New coumarins from the umbels of Seseli sibiricum

Three new coumarins, seselinal, sesibiricol and sibirinol, and 12 known coumarins have been isolated from the umbels of Seseli sibiricum. The new coumarins have been characterized as 5, 7-dimethoxy-8-(2-methyl-2-formylpropyl)-2H-1-benzopyran-2-one, 5-(3-methylbut-2-enyloxy)-7-methoxy-8-(2-hydroxy-3-methylbut-3-enyl)-2H-1-benzopyran-2-one and 5,7-dimethoxy-8-(2-hydroxy-3-methylbut-3-enyl)-2H-1-benzopyran-2-one,respectively. The known ones were identified as sesibiricin, isosibiricin, osthol, coumurrayin, sesebrin, sesebrinol, sibiricin, imperatorin, bergapten, xanthotoxin, isopimpinellin and mexoticin.     

Chromones from the tubers of Eranthis cilicica and their antioxidant activity

Chemical studies on the constituents of Eranthis cilicica led to isolation of ten chromone derivatives, two of which were previously known. Comprehensive spectroscopic analysis, including extensive 1D and 2D NMR data, and the results of enzymatic hydrolysis allowed the chemical structures of the compounds to be assigned as 8,11-dihydro-5-hydroxy-2,9-dihydroxymethyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, 5,7-dihydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 5,7-dihydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-4H-1-benzopyran-4-one, 7-[(β-d-glucopyranosyl)oxy]-5-hydroxy-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-2-methyl-4H-1-benzopyran-4-one, 7-[(β-d-glucopyranosyl)oxy]-5-hydroxy-2-hydroxymethyl-8-[(2E)-4-hydroxy-3-methylbut-2-enyl]-4H-1-benzopyran-4-one, 9-[(O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]methyl-8,11-dihydro-5,9-dihydroxy-2-methyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, 8,11-dihydro-5,9-dihydroxy-9-hydroxymethyl-2-methyl-4H-pyrano[2,3-g][1]benzoxepin-4-one, and 7-[(O-β-d-glucopyranosyl-(1→6)-β-d-glucopyranosyl)oxy]methyl-4-hydroxy-5H-furo[3,2-g][1]benzopyran-5-one, respectively. The isolated compounds were evaluated for their antioxidant activity.     

Estrogenic and anti-estrogenic compounds from the Thai medicinal plant, Smilax corbularia (Smilacaceae)

From the rhizomes of Smilax corbularia Kunth. (Smilacaceae), 11 compounds, (2R,3R)-2″-acetyl astilbin, (2R,3R)-3″-acetyl astilbin, (2R,3R)-4″-acetyl astilbin, (2R,3R)-3″-acetyl engeletin, (2R,3S)-4″-acetyl isoastilbin, 2-(4-hydroxyphenyl)-3,4,9,10-tetrahydro-3,5-dihydroxy-10-(3,4-dihydroxyphenyl)-(2R,3R,10R)-2H,8H-benzo [1,2-b:3,4-b′] dipyran-8-one, 2-(4-hydroxyphenyl)-3,4,9,10-tetrahydro-3,5-dihydroxy-10-(3,4-dihydroxyphenyl)-(2R,3R,10S)-2H, 8H-benzo [1,2-b:3,4-b′] dipyran-8-one, 3,4-dihydro-7-hydroxy-4-(3,4-dihydroxyphenyl)-5-[(1E)-2-(4-hydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, 3,4-dihydro-7-hydroxy-4-(3,4-dihydroxy-phenyl)-5-[(1E)-2-(3,4-dihydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, 3,4-dihydro-7-hydroxy-4-(4-hydroxy-3-methoxyphenyl)-5-[(1E)-2-(4-hydroxyphenyl) ethenyl]-2H-1-benzopyran-2-one, and 5,7,3′,4′-tetrahydroxy-3-phenylcoumarin along with 34 known compounds were isolated and characterized as 19 flavonoids, 14 catechin derivatives, 6 stilbene derivatives, and 6 miscellaneous substances. All isolates had their estrogenic and anti-estrogenic activities determined using the estrogen-responsive human breast cancer cell lines MCF-7 and T47D. The major constituents were recognized as flavanonol rhamnosides by the suppressive effect on estradiol induced cell proliferation at a concentration of 1 μM. Meanwhile, flavanonol rhamnoside acetates demonstrated estrogenic activity in both MCF-7 and T47D cells at a concentration of 100 μM, and they enhanced the effects of co-treated E2 on T47D cell proliferation at concentrations of more than 0.1 μM.     

Coumarins from two Coleonema species

The aerial parts of Coleonema aspalathoides yielded a single coumarin, 7-(3,3-dimethylallyloxy)-coumarin. Coleonema calycinum afforded 11 coumarins including three novel compounds identified on the basis of spectral data as 7-(2-hydroxy-3-methylbut-3-enoxy)-coumarin,7-(E-3-methoxycarbonylbut-2-enoxy)-coumarin and 7-methoxy-8-(2,3-dihydroxy-3-methylbutoxy)-coumarin.     

Two new coumarins in Boenninghausenia albiflora

Two new isomeric coumarins were isolated from leaves of Boenninghausenia albiflora Reichb. Their structures were elucidated as (E)-7-hydroxy-6-(3-hydroxy-3-methyl-1-butenyl)-2(H)-1-benzpyran-2-one and (Z)-7-hydorxy-6-(3-hydroxy-3-methyl-1-butenyl)-2(H)-1-benzopyran-2-one.     

Three isoflavanones with cannabinoid-like moieties from Desmodium canum

Three further derivatives of 5,7,2',4'-tetrahydroxy-6-methyl isoflavanone have been isolated from the root extract of Desmodium canum and assigned the structures 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(1a,2,3,3a,8b,8c-hexahydro-6-hydroxy-1,1,3a-trimethyl-1H-4-oxabenzo[f]cyclobut[c,d]inden-7-yl)-4H-1-benzopyran-4-one (1) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(6a,7,8,10a-tetrahydro-3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl)-4H-1-benzopyran-4-one (2) 2,3-dihydro-5,7-dihydroxy-6-methyl-3-(3-hydroxy-6,6,9-trimethyl-6H-dibenzo[b,d]pyran-2-yl) 4H-1-benzopyran-4-one (3). The three compounds and the previously isolated chromene 4 all derive from the geranylated precursor 5 by a series of cannabinoid-like oxidative rearrangements.     

A chromene an isoprenylated methyl hydroxybenzoate and a C-methyl flavanone from the bark of Piper hostmannianum

In addition to sitosterol, linalool, 5-hydroxy-7-methoxy-6,8-dimethylflavanone and 5,7-dihydroxyflavanone, two new natural products were isolated from Piper hostmannianum and characterized as methyl 2,2-dimethyl-2H-1-benzopyran-6-carboxylate and methyl 4-hydroxy-3-(2′-hydroxy-3′-methylbut-3′-enyl)-benzoate on the basis of spectroscopic data and chemical derivatization.     

Calocalabaxanthone,the putative isoprenyl precursor of calabaxanthone from Calophyllum calaba

The bark of Calophyllum calaba var. calaba contains a new xanthone, 2,8-di-(3-methylbut-2-enyl)-1,3-dihydroxy-7-methoxyxanthone (calocalabaxanthone), the precursor of 5-hydroxy-8-methoxy-2,2-dimethyl-7-(3-methylbut-2-enyl)-2H,6H-pyano-(3,2-b)-xanthen-6-one (calabaxanthone). In addition the bark contains calabaxthone and the other constituents isolated earlier from Calophyllum calaba var. worthingtonii.     

Δ5-7-Ketosterols with modified side chain: The synthesis and the effects on viability and cholesterol biosynthesis in Hep G2 cells

(22E)-3β-Hydroxysitosta-5,22-dien-7-one, (22R,23R)-3β,22,23-trihydroxysitost-5-en-7-one, and (22R,23R)-3β-hydroxy-22,23-isopropylidenedioxysitost-5-en-7-one were synthesized. The cytotoxicity and effects on cholesterol biosynthesis of the resulting 7-ketosterols, 7-ketocholesterol, and (22S,23S)-3β-hydroxy-22,23-oxidositost-5-en-7-one were studied in hepatoblastoma Hep G2 cells.     

Homoisoflavonoids and xanthones from the tubers of wild and in vitro regenerated Ledebouria graminifolia and cytotoxic activities of some of the homoisoflavonoids

Eleven homoisoflavonoids and two xanthones were isolated and characterized from the bulbs of Ledebouria graminifolia. Five of the homoisoflavonoids are new compounds and were identified as: 5-hydroxy-7-methoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-6,7-dimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5,7,8-trimethoxy-3-(4'-hydroxybenzyl)-4-chromanone, 5-hydroxy-3',4',7-trimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one, 5,7-dihydroxy-3',4'-dimethoxyspiro[2H-1-benzopyran-7'-bicyclo[4.2.0]octa-trien]-4-one. Structures were elucidated by extensive 1D, and 2D NMR spectroscopy and HRMS. A method for tissue culture was developed and the bulbs of mature plants were found to contain all the compounds isolated from the wild specimens of L. graminifolia.     

In silico identification of natural product inhibitors for γ-secretase activating protein,a therapeutic target for Alzheimer's disease

Alzheimer's disease (AD) is clinically characterized by the aggregation of neurotoxic amyloid-β (Aβ) peptides in the brain. γ-Secretase catalyzes the reaction of Aβ formation. Inhibition of γ-secretase activating protein (GSAP) reduces Aβ production without disrupting other molecular functions and serves as a promising therapeutic target for lowering Aβ and curing AD. Till date, no proven drug is available for curing AD because of the nonexistence of crystal/NMR structure of GSAP. Thus in the present study, for the first time, we adopted in silico method to predict the 3D structure of GSAP via comparative modeling and studied the architecture and function of GSAP through simulation studies. Docking studies with 4153 phytochemicals revealed that GSAP having a better binding affinity with macaflavanone C, (E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)prop-2-en-1-one, and monachosorin B as compared with the standard drug, imatinib. Further, the molecular dynamics analysis suggested that only two phytochemicals, namely, macaflavanone C and (E)-1-[2,4-dihydroxy-3-(3-methylbut-2-enyl)phenyl]-3-(2,2-dimethyl-8-hydroxy-2H-benzopyran-6-yl)prop-2-en-1-one) significantly disrupt the original property of GSAP and also cleared the absorption, distribution, metabolism, and excretion test. These natural compounds may be utilized in future for curing AD after further investigations.     

Antifungal constituents isolated from the seeds of Aegle marmelos

Antifungal constituents, 2-isopropenyl-4-methyl-1-oxa-cyclopenta[b]anthracene-5,10-dione and (+)-4-(2′-hydroxy-3′-methylbut-3′-enyloxy)-8H-[1,3]dioxolo[4,5-h]chromen-8-one in addition to known compounds imperatorin, β-sitosterol, plumbagin, 1-methyl-2-(3′-methyl-but-2′-enyloxy)-anthraquinone, β-sitosterol glucoside, stigmasterol, vanillin and salicin were isolated during phytochemical investigation on seeds of Aegle marmelos Correa.     

Chemical constituents from the roots of Acanthus ilicifolius var. xiamenensis

Chemical investigation of Acanthus ilicifolius var. xiamenensis led to the isolation of eleven compounds, and their structures were identified to be 2-benzoxazolinone (1), 2-hydroxy-2H-1,4-benzoxazin-3(4H)-one (2), (2R)-2-O-β-d-glucopyranosyl-2H-1,4-benzox azin-3(4H)-one (3), (2R)-2-O-β-d-glucopyranosyl-4-hydroxy-2H-1,4-benzoxazin-3(4H)-one (4), (2R)-2-O-β-d-glucopyranosyl-7-hydroxy-2H-1,4-benzoxazin-3(4H)-one (5), lyoniside (6), 3′-methoxy-luteolin-7-O-β-d-glucopyranoside (7), β-sitosterol-3-O-β-d-glucopyranoside (8), stigmasterol octadecanoate (9), β-sitosterol octadecanoate (10), stigmasterol-3-O-β-d-glucopyranoside (11) on the basis of mass and NMR spectra. This is the first report on the occurrence of compound 6 and 7 in Acanthaceae. This work also represents the first phytochemical work on the roots of A. ilicifolius var. xiamenensis.     

Two New Isoprenylated Stilbenes from Artocarpus chama

Two new stllbenes with two Isoprenoid groups, namely artostllbenes A （compound 1） and B （compound 2）, were Isolated from the stems of Arfocarpus chama Buch.-Ham. by repeated column chromatography. The＆ structures were elucldated as （E）-4-[2-（7-meth-xy-2-2-d-methy-6-（3-methy-but-2-eny-）-2H-1-benz-pyran-5-y-）v-ny-]benzene-1- 2-dlol （compound 1） and （Z）-4-[2-（7-meth-xy-2-2-dimethy--6-（3-methy-but-2-eny-）-2H-1-benz-pyran-5-y-）v-ny-]ben- zene-l,2-dlol （compound 2） by spectroscopic methods, mainly by 1D-, 2D-NMR and MS spectra. Compounds 1 and 2 are two cls- and trans-lsomers and compound 2 is the flrst cis-stllbene isolated from Moraceous plants.     

Chromone derivatives from Halenia elliptica and their anti-HBV activities

Nine water-soluble chromone derivatives, including chromone-2-carboxylic acids, 2-methylchromones and their structural hybrids, were isolated from aerial tissues of Halenia elliptica (Gentianaceae), six of which were previously unknown. Their structures were elucidated by comprehensive mass, 1D and 2D NMR spectroscopic analyses and chemical derivatization. Two unstable structural hybrids of chromone-2-carboxylic acids and 2-methylchromones, viz. 3-acetyl-8-hydroxy-4H-1-benzopyran-4-one-2-carboxylic acid (halenic acid C) and 2-(8-hydroxy-2-methyl-4H-1-benzopyran-4-one-3-yl)-2-oxoacetic acid (halenichromone A), were isomers and were interconvertible. The proposed mechanism of their acid-catalyzed isomerization in aqueous solvent is described. In addition, 2-methylchromones, 8-hydroxy-2-methyl-4H-1-benzopyran-4-one, and 8-methoxy-2-methyl-4H-1-benzopyran-4-one, were found to exhibit a strong inhibitory effect towards hepatitis B virus (HBV) in vitro without showing significant cytotoxicity.     

Cancer chemopreventive constituents from Melicope lunu-ankenda

A study of the chemical constituents obtained from twigs of Melicope lunu-ankenda (Gaertn.) T.G. Hartley (Rutaceae) led to the isolation and structure elucidation of two new coumarins, 7-(4-hydroxy-3-methylbutanoxy) coumarin and 7-(3-methyl-4-carboxybutanoxy) coumarin methyl ester, named melilunumarin A (1) and melilunumarin B (2), respectively. A new benzaldehyde derivative, 3,4-dihydro-3,4-dihydroxy-2,2-dimethyl-2H-1-benzopyran-6-carboxaldehyde, named melilunumane (6), was also isolated and characterized, as well as five previously reported compounds, 6-deoxyhaplopinol (3), marmesin (4), umbelliferone (5), kokusaginine (7) and evolitrin (8). Among the five isolated coumarins, melilunumarin A (1), 6-deoxyhaplopinol (3) and marmesin (4) exhibited significant inhibitory activity towards Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol 13-acetate in Raji cells.     

Secondary metabolites of Sophora mollis subsp. griffithii (Stocks) Ali

Two new compounds, (+)-3,5,7-trihydroxy-3-[3′-hydroxy-2′,4′-dimethoxy-5-(3-methyl-2-butenyl)]-phenyl-(3R)-4H-1-benzopyran-4-one (1) and (?)-3-hydroxy-8,9-methylenedioxy-(6aR,11aS)-pterocarpan (2), were isolated from the methanolic extract of Sophora mollis subsp. griffithii. Two known compounds, β-sitosterol (3) and 19βH-lupeol-methyl-ether (4), were also obtained for the first time from this plant. The structures of 1–4 were identified through their spectroscopic data. CD Spectroscopy was also utilized for the structure elucidation of compounds 1 and 2. Compounds 1, 3 and 4 were studied for their effects on immune cells and only 1 was found to be substantially active.     

Mycochromone and mycoxanthone: Two new metabolites from Mycosphaerella rosigena

Two new metabolites, dimethyl 2-(2-ethenyl-5-hydroxy-4H-1-benzopyran-4-onyl-3)-malonate (mycochromone 1a) and methyl 2-methoxy-8-hydroxy-9-oxo-9H-xanthene-1-carboxylate (mycoxanthone 6a), have been isolated and identified from the mycelium of Mycosphaerella rosigena grown on potato-agar.     

An improved synthesis of an umbelliferyl 5-thioxylopyranoside, precursor of the antithrombotic drug Iliparcil.

4-Ethyl-2-oxo-2H-1-benzopyran-7-yl 2,3,4-tri-O-acetyl-5-thio-beta-D-xylopyranoside, a synthetic intermediate of the orally active antithrombotic compound Iliparcil, has been prepared in 44-47% isolated yield. Different conditions were used for the glycosylation of 4-ethyl-2H-7-hydroxy-1-benzopyran-2-one 6 applying 2,3,4-tri-O-acetyl-5-thio-D-xylopyranosyl bromide (2), the analogous beta-chloride 3 or the alpha-trichloroacetimidate 5 as donors. With halides 2 and 3, the reaction was carried out in the presence of ZnO-ZnCl2 or ZnO alone. Both promoters are cheap, safe and therefore compatible with large-scale industrial processes.     

A constituent of Alpinia katsumadai suppresses allergic airway inflammation

Two new compounds, named as (3R)-5,7-dihydroxy-3-isopropyl-3-methylisochroman-1-one (1), and (1R,3R,4S)-1-(4′-methyl-phenyl)-3,4-dihydro-3,4-dimethyl-1H-2-benzopyran-5,6,8-triol (2), were isolated from seeds of Alpinia katsumadai Hayata. Structures of compounds 1 and 2 were elucidated and determined on the basis of spectroscopic analysis. Additionally, compound 1 significantly suppressed allergic airway inflammation induced by OVA through reducing airway hyperresponsiveness. Moreover, the inflammation suppression was associated with a marked decrease in the Th2 cytokines and IgE production.