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Carbohydrates are important raw materials in the chemical industry and they also play significant roles in biological systems. Ionic liquids (ILs), the promising and designable green solvents, have been proposed as an alternative to traditional organic solvents. In light of their unique physicochemical properties, ILs have a good many applications for carbohydrates. This review provides a compilation on the main results achieved by application of ILs for carbohydrates in both separation and analytical chemistry. The IL-based solid-liquid and liquid-liquid separation processes for carbohydrates (especially for those with high molecular weights), such as carbohydrate isolation from biomass, IL-based aqueous biphasic systems (ABSs), selective precipitation, support tags for purification, and analytical techniques, such as matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), electrospray ionization mass spectrometry (ESI-MS), nuclear magnetic resonance (NMR), high performance liquid chromatography (HPLC), among others, are here reviewed. Key accomplishments and future perspectives in this field are discussed.

Rationale Miglitol (1) derived from 1-deoxynojirimycin is an iminosugar that is useful in the treatment of type 2 diabetes mellitus. Isomers (2, 3, 4) that differ at the C2 and C3 positions of hydroxyl groups from miglitol are impurities resulting from the synthesis of miglitol. The impurity profile of a drug substance is critical to its safety assessment and is important for monitoring the manufacturing process. Therefore, developing a fast and simple method that can rapidly identify the configuration of miglitol and its isomers (2, 3, 4) is necessary. Methods Miglitol (1) and its isomers 2-4 were derivatized with benzoboroxole (o-hydroxymethyl phenylboronic acid) at room temperature, and the cyclic boronate esters of different configurations were generated. Protonated miglitol and its isomers 2-4, as well as their derivatives, were subjected to collision-induced dissociation (CID) experiments by using electrospray ionization tandem mass spectrometry (ESI-MS/MS). Elemental compositions of all the ions were verified by electrospray ion-trap time-of-flight mass spectrometry. Results Fragmentation of the protonated miglitol and its isomers gave the same fragment ions at m/z 190 and m/z 146. Both their fragmentation behavior and abundances were similar. Whereas the CID mass spectra of the precursor ions (m/z 322) of cyclic boronate esters showed four characteristic fragment ions, m/z 214 ([M-C7 H8 O](-) ), m/z 196 ([M-C7 H8 O-H2 O](-) ), m/z 151 ([M-C8 H13 NO3 ](-) ), and m/z 133 ([M-C8 H15 NO4 ](-) ). The abundances of these fragments are different which are related to the stereostructure of miglitol and its isomers. Conclusions A facile method was established for the differentiation of the spatial configuration of miglitol and its isomers using the relative abundances of the fragment ions of boronate esters generated from in-situ reaction between analytes and benzoboroxole by ESI-MS/MS. This approach could be used to rapidly identify the stereoisomers and monitor the epimerization of miglitol and its isomers in chemical reactions and manufacturing processes. Copyright © 2016 John Wiley & Sons, Ltd.

A binding pattern of cyclofructan 6 and p-aminobenzoic acid was disclosed using electrospray ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The complex with stoichiometric composition 1:1 was formed as a result of intermolecular hydrogen bond interaction and ion dipole interaction. Spectrophotometic studies demonstrated that their binding properties could be actuated by modulating the pH from 2.0 to 10.0. This is the first demonstration of development of ‘switching’ binding pattern for cyclofructan 6.

Rationale Electrospray ionization tandem mass spectrometry (ESI-MSn) is an invaluable tool for the study of gas-phase reactions. When N-phenylbenzamide is analyzed in negative ion mode, the nucleophilic deprotonated site of nitrogen or oxygen, together with the adjacent electrophilic phenyl carbon in the same molecule, provides a useful opportunity to study the intramolecular nucleophilic reaction in the gas phase. Methods All MSn experiments of deprotonated N-phenylbenzamides were conducted on an ion trap mass spectrometer using ESI in negative ion mode. The accurate masses of fragments were measured on an ESI quadrupole time-of-flight mass spectrometer in negative ion mode. Theoretical calculations were conducted at the B3LYP/6-31++G(d,p) level of density functional theory using the Gaussian 03 program. Results When the polarity of the substituent on the aniline ring was changed, gas-phase Smiles rearrangement reactions could be initiated by different atoms in the anionic center. Upon collisional activation, loss of CO from deprotonated N-phenylbenzamides could be observed, which can be interpreted as a nitrogen anion triggering the Smiles rearrangement reaction through a three-membered ring transition state. As the aniline ring was substituted by a strong electron-withdrawing group (e.g., NO2, COCH3, or CF3) at the para position, a characteristic phenolate anion was obtained, which was derived from the Smiles rearrangement reaction initiated by the oxygen anion through a four-membered ring transition state. Conclusions In the fragmentation of deprotonated N-phenylbenzamides, the gas-phase Smiles rearrangement reaction initiated by either the nitrogen or the oxygen atom can proceed. The findings in this study have not only enriched knowledge on the gas-phase Smiles rearrangement reactions, but also provided valuable information for understanding the rearrangements of deprotonated aromatic amides in gas phase. Copyright © 2015 John Wiley & Sons, Ltd.

RATIONALE Exploring the fragmentation mechanism of amide ions in mass spectrometry has attracted great interest because of the desire to analyze the amino acid sequences of peptides and proteins. However, the collision-induced dissociation (CID) mechanism of deprotonated small amides has been rarely studied in electrospray ionization mass spectrometry (ESI-MS). The fragmentation of deprotonated N,2-diphenylacetamides exhibited some characteristic fragment ions, which are not derived from the conventional cleavage route. Therefore, clarification of their fragmentation mechanism is very important and useful for structural analysis of related amides and peptides. METHODS All CID experiments were carried out using an electrospray ionization ion trap mass spectrometer in negative ion mode. In addition, the accurate masses of fragments were measured on an ESI quadrupole time-of-flight (Q-TOF) mass spectrometer in negative ion mode. Deuterium-labeled 2-phenyl-N-(4-trifluoromethylphenyl)acetamide was synthesized and its ESI fragmentation spectrum had been obtained. Theoretical calculations were carried out by the density functional theory (DFT) method at the B3LYP level of theory with the 6-31G++(d,p) basis set. RESULTS Deprotonated N,2-diphenylacetamides mainly generate four kinds of ions in CID: benzyl anion, aniline anion, phenyl-ethenone anion and isocyanato-benzene anion bearing respective substituent groups. The benzyl anion and the aniline anion can be generated by direct decomposition. The phenyl-ethenone anion and the isocyanato-benzene anion were proposed to be yielded from proton transfer within an ion-neutral complex, and the intensities of two competitive product ions are well correlated with the substituent constants. The mechanism was also supported by theoretical calculations. CONCLUSIONS The characteristic fragment ions of deprotonated N,2-diphenylacetamides were proposed to be produced via an ion-neutral complex mechanism, which was proved by deuterium-labeling experiments, theoretical calculations and substituent effects. Copyright © 2014 John Wiley & Sons, Ltd.

Supporting information may be found in the online version of this article.Dear Sir,Electrosprayionizationmassspectrometry(ESI-MS),anindispensabletechnique for analyzing a large variety of compounds, plays animportant role in structural identification. However, the structuraland mechanistic information based on the i nterpretation of thefragmentation of gaseous ions is limited because of the abundantunexpected gas-phasereactions,which have attracted great interestsince the early days of organic MS.The amide bond is the fundamental and pivotal linkage fromwhich amino acids can build peptides, proteins and otherimportant molecules widely distributed in nature. So, theinterpretation of amide fragmentation in MS has attracted muchattention.

RATIONALE Two structurally similar bioactive regioisomers, 3-O-tetradecanoylingenol and 20-O-tetradecanoylingenol, from Euphorbia wallichii presented quite different fragmentation behaviors. Revealing the related fragmentation pathways may improve the efficiency of characterization and identification of such type of compounds. METHODS The two regioisomers were subjected to collision-induced dissociation (CID) on Finnigan LCQDECA and LTQ Orbitrap XL instruments. Based on the CID results, the possible fragmentation pathways were proposed and investigated with density functional theory (DFT) calculations. RESULTS Elimination of C14H28O2 (tetradecanoic acid) for 3-O-tetradecanoylingenol and the sequential losses of C4H8 (butylene) for 20-O-tetradecanoylingenol were observed in ESI-MS/MS, witnessed also by HR-ESI-MS/MS. The fragmentation pathways were proposed and verified by calculating the activation energy of their transition states by DFT calculations. CONCLUSIONS Based on the observations, fragmentation pathways for the two regioisomers were proposed and verified by calculating the energy of the reactants, products and the corresponding transition states using DFT. This report should have value in rapid identification of the derivatives of ingenol and other regioisomers in natural products. Copyright © 2012 John Wiley & Sons, Ltd.

The polar compounds such as alkaloid compounds are important bioactive components in traditional Chinese medicines. In present study, a comprehensive method for separation and analysis of polar compounds from the polar fraction of traditional Chinese medicine Stephania yunnanensis was established. Both the major components and minor components were analyzed by counter-current chromatography combined with liquid chromatography tandem mass spectrometry (LC-MS(n)). From 50 mg polar fraction of crude extract, 15.2mg corydine and 4.8 mg stepharine with purities over 90% were successfully separated via a polar solvent system n-butanol: methanol: water (4:1:5, v/v) with 10 mM NaOH as an additive in the lower phase, in one step operation. Their structures were further identified by 1H NMR and FTICR-MS. Besides, three minor components were identified by HPLC-MS(n) based on the fragmentation behavior of the purified compounds.

Unexpected [M?+?15]+ ions were formed during the analysis of aromatic aldehydes by use of methanol in positive-ion electrospray ionization mass spectrometry. Aromatic aldehydes with electron-withdrawing groups or electron-donating groups were all tested to make sure the universality. All the aromatic aldehydes studied with methanol as the solvent could generate [M?+?15]+ ion, and for most of them, the [M?+?15]+ ion was more intense than the [M?+?H]+ ion. Deuterium-labeling experiment, high-performance liquid chromatographyMS experiment, collision-induced dissociation experiment, and theoretical calculations were performed to identify the formation of [M?+?15]+ ion. The proposed reaction mechanism is a gas-phase aldol reaction between protonated aromatic aldehydes and methanol occurring in electrospray source. Understanding and using this unique gas-phase ion/molecule reaction can indeed offer a novel and fast approach for the direct identification of aromatic aldehydes. Copyright (C) 2011 John Wiley & Sons, Ltd.

An on-line column-switching counter-current chromatography (CCC) with solid-phase trapping interphase is presented in this paper. The large volume injection is avoided using solid-phase trapping interphase. Thereby, totally different chemical composition biphasic solvent system can be utilized to enhance system orthogonality. In the present work, a 140 mL-capacity CCC instrument was used in the first dimension, and a parallel three-coil CCC centrifuge (40 mL each coil) was used in the second dimensional separation allowing three injections at the same time. With biphasic solvent system composed of n-hexane: ethyl acetate: methanol: water (1:1:1:1, v/v), five well-separated fractions were obtained in the first dimension. Two fractions were online concentrated and further separated in the second dimension with solvent system composed of methyl tert-butyl ether: acetonitrile: water (2:2:3, v/v), where trifluoroacetic acid (10 mM) was added to the upper organic phase as a retainer and triethylamine (10 mM) to the aqueous mobile phase as an eluter. Four hydroxyanthraquinones were successfully separated and purified from Chinese medicinal plant Rheum officinale in only one step.

A rapid and stable method consisting of high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry was established for the identification and differentiation of common diastereoisomeric ursane-type triterpenoids at the C-3 position. Two characteristic fragment ions, [M–H–H2O–CO2]– and [M–H–H2O–HCOOH]–, exhibited significant stereochemical effects and were utilized to distinguish 3-OH epimers. Based on reference standards, the abundance of the fragment ion [M–H–H2O–HCOOH]– in 3β-OH compounds in the MS3 experiment was dramatically higher compared to [M–H–H2O–CO2]–; however, for 3α-OH compounds, the product ion [M–H–H2O–CO2]– was noted to be higher than [M–H–H2O–HCOOH]–. Energy-resolved mass spectrometric experiments were carried out to support the differentiation of these diastereoisomeric triterpenoids at the C-3 position. Using this method, a total of nine ursane-type triterpenoids from a plant crude extract, including four pairs of epimers at the C-3 position, were identified and distinguished rapidly. Furthermore, offline Fourier transform ion cyclotron resonance tandem mass spectrometry was also performed to assign accurate elemental compositions. Copyright © 2011 John Wiley & Sons, Ltd.

Resveratrol and its oligomers, abundantly present in wine grapes, are believed to be effective phytoalexins for the phenomenon "French paradox" partially by virtue of their powerful antiradical properties. EPR spin-trapping technique was utilized, demonstrating all polyphenols were selective (1)O2 quenchers but not effective (•)OH and O2(•¯) scavengers. On the basis of the HPLC-ESI-MS(2) analysis for the simulated reactions of polyphenols with (1)O2, the molecular weights of the resulting photochemical products were 14 or 28 Da higher than those of their substrates. No fragment C2H2O (42 Da), which was rather distinctive of the resorcinol rings in these cases, had been observed, whereas their MS/MS spectra displayed characteristic neutral fragments including carbon monoxide (CO, 28 Da) and 2-hydroxy[1,4]benzoquinone (C6H4O3, 124 Da). Finally, PM3 semiempirical calculations and HR-FTICR-MS experiments were performed, supporting the assertion that their quenching mechanism involved physical and chemical pathways. Chemical quenching underwent an endoperoxide intermediate form to generate quinones.

(E)-3-(Dimethylamino)-1-(2-hydroxyphenyl)prop-2-en-1-one was found to be an excellent ligand for copper-catalyzed N-arylation of azoles and amides with aryl halides under mild conditions. The reaction took place at 82 °C in MeCN with broad functional-group compatibility. A combination of the ligand and CuI proved to be an efficient catalytic system to promote the coupling reactions of aryl halides with azoles and amides.

Carbapenems, including meropenem and imipenem, exhibit low stability against acid or base reagents. The fragmentation behavior of meropenem and its acid hydrolysis products was investigated by Fourier transform ion cyclotron resonance electrospray ionization tandem mass spectrometry and ion trap tandem multi-stage mass spectrometry in both positive and negative ion mode. Only one neutral loss of CO(2) was observed from the precursor ion to the MS(4) product ions for the acid hydrolysis product and this behavior did not correspond to that expected for the previously accepted 1-pyrroline or 2-pyrroline structure with two carbonyl acid units. The unknown product was then proposed to be 2-(4-(5-(dimethylcarbamoyl)pyrrolidin-3-ylthio)-5-imino-3-methyl-6-oxotetrahydro-2H-pyran-2-yl)-3-hydroxybutanoic acid on the basis of the multi-stage mass spectrometric and accurate mass data. A similar acid hydrolysis product of imipenem was also identified by mass spectrometry, confirming that these carbapenems had the same acid hydrolysis behavior. The proposed structures were further confirmed by NMR experiments.

Euonymus hederaceus is distributed widely in the south of China; its stems and leaves have been used as folk medicines to treat many diseases such as renal deficiency and chronic diarrhea, traumatic injury, and abnormal menstruation. Chemical investigation of the leaves and stems of Euonymus hederaceus resulted in the isolation forthe first time and characterization of a new friedelane type triterpene with a molecular mass of 472 and molecular formula of C(30)H(48)O(4)by high resolution mass spectrometry. The (1)H-NMR (13)C-NMR and DEPT135(0)spectra matched the characteristic data of the proposed triterpene skeleton.The compound was finally identified as 28-hydroxyfriedelan-3-one-29-oic acid on the basis of spectroscopic evidence, including two dimensional nuclear magnetic resonance as well as its IR spectrum.

Liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) was utilized to elucidate the tentative structures of amides in Mallotus lianus Croiz plant materials. Collision-induced dissociation was performed in order to propose the structural information for ten unknown amides on the basis of the fragmentation pathways of the four purified amides, which were supported by their corresponding high resolution FTICR-MS data. This is the first report about the structural identification of amides in M. lianus Croiz by LC-ESI-MS-MS directly, which could eliminate the disadvantages such as tedious and material consuming of traditional phytochemical analysis.

High-performance liquid chromatography/electrospray tandem mass spectrometry was developed to distinguish isomers and compounds of similar structures with different configurations in the rhizomes of Z. cassumunar. Energy-resolved breakdown curves were utilized to differentiate four compounds. Compounds 2 (3R,4S) and 4 (3R,4R) were a pair of stereoisomers which could be distinguished easily by breakdown curves. The breakdown curve of compound 1 was identical to that of compound 2, which suggested that the configuration of compound 1 was (3R,4S) or (3S,4R). The breakdown curve of compound 3 was completely different from those of compounds 1, 2 and 4, and it might be that the configuration of the double bond of compound 3 was different from the other three compounds. Hence, the described method using breakdown curves has great potential in the distinguishing of isomers and compounds of similar structure with different configurations.

A facile method based on high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC/(–)ESI-MSn) has been established for the analyses of polyphenol compounds in the root and stems of Parthenocissus laetevirens. Two characteristic fragments [C3O2 (68 Da) and C2H2O (42 Da)] were utilized for the structural identification of polyphenols. Based on the reference standards, the fragment C3O2 was presented when the compound possessed a 2,3-dihydro-1H-indene-4, 6-diol moiety. Meanwhile, the C2H2O fragment (42 Da) yielded from the resorcinol ring was confirmed by resveratrol and three synthesized compounds identified as (E)-5-styrylbenzene-1,3-diol, (E)-4-styrylphenol and (E)-4-(3,4,5-trimethoxystyryl)phenol. FTICR-MSn was performed to further confirm the structures of the fragments. Overall, 15 polyphenol compounds were characterized. Three polyphenol compounds were initially and tentatively characterized from P. laetevirens for the first time, and one was proposed as a novel compound. Furthermore, a pair of stereoisomers was readily distinguished by breakdown curves, and the trans-, cis-isomers could be identified by HPLC/DAD-UV spectra. Copyright © 2009 John Wiley & Sons, Ltd.

A “green” and practical intramolecular pinacol coupling reaction promoted by InCl 3 /Al catalysts in aqueous media has been developed. Under mild conditions, a novel class of polysubstituted cyclopentane-1,2-diols have been obtained with excellent diastereoselectivity. Keywords: Intramolecular; Pinacol coupling; Indium, Aluminium; Aqueous media Introduction In organic synthesis, the formation of carbon-carbon bonds is one of the most fundamental and important operations in the construction of functional molecules. Pinacol coupling, which involves the homo- or cross reductive dimerization of two carbonyls represents one of the most classical ways of generating carbon-carbon bonds [1]. Since its discovery in 1859 [2], the pinacol coupling reaction has been a focal point in synthetic chemistry not only for its carbon-carbon bond generating power, but also for the wide utility of the 1,2-diols obtained from these reactions. These 1,2-diols are valuable synthons in the synthesis of biologically active natural products or molecular fragments [3-4]. After the first report over a century ago, numerous modified pinacol coupling methods have been developed. Instead of the early use of sodium as catalyst, a variety of other metals or metal/Lewis acids such as Zn [5], Mg [6], Ti [7], Sm [8-9], Cr [10], In [11], and VCl

Conventional cancer therapies, the second leading cause of death worldwide, result in serious side effects and, at best, merely extend the patient's lifespan by a few years. Searching for effective prevention is of high priority in both basic and clinical sciences. In recent decades natural products have been considered to be an important source of cancer chemopreventive agents. Red wine polyphenols, which consisted of various powerful antioxidants such as flavonoids and stilbenes, have been implicated in cancer prevention and that promote human health without recognizable side effects. Since resveratrol, a major component of red wine polyphenols, has been studied and reviewed extensively for its chemopreventive activity to interfere with the multi-stage carcinogenesis, this review focuses on recent progress in studies on cancer chemopreventive activities of red wine polyphenol extracts and fractions as well as other red wine polyphenols, like procyanidin B5 analogues and myricetin.

A two-dimensional counter-current chromatographic system (2D-CCC) for preparative isolation and purification of three prenylflavonoids from Artocarpus altilis is presented. An upright CCC instrument (CCC1, total capacity: 1600 ml) was used as the first dimension. Effluent of interest from CCC1 was collected on-line into a 30 ml sample loop by a laboratory-prepared column-switching interface and introduced into a high-speed CCC instrument (CCC2, total capacity: 210 ml) for the second dimension separation. With this 2D-CCC system and a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water (5:5:7:3 and 5:5:6.5:3.5, v/v/v/v), which had been selected by high-speed CCC, about a 500 mg amount of the crude extract was separated, yielding 9 mg of compound 1, 28 mg of compound 2 and 78 mg of compound 3. The purities of the three prenylflavonoids were 98.7 (1), 98.3 (2) and 97.2% (3), respectively, as determined by HPLC analysis. Their chemical structures were identified by electrospray ionization MS, (1)H NMR and (13)C NMR.

A reversed-phase liquid chromatography/tandem multistage mass spectrometry (MS/MS) method was developed for the characterization of amides from the extracts of Piper longum. The characteristic fragmentations of the amides found in P. longum showed diagnostic structural information. Extracted ion chromatography (EIC) and constant neutral losses were used to guide the search for the amides of interest. Amides of known structures that contain four subtypes of amides were rapidly determined, and novel amides were also identified for this plant. Forty-two amides were rapidly identified, of which 22 were found in this plant for the first time and 9 were new compounds. The method is convenient and sensitive, especially for minor components in the unpurified, complex mixture; the structures of unknown constituents could be determined, in the absence of authentic sample, by comparison of the fragmentation patterns with those of homologous compounds.

Five trace impurities were detected in the bulk drug citalopram using high-performance liquid chromatography with UV detection. A simple and sensitive method suitable for liquid chromatography tandem multistage mass spectrometry (HPLC/MS(n)) analysis was developed. Using this method, the fragmentation behavior of citalopram and the impurities was investigated. Four impurities were rapidly characterized, and an unknown impurity was elucidated as 3-(3-dimethylaminopropyl)-N-(1-(3-dimethylaminopropyl)-1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl)-3-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-carboxamide on the basis of the MS(n) and exact mass evidence, and the proposed structure was further confirmed by nuclear magnetic resonance (NMR) experiments after preparative isolation.

The benzylsilver cation which emerges from the collisional dissociation of silver(I)–N-benzylbenzamide complexes was characterized by deuterium-labeling experiments, theoretical calculations, breakdown curves and substituent effects. The nucleophilic attack of the carbonyl oxygen on an α-hydrogen results in the generation of the benzylsilver cation, which is competitive to the AgH loss with the α-hydrogen.

An alkali-extractable polysaccharide (1) was isolated from the seeds of Retama raetam ssp. gussonei. Its composition and linkage determination have been investigated using component analysis, methylation analysis, hydrolysis studies, and NMR spectroscopic analysis. This was shown to contain d-xylose, d-glucose, and 4-O-methyl-d-glucuronic acid in a molar ratio of 7:2:1 and consisted of a backbone of beta-(1--4)-linked d-xylopyranosyl residues, having branches of alpha-d-glucopyranosyl residues that contain (1--2)-linkages and 4-O-methyl-alpha-d-glucopyranosyluronic acid at O-2. This is the first report on the isolation of an alkali-extractable polysaccharide from this plant.

Two phenylbutenoids, ( E )-4-(3′,4′-dimethoxyphenyl)but-3-enyl acetate and ( E )-4-(3′,4′-dimethoxyphenyl)but-1,3-diene, were separated from the rhizomes of Zingiber Cassumunar using a preparative upright counter-current chromatography (CCC). With a two-phase solvent system composed of light petroleum (b.p. 60–90 °C)–ethanol–diethyl ether–water (5:4:2:1, v/v), 150 mg of ( E )-4-(3′,4′-dimethoxyphenyl)but-3-enyl acetate and 175 mg of ( E )-4-(3′,′-dimethoxyphenyl)but-1,3-diene with the purity of 98.7 and 95.1%, respectively, were obtained from 600 mg of the crude sample of Z. Cassumunar in a single-step separation. Structures of these two compounds were identified by ESI-MS, 1 H NMR and 13 C NMR.

Preparative counter-current chromatography (CCC) purification of valrubicin (AD-32) from crude synthetic drug has been successfully performed for the first time using upright coil planet centrifuge with four multilayer coils connected in series with 1600 ml capacity. The two-phase system used was composed of light petroleum (bp 60–90 °C)–ethyl acetate–tetrachloromethane–methanol–water at an optimized volume ratio of 1:1:8:6:1. Target compound (1.2 g) with a purity of 99.88% was obtained from 1.5 g of crude synthetic drug with a purity 95.49% based on HPLC peak area percentage. Identification of the target compound was performed by electrospray ionization mass spectrometry, one- and two-dimensional nuclear magnetic resonance.

A series of impurities, which were all of the same molecular formula, C17H33NO7, were obtained in the process of voglibose synthesis. After isolation and purification, four isomeric cyclitols were completely assigned by 2D NMR experiments. One of the compounds was established by single-crystal X-ray diffraction analysis as 5,6-dideoxy-5-{[2-hydroxy-1-(hydroxymethyl)ethyl]amino}-1-C-(methoxycycl ohexylmethyl)-D-epi-inositol. (C) 2004 Elsevier Ltd. All rights reserved.

Polysaccharides extracted from Libyan dates with hot water and 0.05 M NaOH were fractionated and purified by ion-exchange and gel-filtration chromatography. According to the methylation and hydrolysis analyses, the results indicate the D-glucan to be linear and to contain both (1-->3)- and (1-->4)-linkages. The anomeric NMR measurements confirm that the sugar residues are beta-glycosidically linked. This is the first report on the isolation of a neutral beta-D-glucan from dates.

The title compound, C10H17N2O+·H2PO4−, consists of a rilmenidine cation and a phosphate anion. In the solid state, the inversion-related phosphate anions are linked by O—H⋯O hydrogen bonds to form a chain along the a axis. The cations are connected to the chain via N—H⋯O hydrogen bonds.

In mass spectrometry of protonated N-benzylbutyrolactams, the added proton is initially localized on the carbonyl oxygen, which is the thermodynamically preferred protonation site. Upon collisional activation, dissociative proton transfer takes place leading to the occurrence of fragmentation reactions. The major fragmentations observed are the cleavages of C(α)-C(β) and C(α)-N bonds on the two sides of the methylene linker, which is different to the cleavage of the amide bond itself seen in most amide cases. Theoretical calculations and isotopic labeling experiments demonstrate that the phenyl ring regulates the proton transfer reactions. The proton directly migrates to the C(β) position via a 1,5-H shift leading to the efficient loss of benzene, while it stepwise migrates to the amide nitrogen resulting in the formation of a benzyl cation. The stepwise proton transfer is achieved via intramolecular proton-transport catalysis. The C(γ) position accepts the proton from the carbonyl oxygen via a 1,6-H shift, and then donates it to the amide nitrogen via a 1,4-H shift. The general 1,3-H shift from the carbonyl oxygen to the amide nitrogen can be excluded in this case due to its significant energy barrier. The substituent effects are also applied to explore the reaction mechanism, and it proves that both C(β) and C(γ) are involved in the dissociative proton transfer processes. For monosubstituted N-benzylbutyrolactams, the abundance ratios of the two competing product ions are well correlated with the nature of the substituents.

The traditional methods used in natural product separation primarily target the major components and the minor components may thus be lost during the separation procedure. Consequently, it’s necessary to develop efficient methods for the preparative separation and purification of relatively minor bioactive components. In this paper, a LC/MS method was applied to guide the separation of crude extract of lotus (Nelumbo nucifera Gaertn.) leaves whereby a minor component was identified in the LC/MS analysis. Afterwards, an optimized pH-zone-refining CCC method was performed to isolate this product, identified as N-demethylarmepavine. The separation procedure was carried out with a biphasic solvent system composed of hexane-ethyl acetate-methyl alcohol-water (1:6:1:6, v/v) with triethylamine (10 mM) added to the upper organic phase as a retainer and hydrochloric acid (5 mM) to the aqueous mobile phase eluent. Two structurally similar compounds – nuciferine and roemerine – were also obtained from the crude lotus leaves extract. In total 500 mg of crude extract furnished 7.4 mg of N-demethylarmepavine, 45.3 mg of nuciferine and 26.6 mg of roemerine with purities of 90%, 92% and 96%, respectively. Their structures were further identified by HPLC/ESI-MSn, FTICR/MS and the comparison with reference compounds.

A Broensted acid catalyzed redox amination of indoline with aldehydes for the synthesis of N-alkylindoles (III) proceeds via intramolecular hydride transfer.

A palladium-catalyzed domino Heck reaction and dealkylation for the preparation of 2-substituted indoles is described. This novel transformation is based on an intramolecular Heck reaction followed by dealkylation.

A preparative two-dimensional counter-current chromatographic system (2D-CCC) for simultaneous separation and purification of oridonin and ponicidin from the crude extract of Rabdosia rubescens was presented. It was based on the use of a high-speed CCC (HSCCC, total column volume V(c)=146ml) instrument in the first dimension (1st-D) and a preparative upright CCC (UCCC, V(c)=1500ml) column in the second dimension (2nd-D). The interface was a homemade column-switching system with a 50-ml sample loop. In this way, almost the whole interested region from the first dimension was transferred on-line to the second dimension for further separation. The use of a pair of two-phase solvent systems composed of n-hexane-ethyl acetate-methanol-water (1:5:1:5 and 3:5:3:5, v/v) in the two dimensions permitted the simultaneous separation of oridonin and ponicidin, making this 2D-CCC system with satisfactory resolution and peak capacity. During about 9h separation, two injections with about a 250mg amount of the crude extract for each, was accomplished using this 2D-CCC system, yielding 60mg of oridonin (1) and 10mg of ponicidin (2) all at a purity of over 95% as determined by HPLC analysis. Their chemical structures were identified by electrospray ionization (ESI) MS, (1)H NMR and (13)C NMR.

The gravitational force exerts an important effect on the counter-current chromatography (CCC) and has been used to retain the stationary phase and improve the efficiency in the various CCC separations. This paper deals with the effect of gravitational force on type-J CCC, one of the most popular CCC methods by the mathematical analysis for the first time. The theoretical analyses reveal a close relationship between the effect of gravitational force, the placed orientation of type-J CCC apparatus, and the revolutional speed. Two placed orientations are more suitable for preparative CCC separation: one is common horizontal, and the other upright. Thus, there are three optimum conditions for type-J CCC separation, the first using horizontal apparatus at very low revolutional speed around 10 rpm in the gravitational filed, the second by use of upright apparatus at moderate revolutional speed around 100 rpm in the three-dimensional complex force field composed of centrifugal and orthogonal gravitational force, and the third employing the apparatus placed at any orientation including horizontal and upright CCC apparatus at high revolutional speed above 300 rpm in the centrifugal force field. Therefore, we should consider the effect of gravitation force on CCC at the selection of proper operational conditions according to properties of two immiscible phases, the desired revolutional speed and the parameters of apparatus in order to utilize efficiently the effect of gravitational force. These analyses and results will benefit to improve the efficiency of CCC separation, especially large-scale industrial preparation.

Preparative counter-current chromatography (CCC) isolation of liensinine and its analogues, isoliensinine and neferine from embryo of the seed of Nelumbo nucifera GAERTN. has been successfully performed for the first time using upright coil planet centrifuge with four multilayer coils connected in series with 1600 mL capacity. Two kinds of two-phase solvent systems were applied to preparative CCC isolation. The first was the system composed of light petroleum (b.p. 60-90 degrees C)-ethyl acetate-tetrachloromethane-chloroform-methanol-water (1:1:4:4:6:2, v/v) which was very suitable for fast and small-scale CCC isolation. The second was the system composed of ethyl acetate-tetrachloromethane-methanol-water (1:6:4:1, v/v), which was the optimum for large-scale CCC isolation. Using the first system, 1102 mg of the crude alkaloid was purified in one-step separation of 150 min, yielding 350 mg neferine, 100 mg isoliensinine and 95 mg liensinine with over 95% purity. While using the second solvent system, 5850 mg of the crude alkaloid was purified in one-step separation of 9 h, yielding 2545 mg neferine, 698 mg isoliensinine and 650 mg liensinine with over 97% purity. Structures of the compounds were identified by electrospray ionization multiple mass spectrometry, one- and two-dimensional NMR.

The title compound, C17H19N2OS+·Cl−, was synthesized through a diastereoselective three-component condensation in one pot. The six-membered heterocycle adopts a half-chair conformation which is slightly twisted at 298 K. The cations and the Cl− anions of the structure are connected through a two-dimensional network of N—H⋯Cl and C—H⋯Cl hydrogen bonds. Phenyl rings inter­calate between layers, and no π⋯π stacking is observed in the structure.

The extracellular polysaccharide (1) extracted from the mycelia of Cordyceps sinensis with hot water was fractionated and purified by ion-exchange and gel-filtration chromatography. The structure was investigated using methylation and hydrolysis analysis, periodate oxidation, NMR spectroscopy, and reaction with beta-D-glucanase, and the results indicated that this D-glucan consisted of a backbone composed of (1--3)-beta-D-glucosyl residues and carried a single (1--4)-beta-linked D-glucosyl residue. NMR and IR spectroscopic measurements showed that the sugar residues were beta-glycosidically linked.