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.     

Geranylated phenolic constituents from the fruits of Artocarpus nobilis

Chemical investigation of the combined dichloromethane and ethyl acetate extracts of the fruits of Artocarpus nobilis, furnished four new geranylated phenolic constituents, 2,4,4'-trihydroxy-3-[(2E)-5-methoxy-3,7-dimethylocta-2,6-dienyl]chalcone (4), 1-(3,4-dihydro-3,5-dihydroxy-2-methyl-2-(3-methyl-2-butenyl)-2H-1-benzopyran-6-yl-3-(4-hydroxyphenyl)-2(E)-propen-1-one (5), 8-geranyl-3',4',7-trihydroxyflavone (8), 3'-geranyl-4',5,7-trihydroxyflavanone (9), together with known related compounds, xanthoangelol (1), xanthoangelol B (2), 3-geranyl-2,3',4,4'-tetrahydroxychalcone (3), lespeol (6), 8-geranyl-4',7-dihydroxyflavanone (7), and isonymphaeol-B (10). Compounds 3, 8 and 10 showed strong antioxidant activity against DPPH radical by spectrophotometric method.     

Synthesis and antihypertensive activity of novel 3-benzyl-2-substituted-3H-[1,2,4]triazolo[5,1-b]quinazolin-9-ones

A series of 3-benzyl-2-substituted-3H-[1,2,4]triazolo[5,1-b]quinazolin-9-ones have been synthesized by the cyclocondensation of 3-amino-2-benzylamino-3H-quinazolin-4-one with a variety of one-carbon donors. The starting material 3-amino-2-benzylamino-3H-quinazolin-4-one was synthesized from methyl anthranilate by a novel innovative route. The title compounds were evaluated for their in vivo antihypertensive activity using spontaneously hypertensive rats (SHR). While all the test compounds exhibited significant antihypertensive activity, 3-benzyl-2-methyl-3H-[1,2,4]triazolo[5,1-b] quinazolin-9-one exhibited antihypertensive activity more than the reference standard prazocin.     

Phytotoxic naphthopyranone derivatives from the coprophilous fungus Guanomyces polythrix.

Reinvestigation of the fermentation broth and mycelium of the coprophilous fungus Guanomyces polythrix, grown in static conditions, led to the isolation of several phytotoxic compounds, including two new naphthopyranone derivatives, namely (2S, 3R)-5-hydroxy-6,8-dimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one and (2S, 3R)-5-hydroxy-6,8,10-trimethoxy-2,3-dimethyl-2,3-dihydro-4H-naphtho[2,3-b]-pyran-4-one. The structures of the new compounds were established by spectral and chiroptical methods. In addition, the structure of 8-hydroxy-6-methyl-9-oxo-9H-xanthene-1-carboxylic acid methyl ester was unambiguously determined by X-ray analysis. The isolates caused significant inhibition of radicle growth of two weed seedlings (Amaranthus hypochondriacus and Echinochloa crusgalli) and interacted with both spinach and bovine brain calmodulins.     

The chemical constituents of the fungus Stereum sp

Four new compounds, including a sesquiterpene and three aromatic compounds, and a known compound were isolated from a culture broth of the fungus Stereum sp. The novel sesquiterpene was determined to be stereumone A ((+)-2,3,4a,5,6,7,8a,9-octahydro-5-hydroxy-6,6,9-trimethyl-4,8a-epoxynaphtho[2,3-b]furan-8(8H)-one; 1), and the three new aromatic compounds were elucidated as 3,5-dihydroxy-4-(3-methylbut-2-enyl)benzene-1,2-dicarbaldehyde (2), 5,7-dihydroxy-6-(3-methylbut-2-enyl)isobenzofuran-1(3H)-one (3), butyl 2,4-dihydroxy-6-methylbenzoate (4), together with the known compound methyl 2,4-dihydroxy-6-methylbenzoate (5). The structures were established by spectroscopic methods including 2D-NMR techniques. Compounds 2 and 4 showed evident nematicidal activity against nematode Panagrellus redivivus.     

Synthesis, cytotoxicity, and anti-inflammatory evaluation of 2-(furan-2-yl)-4-(phenoxy)quinoline derivatives. Part 4

A number of 2-(furan-2-yl)-4-phenoxyquinoline derivatives have been synthesized and evaluated for anti-inflammatory evaluation. 4-[(2-Furan-2-yl)quinolin-4-yloxy]benzaldehyde (8), with an IC(50) value of 5.0 microM against beta-glucuronidase release, was more potent than its tricyclic furo[2,3-b]quinoline isomer 3a (>30 microM), its 4'-COMe counterpart 7 (7.5 microM), and its oxime derivative 13a (11.4 microM) and methyloxime derivative 13b (>30 microM). For the inhibition of lysozyme release, however, oxime derivative 12a (8.9 microM) and methyloxime derivative 12b (10.4 microM) are more potent than their ketone precursor 7 and their respective tricyclic furo[2,3-b]quinoline counterparts 4a and 4b. Among them, 4-[4-[(2-furan-2-yl)-quinolin-4-yloxy]phenyl]but-3-en-2-one (10) is the most active against lysozyme release with an IC(50) value of 4.6 microM, while 8 is the most active against beta-glucuronidase release with an IC(50) value of 5.0 microM. (E)-1-[3-[(2-Furan-2-yl)quinolin-4-yloxy]phenyl] ethanone oxime (11a) is capable of inhibiting both lysozyme and beta-glucuronidase release with IC(50) values of 7.1 and 9.5 microM, respectively. For the inhibition of TNF-alpha formation, 1-[3-[(2-furan-2-yl)quinolin-4-yloxy]phenyl]ethanone (6) is the most potent with an IC(50) value of 2.3 microM which is more potent than genistein (9.1 microM). For the inhibitory activity of fMLP-induced superoxide anion generation, 11a (2.7 microM), 11b (2.8 microM), and 13b (2.2 microM) are three of the most active. None of above compounds exhibited significant cytotoxicity.     

Synthesis and biological evaluation of thienopyrrolizines, a new family of CDK/GSK-3 inhibitors

Fifteen new thieno[2,3-b ]- and thieno[3,4-b]pyrrolizines were synthesized and tested against two protein kinases, CDK1/cyclin B and GSK-3. Among these compounds, 3-(3-hydroxy-4-methoxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one 4g was identified as a moderate inhibitor of these kinases. Its molecular modeling study brought to the fore the pivotal role of the 2-methoxyphenol grouping and the interest in replacing it by bioisosteric moieties in future pharmacomodulations.     

Isofuranonaphthoquinone derivatives from cultures of the lichen Arthonia cinnabarina (DC.) Wallr

Two isofuranonaphthoquinone derivatives, named arthoniafurones A (1-acetyl-8-hydroxynaphtho[2,3-c]furan-4,9-dione) and B [1-acetyl-4,8-dihydroxynaphtho[2,3-c]furan-9(4H)-one], were isolated from a spore-derived culture of the mycobiont of the lichen Arthonia cinnabarina, that is new to Japan. Bostrycoidin and 8-O-methylbostrycoidin were also identified in the A. cinnabarina culture.     

Yellow Pigments of Aspergillus niger and Aspergillus awamori

Alkaline degradation of Aurasperone A, C₃₂H₂₆O₁₀, gave a binaphthyl (IIa), m.p. 255°C and acetone. (IIa) afforded a tetraacetate (IIb), C₃₂H₃₀O₁₂ m.p. 219°C and a tetramethyl ether (IId), C₂₈H₃₀O₈, m.p. 188°C. These facts along with the NMR spectra of aurasperone A and (IIb) confirm that aurasperone A is a dimeric 2-methyl-5-hydroxy-6,8-dimethoxy-4H-naphtho[2,3-b]pyran-4-one with asymmetric C-C linkage (7-10′ or 9-10′). The ether (IId) is not identical with 1,1′ ,3,3′ ?6,6′ ,8,8′-octamethoxy-4,4′-binaphthyl. Thus, it follows that (IId) is a 2,4′-binaphthyl and hence aurasperone A is 2,2′-dimethyl-5,5′- dihydroxy-6,6′,8,8′-tetrahydroxy-7,10′-bi[4H-naphtho[2,3-b]pyran-4-one] (I).     

Design, synthesis and antiproliferative activity of tripentones: a new series of antitubulin agents

Structure-activity relationship studies of a new series of tripentones (thieno[2,3-b]pyrrolizin-8-ones), led us to prepare several derivatives with antiproliferative activities. The most promising 3-(3-hydroxy-4-methoxyphenyl)thieno[2,3-b]pyrrolizin-8-one 20 (leukemia L1210, IC(50)=15 nM) was shown to be a potent inhibitor of tubulin polymerization.     

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.     

椭圆嗜蓝孢孔菌子实体的化学成分

从椭圆嗜蓝孢孔菌Fomitiporia ellipsoidea子实体的石油醚提取物中分离得到6个化合物,分别是麦角甾-7,22,25-三烯-3-酮,21-羟基羊毛甾-7,9(11),24-三烯-3-酮,麦角甾-7,22-二烯-3β-棕榈酸酯,麦角甾-7,22-二烯-3-酮,麦角甾醇和过氧化麦角甾醇;从其脱脂后的氯仿提取中分离得到了3个化合物,分别是：苯并(1,2-b;5,4-b′)二呋喃-3,5-二酮-8-甲酸甲酯,麦角甾-7,22-烯-3b-醇和b-谷甾醇。其中苯并(1,2-b;5,4-b′)二呋喃-3     

2''-Deoxy-3,7-dideazaguanosine and related compounds. Synthesis of 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl) and 1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]pyridin-4(5H)-one via direct glycosylation of a pyrrole precursor.

The synthesis of two new analogs of 2'-deoxyguanosine, 6-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H-pyrrolo[3,2-c] pyridin-4(5H)-one (8) and 6-amino-1-beta-D-arabinofuranosyl-1H-pyrrolo[3,2-c]-pyridin-4(5H)-one (13) has been accomplished by glycosylation of the sodium salt of ethyl 2-cyanomethyl-1H-pyrrole-3-carboxylate (4c) using 1-chloro-2-deoxy-3,5-di-O-p-toluoyl-alpha-D-erythro-pentofuranose( 5) and 1-chloro-2,3,5-tri-O-benzyl-alpha-D-arabinofuranose (9), respectively. The resulting blocked nucleosides, ethyl 2-cyanomethyl-1-(2-deoxy-3,5-di-O-p-toluoyl-beta-D-erythro- pentofuranosyl)-1H-pyrrole-3-carboxylate (6) and ethyl 2-cyanomethyl-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)- 1H-pyrrole-3-carboxylate, were ring closed with hydrazine to form 5-amino-6-hydrazino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-1H- pyrrolo[3,2-c]-pyridin-4(5H)-one (7) and 5,6-diamino-1-(2,3,5-tri-O-benzyl-beta-D-arabinofuranosyl)-1H- pyrrolo[3,2-c]pyridin-4(5H)-one (11), respectively. Treatment of 7 with Raney nickel provided the 2'-deoxyguanosine analog 8 while reaction of 11 with Raney nickel followed by palladium hydroxide/cyclohexene treatment gave the 2'-deoxyguanosine analog 13. The anomeric configuration of 8 was assigned as beta by proton NMR, while that of 13 was confirmed as beta by single-crystal X-ray analysis of the deblocked precursor ethyl 2-cyanomethyl-1-beta-D-arabinofuranosyl-1H-pyrrole-3-carboxylate (10a).     

Potential inhibitors of angiogenesis. Part II: 3-(azolylmethylene)-2,3-dihydrobenzo[b]furan-2-ones

The synthesis and pharmacological evaluation of new 3-(imidazol-4(5)-ylmethylene)-2,3-dihydrobenzo[b]furan-2-ones 8-10 and 3-(3,5-dimethylpyrrol-2-ylmethylene)-2,3-dihydrobenzo[b]furan-2-one 11, analogues of SU-5416, as potential inhibitors of angiogenesis, are reported. Compounds 8 and 11 were prepared by a Knoevenagel reaction starting from 2-hydroxyphenylacetic acid 2 and 4-formylimidazole 5 or 2-formyl-3,5-dimethylpyrrole 7, followed by acid-catalysed cyclodehydration. For compounds 9 and 10, an alternative method was used; it consisted in carrying out the Knoevenagel reaction with the 2,3-dihydrobenzo[b]furan-2-ones 3 and 4. The antiangiogenic activity of these compounds was evaluated in the three-dimensional in vitro rat aortic rings test at 1microM. At this concentration, compound 11 induced a decrease of angiogenesis comparable to that observed with SU-5416; the vascular density index at 1 microM of 11 and SU-5416 were 30 +/- 10 and 22 +/- 4% of control, respectively.     

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.     

Further furoquinolone alkaloids from Ruta chalepensis

Two new alkaloids, 9-ethyl-8-methoxy-furo[2,3]quinol-4-one and 9-ethyl-7,8-dimethoxy-furo-[2,3]quinol-4-one, and the known furocoumarin chalepin were isolated from Ruta chalepensis.     

Effects of various radicinin analogs on pulse amplitude and arterial blood pressure

The action of some radicinin analogues on the pulse amplitude in urethane anesthetized rats has been studied. The compounds used are:2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (I); 2,3-dihydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (II) 7,8-dihydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione (III) 2,3,7,8-tetrahydro-2,7-dimethyl-4H,5H-pyrano[4,3-b]pyran-4,5-dione(IV); 2,3,7,8,4',8'-hexahydro-2,7-dimethyl-4H,5H-pyrano[4, 3-b]pyran-4,5-dione (V); 3-crotonyl-4-hydroxy-6-methyl-2H-pyran-2-one (VI); 3-hexanoyl-4-hydroxy-6-methyl-2H-pyran-2-one (VII); 3-hexanoyl-5,6-dihydro-4-hydroxy-6-methyl-2H-pyran-2-one (VIII). A clear increase in the pulse has been seen with the compounds (II), (V) and (VII) especially at the lowest doses, while a decrease in the pulse is caused by the compounds (I) and (VIII). The studied substances have no effects on systolic blood pressure in normotensive unanesthetized rats.     

Chemical and anti-platelet constituents from Formosan Zanthoxylum simulans

A pyrrole alkaloid, pyrrolezanthine [5-hydroxymethyl-1-[2-(4-hydroxyphenyl)-ethyl]-1H-pyrrole-2-carbaldehyde]; a lignan, (-)-simulanol [4- [3-hydroxymethyl-5-((E)-3-hydroxypropenyl)-7-methoxy-2,3-dihydrobenzofuran-2-yl]-2,6-dimethoxy-phenol] and a monocyclic gamma-pyrone, zanthopyranone [3,5-dimethoxy-2-methyl-pyran-4-one], together with 28 known compounds were isolated from the stem wood of Formosan Zanthoxylum simulans. Their structures were determined through spectral analyses. Among the isolates, 11 compounds showed anti-platelet aggregation activity in vitro.     

Furoquinoline alkaloids from the southern African Rutaceae Teclea natalensis

The chloroform and ethyl acetate extracts of the leaves of Teclea natalensis have yielded two furoquinoline alkaloids, 6-[(2,3-epoxy-3-methylbutyl)oxy]-4,7-dimethoxyfuro[2,3-b]quinoline and 4,7-dimethoxy-6-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, and the known alkaloids 4,7-dimethoxy-8-[(3-methyl-2-butenyl)oxy]furo[2,3-b]quinoline, flindersiamine and dictamnine.     

Inhibitors of sterol synthesis. Spectral characterization of derivatives of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one

Described herein are the chemical syntheses of a number of deuterated derivatives of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one. These include the [2,2,3 alpha,4,4,7,7,9 alpha,16,16-2H10]-, [7 alpha,9 alpha,16,16-2H4]-, [7,7,9 alpha,16,16-2H5]-, and [2,2,3 alpha,4,4-2H5]-analogs of the delta 8(14)-15-ketosterol. Also included are the syntheses of the 3 beta-acetate derivatives of the latter three deuterated analogs and of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, and 5 alpha-cholest-8(14)-en-3 alpha-ol-15-one. Low resolution mass spectral data on these compounds and on 5 alpha-cholest-8(14)-en-15-one, 5 alpha-cholest-8(14)-en-3 beta-ol-15-one, 5 alpha-cholest-8(14)-en-3 alpha-ol-15-one, 3 beta-benzoyloxy-5 alpha-cholest-8(14)-en-15-one, and the trimethylsilyl ethers of the free sterols have been presented. The results of these studies, supplemented with high resolution mass spectral data on five of these compounds, have been used to evaluate the electron impact mass spectral fragmentation of the delta 8(14)-15-ketosterols and their derivatives. Also presented herein are the results of 1H, 2H, and 13C nuclear magnetic resonance studies of 5 alpha-cholest-8(14)-en-3 beta-ol-15-one and its derivatives.