phenyl, 1% vinyl methyl polysiloxane is shown to be more polar than OV-1701, more temperature stable, easily crosslinked and suitable for use in supercritical fluid chromatography.     

Novel stationary phases for high-performance liquid chromatography analysis of cyclodextrin derivatives

Novel stationary phases were prepared for separation of cyclodextrins and cyclodextrin derivatives by bonding substituted aromatic groups (phenyl and naphthyl) to the silica gel matrix. Both the electron-withdrawing (nitro) and the hydrogen-donor/acceptor (amide or carbamide) substituents of the phenyl group play essential role in the separation of cyclodextrins and cyclodextrin derivatives. On the basis of the comparison of experimental data obtained on different columns the N-(4-nitrophenyl)-carbamide group bonded silica gel stationary phase was selected as the most effective one for analysis of cyclodextrin derivatives. Improved separation potency was observed for hydroxypropylated, methylated and several other cyclodextrin derivatives compared with the previously and presently used stationary phases. Owing to the strong retention of cyclodextrins and its derivatives on the selected column, detection of their decomposition products was easily achieved. Determination of unsubstituted, natural cyclodextrin as an impurity in the cyclodextrin derivatives was implemented. Identification and characterization of cyclodextrin derivatives in industrial products could also be performed.     

Preliminary evaluation of a standard reference material for chiral stationary phases used in liquid and supercritical fluid chromatography

The applicability of a new Standard Reference Material (SRM) for the evaluation of chiral stationary phase (CSP) performance was demonstrated by utilizing the SRM to characterize the chromatographic behavior of eight commercially available CSPs in liquid and supercritical fluid chromatography. The SRM consists of five ethanolic solutions, each containing one chiral compound. These test mixtures can be used to assess changes in column performance over time and to evaluate lot-to-lot variability in column manufacturing. The SRM was also used to probe the effect of various parameters on column performance.     

Polymer coatings as stationary phases in high-performance liquid chromatography

Modern biochromatography demands highly sophisticated packing materials in terms of biocompatibility, (substrate-) selectivity and recovery. Polymers can be designed in a wide variety and therefore deliver solutions to specific chromatographic problems. Thus, tailor-made polymer coatings are an alternative to the classical chemically bonded stationary phases.     

Separation of chiral furan derivatives by liquid chromatography using cyclodextrin-based chiral stationary phases

The enantiomeric separation of a set of 30 new chiral furan derivatives has been achieved on native and derivatized beta-cyclodextrin stationary phases using high performance liquid chromatography (HPLC). The hydroxypropyl-beta-cyclodextrin (Cyclobond RSP), the 2,3-dimethyl-beta-cyclodextrin (Cyclobond DM), and the acetyl-beta-cyclodextrin (Cyclobond AC) stationary phases are the most effective chiral stationary phases (CSPs) for the separation of these racemates in the reverse phase mode. No enantioseparations have been observed on the native beta-cyclodextrin chiral stationary phase (Cyclobond I 2000) and only a few separations have been attained on the S-naphthylethyl carbamate beta-cyclodextrin (Cyclobond SN) and 3,5-dimethylphenyl carbamate beta-cyclodextrin (Cyclobond DMP) chiral stationary phases in the reverse phase mode. The polar organic and the normal phase mode on these CSPs are not effective for separation of these compounds. The characteristics of the analytes, including steric bulk, hydrogen bonding ability, and geometry, play an important role in the chiral recognition process. The pH affects the enantioseparation of compounds with ionizable groups and the addition of 0.5% methyl tert-butyl ether to the mobile phase significantly enhances the separation efficiency for some highly retained compounds.     

Separation of stereoisomers of several furan derivatives by capillary gas chromatography-mass spectrometry,supercritical fluid chromatography,and liquid chromatography using chiral stationary phases

The direct separation of several stereoisomers (enantiomers and geometrical isomers) of furan derivatives, important intermediates for the synthesis of physiologically active natural products, was achieved using capillary gas chromatography/mass spectrometry with a per-O-methyl-beta-cyclodextrin, supercritical fluid chromatography and high-performance liquid chromatography with a tris(3,5-dimethylphenylcarbamate) of cellulose or amylose for the chiral stational phases, respectively. The temperature dependence of the peak resolution (Rs) and the retention factor (k) over the range of 110-130 degrees was studied using crotyl furfuryl ether in gas chromatography. Successive increases in the Rs value and of the difference between the k value of the E-isomer and the k value of the Z-isomer were observed when the gradient temperature was decreased. The per-O-methyl-beta-cyclodextrin column was suitable for use with volatile furan ethers whose molecular masses are between 150 and 180. In conclusion, the separation of thermally unstable furan derivatives was accomplished using supercritical fluid chromatography and high-performance liquid chromatography.