Studies on the Constituents of Formosan Salvia Plebeia R. Br. (I) On the Flavonoid Components of Salvia Plebeia R. Br.

Salvia plebeia R. Br. is an annual herb of Labiatae and is widely distributed in the central area of Taiwan. It has been used as folk-medicine for the treatment of hepatitis and tumors.¹⁾ From the flavonoid enriched fraction (B) of the alcoholic extracts of this plant, four kinds of flavonoid compound were isolated. Two of these were confirmed as 5,4′-dihydroxy-6-methoxy-7-glucosyloxy flavone (I). (homoplantaginin, hispidulin-7-glucoside) and 5, 7, 4′-trihydroxy-6-methoxy flavone (II) (hispidulin) on the basis of their spectral, chemical evidences and comparison with authentic samples. The other two were assigned to be 5, 3′, 4′-trihydroxy-6-methoxy-7-glucosyloxy flavone (III) (nepitrin, eupafolin-7-glucoside) and 5,7,3′,4′-tetrahydroxy-6-methoxy flavone (IV) (eupafolin, nepetin) on the basis of chemical and spectral properties. The flavones, II (hispidulin) and IV (eupafolin), have been shown to have cytotoxic activity against human carcinoma of the nasopharynx carried in cell culture (KB).¹³⁾     

LC Method for Determination and Pharmacokinetic Study of 5,6,7,8,3′,4′-Hexamethoxy-3-sulfonyl Flavone in Rat Plasma

A sensitive, specific and rapid high-performance liquid chromatography method was developed for determination of 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone in rat plasma. A simple methanol-induced protein precipitation was applied to extract 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone and Picroside II (the internal standard) from rat plasma. Chromatographic separation was achieved on a Hypersil ODS₂ analytical column (200 mm × 4.6 mm, 5 μm) with acetonitrile–0.04% triethylamine solution (adjusted to pH 5.8 using phosphoric acid) (24:76, v/v) as mobile phase. The calibration curves were linear over the range of 0.2–40 μg mL⁻¹. Absolute recoveries of 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone were 82.7–95.9% from rat plasma. The intra- and inter-day relative standard deviation precisions were less than 5 and 9%, respectively. The method was successfully applied to the pharmacokinetic study of 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone in rats after intravenous administration.

     

Two new flavonoids from Artemisia argyi with their anticoagulation activities

A new flavone glycoside, eupatilin 7-O-β-d-glucopyranoside (1) and a new flavone, 5,6,2′,4′-tetrahydroxy-7,5′-dimethoxyflavone (2), were isolated from Artemisia argyi. Their structures were unambiguously elucidated by extensive spectroscopic analysis. Both flavonoids were evaluated for in vitro anticoagulation activities. Compound 1 significantly extended thrombin time. Compound 2 had obvious effect in increasing prothrombin time.     

A new ent-clerodane diterpenoid from Crassocephalum bauchiense Huch. (Asteraceae)

A phytochemical investigation of the whole plant of Crassocephalum bauchiense Huch. resulted in the isolation of a new clerodane diterpenoid, ent-2β,18,19-trihydroxycleroda-3,13-dien-16,15-olide (1), together with two known flavonoids 3′,5-dihydroxy-4′,5′,6,7,8-pentamethoxyflavone (2) and 4′,5-dihydroxy-3′,5′,6,7,8-pentamethoxyflavone (3). The compounds were tested against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compound 2 showed weak activity (IC₅₀ = 10.1 g/mL) whilst compounds 1 and 3 were inactive. The structures of the compounds were elucidated by using detailed spectral analyses, especially ¹H and ¹³C NMR, ¹H–¹H COSY, NOESY, HMBC and HR-ESI-MS.     

Metabolism of eupatilin in rats using liquid chromatography/electrospray mass spectrometry

Eupatilin (5,7-dihydroxy-3',4',6-trimethoxy flavone) is an active ingredient of an ethanol extract of Artemisia asiatica (DA-9601) that is used in the treatment of gastritis. In vitro and in vivo metabolism of eupatilin in the rats has been studied by LC-electrospray mass spectrometry. Rat liver microsomal incubation of eupatilin in the presence of NADPH and UDPGA resulted in the formation of four metabolites (M1-M4). M1, M2, M3 and M4 were tentatively identified as 3'- or 4'-O-demethyl-eupatilin glucuronide, eupatilin glucuronide, 6-O-demethyleupatilin and 3'- or 4'-O-demethyl-eupatilin, respectively. Those metabolites from in vitro study were also characterized in bile, plasma or urine samples after an intravenous administration of eupatilin to rats. In rat bile, plasma and urine samples, eupatilin glucuronide (M2) was a major metabolite, whereas M3, M4 and M4 glucuronide (M1) were the minor metabolites.     

Preparative separation of six coumarins from the pummelo (Citrus maxima (Burm.) Merr. Cv. Shatian Yu) peel by high-speed countercurrent chromatography

In this work, six coumarins, including two new ones, 8-(3-hydroxy-2,2-dimethylpropyl)-7-methoxy-2H-chromen-2-one (2) and 5-[(7′,8′-dihydroxy-3′,8′-dimethyl-2-nonadienyl)oxy] psoralen (4), as well as four known ones, 5-[(6′,7′-dihydroxy-3′,7′-dimethyl-2-octenyl) oxy] psoralen (1), marmin (3), epoxybergamottin (5), and aurapten (6) were successfully separated from the crude extract of pummelo (Citrus maxima (Burm.) Merr. Cv. Shatian Yu) peel by high-speed countercurrent chromatography in a single run with petroleum-ether–ethyl acetate–methanol–water (4:6:6:4, v/v). The structures of these six coumarins were elucidated by ESI-MS, extensive 1D and 2D NMR spectroscopy.     

Synthesis of some novel pyrazolo[1,5-a]quinazolines and their fused derivatives

New pyrazolo[1,5-a]quinazoline-3-carbonitriles 4a,b were obtained via cyclocondensation of 5-amino-3-cyanomethyl-1H-pyrazole-4-carbonitrile (1) with enaminones of 1,3-cyclohexanedione derivatives 2a,b in refluxing glacial acetic acid. Condensation of compounds 4a,b with various aromatic aldehydes furnished the corresponding arylidene derivatives 6a–j. On the other hand, condensation of 4a,b with o-hydroxybenzaldehydes yielded the polyheterocyclic compounds 10a–h. Coupling of compounds 4a,b with aryldiazonium chlorides led to formation of 2-arylhydrazono derivatives 12a–h. Also, reaction of compounds 4a,b with phenyl isothiocyanate, followed by addition of ethyl chloroacetate and chloroacetonitrile, afforded the polyheterocyclic compounds based on pyrazolo[1,5-a]quinazoline core. The reaction of compounds 4a,b with phenyl isothiocyanate and elemental sulfur gave the thiazole-2-thione derivatives 25a,b. The reaction of enamines of compounds 4a,b with each of hydrazine hydrate and guanidine hydrochloride afforded pyrazolo[4″,3″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-8-ones 30a,b and pyrimido[5″,4″:5′,6′]pyrido[4′,3′:3,4]pyrazolo[1,5-a]quinazolin-9(10H)-ones 33a,b, respectively. The structures of all the newly synthesized compounds were elucidated by elemental analyses and spectral data. The plausible mechanisms have been postulated to account for their formation.     

LC Method for Determination and Pharmacokinetic Study of 5,6,7,8,3′,4′-Hexamethoxy-3-sulfonyl Flavone in Rat Plasma

A sensitive, specific and rapid high-performance liquid chromatography method was developed for determination of 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone in rat plasma. A simple methanol-induced protein precipitation was applied to extract 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone and Picroside II (the internal standard) from rat plasma. Chromatographic separation was achieved on a Hypersil ODS₂ analytical column (200 mm × 4.6 mm, 5 μm) with acetonitrile–0.04% triethylamine solution (adjusted to pH 5.8 using phosphoric acid) (24:76, v/v) as mobile phase. The calibration curves were linear over the range of 0.2–40 μg mL^?1. Absolute recoveries of 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone were 82.7–95.9% from rat plasma. The intra- and inter-day relative standard deviation precisions were less than 5 and 9%, respectively. The method was successfully applied to the pharmacokinetic study of 5,6,7,8,3′,4′-hexamethoxy-3-sulfonyl flavone in rats after intravenous administration.     

Studies on the chemical constituents of Eucalyptus robusta Sm.: Isolation and identification of robustaol B and other constituents

Nine known compounds, 5-hydroxy-4′,7-dimethoxy-6,8-dimethylflavone, 4′,5-dihydroxy-7-methoxy-6,8-dimethylflavone, 3β-hydroxy-urs-11-ene-28-oic-13(28)-lactone, 3β-acetoxy-urs-11-ene-28-oic-13(28)-lactone, uvaol, β-sitosterol, 7β-O-glucoside of 5,7-dihydroxy-2-methylchromone, 1-triacontanol and 1-triacontanoic acid, and a new acylphloroglucinol named robustaol B 6 were isolated from the leaves of Eucalyptus robusta Sm. 6 was shown to be 4,6-dihydroxy-2-methoxy isobutyrophenone by spectral analyses and was confirmed by synthesis. 6 showed inhibition against Staphylococcus aureus 209P and Bacillus subtilis 6633 in vitro.     

Further mass spectral studies of flavones

Further evidence supporting the structure of the [M ? 1]⁺ ion found in the mass spectrum of flavone as being the [dibenzo-β-tropolone ? H]⁺ species was obtained by comparison of linked scan measurements performed in flavone, 3-deuteroflavone, 5,6,7,8-tetradeuteroflavone, 2′,3′,4′,5′,6′-pentadeuteroflavone and dibenzo-β-tropolone. This fragmentation process has also been demonstrated in the case of 3-methoxyflavone by high-resolution measurements, deuterium labelling, metastable decompositions and evaluation of the subspectra of 9-methoxyfluorenol, fluorenone and biphenylene. The structure of the ion at m/z 181 in the spectrum of flavone was found to be the [2-phenylbenzoxetane ? 1]⁺ species.     

Identification de xanthones et de nouveaux arabinosides de C-glucosides flavoniques dans Swertia perennisL.

Identification of xanthones and new arabinosides of flavone C-glucosides from Swertia perennis L. – Seven tetraoxygenated xanthones [1,3,7,8-tetrahydroxy-xanthone ( 1 ); 1,8-dihydroxy-3,7-dimethoxy-xanthone ( 2 ); 1,7-dihydroxy-3,8-dimethoxy-xanthone ( 3 ); 1-hydroxy-3,7,8-trimethoxy-xanthone ( 4 ); 3,7,8-trihydroxy-xanthone-xanthone-1-0-β-glucoside ( 5 ); 3,7,8-trimethoxy-xanthone-1-0-primeveroside ( 6 ); 8-hydroxy-3,7-dimethoxy-xanthone-1-0-primeveroside ( 7 )] have been isolated chromatographically, using polyamide columns, from roots of Swertia perennis L . From leaves and stems of the same plant, six xanthones [1,5,8-trihydroxy-3-methoxy-xanthone ( 8 ); 1,5-dihydroxy-3-methoxy-xanthone-8-0-β-glucoside ( 9 ); mangiferin ( 10 ); 1 ; 4 ; 5 ] and four flavone C-glycosides [iso-orientin ( 11 ); isovitexin ( 12 ); iso-orientin-6″-arabinoside ( 13 ); isovitexin-6″-arabinoside ( 14 )] have also been isolated. Among these compounds, 7 , 13 and 14 were not encountered before in nature. In the last two compounds, the position of arabinose on the C-glucoside moiety of the flavone was established by ¹³C-NMR. spectroscopy.     

Scillapersicene: a new homoisoflavonoid with cytotoxic activity from the bulbs of Scilla persica HAUSSKN

The phytochemical investigation of Scilla persica HAUSSKN bulbs led to the isolation of a novel homoisoflavonoid that named Scillapersicene (1) and identified as 3-(3′,4′-dihydroxybenzylidene)-8-hydroxy-5,7-dimethoxychroman-4-one along with five known homoisoflavonoids 2–6, whose structures were elucidated using HRFAB-MS, 1D and 2D NMR spectroscopic data. The known compounds were identified as 3-(3′,4′-dihydroxybenzyl)-5,8-dihydroxy-7-methoxychroman-4-one (2), 3,9-dihydro-autumnalin (3), autumnalin (4), 3-(3′,4′-dihydroxybenzylidene)-5,8-dihydroxy-7-methoxychroman-4-one (5) and scillapersicone (6). All compounds obtained, expect 2 and 4, showed strong cytotoxic activity against AGS cell line. The toxicity on AGS cell line was measured by 1, 3, 5 and 6 with IC₅₀ values of 8.4, 30.5, 10.7 and 24.2 μM, respectively. In addition, the physico-chemical properties of these natural compounds were optimised using density functional method (B3LYP) with standard 6-311+G* basis set. These natural products have low-energy gaps between the first ionisation potentials and highest occupied molecular orbital. In conclusion, the low-energy gap could cause reason for cytotoxic activity of homoisoflavonoids.     

New flavone and isoflavone glycoside from Belamcanda chinensis

The new flavone, 5,4'-dihydroxy-6,7-methylenedioxy-3'-methoxyflavone, and one new isoflavone glycoside, 3',5'-dimethoxy irisolone-4'-O-β-D-glucoside were isolated from the rhizomes of Belamcanda chinensis. Their structures were established based on the spectroscopic methods.     

Chemical Components of Seriphidium Santolium Poljak

A new biflavonoid glucoside, apigenin‐7‐O‐β‐D‐glucopyranoside‐(3′‐O‐7″)‐quercetin‐3″‐methyl ether ( 1 ) together with twenty known compounds, apigenin ( 2 ), luteolin ( 3 ), chrysoeriol ( 4 ), tricin ( 5 ), hispidulin ( 6 ), pectolinarigenin ( 7 ), eupatilin ( 8 ), 5,7‐dihydroxy‐6,3′,4′,5′‐tetramethoxyflavone ( 9 ), 5,7,4′‐trihydroxy‐6,3′,5′‐trimethoxyflavone ( 10 ), 3,6‐O‐dimethylquercetagetin‐7‐O‐β‐D‐glucoside ( 11 ), 6‐hydroxy‐5,7‐dimethoxy‐coumarin ( 12 ), taraxerol ( 13 ), taraxeryl acetate ( 14 ), a mixture of β‐sitosterol ( 15 ) and stigmasterol ( 16 ), a mixture of the n‐alkyl trans‐p‐coumarates ( 17 ), a mixture of the n‐alkyl trans‐ferulates ( 18 ), 2‐hydroxy‐4,6‐dimethoxyacetophenone ( 19 ), 4‐hydroxy‐2,6‐dimethoxyphenol‐1‐O‐β‐D‐glucopyranoside ( 20 ), and 2‐hydroxycinnamoyl‐β‐D‐glucopyranoside ( 21 ), were isolated from the whole plant of Seriphidium santolium Poljak. The structures of these compounds were determined by means of spectral and chemical studies.     

Syntheses,characterizations of copper compounds containing a series of S-, N-containing aromatic heterocyclic 2,2′:6′,2″-terpyridine derivatives

A series of 2,2′:6′,2″-terpyridine (TPY) based aromatic heterocyclic compounds, extended by thiophene, 4-dibenzothiophene, and thiazole units at the para position of the central pyridine ring in TPY, are described in this paper. A new compound, 4′-(4′-dibenbenzothiophene-5-thiophene-2-yl)-2,2′:6′,2″-terpyridine (L_a), serves as a tridentate ligand to react with Cu(NO₃)₂·3H₂O and CuCl₂·2H₂O, respectively, to produce two different Cu(II) complexes [Cu(L_a)₂](NO₃)₂ and [CuL_aCl₂] with 1?:?2 and 1?:?1 metal/ligand ratios. Dibenzothiophene is first introduced to TPY via the thiophene bridge. The alterations in cis and trans configuration, dihedral angles between adjacent aromatic rings, and photophysical properties have been observed before and after Cu(II) complexation, which has been verified by their crystal structures, UV–vis and fluorescence spectra.     

Efficient PEG-mediated green synthesis of isoaurones: First synthesis of 4′,6-dihydroxy-4-methoxyisoaurone isolated from Trichosanthes kirilowii

An efficient and green protocol for the synthesis of isoaurones by condensation of benzofuranone with benzaldehydes using polyethylene glycol (PEG) is demonstrated. Excellent yields, no reagents/additional catalysts, E-selectivity, short reaction times, and no work-up/extraction makes an attractive benign procedure. Additionally, 4′,6-dihydroxy-4-methoxyisoaurone isolated from Trichosanthes kirilowii has been synthesized for the first time and confirmed its geometry as E.     

Contribution à la phytochimie du genre Gentiana. VII. Etude des composés flavoniques et xanthoniques dans les feuilles de Gentiana vernaL. (1ère communication)

A new xanthone-O-glycoside, the 1,7-dihydroxy-3-methoxyxanthone-8-O-β-D-glucopyranoside ( 7 ), has been isolated from the leaves of Gentiana verna L. by means of column chromatography on polyamid. Six known xanthones: 1-hydroxy-3,7,8-trimethoxyxanthone-1-O-primerveroside ( 2 ); 1,7,8-trihydroxy-3-methoxyxanthone ( 3 ); 7-hydroxy-3,8-dimethoxyxanthone-1-O-primeveroside ( 4 ); 7,8-dihydroxy-3-methoxyxanthone-1-O-primeveroside ( 5 ); mangiferin 6 and the flavone C-glycoside isoorientin 8 have also been isolated and identified.     

Physical and chemical properties of hydroxyflavones. IV. Infrared absorption spectra of dihydroxyflavones containing the 5-hydroxyl group

Solid state infrared curves (O-H and C-H stretching region) are given for 5, n-dihydroxyflavones, where n is 2′, 3′, 4′, 6, 7 and 8. In chloroform solution spectra of 3,5-dihydroxyflavone and 3-hydroxy-5-methoxyflavone, the 3-OH stretching band appears at 3400 and 3334 cm^?1, respectively, indicative of a stronger hydrogen bond in the latter substance. Solid state and solution carbonyl bands are presented for twenty-six flavone derivatives which contain a hydroxyl, methoxyl or acetoxyl group at the 5-position. The solution spectra (dioxane or carbon tetrachloride) of fourteen flavone derivatives containing a free 5-hydroxyl group show carbonyl bands at 1655±2 cm^?1. Eleven flavones in which the 5-hydroxyl is blocked (carbon tetrachloride solution) give spectra with flavone carbonyl bands at 1653±3 cm^?1. The high resolution chloroform solution spectrum of 3, 5-dihydroxyflavone possesses a multi-peaked carbonyl band with midpoint at 1641 cm^?1. The chloroform solution spectrum of 3-hydroxy-5-methoxyflavone has a very strong band at 1616 cm^?1, with shoulder at 1646 cm^?1. Spectral data of this and a previous paper support the postulate that in 4′-hydroxyflavone the flavone carbonyl oxygen is the donor atom in an intermolecular hydrogen bond. Certain details of synthesis, and analytical data, are given for 3, 5-dihydroxyflavone.     

Isoprenoids and Flavonoids with Antimicrobial Activity from Ficus conraui Warburg (Moraceae)

A new triterpene, conrauidienol ( 1 ), and a new dihydroflavonol, conrauiflavonol ( 2 ), along with β‐amyrin acetate ( 3 ), betulinic acid ( 4 ), ursolic acid ( 5 ), 6β‐hydroxystigmasta‐4,22‐dien‐3‐one ( 6 ), 8‐prenylapigenin ( 7 ), β‐sitosterol glucoside ( 8 ), and 3,4′,5‐trihydroxy‐6″,6″‐dimethylpyrano[2,3‐g]flavone ( 9 ) were isolated from the stem barks of Ficus conraui Warburg (Moraceae). Their structures were elucidated by spectroscopic analysis. The hexane, AcOEt, and MeOH extracts, as well as the new isolated compounds exhibited selective antimicrobial activities varying from weak to moderate.