High-speed counter-current chromatography assisted preparative isolation of phenolic compounds from the flowers of Chrysanthemum morifolium cv. Fubaiju

Chrysanthemum morifolium cv. Fubaiju is rich in phenolic compounds with various benefits such as anti-inflammatory, antioxidant, and cardiovascular protection. In this study, 12 phenolic compounds, including five flavonoid glycosides and seven quinic acid derivatives, were successfully separated from the flowers of Chrysanthemum morifolium cv. Fubaiju by high-speed counter-current chromatography and preparative high-performance liquid chromatography. Ethyl acetate-n-butanol–acetonitrile–water–acetic acid (5:0.5:2.5:5:0.25, v/v/v/v/v) was selected as solvent system to separate six fractions from the flowers of Chrysanthemum morifolium cv. Fubaiju, and 20% aqueous acetonitrile (containing 0.1% formic acid) was chosen to be the elution solvent in preparative high-performance liquid chromatography for purifying the fractions above. Luteolin-7-O-β-D-glucoside ( 1 ), luteolin-7-O-β-D-glucuronide ( 2 ), apigenin-7-O-β-D-glucoside ( 3 ), luteolin-7-O-β-D-rutinoside ( 4 ), diosmetin-7-O-β-D-glucoside ( 5 ), chlorogenic acid ( 6 ), 1,5-dicaffeoylquinic acid ( 7 ), 1,4-dicaffeoylquinic acid ( 8 ), 3,4-dicaffeoylquinic acid ( 9 ), 3,4-dicaffeoyl-epi-quinic acid ( 10 ), 3,5-dicaffeoylquinic acid ( 11 ), and 4,5-dicaffeoylquinic acid ( 12 ) were isolated with purities all above 95%, respectively. In addition, all isolates were evaluated for their protective effects on H₂O₂-induced oxidative damage in adult retinal pigment epithelial cells.     

A Rapid Method for Qualitative and Quantitative Analysis of Major Constituents in Dengzhanxixin Injection by LC-DAD-ESI–MSn

For the first time a rapid method for qualitative and quantitative analysis of constituents in Dengzhanxixin injection was established by liquid chromatography with electrospray ionization–tandem mass spectrometry. Eighteen compounds including flavonoids and phenolic acids were characterized or tentatively identified. Ten of these compounds, including 5-O-caffeoylquinic acid, caffeic acid, 1,3-O-dicaffeoylquinic acid, 6′-O-caffeoylerigeroside, scutellarin, 3,4-O-dicaffeoylquinic acid, 3,5-O-dicaffeoylquinic acid, erigoster B, apigenin-7-O-glucuronide and 4,5-O-dicaffeoylquinic acid, were further quantified as marker substances by LC-DAD using a C₁₈ column at 0.4 mL min^?1 within 37 min. The quantitative method was validated for ten interesting compounds, including linearity, accuracy, precisions, LOQ and LOD, which was proved to be sensitive, reproducible and accurate. The study might provide a comprehensive method for the quality assessment of dengzhanxixin injection.     

New Quinic Acid Derivatives from Hepatoprotective Inula crithmoides Root Extract

Fractionation directed by hepatoprotective activity of Inula crithmoides L. root resulted in the isolation of two new quinic acid derivatives, 3,5‐di‐O‐caffeoylquinic acid 1‐methyl ether ( I ; caffeoyl=(E)‐3‐(3,4‐dihydroxyphenyl)prop‐2‐enoyl; quinic acid=1,3,4,5‐tetrahydroxycyclohexanecarboxylic acid) and 4,5‐di‐O‐caffeoylquinic acid 1‐methyl ether ( II ), in addition to the well‐known hepatoprotective compound, 1,5‐di‐O‐caffeoylquinic acid ( III ). The hepatoprotective effect was indicated by the significant decrease in the level of four measured serum biochemical parameters (SGOT, SGPT, ALP, and bilirubin) in experimental rats. The structures of the isolated compounds were determined by analyses of 1D‐ and 2D‐NMR spectroscopic data.     

Cyclohexanecarboxylic-Acid Derivatives from Psiadia trinervia

From a MeOH extra of Psiadia trinervia, seven phenolic compounds were isolated by gel filtration and reversed-phase chromatography. Six of them are known compounds, namely 3,4-di-O-caffeoylquinic acid ( 2 ), 3,5-di-O-caffeoylquinic acid ( 3 ), caffeic acid, and three 3-methoxyflavonoids. Compound 1 is a 3,4-di-O-caffeoyl derviative of (1S,3R,4R,5R)-1,3,4, 5-tetrahydroxycyclohexanecarboxylic acid, a novel steroisomer of (?)-quinic acid. Following hydrolytic treatment of the MeOH extract, ethyl 3-O-caffeoylquinate ( 4 ), ethyl 3,4-di-O-caffeoylquinate ( 5 ), and ethyl 3,5-O-caffeoylquinate ( 6 ) were isolated. The latter three compounds are artifacts. The configuration of 1-3 was established by NMR and CD (exciton chirality method).     

Syntheses of 3-, 4-, and 5-O-feruloylquinic acids

The efficient synthesis of 3-, 4-, and 5-O-feruloylquinic acids starting from d-(?)-quinic acid is described. Esterification of suitably protected quinic acid derivatives with 3-(4-acetoxy-3-methoxyphenyl)-acryloyl chloride and subsequent hydrolysis of all the protecting groups afforded the title products in overall yields of 33%, 15%, and 45%, respectively, (from quinic acid).     

Antioxidant activities and phenolics profiling of different parts of Carica papaya by LCMS-MS

This article deals with the comparison of the antioxidant activity of aqueous extracts of various parts of Carica papaya L. The evaluation of total phenolic content and total flavonoid content revealed high antioxidant potential of the seeds and fruits. The free radical-scavenging potential of the aqueous extracts indicated the seeds to have better DPPH-scavenging activity than fruits. The results were augmented by the FRAP activity as well. The phenolics present in the extracts were separated and identified as 5-hydroxy feruloyl quinic acid, acetyl p-coumaryl quinic acid, quercetin-3-O-rhamnoside, syringic acid hexoside, 5-hydroxy caffeic quinic acid, peonidin-3-O-glucoside, sinapic acid-O-hexoside, cyaniding-3-O-glucose and methyl feruloyl glycoside by LCMS-MS technique.     

A highly stereoselective synthesis of d-erythrose derivatives by one-carbon homologation of 2,3-O-isopropylidene-d-glyceraldehyde with (R)-methyl p-tolyl sulfoxide

A highly diastereoselective three-step synthesis of 2-O-benzyl-3,4-O-isopropylidene-d-erythrose 9 is described (de >98%; 50% overall yield) starting from d-glyceraldehyde acetonide and (R)-methyl p-tolyl sulfoxide. Treatment of 9 with trifluoroacetic acid gives 2-O-benzyl-d-erythrofuranose.     

A facile synthesis and highly atom economic 1,3-dipolar cycloaddition of hexahydropyrido[3,4-c][1,5]benzothiazepines with nitrile oxide: stereoselective formation of hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines

A series of new 2-methyl-11-aryl-4-[(E)-arylmethylidene]-1,2,3,4,11,11a-hexahydropyrido[3,4-c][1,5]benzothiazepines were obtained by the reaction of o-aminothiophenol and (E)-1-methyl-3,5-bis(arylidene)-4-piperidones in the presence of a catalytic amount of acetic acid under solvent-free microwave irradiation. These dipolarophiles undergo a highly atom economic 1,3-dipolar cycloaddition with nitrile oxide to afford a series of novel 6-methyl-1-phenyl-8-aryl-4-[(E)-arylmethylidene]-4,5,6,7,7a,8-hexahydro[1,2,4]oxadiazolo[5,4-d]pyrido[3,4-c][1,5]benzothiazepines stereoselectively.     

Heterocyclizations of 5-methylpyrazol-3-amine with unsaturated arylaliphatic carboxylic acid derivatives

Cyclocondensation of 5-methylpyrazol-3-amine with methyl cinnamate and arylmethylidenemalonic acids in DMF and methanol leads to the formation of 7-aryl-2-methyl-6,7-dihydropyrazolo[1,5-a]-pyrimidin-5(4H)-ones. Arylmethylidenemalonic acids react with the title amine at a ratio of 1:2 in nitrobenzene to give 4-aryl-3,5-dimethyl-1,7-dihydrodipyrazolo[3,4-b:4′,3′-e]pyridines. Heterocyclizations of 5-methylpyrazol-3-amine with 5-arylmethylidene-2,2-dimethyl-1,3-dioxane-4,6-diones or their precursors, para-substituted benzaldehydes and 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum’s acid) in all solvents (methanol, DMF, and nitrobenzene) give the corresponding 4-aryl-3-methyl-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-ones. The structure of 3-methyl-4-(4-nitrophenyl)-2,4,5,7-tetrahydropyrazolo[3,4-b]pyridin-6-one was proved by X-ray analysis.     

New constituents from Mikania laevigata Shultz Bip. ex Baker

A new phenylpropanoid and two new diterpenes were isolated from the leaves of the plant Mikania laevigata Shultz Bip. ex Baker. The structures of these compounds were established by 1D- and 2D-nuclear magnetic resonance spectroscopic techniques and mass spectrometry data. Taraxerol, lupeol, coumarin, syringaldehyde, trans-melilotoside, cis-melilotoside, adenosine, patuletin 3-O-β-d-glucopyranoside, kaempferol 3-O-β-d-glucopyranoside, quercetin 3-O-β-d-glucopyranoside, methyl 3,5-di-O-caffeoyl quinate, and 3,3′,5-trihydroxy-4′,6,7-trimethoxyflavone were isolated too. In addition, the compounds dihydrocoumarin, spathulenol, caryophyllene oxide, kaurenoic acid, beyerenoic acid, and lupeol acetate were identified by GC-MS.     

Synthesis of 3,5-difunctionalized 1-methyl-1H-pyrazolo[3,4-b]pyridines involving palladium-mediated coupling reactions

Indirect iodination of 2-chloro-nicotinonitrile gave 2-chloro-5-iodonicotinonitrile, which was cyclized with methylhydrazine to lead to 3-amino-5-iodopyrazolo[3,4-b]pyridine. Position 3 was then protected by pivaloyl group and the resulting 5-iodo-3-pivaloylaminopyrazolo[3,4-b]pyridine was engaged in palladium-promoted coupling reactions with various reagents to give 3-pivaloylamino-5-substituted compounds. Deprotection and iododediazoniation followed by cross-coupling reactions in position 3 afforded novel unsymmetrical 3,5-disubstituted pyrazolo[3,4-b]pyridine species.     

Simultaneous Quantification of Seven Caffeoylquinic Acids in Ecotypes of Blumea balsamifera at Various Life Stages by High-Performance Liquid Chromatography

Blumea balsamifera is a traditional Chinese medicine containing various bioactive caffeoylquinic acids and usually used for the treatment of rheumatism, eczema, and dermatitis. An accurate and reliable high-performance liquid chromatography method was established for simultaneous determination of 5-O-caffeoylquinic acid, 3-O-caffeoylquinic acid, 4-O-caffeoylquinic acid, 1,3-di-O-caffeoylquinic acid, 3,4-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4,5-di-O-caffeoylquinic acid in B. balsamifera. The method was rigorously verified and was successfully applied to simultaneous quantification of seven caffeoylquinic acids in four ecotypes of B. balsamifera at five life stages. The results showed that the highest concentrations of seven compounds were present in September, October, and November, indicating that the optimal harvest time of B. balsamifera is in the autumn. Therefore, this method is suitable for the quantification of the seven compounds and quality control for B. balsamifera.     

l-Ascorbic acid in organic synthesis: DBU-catalysed one-pot synthesis of tetramic acid derivatives from 5,6-O-isopropylidene ascorbic acid

Reaction of 5,6-O-isopropylidene-2,3-bis-O-alkyl ascorbic acid with different amines in the presence of DBU at ambient temperature resulted in the formation of 3,4-bis-O-alkyl-1-alkyl-5-(2-hydroxy ethyl)-5-hydroxy-1,5-dihydropyrrol-2-ones in moderate yields.     

Ring conformations of d-glucose derivatives possessing two bulky silyl protecting groups at the 3,4-positions; the first observation of a stable full-axial chair conformer without bridge structures

The ring conformations of 3,4-bis-O-tert-butyldimethylsilyl- and 3,4-bis-O-tert-butyldiphenylsilyl-d-glucopyranoses as well as the corresponding phenyl 1-thio-d-glucopyranosides were investigated. Observations showed that the introduction of the two tert-butyldiphenylsilyl groups can flip the pyranose-ring into the ¹C₄ conformation possessing more axial substituents. All the substituents of the 3,4-bis-O-tert-butyldiphenylsilyl-β-d-glucopyranose were axially oriented.     

Convenient construction of spiro[indoline-3,5'-pyrrolo[3,4-c]carbazole] and spiro[indene-2,5'-pyrrolo[3,4-c]carbazole] via acid-catalyzed Diels-Alder reaction

p-TsOH catalyzed Diels-Alder reaction of 3-(indol-3-yl)maleimides with 3-phenacylideneoxindoles in toluene at 80 °C for two hours afforded cis/trans isomers of 3a',4′,6′,10c'-tetrahydrospiro[indoline-3,5′-pyrrolo[3,4-c]carbazoles] in nearly comparable yields, which could be easily converted to the corresponding 4′,6′-dihydrospiro[indoline-3,5′-pyrrolo[3,4-c]carbazole] in high yields and with high diastereoselectivity by further DDQ oxidation. Additionally, the similar reaction of 3-(indol-3-yl)maleimides with 2-arylidene-1,3-indanediones in toluene 80 °C and sequential DDQ oxidation afforded functionalized dihydrospiro[indene-2,5′-pyrrolo[3,4-c]carbazoles] as major products.     

Synthesis and asymmetric oxidation of thioglycosides derived from neomenthanethiol and α-d-galactose

6-Deoxy-6-[(1S,2S,5R)-2-isopropyl-5-methylcyclohexylsulfanyl]-1,2:3,4-di-O-isopropylidene-α-d-galactopyranose was synthesized in 94% yield from 1,2 : 3,4-di-O-isopropylidene-α-d-galactopyranose and neomenthanethiol, and its oxidation gave the corresponding diastereoisomeric sulfoxides in up to 84% yield and de values of up to 52%. The isopropylidene protective groups were removed from the sulfide and sulfoxides by treatment with trifluoroacetic acid in chloroform.     

Assay of caffeoylquinic acids in Baccharis trimera by reversed-phase liquid chromatography

Baccharis trimera commonly named ‘carqueja’, is wide-spread in South America and are used as raw material for herbal medicines. A reversed-phase liquid chromatography (RP-LC) method coupled to diode array detector was developed for the analysis of caffeoylquinic acids (CQAs), the main compounds responsible for its digestive activity. The identity of the quinic acids was established by mass spectrometry and were them: 5-O-[E]-caffeoylquinic acid, 3,4-O-[E]-dicaffeoylquinic acid, 3,5-O-[E]-dicaffeoylquinic acid, 4,5-O-[E]-dicaffeoylquinic acid and a tricaffeoylquinic acid. The RP-LC method for the quantitation of the caffeoylquinic acids was validated according to ICH guidelines, based on the following parameters: linearity, selectivity, robustness, limits of detection and quantification, precision and recovery. Hydroalcoholic extracts were prepared by the maceration of the plant material with ethanol:water 1:1 (v/v) in a 0.1:25 g mL^?1 plant:solvent ratio in a water bath at 40 °C. Validation data indicated that the HPLC method proposed is suitable for the analysis of caffeoylquinic acids in B. trimera raw material. The results of the LOD and LOQ analyses for the 5-CQA were 4.1 μg mL^?1 and 12.5 μg mL^?1, respectively, 1.3 μg mL^?1, 3.9 μg mL^?1 for 4,5-diCQA and 1.7 μg mL^?1, 5.1 μg mL^?1 for triCQA. The levels of total CQAs ranged from 2.1 to 4.0 g% (w/w). The influence of season harvest and site collection was also evaluated and variations were observed in the results and can be related to phonologic phase, different locations, seasons and soil. Long term and photostability of plant material were carried out and was observed a stable behavior during the time of the experiments.     

Synthesis of some novel sulfonyl ester derivatives derived from d-mannitol

The preparation of sulfonate-derivatives of d-mannitol i.e. 1,2:3,4-di-O-isopropylidene-3,4-di-O-p-toluenesulfonate-d-mannitol (3a), 1,2:3,4-di-O-isopropylidene-3,4-di-O-methanesulfonate-d-mannitol (3b), and 1, 2:3,4-di-O-isopropylidene-3,4-di-O-trifluoromethanesulfonate-d-mannitol (3c) is described. Full characterization and methodologies of these sulfonate-d-mannitol derivatives have been described as well.     

One-pot synthesis of thiazolo[3,4-a]quinoxalines and the related heterocyclic systems using 4-hydroxy-4-alkoxycarbonyl-3,5-diaryl-2-aryliminothia(selena)zolidines as versatile reagents

An efficient and versatile one-step method for the synthesis of thiazolo[3,4-a]quinoxalines and related new heterocyclic systems have been developed on the basis of a new strategy for the construction of the pyrazine ring system. The key step of the process involves the cascade annulation of the iminothiazolopyrazine system to benzene in the reaction of 4-hydroxy-3,5-diaryl-2-phenyliminothiazolidines with 1,2-diaminobenzenes. The use of selenium analogues instead of thiazolidine derivatives in this reaction, leads to selenazolo[3,4-a]quinoxalines and the use of aza analogues instead of 1,2-diaminobenzenes gives aza analogues of thiazolo[3,4-a]quinoxalines.     

Reaction of 3,4-diiodo-2,5-dimethyl-1H-pyrrole with thioamides

3,4-Diiodo-2,5-dimethyl-1H-pyrrole reacted with thioacetamide in polar solvents or under solvent-free conditions to give 2,4,6-trimethyl-5H-pyrrolo[3,4-d][1,3]thiazole. The major product in the reaction of the title compound with thiobenzamide was 3,5-diphenyl-1,2,4-thiadiazole.