Resolution of α-cyclohexyl-mandelic acid enantiomers by two-phase (O/W) recognition chiral extraction

This paper presents a new chiral separation technology: two-phase (O/W) recognition chiral extraction. Distribution behavior of α-cyclohexyl-mandelic acid enantiomers was studied in the extraction system with D(L)-isobutyl tartrate in 1,2-dichloroethane organic phase and β-CD derivatives in aqueous phase, and the influence of the kind and concentration of extractant and pH on extraction performance was investigated. The experimental results indicate that two-phase (O/W) recognition chiral extraction is of strong chiral separation ability. HP-β-CD, HE-β-CD and Me-β-CD have higher recognition ability for S-CHMA than that for R-CHMA, among which HP-β-CD has the strongest ability; whereas, D-isobutyl tartrate has reversed recognition ability for them. In the extraction system containing HP-β-CD and D-isobutyl tartrate, e.e.% of S-CHMA in aqueous phase reached 27.6% by one stage extraction, and the distribution ratio for R-CHMA(kR) and for S-CHMA(kS) and separation factor (α) are 2.44, 0.89 and 2.49, respectively. Meanwhile, pH and concentration of extractant have great effects on chiral separation ability. Two-phase (O/W) recognition chiral extraction has great significance for preparative separation of racemic compounds.     

Chiral Separation of Erythromycin as a New Chiral Selector on CE

Erythromycin as a new chiral selector was first used for chrial separation of four derivatives of biphenyldimethylester enantiomers on CE.The influence of pH,the chiral selector concentration and organic modifiers were preliminarily studied.Experiments show that the erythromycin as chiral selector is useful to CE.     

Direct chiral high performance liquid chromatography separation of O-ethyl O-phenylN - isopropylphosphoroamidothioates

The enantiomers of thirty-nine O-ethyl O-phenyl N-isopropyl phosphoroamidothioates have been separated by high performance liquid chromatography on a Pirkle model chiral stationary phase using ten mobile phase. Chromatographic data are presented for the separation of these organic phosphorus enantiomers on the chiral phase. The influences of molecular structures and compositions of mobile phases have been described.     

COVALENTLY BONDING CHIRAL POLYURETHANE ON AMINATED SILICA GEL： A NEW STRATEGY TO PREPARE CHIRAL STATIONARY PHASE FOR HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

Two polyurethanes of different molecular weights were prepared by the copolymerization of phenyl diisocyanate and diisopropyl tartrate. The polyurethanes having terminal isocyanate groups were reacted with 3-aminopropyl silica gel to afford two chiral stationary phases. The Mn of the two polyurethanes were 4057 g/mol and 6442 g/mol. The polyurethanes and the corresponding chiral stationary phases were characterized by FT-IR, 1H NMR and elemental analysis. The loading capacities of the polyurethanes on silica gel were 0.68 mmol units/g and 0.61 mmol units/g, respectively. The separation performance and the influence of additives, triethylamine and trichloroacetic acid, on the separation of chiral compounds were investigated by HPLC. The chiral stationary phase prepared from polyurethane with Mn of 4057 g/mol demonstrated better enantioseparation capability than that with Mn of 6442 g/mol. Additionally, it was found that the addition of triethylamine and trichloroacetic acid in the mobile phases significantly improved the enantioseparation for these two chiral stationary phases.     

牛血清白蛋白手性毛细管整体柱的制备及对映体的分离

A silica-bonded bovine serum albumin (BSA) chiral monolithic stationary phase for capillary electrochromatography(CEC) was introduced. An inorganic-organic hybrid monolithic column was firstly prepared by sol-gel chemistry with homogeneously distributed aminopropyl groups throughout the silica matrix. Then the chiral stationary phase was synthesized by the in situ covalent immobilization of BSA on the monolithic column activated with glutaraldehyde. The effects of pH value and concentration of phosphate buffer on the separation of D,L-tryptophan were investigated. The separation factor of D,L-tryptophan reached 3.37 on CEC mode.     

Optimization separation of five phosphoamidothioate enantiomers using a series of silica and chiral column by high-performance liquid chromatography

A computer-assisted method is described for optimization of multi-component,mobile phase selection for separation of five phosphoamidothioate enantiomers with a series of silica and chiral columns in normal phase HPLC.The method is based on the triangular solvent selection concept using a statistical scanning method.The optimization of the separation over the experimental region is based on a special polynomial estimation from seven experimental runs,and resolution (Rs) is used as the selection criterion.Excellent agreement was obtained between predicted and experimental data.     

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.     

Preparation of High Selective Molecularly Imprinted Polymers for （S）-4-Phenyl-2-oxazolidinone

Molecular imprinting is a promising technique for the preparation of polymers which have highly selective recognition properties and serve as separation media, especially for chiral molecules1-2. The process of molecular imprinting mainly involves organiz…     

Stereoselective interactions of chiral dipeptides on amylose based chiral stationary phases

Dipeptides are stereo-specifically involved in several biological functions that are challenging to separate enantiomerically. Elution order of enantiomers is an important issue in chiral chromatography. Amylose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase(CSP) is the best and most-widely-used CSP in chiral separations, but experimental data of enantiomeric separation of dipeptides on this CSP is lacking. Simulation studies were conducted to determine the order of elution and the chiral recognition mechanism of didpetides on this CSP. Results indicated that the docking energy of SR-enantiomers were higher than SS-antipodes. The range of docking energies for SR-enantiomers was -7.44 to -5.92 kcal/mol with CSP, but -7.15 to -5.87 kcal/mol for SS-stereoisomers. Therefore it is predicted that SS-enantiomer will elute first, followed by SR-antipode. Furthermore, hydrogen bondings, van der Waal’s interactions and electrostatic interactions were observed among SR- and SSenantiomers and chiral grooves of CSP. The number of hydrogen bonds was one in each enantiomer binding except S-Ala-R-Tyr, which contained two hydrogen bonds. No hydrogen bond was found in S-Ala-R-Trp, S-Leu-S-Trp, and S-Leu-S-Tyr dipeptides bindings. The chiral recognition mechanisms dictate different strengths of stereoselective bindings of the enantiomers on CSP.     

Separation of chiral phosphorus compounds on the substituted P-cyclodextrin stationary phase in normal-phase liquid chromatog-raphy

The separation of enantiomers of a series of eighteen novel nitrogen mustard linked phosphoryl diamide derivatives was investigated on the prepared phenyl carbamate derivative β-cy-clodextrin bonded phase in normal-phase HPLC. Some of the enantiomers could be separated in baseline. The chiral recognition mechanism was also suggested for the separation of chiral phosphorus organic compounds.     

THE ORIGIN OF BIOLOGICAL CHIRALITY AND WEAK INTERACTION

Interaction between polarized electrons and chiral molecules is discussed. It is proved that the direct scattering is the dominant one for producing of the asymmetry of cross sections by comparing with other contributions. The left-right asymmetry of chemical reaction rate induced by inelastic transition of chiral molecules and other related problems concerning the origin of biochirality are discussed.     

Chiral separation abilities of homogeneously synthesized cellulose 3,5-dimethylphenylcarbamates: Influences of degree of substitution and molecular weight

A series of cellulose 3,5-dimethylphenylcarbamates(CDMPCs) with different degrees of substitution(DS) and degrees of polymerization(DP) were homogeneously synthesized in 1-allyl-3-methylimidazolium chloride(Amim Cl). Then, the CDMPCs were coated on silica gel and used as chiral stationary phases(CSPs), and their chiral recognition abilities for seven racemates were evaluated by high performance liquid chromatography. The results showed that DS and DP of CDMPCs had a great influence on chiral recognition abilities of the CSPs. The CSPs with the DS ≈ 1 gives a low chiral recognition to most racemates. On the contrast, the CSPs with the DS ? 2 exhibited high chiral separation abilities. For example, six racemates could be separated on the CSP with CDMPC of DS ≈ 2(CSP-2). Especially, for the enantioseparation of 1-(2-naphthyl) ethanol and Tr?ger's base, CSP-2 gave the highest separation ability in all of CSPs. On the other hand, when the DP of cellulose was in a range from 39 to 220, the chiral separation abilities of CDMPCs increased as the DP increased. This work demonstrates that the structure of cellulose esters such as DS and DP has important effect on their chiral separation ability, and therefore provides a practical method to design and prepare desirable CSPs for different racemates.     

Preparation and chromatographic characteristics of a novel 2,6-dimethyl-β-CD bonded HPLC chiral stationary phase

A novel 2,6-dimethyl-b-CD bonded and silica based HPLC chiral stationary phase（CSP） was prepared.The diphenylmethane diisocyanate（MDI） was applied for the first time in the immobilization of 2,6-dimethyl-b-CD onto the surface of aminized silica gel under mild conditions. The composite materials obtained were used as the CSP for chiral separation processes and this kind of CSP exhibits good enantioselectivity for a variety of chiral compounds under reversed-phase conditions.     

Enantiomeric Separation of Epinephrine and Salbutamol by Micellar Electrokinetic Chromatography Using β-Cyclodextrin as Chiral Additive

Introduction The development of chiral substances, especially inthe pharmaceutical field, places increasing demands onanalytical methods for the separation of these kinds ofisomers and the chiral purity control of drugs in phar-macokinetic studies. As the enantiomers of epinephrineand salbutamol have different pharmacological andtoxicological characteristics, separation and quantitationof the single enantiomers are required. Analytical methods used so far for the enantiomerseparation inclu…     

Antibodies as Tailor-Made Chiral Selectors: an Interdisciplinary Approach to Enantiomer Separation and Detection

 It has long been known that the configurational isomers of biologically active compounds, e.g., nutrients, pesticides, and drugs, may exhibit different activities in a chiral environment such as the human body. Although the majority of drugs presently in development are chiral, analytical and preparative methods for the quantitative determination and purification of stereoisomers still lag behind. One reason is that commonly used chiral selectors for the direct resolution of enantiomers are not tailor-made for a specific analyte. The identification of suitable selectors for a particular pair of enantiomers still requires considerable experimentation and is generally demanding with regard to material, time and labor. The rational design of chiral host molecules, therefore, represents a challenge in facilitating enantiomer analysis. In this article, we describe how a combination of techniques ranging from organic synthesis to molecular biology yields antibodies of predetermined specificity and stereoselectivity that can be used as tailor-made chiral selectors for the chromatographic separation of enantiomers and their sensitive detection in immunosensors.     

Asymmetric Diethylzinc Addition to N-Diphenylphosphinoyl Benzalimine Mediated by Imino Alcohols

As our continuous efforts to search for easily accessible ligands for dialkylzinc addition to imines,[1] in this paper,we would like to present a family of chiral imino alcohols 3 derived from 1,2-diphenyl-2-aminoethanol which will be evaluated for the titled reaction. We believed that this kind of chiral ligands could be good chiral ligands for the diethylzinc addition to imines based on two points: (1) The excellent asymmetrically inductive properties of 1,2-diphenyl-2-aminoethanol and its derivatives have been proven in many reactions. (2) The conformation of the nitrogen in the chiral imines 3 is restricted by imine function which is similar to chiral oxazolines reported in our recent work.     

高效液相色谱手性固定相的研究 I:L-缬氨酸-叔丁酰胺型固定相的制备及对映体拆分

A new chiral chemically bonded stationary phase for direct resolution of optical isomers in HPLC was prepared. The experiemental data showed that the chiral stationary phase gave good resolution for the racemic α-amino acid derivatives and that there was no significant influence on the resolution as the eluting rate varied from 0.6 to 2.0 mL/min. The content of isopropanol in the eluent significantly affected the resolution of the enantiomers. The eluent consisting of 1% isopropanol in hexane gave most favorable result, but the retention times were a little longer. It is evident that the resolution was also influenced by the structure of the solute. In all cases, the resolution of N-Ac-DL-Phe-OMe is lower than that of N-Ac-DL-Leu-OMe and N-Ac-DL-Val-OMe. Although the capacity factor of N-Ac-DL-Tyr-Ome varied greatly in different eluting systems, the separation factor and resolution were very close. It was observed that D-amino acid derivatives eluted faster than the corresponding L-isomers. In the above chromatographic conditions N-acetyl-DL-α-phenylethylamine could not be resolved.     

Construction of Post-column Micro-membrane Reactor for Protein Analysis in Capillary Electrophoresis with Laser Induced Fluorescence Detection

Proteomics is becoming more and more mature,but the detection of low abundance proteins is still a difficult task.Laser-induced fluorescence(LIF) detection is one of the most sensitive detection methods in a capillary electrophoresis(CE)system[1-3].However,most proteins do not exhibit favourable native fluorescence,a derivatization procedure is necessary for LIF detection of proteins.Since the derivatization reaction between protein and fluorescent reagent takes place after the separation of protein,the separation cannot be compromised by multiple derivatization products,the post-column derivatization becomes an attractive method for derivatization in CE-LIF system[4'5].The gap reactor,coaxial reactor and sheath flow cuvette reactor have been widely used for post-column derivatization in CE-LIF system[6].The gap reactor is constructed by aligning separation and reaction capillaries with a small gap[7,8].     

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.     

高效液相色谱法测定联苯取代衍生物的三种异构体

A method for the separation and deternunation of three isomers of 4-nitro-methyldiphenyl by reversed-phase HPLC is described.The method for quantitative analysis without standard substance was studied with satisfactory results.