Highly oxidized ergosterols and isariotin analogs from an entomopathogenic fungus,Gibellula formosana,cultivated in the presence of epigenetic modifying agents

The concomitant addition of a histone deacetylase inhibitor, suberoyl bis-hydroxamic acid, and a DNA methyltransferase inhibitor, RG-108, to the culture medium of Gibellula formosana, an entomopathogenic fungus, induced a significant increase in diversity of secondary metabolites. From the culture media were isolated two new highly oxidized ergosterols, formosterols A (1) and B (2), and five new isariotin analogs, 12′-O-acetylisariotin A (4), 1-epi-isariotin A (5), and isariotins K–M (6–8), together with 22,23-epoxy-3,12,14,16-tetrahydroxyergosta-5,7-dien-11-one (named formosterol C) (3), isariotins A (9), C (10), and E (11), TK-57-164A (12), and beauvericin (13). The NMR spectra, X-ray single crystallographic diffraction, and chemical transformations revealed the structures of the two new formosterols and five new isariotins. The stereochemistry of formosterol C (3) was deduced from its spectroscopic data. The side chains of formosterols A–C (1–3) contained cis-22,23-epoxide, which is rarely present in naturally occurring sterols and triterpenes.     

Isolation,structure elucidation,and antibacterial evaluation of the metabolites produced by the marine-sourced Streptomyces sp. ZZ820

New indole alkaloids streptoprenylindoles A–C (1–3) and diterpenoids 18-acetyl-cyclooctatin (8), 5,18-dedihydroxy-cyclooctatin (9), and 5-dehydroxy-cyclooctatin (10) were isolated from the culture of marine-derived Streptomyces sp. ZZ820, along with known 3-cyanomethyl-6-[3-methyl-2-butenyl]indole (4), N-(2-(1H-indol-3-yl)ethylacetamide (5), 1-acetyl-β-carboline (6), indole-3-methylethanoate (7), cyclooctatin (11), and chromomycin A₃ (12). Their structures were elucidated by a combination of extensive spectroscopic analyses, ECD calculation, and the Mosher's method. Streptoprenylindoles A (1) and B (2) are enantiomers that were separated through the preparation of their Mosher esters. Three new diterpenoids (8–10) showed antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli with MIC values of 24.11–55.12?μM, while chromomycin A₃ (12) showed potent antibacterial activities against MRSA (MIC: 0.59?μM) and E. coli (MIC 0.04?μM).     

Aplyronines D–H from the sea hare Aplysia kurodai: isolation,structures, and cytotoxicity

Five cytotoxic macrolides, aplyronines D–H (4–8), were isolated from the Japanese sea hare Aplysia kurodai. They are new congeners of the antitumor compound aplyronine A (1), which was previously isolated from the same organism. Their structures were determined by spectroscopic analysis (NMR and MS). The cytotoxicity of these new compounds was evaluated in comparison with that of aplyronines A–C (1–3), suggesting the importance of the 7-O-seryl ester group for mediating the potent cytotoxicity of aplyronines.     

Sinuhirtins A and B,two uncommon norhumulene-type terpenoids from the South China Sea soft coral Sinularia hirta

Two new uncommon norhumulene-type norsesquiterpenoids, namely sinuhirtins A (1) and B (2), along with two known norcaryophyllene-type norsesquiterpenoids (3 and 4), were isolated from the South China Sea soft coral Sinularia hirta. The structures and absolute configurations of the new compounds were determined by extensive spectroscopic data analyses, and computer-assisted methods including GIAO ¹³C NMR and TDDFT-ECD calculations. A plausible biogenetic relationship of 1–4 was proposed.     

Erysacleuxins C and D,new isoflavones from the twigs of Erythrina sacleuxii Hua and their cytotoxic activity

Two previously undescribed isoflavones, erysacleuxin C (1) and erysacleuxin D (2), together with seven known compounds (3–9), were isolated and identified from the EtOAc extract of the twigs of Erythrina sacleuxii Hua (Leguminosae). The structures of the isolated compounds were determined on the basis of their spectroscopic and spectrometric data. Evaluation of their cytotoxicity against the human cancer HeLa-S3 cell lines indicated IC₅₀ values of 130.4, 54.9 and 73.9 µM for erysacleuxin C (1), erysacleuxin D (2) and butin (9), respectively.     

Dysotriflorins A–M,triterpenoids from Dysoxylum densiflorum

Thirteen new triterpenoids, dysotriflorins A–M (1–13), were isolated from Dysoxylum densiflorum barks, and their structures were elucidated on the basis of NMR spectroscopic data and X-ray crystallography. Dysotriflorins A, B, and K–M (1, 2, and 11–13) were concluded to be unique 13,17-secodammarane triterpenoids, and dysotriflorins C–J (3–10) to be dammarane triterpenoids. Dysotriflorins showed in vitro cytotoxic activity against several cancer cell lines.     

Sartorymensin,a new indole alkaloid,and new analogues of tryptoquivaline and fiscalins produced by Neosartorya siamensis (KUFC 6349)

Seven new indole alkaloids including a new indoloazepinone derivative (2), two new quinazolinone derivatives (7, 8) and four new pyrazinoquinazolinone derivatives: epi-fiscalin C (10), epi-fiscalin A (12), neofiscalin A (13), epi-neofiscalin A (14) were isolated, together with 4-dihydroxy-3-methylacetophenone (1), tryptoquivaline (3), tryptoquivalines L (4), H (5), F (6) as well as fiscalins A (11) and C (9), from the culture of the fungus Neosartorya siamensis (KUFC 6349). The absolute configuration of the stereogenic carbons of the previously reported tryptoquivalines F, H, L was revised using the data obtained from an X-ray analysis of tryptoquivaline l and the NOESY correlations. The structures of the new pyrazinoquinazolinone derivatives (10, 12, 13, 14) were established based on 1D and 2D NMR spectral analysis, and the absolute configuration of their stereogenic carbons was determined by an X-ray crystallographic analysis of fiscalin C (9) and a new compound epi-fiscalin C (10), in conjunction with the correlations observed in their NOESY and long range COSY spectra. Compounds 2–8 and 12 were evaluated for their in vitro growth inhibitory activity on the human U373 and Hs683 glioblastoma, the A549 non-small cell lung cancer, the MCF-7 breast cancer and the SKMEL-28 melanoma cell lines by MTT colorimetric assay.     

Glabralides A – C,three novel meroterpenoids from Sarcandra glabra

Glabralides A–C (1–3), three novel meroterpenoids including two unprecedented skeletons were isolated from the whole plants of Sarcandra glabra. Glabralide A (1) represented a unique skeleton of the chalcone-coupled monoterpenoid, bearing a bicyclo [2.2.2] octene core unit with five chiral centers. The structures were established by spectroscopic methods, including 2D NMR experiments, and the absolute configurations were determined using circular dichroic (CD) spectra. The plausible biogenetic pathway for 1 suggested that α-phellandrene was conjugated with chalcone by Diels-Alder cyclization, and for 3 implied that α-phellandrene and o-hydroxy phenylacetate cyclized by an uncommon radical addition and cationic cyclization.     

Studies on the constituents of asclepiadaceae plant—LVII: The structures of six glycosides,wilfoside c1n,c2n,c3n,c1g,c2g and c3g,with novel sugar chain containing a pair of optically isomeric sugars

Six new glycosides named wilfoside C3N (l), C1N (2), C2N (3), C3G (4), C1G (5) and C2G (6) were isolated from Cynanchum wilfordi hemsley (Asclepiadaceae) and their structures were deduced on the basis of the chemical and spectral evidence. It is quite unusual that 2, 3, 5 and 6 include both D-cymarose and L-cymarose in each sugar chain.     

Cytotoxic tropolones from the fungus Nemania sp. BCC 30850

Twelve new compounds, including nine tropolones, nemanolones A?I (1–9), three 7-isochromenones, nemanecins A?C (10–12), and a new naturally isolated 4-isochromanone (13), along with two known compounds, 7,8-dihydroxy-3-methyl isochroman-4-one (XJP), and chaetoquadrin F, were isolated from culture broth of the fungus Nemania sp. BCC 30850. Structures of these compounds were elucidated by NMR and MS spectroscopic analyses. Nemanolones exhibited cytotoxic activities and two of them, compounds 1 and 2, also showed antibacterial activity against Bacillus cereus and antifungal activity against Candida albicans.     

New azaphilones from Chaetomium globosum isolated from the built environment

A strain of Chaetomium globosum (DAOM 240359) was isolated from an indoor air sample in Ottawa, Ontario, Canada. When fermented in liquid culture, this strain produced a number of known metabolites including chaetoglobosins A (6), C, and F (7), chaetomugilin D (5), chaetoviridin A (4), and three new nitrogenous azaphilones; 4′-epi-N-2-hydroxyethyl-azachaetoviridin A (1), N-2-butyric-azochaetoviridin E (2), and isochromophilone XIII (3). The structures were elucidated by spectroscopic analysis including; HRMS, 1D and 2D NMR, UV, and ORD. Compounds 2–7 were antimicrobial when tested using quantitative growth inhibition assays.     

Polyketides and nitrogenous metabolites from the endophytic fungus Phomopsis sp. D15a2a

Three new polyketides, phomopones A−C (1–3), one new cyclic tetrapeptide, 18-hydroxydihydrotentoxin (4), and a new amide, 6-hydroxyenamidin (5) together with a known derivative, enamindin (6) were obtained from the endophytic fungus Phomopsis sp. D15a2a isolated from the plant Alternanthera bettzickiana. The structures of the new compounds were elucidated by 1D, 2D NMR and HRMS data. The absolute configurations of the isolated metabolites were determined either by X-ray crystallography, Marfey’s method or by converting the compounds to Mosher esters.     

Chlorinated chromone and diphenyl ether derivatives from the mangrove-derived fungus Pestalotiopsis sp. PSU-MA69

Four new diphenyl ethers, pestalotethers A–D (1–4), three new chromones, pestalochromones A–C (5–7), one new xanthone, pestaloxanthone (8), and one new butenolide, pestalolide (9), together with 11 known compounds were isolated from the mangrove-derived fungus Pestalotiopsis sp. PSU-MA69. Their structures were established by spectroscopic techniques. Compounds 1–3 and 5–7 are the rare chlorinated fungal metabolites of diphenyl ethers and chromones, respectively. Pestalolide (9) displayed weak antifungal activity against Candida albicans and Cryptococcus neoformans.     

Leucomidines A–C,novel alkaloids from Leuconotis griffithii

Two novel indole alkaloids and new quinazoline alkaloids, namely leucomidines A–C (1–3), were isolated from the barks of Leuconotis griffithii. The structures including the absolute configuration were elucidated on the basis of spectroscopic data, chemical means, and CD calculations. The quinazoline alkaloid, 3, is proposed to be derived from the same biogenetic precursor as the indole alkaloids 1 and 2.     

Pyridone alkaloids from the scale-insect pathogenic fungus Hypocrella discoidea BCC 71382

Hypocrellutins A–C (1–3), 2- and 4-pyridone alkaloids, were isolated from cultures of the scale-insect pathogenic fungus Hypocrella discoidea BCC 71382. The structures were elucidated on the basis of NMR spectroscopic and mass spectrometry data. The absolute configuration of hypocrellutin B (2) was determined by ECD calculation. Their plausibly biosynthetic pathways are proposed. All isolated compounds were inactive in the antifungal, antimalarial, antitubercular, and cytotoxic activity assays.     

Novel trichothecanes, paecilomycine A, B, and C, isolated from entomopathogenic fungus, Paecilomyces tenuipes

Paecilomycine A (1), B (2), and C (3) were isolated from cultivated fruiting bodies of Paecilomyces tenuipes (Isaria japonica), which is a popular entomopathogenic fungus used in folk medicine and health foods in China, Korea, and Japan. The structures of 1-3 were deduced from their spectroscopic data and their absolute configurations were elucidated by preparing their MPA esters. Compound 1 showed activity in the neurotrophic factor biosynthesis in glial cells.     

Trichiliasinenoids A–C,three 6,7-secomexicanolide limonoids with a 7,29-linkage from Trichilia sinensis

Trichiliasinenoids A–C (1–3), three new limonoids with an unprecedented C-29-C-7 connecting carbon skeleton formed by migration of C-7 from C-6 to C-29 of a mexicanolide-type limonoid precursor were isolated from the leaves and twigs of Trichilia sinensis. Their structures were assigned by spectroscopic analysis, and the absolute configurations were determined by X-ray crystallography (1) and ECD calculation (2 and 3). A possible biosynthetic pathway of 1 was also proposed. Compound 2 exhibited moderate cytotoxicity against HL-60 cells and weak cytotoxicity against SMMC-7721cells.     

Poecillastrin E,F, and G,cytotoxic chondropsin-type macrolides from a marine sponge Poecillastra sp.

Poecillastrin E (1), F (2), and G (3) were isolated from a marine sponge Poecillastra sp. as the cytotoxic constituents. Their planar structures were determined by analyzing the MS and NMR spectra. They are closely related to the known poecillastrin C (4). The absolute configuration of the β-hydroxyaspartic acid (OHAsp) residue was determined to be D-threo by Marfey's analysis of the hydrolysate. The mode of lactone ring formation of OHAsp residue in 1–3 was determined by selective reduction of the ester linkage followed by acid hydrolysis.     

Guianofruits C–I from fruit oil of andiroba (Carapa guianensis,Meliaceae)

Two novel chukrasone-type limonoids, named Guianofruits C and D (1 and 2), a guianolide derivative named Guianofruit E (3), and four novel phragmalin–type limonoids named Guianofruits F–I (4–7), were isolated from the fruit oil of Carapa guianensis AUBLET (Meliaceae), a traditional medicine in Brazil and Latin American countries. Their structures were mainly elucidated based on spectroscopic analyses using 1D and 2D NMR techniques. The effects of compounds 1–6 on the production of NO by LPS-activated mouse peritoneal macrophages were investigated. Two new chukrasone-type limonoids, Guianofruits C (1) and D (2), exhibited moderate inhibitory activities.     

Heteroaromatic alkaloids,nakijinamines, from a sponge Suberites sp.

The structures of seven new secondary metabolites isolated from an Okinawan marine sponge Suberites sp., nakijinamines A (1), B (2), and F–I (3–6) and 6-bromoconicamin (7), have been elucidated on the basis of spectroscopic analysis, chemical conversion, and conformational analysis. These analyses disclosed that 1–6 were heteroaromatic alkaloids having the hybrid structures of an aaptamine-type alkaloid and an indole alkaloid, while 7 was a bromoindole alkaloid. Nakijinamine I (6) is the first example of an aaptamine-type alkaloid possessing a 1,4-dioxane ring. Antimicrobial activities of 1–7 were evaluated.