Separation of chiral phosphorus compounds on the substituted β‐cyclodextrin stationary phase in normal‐phase liquid chromatography

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‐cyclodextrin 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.     

涂敷纤维素类手性固定相对甲霜灵中间体的高效液相色谱拆分

通过在自制的球形氨丙基硅胶上涂敷纤维素－三（3，5－二甲基苯基氨基甲酸酯）（CDMPC）制备了手性固定相，并采用该手性固定相成功地对甲霜灵中间体进行了高效液相色谱拆分；考察了由不同比例的正己烷和异丙醇组成的流动相对甲霜灵中间体分离效果的影响。     

Gas-liquid chromatography-mass spectrometry of acetates of partially methylated methyl glycosides. VII. Mono- and dimethylheptoses

The partial methylation of methyl β-glucoheptopyranoside has given a complex mixture of methyl ethers, from which five monomethyl ethers have been isolated by preparative GLC. Methylation of the latter gave a mixture in which ten dimethyl ethers were detected. The retention indices on the phase NPGS of the mono- and dimethyl ethers of methyl β-glucoheptopyranoside have been measured, and their mass spectra have been recorded and discussed. The mass spectra of these position isomers unambiguously characterize the pattern of methylation.     

Application of bromoacetate‐substituted β‐CD‐bonded silica particles as chiral stationary phase for HPLC

Bromoacetate‐substituted [3‐(2‐O‐β‐cyclodextrin)‐2‐hydroxypropoxy]propylsilyl‐appended silica particles (BACD‐HPS), an important and useful synthetic intermediate for preparation of novel types of macrocycles‐capped β‐CD‐bonded silica particles including crown ether/cyclam/calix[4]arene‐capped β‐CD‐bonded silica particles, have been prepared and used as chiral stationary phase for HPLC. This synthetic stationary phase is characterized by means of elemental analysis. For the first time, the chromatographic behavior of BACD‐HPS was systematically evaluated with several disubstituted benzenes and some chiral drug compounds under both normal and RP conditions in HPLC. The results show that BACD‐HPS has excellent selectivity for the separation of aromatic positional isomers and chiral isomers of some drug compounds when used as stationary phase in HPLC.     

L-苏氨酸手性分子印迹硅胶分离固定相的制备及分离性能研究

本文使用堆砌硅珠法以硅溶胶为原料、苏氨酸(L-Thr)为手性源构造手性环境,制备具有手性分离能力的全无机介孔手性硅胶球,对其进行元素分析、红外光谱法分析、透射电镜、扫描电镜和氮气吸附等表征,采用HPLC法探究无机介孔硅胶球制备的固定相对手性异构体和苯系位置异构体的拆分性能,成功分离了9对外消旋化合物和8种苯系位置异构体。L-Thr手性硅胶球在手性分离方面具有一定的可行性,并且在位置异构体的分离上具有良好的分离性能,色谱的重复性良好。     

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 divinyl ether fatty acid isomers by micellar electrokinetic chromatography

A micellar electrokinetic chromatography (MEKC) method has been developed for the direct resolution of divinyl ether type of hydrophobic fatty acid isomers. The fatty acid isomers resolved include colneleic acid (CL), colnelenic acid (CLn), 14(Z)-etheroleic acid (14(Z)-EL), 14(Z)-etherolenic acid (14(Z)-Eln), 11(Z)-etheroleic acid (11(Z)-EL), 11(Z)-etherolenic acid (11(Z)-Eln), etheroleic acid (EL) and etherolenic acid (Eln). These fatty acid isomers differ in number, position and spatial arrangement of the double bonds and the position of the ether oxygen. A central composite design was employed for the optimization of the key variables of the separation, namely the concentrations of sodium dodecyl sulfate (SDS) and organic modifiers. The use of micelles combined with an organic modifier in the background electrolyte made it possible to dissolve and separate relatively hydrophobic fatty acid isomers, and to achieve high separation efficiency. Using heptakis-(2,3-dimethyl-6-sulfato)-beta-cyclodextrin (HDMS-beta-CD) as a buffer additive, complete separation of the examined eight divinyl ethers was achieved. Separation efficiencies up to 5 x 10(5) theoretical plates/m were achieved under optimized conditions. Direct UV was applied for detection of the fatty acids. The results were compared with those obtained from high-performance liquid chromatography (HPLC) separation.     

Total synthesis of the proposed structures of the DNA methyl transferase inhibitors peyssonenynes, and structural revision of peyssonenyne B

The purported structures of the peyssonenynes A and B isolated from Peyssonnelia caulifera, and considered to be geometric isomers at the acetoxyenediyne moiety, have been synthesized. The E and Z geometries of the synthetic compounds were secured by the magnitude of the (3)J(H9-C7) values measured using the EXSIDE band-variant of the gradient HSQC pulse sequence and by the chemical shifts of C(6). Comparison of the NMR data of the synthetic and natural products revealed that only those of the Z isomers matched, which correspond to peyssonenyne A. Using HPLC analysis it was found that peyssonenyne B must correspond to the sn-2 positional isomer of the Z sn-1/3 counterpart. The four synthetic sn-1/3 diastereomers are roughly equipotent as DNMT1 inhibitors when evaluated on a radioactive methyl transfer enzymatic assay after immunoprecipitation from K562 human leukemia cells with anti-DNMT1 antibody.     

基于L-谷氨酸的手性硅胶球的制备及其应用

无机介孔硅球因其具有足够的机械强度、热稳定性,以及适应多种流动相的优点,成为高效液相色谱(HPLC)柱填料中使用最广泛和最重要的材料。但在此研究领域中,并未见球形的全无机手性硅胶用作HPLC手性固定相。该文以无机球形介孔硅胶作为研究对象,通过堆砌硅珠法,以硅溶胶为原料,L-谷氨酸(L-Glu)为手性源,在手性环境中制造出脲醛树脂与胶体二氧化硅混合的小球,在550 ℃高温下煅烧除去树脂部分,制备基于L-Glu的无机介孔硅胶球。通过元素分析、红外光谱、扫描电镜、透射电镜和氮气吸附等表征证明这是一种具有规则球形的手性硅胶球,其手性来源于硅胶球自身的骨架和孔结构。将L-Glu手性硅胶球作为固定相制备了HPLC色谱柱,以正己烷-异丙醇(9∶1, v/v)作为流动相,流速为0.1 mL/min,考察了该手性柱对一系列外消旋化合物的拆分性能。实验表明,该手性柱拆分了15种外消旋化合物,其中特罗格尔碱、吡喹酮、3-苄氧基-1,2-丙二醇、1,2-环氧己烷、3-羟基-2-丁酮、2-甲基四氢呋喃-3-酮、异丙基缩水甘油醚达到基线分离;还分离了10种苯系位置异构体,o,m,p-氨基苯酚、o,p-氯苯酚、o,m,p-碘苯胺、o,m,p-甲苯胺、o,m,p-二硝基苯、o,m,p-氯苯胺、o,m,p-硝基苯酚、o,m,p-溴苯胺达到基线分离。实验表明,L-Glu手性硅胶球在手性分离方面具有良好的可行性,与普通硅胶相比不需要进一步修饰就可以有较好的手性分离效果,是一种低成本、制备便捷的手性无机硅胶固定相。     

Synthesis of peptides with alpha,beta-dehydroamino acids. XIII photoisomerization of Ac-(Z)-delta Phe-NHMe: Ac-(E)-delta Phe-NHMe

Easily accessible Ac-(Z)-delta Phe-NHMe was photoisomerized to so far unknown Ac-(E)-delta Phe-NHMe. Some parameters of the process leading to a diastereomeric mixture of ratio 90(Z):10(E) have been tested and the photoisomerization has been carried out on a preparative milligram scale. The isomers were separated via crystallization followed by preparative HPLC.     

Separation of racemic sulfoxides and sulfinate esters on four derivatized cyclodextrin chiral stationary phases using capillary gas chromatography

The separation of 17 chiral sulfoxides and eight chiral sulfinate esters by gas chromatography (GC) on four derivatized cyclodextrin chiral stationary phases (CSPs) (Chiraldex G-TA, G-BP, G-PN, B-DM) is presented. Many of these compounds are structural isomers or part of a homologous series. Differences in enantioselectivity of the methyl phenyl sulfoxide isomers on the derivatized gamma cyclodextrin and the heptakis 2,6-di-O-methyl-beta-cyclodextrin (i.e. B-DM) CSPs are discussed. Under the conditions of this study, the molecular mass cut-off for the GC separation of these compounds was approximately 230. Compounds of higher molecular mass were not eluted from the CSPs at reasonable times and temperatures, but these higher molecular mass enantiomers can be separated by liquid chromatography and capillary electrophoresis. The enantiomeric separation and elution order of a sulfinate ester containing two stereogenic centers as well as 15 chiral sulfoxides is presented. The G-TA and B-DM CSPs generally gave opposite elution orders for most of the compounds studied.     

Chromatographic determination of position and configuration isomers of methyl oleate hydroxides from corresponding hydroperoxides

Summary Studies of lipid oxidation usually employ such model systems as purified fatty-acid methyl ester. While methyl oleate hydroperoxides (MOPHs) can only be readily separated from the matrix by HPLC, because of their heat-susceptibility and relative instability, these same techniques are unable to separatecis MOHP fromtrans isomers. The present study reports an enhanced, rapid separation method forcis andtrans isomers of methyl oleate hydroxides, as well as HPLC determination of positional isomers per fraction of configuration isomer and isomer identification by gas chromatography-mass spectrometry.     

Chiral stationary phases for separation of intermedine and lycopsamine enantiomers from Symphytum uplandicum

Enantioseparation of the pyrrolizidine alkaloid isomers intermedine and lycopsamine, isolated from Symphytum uplandicum, is discussed. The separatory power of two immobilized carbohydrate‐based chiral HPLC columns, Chiralpak IA and IC, in different chromatographic conditions is compared. The study demonstrated the importance of solvent and column selection while developing such chiral HPLC separation methods. The baseline HPLC separation of the two alkaloid isomers in preparatory scale is reported for the first time. The optimized separations were achieved on a Chiralpak IA column with mobile phases of ACN/methanol (80:20) and methanol/methyl‐t‐butyl ether (90:10), both containing 0.1% diethylamine.     

Stereocontrolled synthesis and cycloaddition of 1,2,4-trioxygenated 1,3-dienes

A new stereocontrolled synthetic pathway to 1,2,4-trioxygenated 1,3-dienes from pyruvic aldehyde dimethyl acetal (14a) is described. Reacting the cyclohexylamine-derived imine of this starting material with chloroalkyl ethers under basic conditions affords ketoacetals 18-20, which were then transformed into eight different enoxysilanes 12. A delta-elimination triggered by tert-butyllithium yields 1,2,4-trioxygenated dienes 13. Increasing the bulkiness of the silyloxy group or that of the acetal moiety leads stereoselectively to the (1E,3E) or (1Z,3E) isomers of 13, respectively. Hyperbaric [4 + 2] cycloadditions between 13 (13c, 13d, 13g) and N-methylmaleimide or methyl- and phenylacrylates give access to the expected cycloadducts with fine stereo- and regiocontrol.     

Enantiomeric separation of oxybutynin by recycling high‐speed counter‐current chromatography with hydroxypropyl‐β‐cyclodextrin as chiral selector

Recycling high‐speed counter‐current chromatography was successfully applied to the preparative separation of oxybutynin enantiomers. The two‐phase solvent system consisted of n‐hexane, methyl tert‐butyl ether, and 0.1 mol/L phosphate buffer solution (pH = 5.0) with the volume ratio of 6:4:10. Hydroxypropyl‐β‐cyclodextrin was employed as the chiral selector. The influence of factors on the chiral separation process, including the concentration of chiral selector, the equilibrium temperature, the pH value of the aqueous phase were investigated. Under optimum separation conditions, 15 mg of oxybutynin racemate was separated with the purities of both the enantiomers over 96.5% determined by high‐performance liquid chromatography. Recovery for the target compounds reached 80–82% yielding 6.00 mg of (R)‐oxybutynin and 6.15 mg of (S)‐oxybutynin. Technical details for recycling elution mode were discussed.     

Analysis of diethylstilbestrol and its impurities in tablets using reversed-phase high-performance liquid chromatography

A high-performance liquid chromatographic (HPLC) method is described which is capable of resolving cis- and trans-diethylstilbestrol (DES), DES mono- and dimethyl ethers and 4,4'-dihydroxystilbene. The mobile phase and internal standard used stabilise the cis-trans DES isomer ratio, and the method is capable of quantitating both isomers in dosage forms without derivatisation. Recovery of DES from tablets is quantitative. Results of tablet analyses using this method are compared with those obtained with the official spectrophotometric procedure.     

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri-(3,5-dimethylphenycarbamate) column (Chiralcel OD-RH) and its recognition mechanisms

Enantiomeric separation of six antihistamine agents was first systematically investigated on a cellulose-based chiral stationary phase (CSP), that is, cellulose tris-(3,5-dimethyl phenyl carbamate) (Chiralcel OD-RH), under the reversed-phase mode. Orphenadrine, meclizine, terfenadine, dioxopromethazine, and carbinoxamine enantiomers were completely separated under the optimized mobile phase conditions with resolutions of 5.02, 1.93, 1.68, 1.67, and 1.54, respectively. Mequitazine was partially separated with a resolution of 0.77. The influences of type and concentration of buffer salt, the pH of buffer solution, and the type and ratio of organic modifier on the chiral separation were evaluated and optimized. For a better insight into the enantiorecognition mechanisms, molecular docking was carried out via the Autodock software. The lowest binding energy and the optimal conformations of the analytes/CSP complexes were supplied, and the mechanisms of chiral recognition were determined. According to the results, the key interactions for the chiral recognition of these six analytes on CDMPC were π–π interactions, hydrophobic interactions, hydrogen bond interactions, and some special interactions.     

苯磺酸顺阿曲库铵原料中的R-S异构体和S-S异构体的高效液相色谱法测定

采用手性色谱柱(Chiralcel OD-RH 150×4.0 mm,5μm),以0.05 mol/L的KPF6缓冲液(用磷酸调节pH值为3.0)-乙腈(体积比50∶50)为流动相,在流速1.0 mL.min-1、检测波长280 nm条件下分离和测定了苯磺酸顺阿曲库铵的R-S和S-S异构体.结果表明,利用高效液相色谱法可以实现苯磺酸顺阿曲库铵的R-S和S-S异构体的手性拆分及其快速、简便、准确测定.     

Synthesis,characterization, and properties of novel aromatic bispropenyl ethers

Aromatic bispropenyl ethers are a new class of highly reactive thermosetting monomers that have been prepared and characterized. Two synthetic routes to their preparation have been developed. The first of these involves the base-catalyzed isomerization of bisallyl ether precursors that gives predominantly the Z bispropenyl ether isomers. The second method employs tris(triphenylphosphine)ruthenium(II) dichloride as an isomerization catalyst and produces predominantly the E isomers. Using these methods, a number of bispropenyl ether monomers containing different aromatic groups have been synthesized. The cationic polymerization of these novel monomers to give crosslinked network polymers using diaryliodonium salts as photo and thermal initiators has been studied.     

Chromatographic separation of benzo(a)pyrene isomers on nematic liquid crystal GC and polymeric reversed-phase HPLC phases

Summary The use of two nematic liquid crystals (BABT and BPhBT) as GC stationary phases for the separation of monohydroxybenzo(a)pyrenes. as their TMS ethers, and monomethylbenzo(a)pyrenes was developed and compared with the separation of these isomers by HPLC using a polymeric ODS reversed-phase column. It was found that while HPLC and GC gave comparable separation of the hydroxy isomers, 10 out of 12 separated, better separation of the methyl isomers was obtained using HPLC. A simultaneous use of both HPLC and GC would resolve the twelve hydroxy isomers in about 70min. The results indicated that HPLC, using polymeric reversed-phase columns, is as powerful a tool as GC using nematic liquid crystal phases, for the separation of benzo(a)pyrene isomers. A discussion of the effect of solute length-to-breadth ratio on elution order is presented.Presented in part at the 1981 Pittsburgh Conference on Analytical Chemistry and Applied Spectroscopy, Atlantic City, NJ; paper No. 51.