Dactylospongiaquinone, a new meroterpenoid from the Australian marine sponge Dactylospongia n. sp.

Chemical investigation of the sponge Dactylospongia n. sp. collected near Mooloolaba, S.E. Queensland, has led to the isolation of dactylospongiaquinone (7) together with the known quinones (2-5). The new metabolite 7 possesses a different carbon framework from the known dictyoceratidaquinone (9) and is suggested to possess a cis-fused ring junction by extensive NOESY studies combined with molecular modelling calculations. The relative stereochemistry of the previously described cyclospongiaquinone-1 (3) and dehydrocyclospongiaquinone-1 (4) is also assigned on the basis of NOESY analyses. Full NMR spectroscopic assignments are provided for all compounds.     

New resveratrol oligomers in the stem bark of Vatica pauciflora

Five new resveratrol oligomers; pauciflorols A-C (1-3), isovaticanols B (6) and C (8), and three new oligostilbene glucosides; pauciflorosides A (11), B (13), C (14), were isolated from the stem bark of Vatica pauciflora (Dipterocarpaceae) together with known 17 resveratrol oligomers (4, 5, 7, 9, 10, 12 and 15-25) and bergenin (26). The structures of isolates were established on the basis of detailed spectroscopic analysis. The typical and characteristic spectral properties of some resveratrol oligomers were also discussed.     

Structural and stereochemical investigations into bromotyrosine-derived metabolites from southern Australian marine sponges, Pseudoceratina spp.

Chemical investigation of a southern Australian sponge, Pseudoceratina sp., resulted in the isolation of twelve bromotyrosine-derived alkaloids, comprising four new metabolites, aplysamine-7 (1), (−)-purealin B (2), purealin C (3) and purealin D (4); two new spiroisoxazole enantiomers, (−)-purealidin R (5) and (−)-aerophobin-2 (6); five known metabolites (−)-pseudoceratinine A (7), (−)-aeroplysinin-1 (8), aplysamine-2 (9), purpuramine G (10) and purpuramine J (11); and an artifact 12 derived from ethanolysis of 5. Structures for 1-12 were assigned on the basis of detailed spectroscopic analysis. A second southern Australian Pseudoceratina sp. afforded the first recorded account of a racemic bromotyrosine-derived spiroisoxazole, (±)-purealin (13b), together with the known achiral precursor purealidin A (15). A literature review of marine bromotyrosine-derived spiroisoxazoles reaffirmed the published dominance of (+)-spiroisoxazoles, acknowledging several accounts of (−)-spiroisoxazoles, while also revealing a wide range of chiroptical measurements suggestive of variable optical purity. The Pseudoceratina sp. metabolites 1-12, 13b and 15 were assessed for antibiotic properties, with the new metabolites 3 and 13b exhibiting broad spectrum activity against several Gram-positive bacteria.     

Aigialomycins and related polyketide metabolites from the mangrove fungus Aigialus parvus BCC 5311

Reinvestigation of the secondary metabolites from the marine mangrove fungus Aigialus parvus BCC 5311 led to the isolation of six new nonaketide metabolites, aigialomycins F (4) and G (5a/5b), 7′,8′-dihydroaigialospirol (7), 4′-deoxy-7′,8′-dihydroaigialospirol (8), and rearranged macrolides 9 and 10, along with six previously described compounds, hypothemycin (1), aigialomycins A (2) and B (3), aigialospirol (6), 4-O-demethylhypothemycin (11), and aigialone (12). The structures of the new compounds were elucidated by analyses of the NMR spectroscopic and mass spectrometry data in combination with chemical means.     

Synthetic studies of neoclerodane diterpenoids from Salvia splendens and evaluation of opioid receptor affinity

Salvinorin A (1), a neoclerodane diterpene from the hallucinogenic mint Salvia divinorum, is the only known non-nitrogenous and specific κ-opioid agonist. Several structural congeners of 1 isolated from Salvia splendens (2-8) together with a series of semisynthetic derivatives (9-24), some of which possess a pyrazoline structural moiety (9, 19-22), have been tested for affinity at human μ, δ, and κ opioid receptors. None of these compounds showed high affinity binding to these receptors. However, 10 showed modest affinity for κ receptors suggesting that other natural neoclerodanes from different Salvia species may possess opioid affinity.     

Structures and cytotoxicities of fascaplysin and related alkaloids from two marine phyla—Fascaplysinopsis sponges and Didemnum tunicates

The structural variations and bioactivity properties of the alkaloids in the fascaplysin (1) and the reticulatine (3) families were examined. Four organisms were analyzed consisting of two collections of the sponge Fascaplysinopsis reticulata and two collections of the tunicate Didemnum sp. Reported are the isolation of three new compounds: 3-bromofascaplysin (2), 14-bromoreticulatine (4), and 14-bromoreticulatate (6) along with reticulatate (5) previously known as a semi-synthetic product of 1. Compounds 1 and 5 showed selectivity in a cell based cytotoxicity assay.     

Five novel norcembranoids from Sinularia leptoclados and S. parva

Three new norcembrane-based diterpenoids, leptocladolides A (1), B (4) and C (5), along with five known metabolites 6-10, have been isolated from the dichloromethane extract of a Taiwanese soft coral Sinularia leptoclados. Furthermore, a chemical investigation on the dichloromethane extract of S. parva has resulted in the isolation of two new related isomers, 1-epi-leptocladolide A (2) and 7E-leptocladolide A (3), in addition to 1 and 7. The structures of new metabolites 1-5 were elucidated on the basis of extensive spectroscopic analyses and their relative stereochemistries were determined by NOESY experiments. The new metabolites 1 and 3 have been shown to exhibit significant cytotoxic activity against KB and Hepa59T/VGH cancer cell lines.     

Metachromins L-Q, new sesquiterpenoid quinones with an amino acid residue from sponge Spongia sp.

Six new sesquiterpenoid quinones with an amino acid residue, metachromins L-Q (1-6), have been isolated from an Okinawan marine sponge Spongia sp. The structures and stereochemistry of 1-6 were elucidated on the basis of the spectroscopic data and chemical correlations. Metachromins L (1) and M (2) showed modest cytotoxicity.     

Seven new alkaloids from the roots of Stemona tuberosa

Seven new alkaloids, named as 1,9-epoxy-9a-hydroxystenine (1), tuberostemoline A (2), tuberostemoline B (3), tuberostemoninol C (4), oxotuberostemonine A (5), the mixture of bisdehydrotuberostemonine D (6), and bisdehydrotuberostemonine E (7), together with four known alkaloids neotuberostemonine (8), sessilifoline B (9), stemoxazolidinone F (10), and tuberostemoninol A (11), were isolated from the roots of Stemona tuberosa. The structures of 1–7 were elucidated through extensive spectroscopic analysis, and the relative configurations of 1–6 and 8 were further confirmed by X-ray crystallographic data. Compounds 8, 9 and the mixture of 6 & 7 exhibited potential acetylcholinesterase (AChE) inhibitory activities.     

Bioactive meroditerpenes and indole alkaloids from the soil fungus Neosartorya fischeri (KUFC 6344), and the marine-derived fungi Neosartorya laciniosa (KUFC 7896) and Neosartorya tsunodae (KUFC 9213)

Two new metabolites including a new aszonalenin analogue (1c) and a new meroditerpene (3) were isolated, together with aszonalenin (1a), acetylaszonalenin (1b), 13-oxofumitremorgin B (2), aszonapyrone A (4b) and helvolic acid, from the culture of the soil fungus Neosartorya fischeri (KUFC 6344). While the ethyl acetate extract of the culture of the diseased coral-derived fungus Neosartorya laciniosa (KUFC 7896) furnished aszonapyrone B (4a), aszonapyrone A (4b), tryptoquivaline L and 3′-(4-oxoquinazolin-3-yl) spiro[1H-indole-3,5′-oxolane]-2,2′-dione, the ethyl acetate extract of the culture of the marine sponge-associated fungus Neosartorya tsunodae (KUFC 9213) yielded a new analogue of chevalone C (5) and helvolic acid. The structures of the new compounds were established based on 1D and 2D NMR spectral analysis as well as HR-ESIMS. Compounds 1a–c, 2, 3, 4a, 4b and 5 were evaluated for their in vitro growth inhibitory activity on the MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and A375-C5 (melanoma) cell lines by the protein binding dye SRB method.     

Botryllamides K and L, new tyrosine derivatives from the Australian ascidian Aplidium altarium

Chemical investigation of the Australian ascidian Aplidium altarium led to the isolation of two new tyrosine derivatives, botryllamides K (1) and L (2), together with six known metabolites, botryllamides A-C (3-5), botryllamide G (6) and perspicamides A (7) and B (8). The structures of these compounds were elucidated by spectroscopic analysis. This is the first reported chemistry from this species. Compounds 1-8 were evaluated for their cytotoxicity towards the tumour cell lines, MCF-7 (breast), H460 (lung) and SF268 (central nervous system).     

Trypanocidal constituents of Dracocephalum komarovi

Trypanocidal constituents of Dracocephalum komarovi were investigated. Under guidance of the in vitro trypanocidal activity against epimastigotes of Trypanosoma cruzi, the causative agent of Chagas' disease, two new diterpenes, dracocequinones A (1) and B (2), and two known triterpene acids, ursonic acid and ursolic acid, were isolated as trypanocidal constituents, in addition to previously reported diterpenes, cyclocoulterone (4), komaroviquinone (5), dracocephalone A (6) and komarovispirone (7). Furthermore a new diterpene, komarovinone A (3), was isolated, together with four known terpenes. Among these compounds, komaroviquinone (5) showed the most potent activity with minimum lethal concentration of 0.4 μM. Structure elucidation of the new diterpenes 1-3 was described.     

Novel cyclopropyl diketones and 14-membered macrolides from the soil fungus Hamigera avellanea BCC 17816

Two novel cyclopropyl diketones, hamavellone A (1) and B (2), and two new 14-membered nonaketide macrolactones, hamigeromycin A (3) and B (4), together with six known compounds, 89-250904-F1 (radicicol analogue A, 5), pseurotin A (6), emodin (7), ω-hydroxyemodin (8), and emodin bianthrones (9 and 10) were isolated from the soil fungus Hamigera avellanea BCC 17816. The structures of the new compounds were defined by analysis of NMR and MS data. The absolute stereochemistry of 3 was addressed by chemical correlation to 5. Hamavellone B (2) exhibited antimalarial activity with an IC₅₀ of 5.2 μg/mL, whereas it also showed comparable cytotoxicity.     

New antitumor sesquiterpenoids from Santalum album of Indian origin

Three new campherenane-type (1, 4, 7) and three new santalane-type (9, 11, 12) sesquiterpenoids, and two aromatic glycosides (21, 22) together with 12 known metabolites including α,β-santalols (14, 18), (E)-α,β-santalals (15, 19), α,β-santaldiols (16, 20), α-santalenoic acid (17), and vanillic acid 4-O-neohesperidoside were isolated from Santalum album chips of Indian origin. The structures of the new compounds, including absolute configurations, were elucidated by 1D- and 2D-NMR spectroscopic and chemical methods. The antitumor promoting activity of these isolates along with several neolignans previously isolated from the same source was evaluated for both in vitro Epstein-Barr virus early antigen (EBV-EA) activation and in vivo two-stage carcinogenesis assays. Among them, compound 1 exhibited a potent inhibitory effect on EBV-EA activation, and also strongly suppressed two-stage carcinogenesis on mouse skin.     

Unusual enniatins produced by the insect pathogenic fungus Verticillium hemipterigenum: isolation and studies on precursor-directed biosynthesis

Two new enniatins H (3) and I (4), whose substituents on 2-hydroxycarboxylic acid moieties were different from those of known compounds, were isolated, together with known enniatins B (1) and B₄ (2), from the insect pathogenic fungus Verticillium hemipterigenum BCC 1449. Structures of these compounds were elucidated by spectroscopic means. Studies on precursor-directed biosynthesis with strain BCC 1449 led to the production and identification of three analogs, enniatins G (5), C (6) and MK1688 (7), as well as the stereochemical elucidation of 3 and 4. Enniatins 1-7 were evaluated for their antiplasmodial and antimycobacterial activities.     

Banchromene and other secondary metabolites from the endophytic fungus Fusarium sp. obtained from Piper guineense inhibit the motility of phytopathogenic Plasmopara viticola zoospores

A new chromene, (S)-banchromene (1), together with seven known compounds, ergosterol, beauvericin (2), fusaproliferin (3), radicinin (4), poly(3-hydroxybutyric acid) (PHB, 5), N-methylpyrrolidone and an inseparable mixture of isochromene derivatives 6a, 6b, were isolated from a culture of Fusarium sp. strain CAMKT24b1, an endophytic fungus from the leaves and twigs of Piper guineense (Piperaceae). The structures of these metabolites were elucidated on the basis of their spectroscopic data; the absolute configuration of 1 was determined by ab initio-calculation of the optical rotation. In tests with the zoospores of the grapevine downy mildew pathogen Plasmopara viticola, compounds 1–4 showed moderate to high levels of motility-impairing activity at concentrations as low as 2.5 μg/mL. Compound 2 was the most active, exhibiting both motility-halting and lytic activities. Furthermore, compounds 2 and 3 displayed significant cytotoxic activity against brine shrimp larvae (Artemia salina) at 10 μg/mL. This is the first report on motility inhibitory and lytic activities of metabolites from an endophytic Fusarium species against the zoospores of the downy mildew pathogen P. viticola.     

Polyketides from the mangrove-derived endophytic fungus Acremonium strictum

Five new polyketide derivatives, 6′-hydroxypestalotiopsone C (1), acropyrone (2), bicytosporone D (3), waol acid (4), and pestalotiopene C (5), together with seven known metabolites (6–12), were obtained from extracts of the endophytic fungus Acremonium strictum, isolated from the mangrove tree Rhizophora apiculata. The structures of the isolated compounds were elucidated on the basis of comprehensive NMR and MS analysis. Compounds 6, 7, and 9 showed moderate cytotoxic activity against human cisplatin-sensitive (IC₅₀ values 27.1, 76.2, and 8.3 μM, respectively) and resistant A2780 cell lines (IC₅₀ values 12.6, 30.1, and 19.0 μM, respectively), whereas only 9 exhibited antibacterial activity against Staphylococcus aureus (MIC value 14.3 μM).     

Isolation,characterization, and NMR spectroscopic data of indole and oxindole alkaloids from Mitragyna speciosa

A new indole alkaloid, 7β-hydroxy-7H-mitraciliatine (1) and a new oxindole alkaloid, isospeciofoleine (2) together with nine known alkaloids were isolated from Mitragyna speciosa and characterized by NMR, CD, and MS spectroscopic data analyses. The ¹H and ¹³C NMR spectroscopic data of isospeciofoline (3), isorotundifoline (4), paynantheine (5), and 3-isopaynantheine (6) were also reported for the first time.     

Benzopyranone,benzophenone, and xanthone derivatives from the soil fungus Penicillium citrinum PSU-RSPG95

Two new benzopyranones, named coniochaetones E (1) and F (2), one new xanthone, penicillone C (3), and one new benzophenone, penicillanone (4), are isolated from the soil fungus Penicillium citrinum PSU-RSPG95, together with ten known compounds. Their structures are identified on the basis of spectroscopic data. The isolated compounds are evaluated for their cytotoxic activity.     

Bis-spiro-azaphilones and azaphilones from the fungi Chaetomium cochliodes VTh01 and C. cochliodes CTh05

Four new dimeric spiro-azaplilones, cochliodones A-D (1-4), two new azaphliones, chaetoviridines E and F (5 and 6), a new epi-chaetoviridin A (7), together with five known compounds, chaetoviridin A (8), ergosterol (9), chaetochalasin A (10), 24(R)-5α,8α-epidioxyergosta-6-22-diene-3β-ol (11), and ergosterol-β-d-glucoside (12) were isolated from the fungi Chaetomium cochliodes VTh01 and C. cochliodes CTh05. Structures and stereochemistry of the atropisomers 1-3 were determined by single-crystal X-ray diffraction analysis. Compounds 5, 10, and 11 exhibited antimalarial activity against Plasmodium falciparum, while 3, 5, 6, 10, and 11 showed antimycobacterial activity against Mycobacterium tuberculosis. In addition, 5 and 6 also showed cytotoxicity against the KB, BC1, and NCI-H187 cell lines.