Fusamarin,a New Metabolite from a Species of Fusarium

Fusamarin, C₁₈H₂₄O₄, a metabolite of Fusarium sp., has been shown to be ((?)-(R)-(3)-trans-pentenyl-(3)-5-n-butyl-6,8-dihydroxy-3,4-dihydroisocoumarin) (1) on the basis of chemical and spectroscopic evidences.     

Production of 3-Methyl-6-Methoxy-8-Hydroxy-3,4-Dihydroisocoumarin by Aspergillus caespitosus

Aspergillus caepitosus Raper and Thom cultured on autoclaved cracked, yellow field corn produced 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin which was extracted and then purified by silica gel columns. The physical and spectral properties of the colorless crystals from methylene chloride:hexane were consistent with those published for 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin. Yield of high purity 3-methyl-6-methoxy-8-hydroxy-3,4-dihydroisocoumarin was about 140 mg of corn per kg.     

Studies on the Compounds Produced by Molds

Three isocoumarin compounds (BV 1, 2 and 3) were isolated from the cultural broth of Aspergillus oniki 1784. BV 1 was mellein (3-methyl-8-hydroxy-3,4-dihydroisocoumarin). BV 2 and 3 were assigned to be 3-methyl-4,8-dihydroxy-3,4-dihydroisocoumarin, 3-methyl-3,8-dihydroxy-3,4-dihydroisocoumarin, respectively. These two compounds (BV 2, 3) were newly isolated. Also another component named BV 4 was proved to be 6-methylsalicylic acid.     

Design, synthesis, and pharmacological evaluation of new neuroactive pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives with in vivo hypnotic and analgesic profile

The present study describes the synthesis and pharmacological profiles of four novel pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives 2-5, which were structurally designed by using the sedative and analgesic drug zolpidem 1 as lead compound. The heterotricyclic system present in the target compounds 2-5 was constructed in good yields, exploiting a regioselective hetero Diels-Alder reaction of the key azabutadiene derivative 7 and functionalized N-phenylmaleimides 9-12. Additionally, we identified that 1-methyl-7-(4-nitrophenyl)-3-phenyl-3,6,7,8-tetrahydropyrazolo[3,4-b]pyrrolo[3,4-d]pyridine-6,8-dione derivative (LASSBio-873, 5) presented not only the most potent ability to promote sedation, which was similar to that induced by the standard benzodiazepine drug midazolam, but also potent central antinociceptive effect.     

Isolation of novel phenolic compounds with multidrug resistance (MDR) reversal properties from Onychium japonicum

We isolated seven novel compounds, namely, 3',4',6-trihydroxy-2,4-dimethoxy-3-(3″,4″-dihydroxybenzyl)chalcone (1), 3',6-dihydroxy-2,4,4'-trimethoxy-3-(3″,4″-dihydroxybenzyl)chalcone (2), α,β-dihydro-3',6-dihydroxy-2,4,6'-trimethoxy-3-(3″,4″-dihydroxybenzyl)chalcone (3), 3',4,4'-trihydroxy-2,6-dimethoxychalcone (4), 4',5,7-trihydroxy-6-(3″,4″-dihydroxybenzyl)flavone (5), 3-(3',4'-dihydroxybenzyl)-6,7-dihydroxycoumarin (6), 3-(3',4'-dihydroxyphenyl)-3,4-dihydroisocoumarin (7), as well as a known compound, 3',4',7-trihydroxy-5-methoxyflavanone (8) from the whole grass of Onychium japonicum, and elucidated their structures by spectroscopic methods. Compounds 1-3 exhibited significant multidrug resistance (MDR) reversal effects on MCF-7/ADR and Bel-7402/5-Fu cell lines.     

Discovery of novel methanone derivatives acting as antimycobacterial agents

A series of pyrazoline derivatives were synthesized and in vitro activity against Mycobacterium tuberculosis H37Rv was carried out. Among the synthesized compounds, compounds (4d) and (4f) 4-aminophenyl-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone and 4-aminophenyl-6,7-dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone were found to be the most active agent against M. tuberculosis H37Rv with a minimum inhibitory concentration of 10 μg/mL.     

Plant Growth Promoting Metabolites of Sclerotinia sclerotiorum

In the research on the plant growth regulators produced by phytopathogenic fungi, two active metabolites, sclerotinin A and B, in addition to sclerin have been isolated from the culture filtrate of S. sclerotiorum. Sclerotinin A and B have been shown to be 3,6,8-tri-hydroxy-3,4,5,7-tetramethyl-3,4-dihydroisocoumarin and 3,6,8-trihydroxy-3,5,7-trimethyl-3,4- dihydroisocoumarin, respectively.     

A flavanone and a dihydrodibenzoxepin from Bauhinia variegata

Phytochemical analysis of the root bark of Bauhinia variegata Linn yielded a new flavanone, (2S)-5,7-dimethoxy-3',4'-methylenedioxyflavanone (1) and a new dihydrodibenzoxepin, 5,6-dihydro-1,7-dihydroxy-3,4-dimethoxy-2-methyldibenz [b,f]oxepin (2) together with three known flavonoids (3-5). The structures of the new compounds were determined on the basis of spectral studies.     

Dihydrocinnamic acids from Hortia badinii

Hortia badinii (Rutaceae) contains rutecarpine and hortiacine in the bark, as well as coumurrayin, methyl 3-[2-methoxy-6′, 6′-dimethylpyrano(2′,3′:3,4)phenyl]-propionate, 3-[2,6-dimethoxy-6′,6′-dimethylpyrano(2′,3′: 3,4)phenyl]-propionic acid, methyl 3-[2,6-dimethoxy-6′,6′-dimethylpyrano(2′, 3′: 3,4)phenyl]-propionate and methyl 3-[2,4-dimethoxy-3-prenylphenyl]-propionate in the wood.     

Discovery of novel methanone derivatives acting as antimycobacterial agents

A series of pyrazoline derivatives were synthesized and in vitro activity against Mycobacterium tuberculosis H37Rv was carried out. Among the synthesized compounds, compounds (4d) and (4f) 4-aminophenyl-3-(3,4-dimethoxyphenyl)-6,7-dimethoxy-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone and 4-aminophenyl-6,7-dimethoxy-3-phenyl-2,3,3a,4-tetrahydroindeno[1,2-c]pyrazol-2-ylmethanone were found to be the most active agent against M. tuberculosis H37Rv with a minimum inhibitory concentration of 10?μg/mL.     

Microbial degradation of papaverine (author's transl)]

A bacterium growing on papaverine as sole carbon and nitrogen source was isolated by incubation of soil with papaverine. The bacterium could be identified as a Nocardia strain by morphological and physiological tests. When growing on papaverine, this strain excretes metabolites into the medium. Based on the structure of the metabolites 1--9 a degradation pathway is proposed. 1 = 1-(3,4-Dimethoxybenzyl)-3,4-dihydro-6,7-dimethoxy-3,4-isoquinolinediol; 2 = 1-(3,4-dimethoxybenzyl)-6,7-dimethoxy-3,4-isoquinolinediol; 3 = 2-(3,4-dimethoxyphenyl)-1-[2-(2-hydroxyethyl)-4,5-dimethoxyphenly]ethanone; 4 = 2-hydroxy-4,5-dimethoxybenzeneethanol; 5 = 3,4-dimethoxybenzeneacetic acid; 6 = 2-hydroxy-4,5-dimethyoxybenzeneacetic acid; 7 = 4-hydroxy-3-methoxybenzeneacetic acid; 8 = 3,4-dimethoxybenzaldehyde; 9 = 2-(hydroxymethyl)-4,5-dimethoxybenzeneethanol.     

An isocoumarin and other phenolic components of Ononis natrix

From the n-hexane extract of the whole aerial part of flowering Ononis natrix, besides homopterocarpin and some known terpenoids and sterols, three new compounds: 8-hydroxy-6-methoxy-3-undecyl-3,4-dihydroisocoumarin, 5-(2-acetoxytridecyl)-3-methoxyphenol and 5-(2-hydroxytridecyl)-3-methoxyphenol have been isolated.     

Homoisoflavonoids from Ophiopogon japonicus Ker-Gawler

From the ethyl acetate extract of the tuberous roots of Ophiopogon japonicus (Liliaceae) eight known and five new homoisoflavonoidal compounds were isolated. The new compounds are 5,7-dihydroxy-8-methoxy-6-methyl-3-(2'-hydroxy-4'-methoxybenzyl)chroman-4-one (1), 7-hydroxy-5,8-dimethoxy-6-methyl-3-(2'-hydroxy-4'-methoxybenzyl)chroman-4-one (2), 5,7-dihydroxy-6,8-dimethyl-3-(4'-hydroxy-3'-methoxybenzyl)chroman-4-one (3), 2,5,7-trihydroxy-6,8-dimethyl-3-(3',4'-methylenedioxybenzyl)chroman-4-one (4) and 2,5,7-trihydroxy-6,8-dimethyl-3-(4'-methoxybenzyl)chroman-4-one (5). Their structures have been elucidated by mass and NMR spectroscopy. Compounds 4 and 5 are the first isolated homoisoflavonoids with a hemiacetal function at position 2.     

Neuroprotective metabolites from the endophytic fungus Penicillium citrinum of the mangrove Bruguiera gymnorrhiza

Two new compounds, named as (Z)-7,4′-dimethoxy-6-hydroxy-aurone-4-O-β-glucopyranoside (1), and (1S,3R,4S)-1-(4′-hydroxyl-phenyl)-3,4-dihydro-3,4,5-trimethyl-1H-2-benzopyran-6,8-diol (2), were isolated from the endophytic fungus Penicillium citrinum of Bruguiera gymnorrhiza. Their structures were elucidated on the basis of spectroscopic analysis. Additionally, compound 1 exhibited potent neuroprotective activity in 1-methyl-4-phenylpyridinium-induced oxidative damage in PC12 cells.     

Dihydroisocoumarins and a tetralone from Cytospora eucalypticola

Two dihydroisocoumarins, 3,5-dimethyl-8-hydroxy-7-methoxy-3,4-dihydroisocoumarin and 3,5-dimethyl-8-methoxy-3,4-dihydroisocoumarin were isolated from a culture filtrate of Cytospora eucalypticola, together with three known dihydroisocoumarins and a tetralone derivative. Their structures were determined by spectroscopic methods. These isocoumarins are mildly antifungal, and antibacterial towards gram positive bacteria. A known compound, 5-hydroxymethylmellein, showed mild antifeedant activity towards Spodoptera littoralis.     

Original preparation of conjugates for antibody production against Amicoumacin-related anti-microbial agents

Amicoumacins are natural products with potent anti-ulcerogenic and anti-bacterial activities, and have been isolated from different Bacillus genera. They belong to a family of 3,4-dihydroisocoumarin derivatives bearing hydroxylated amino acid side chains. The 3,4-dihydroisocoumarin moiety of Amicoumacins has been obtained in two steps from 2-methoxybenzoic acid by combining directed and benzylic metalation strategies. The use of s-BuLi in both steps gave satisfactory and reproducible yields. For the development of an immunoassay (ELISA) of Amicoumacin-related compounds in biological media, the deprotected 3,4-dihydroisocoumarin moiety has been coupled to the BSA carrier protein via a homobifunctional linker deriving from d-tartaric acid. This approach enabled to introduce the hydroxylated portion of Amicoumacin directly during the preparation of hapten-protein conjugates. The coupling ratio was evaluated by mass spectrometry. The hapten-protein conjugate showing the best coupling ratio was used to generate polyclonal immunosera in rabbits. After immunoserum titration, ELISA conditions were set up and specificity tests were performed on solutions of pure parent compounds, semi-purified Amicoumacin B as well as on culture supernatants of strains known for their Amicoumacin production. This immunoassay is suitable for a rapid and simple screening test for the production of Amicoumacins and its related compounds by bacterial strains.     

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.     

宁夏枸杞根和茎的化学成分及抗炎活性研究

研究宁夏枸杞(Lycium barbarum L.)根部和茎部的化学成分。采用硅胶柱、ODS开放柱、Sephadex LH-20葡聚糖凝胶柱及半制备反相高效液相等色谱手段,对宁夏枸杞根和茎部乙醇提取物的石油醚部位及乙酸乙酯部位化学成分进行分离纯化,根据其理化性质以及波谱数据鉴定得到12个化合物,分别为N-[2-(3,4-dihydroxyphenyl)-2-hydroxyethyl]-3-(4-methoxyphenyl)prop-2-enamide(1)、3-(4-hydroxy-3-methoxy phenyl)-N-2-(4-hydroxyphenyl)-2-methoxyethyl]acrylamide(2)、N-trans-coumaroyloctopamine(3)、(E)-2-(4,5-dihydroxy-2-{3-[(4-hydroxyphenethyl)amino]-3-oxopropyl}phenyl)-3-(4-hydroxy-3,5-dimethoxyphenyl)-N-(4-acetamidobutyl)acrylamide(4)、1,2-dihydro-6,8-dimethoxy-7-hydroxy-1-(3,4-dihydroxy-phenyl)-N1,N2-bis[2-(4-hydroxyphenyl)ethyl]-2,3-naphthalene dicarboxamide(5)、(+)-syringaresinol(6)、zhebeiresinol(7)、(±)-eriodictyol(8)、isovanilin(9)、5,5′-dimethoxybiphenyl-2,2′-diol(10)、p-hydroxyphenethyltrans-ferulate(11)、E-ferulic acid hexacosyl ester(12),所有化合物均为首次从该植物中分离得到。此外,采用MTT法和抑制一氧化氮(NO)生成实验,从细胞毒活性和抗炎活性两方面评估了化合物的生物活性。结果表明,化合物2具有显著的抗炎活性,其IC50值(17.00±1.11μmol/L)小于阳性对照药槲皮素的IC50值(17.21±0.50μmol/L)。     

Anthraquinones from Cassia sophera heartwood

From the heartwood of Cassia sophera two new isomeric anthraquinones, 1,2,7-trihydroxy-6,8-dimethoxy-3-methyl- and 1,2,6-trihydroxy-7,8-dimethoxy-3     

Secondary metabolites from the leaves of the medicinal plant goldenseal (Hydrastis canadensis)

The study presented herein constitutes an extensive investigation of constituents in Hydrastis canadensis L. (Ranunculaceae) leaves. It describes the isolation and identification of two previously unknown compounds, 3,4-dimethoxy-2-(methoxycarbonyl)benzoic acid (1) and 3,5,3′-trihydroxy-7,4′-dimethoxy-6,8-C-dimethyl-flavone (2), along with the known compounds (±)-chilenine (3), (2R)-5,4′-dihydroxy-6-C-methyl-7-methoxy-flavanone (4), 5,4′-dihydroxy-6,8-di-C-methyl-7-methoxy-flavanone (5), noroxyhydrastinine (6), oxyhydrastinine (7) and 4′,5′-dimethoxy-4-methyl-3′-oxo-(1,2,5,6-tetrahydro-4H-1,3-dioxolo-[4′,5′:4,5]-benzo[1,2-e]-1,2-oxazocin)-2-spiro-1′-phtalan (8). Compounds 3–8 have been reported from other sources, but this is the first report of their presence in H. canadensis extracts. A mass spectrometry based assay was employed to demonstrate bacterial efflux pump inhibitory activity against Staphylococcus aureus for 2, with an IC₅₀ value of 180 ± 6 μM. This activity in addition to that of other bioactive compounds such as flavonoids and alkaloids, may explain the purported efficacy of H. canadensis for treatment of bacterial infections. Finally, this report includes high mass accuracy fragmentation spectra for all compounds investigated herein which were uploaded into the Global Natural Products Social molecular networking library and can be used to facilitate their future identification in H. canadensis or other botanicals.