Absolute configuration and antibiotic activity of neosartorin from the endophytic fungus Aspergillus fumigatiaffinis

Neosartorin (1) was isolated from the endophytic fungus Aspergillus fumigatiaffinis. The absolute configuration of 1, including both axial and central chirality elements, was established as (aR,5S,10R,5′S,6′S,10′R) for the first time on the basis of its electronic circular dichroism (ECD) spectra aided with TDDFT–ECD calculations. Neosartorin (1) exhibited substantial antibacterial activity against a broad spectrum of Gram-positive bacterial species including staphylococci, streptococci, enterococci, and Bacillus subtilis with minimal inhibitory concentrations in the range of 4–32 μg/mL. When the toxicity of 1 against eukaryotic cells was measured using a panel of different cancer cell lines such as HELA and BALB/3T3, the average IC₅₀ values exceeded 32 μg/mL.     

Cyclopeptides and polyketides from coral-associated fungus, Aspergillus versicolor LCJ-5-4

Three new cyclopentapeptides, versicoloritides A-C (1-3), a new orcinol tetramer, tetraorcinol A (4), and two new lactones, versicolactones A and B (5 and 6) together with three known metabolites, diorcinol, glyantrypine, and cordyol C were isolated from the fermentation broth of the coral-associated fungus Aspergillus versicolor LCJ-5-4. Their structures were elucidated by spectroscopic and chemical methods. The new compounds 1-4 were evaluated for their radical-scavenging activity and antimicrobial activity against Staphylococcus aureus, Escherichia coli, Enterobacter aerogenes, Bacillus subtilis, Pseudomonas aeruginosa, and Candida albicans and cytotoxicity against P388 and Hela cell lines. Compound 4 showed weak radical-scavenging activity against the DPPH radical with an IC₅₀ value of 67 μM.     

Janoxepin and brevicompanine B: antiplasmodial metabolites from the fungus Aspergillus janus

Two compounds janoxepin (1) and brevicompanine B (2) were isolated from the fungus Aspergillus janus and the structures elucidated by one- and two-dimensional NMR spectroscopic methods and mass spectrometry. Janoxepin is a novel oxepin derivative with a rare d-leucine incorporated. Brevicompanine B has previously only been isolated from Penicillium brevicompactum. Both compounds were tested in antimicrobial assays and found to be active against the malaria parasite Plasmodium falciparum 3D7 (IC₅₀-values of 28 and 35 mg/ml, respectively). However, no activity was observed in antifungal or antibacterial assays.     

Dihydroanthracenone metabolites from the endophytic fungus Diaporthe melonis isolated from Annona squamosa

Chemical investigation of the endophytic fungus Diaporthe melonis, isolated from Annona squamosa, yielded two new dihydroanthracenone atropodiastereomers, diaporthemins A (1) and B (2), together with the known flavomannin-6,6′-di-O-methyl ether (3). The structures of the new compounds were established on the basis of extensive 1D and 2D NMR spectroscopy, as well as by high resolution mass spectrometry and by CD spectroscopy. Compounds 1–3 were tested for their antimicrobial activity against a multi-resistant clinical isolate of Staphylococcus aureus 25697, a susceptible reference strain of S. aureus ATCC 29213 and against Streptococcus pneumoniae ATCC 49619. Compound 3 strongly inhibited S. pneumonia growth with a MIC value of 2 μg/mL, and showed moderate activity against the S. aureus multi-resistant clinical isolate and susceptible reference strain (MIC 32 μg/mL), whereas 1 and 2 were not active against the tested strains.     

Neomacrophorin I,II, and III,novel drimenyl cyclohexanes with hydroxylated butanoates from Trichoderma sp. 1212-03

Neomacrophorins I (1), II (2), and III (3) were isolated from the culture broth of Trichoderma sp. 1212-03, which was collected at Shirakami Mountainous area in Japan. Structural analyses disclosed that these resemble known macrophorins but possess axial-hydroxy group at C3 as well as different side chains at C7′. These are diastereomeric forms of macrophorins for 5′,6′-epoxide functionality. The NMR analyses suggested their relative configurational relationship between the C1–C15 drimene and C1′–C7′ epoxyquinone moieties. ECD spectral discussions verified them particularly for C5′,C6′-epoxyquinone (1), C5′,C6′-epoxysemiquinone (2 and 3), and 2″,3″-dihydroxybutanoate moiety in 1 and 2. The configuration of C3″-stereocenter of 3 was determined by chiral GC–MS after converting into methyl (S)-3″-hydroxybutanoate by basic of 3 methanolysis. Biological assays disclosed that 1 induces hyphal branching of Cochliobolus miyabeanus as well as cytotoxicity against human colorectal cancer COLO 201.     

Sorbifuranones A-C, sorbicillinoid metabolites from Penicillium strains isolated from Mediterranean sponges

Three novel natural products, sorbifuranones A-C (4-6), were isolated from a Penicillium chrysogenum fungus isolated from the marine sponge Ircinia fasciculata. Sorbifuranones B (5) and C (6) and 2′,3′-dihydrosorbicillin, a putative precursor to sorbifuranone B, were also found in the culture of another Penicillium strain, which was isolated from the sponge Tethya aurantium. Their constitutions were elucidated mainly by 2D NMR. NOE correlations in combination with quantum chemical calculations and comparison of experimental and calculated electronic circular dichroism (CD) spectra permitted assignment of the absolute configuration of sorbifuranone C. The structures hint at a two-step cleavage-cyclization sequence of sorbifuranone A (4) leading to the spiro compound sorbifuranone C, while sorbifuranone B is likely to be the respective cleavage product of a putative 2′,3′-dihydrosorbifuranone A, which cannot cyclize further.     

Alashinol H,an epoxylignan with an unusual six-membered cyclic hemiacetal from Syringa pinnatifolia

A new 7, 9′-epoxylignan, alashinol H (1), which features a rare six-membered cyclic hemiacetal, was isolated from the stem barks of Syringa pinnatifolia. The structure was elucidated based on spectroscopic data including HRESIMS and NMR. Its absolute configuration was resolved by GIAO NMR shifts and ECD calculations. A putative biosynthetic pathway of this compound is proposed. Alashinol H showed a moderate inhibitory effect against NO production in BV-2 murine microglia cells.     

Ten new calyxins from Alpinia katsumadai: a systematically studies on the stereochemistry of calyxins

Ten new calyxin natural products, named calyxin N (1), ent-calyxin N (2), calyxin O (3), ent-calyxin O (4), calyxin P (5), 9″-epicalyxin P (6), calyxin Q (7), calyxin R (8), calyxin S (9) and 5-epicalyxin S (10), were isolated from the seeds of Alpinia katsumadai. Their planar structures were elucidated by a combination of various spectroscopic methods, primarily NMR and MS, while the absolute configurations of the isolated calyxins were comprehensively studied by the modified Mosher's method, electronic circular dichroism (ECD) and theoretical calculations. This is the first systematically study on the absolute configurations of calyxins. Most of the isolated compounds showed moderate to strong antiproliferative activities against NCI-H460, HeLa, SMMC-7721 and HCT-116 cancer cell lines.     

Modiolin and phthalide derivatives from the endophytic fungus Microsphaeropsis arundinis PSU-G18

One new modiolin, microsphaerodiolin (1), and seven new phthalides, microsphaerophthalides A-G (2-8), together with 12 known compounds were isolated from the endophytic fungus Microsphaeropsis arundinis PSU-G18. Their structures were elucidated by spectroscopic methods. The new 3-oxygenated phthalides are rare natural products. The known 1-(2,5-dihydroxyphenyl)-2-buten-1-one exhibited significant antifungal activity against Microsporum gypseum SH-MU-4 with an MIC value of 8 μg/mL, moderate antimalarial activity with an IC₅₀ value of 9.63 μg/mL and strong radical scavenging potency with the IC₅₀ value of 0.018 mg/mL. The new compounds 2 and 6 showed moderately antifungal activity against M. gypseum SH-MU-4 and Cryptococcus neoformans, respectively, with equal MIC values of 64 μg/mL.     

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.     

Structure and absolute configuration of penicilliumine,a new alkaloid from Penicillium commune 366606

Penicilliumine (1), a new structure was isolated from the fermentation Penicillium commune 366606, a marine-derived fungus isolated from the sea water collected at Qingdao, China. HPLC chiral separation of 1 afforded two enantiomers (−)-penicilliumine and (+)-penicilliumine, respectively. The structure of 1 was established by comprehensive spectroscopic data, and single-crystal X-ray diffraction. The absolute configuration of enantiomers was determined by quantum mechanical computation of electronic circular dichroism (ECD).     

New tetramic acid derivatives from the deep-sea-derived fungus Cladosporium sp. SCSIO z0025

Eight new tetramic acid derivatives, cladosporiumins A–H (1–8) were isolated from a culture broth of Cladosporium sp. SCSIO z0025 derived from the deep-sea sediment collected from Okinawa Trough. Their structures were elucidated by extensive spectroscopic data analysis. Compounds 1–3 were unique 3-acyltetramic acids with a hexyl enic alcohol side chain and a six-membered lactone ring substituted at C-3 of the 2, 4-pyrrolidinedione skeleton. The absolute configurations of chiral carbons of the 2, 4-pyrrolidinedione unit in 1–4 and 7 were established by quantum chemical calculations of the electronic circular dichroism (ECD) spectra. And the absolute configurations of chiral carbons of the six-membered lactone ring in 1–3 were established by density functional theory calculation of their ¹³C NMR chemical shifts. In addition, all the compounds were tested for cytotoxic, antibacterial, anti-biofilm, and AchE inhibitory activities.     

Emervaridione and varioxiranediol, two new metabolites from the endophytic fungus, Emericella variecolor

Two new compounds, emervaridione and varioxiranediol, together with the three known compounds, stellatic acid, ergosterol and dihydroterrein, were isolated from the endophytic fungus, Emericella variecolor. The structures of emervaridione and varioxiranediol were established from spectroscopic and X-ray crystallographic analysis.     

Depsides and depsidones from the soil-derived fungus Aspergillus unguis PSU-RSPG204

Three new depsides, aspergisides A-C, and one new depsidone, aspergisidone, were isolated from the soil-derived fungus Aspergillus unguis PSU-RSPG204 together with one phthalide derivative and 11 depsidones including emeguisin A, aspersidone and folipastatin. The structures were determined by spectroscopic evidence. Aspersidone and emeguisin A showed remarkably antibacterial activity against Staphylococcus aureus and methicillin-resistance S. aureus with equal MIC values of 0.5?μg/mL. Emeguisin A, which displayed the highest activity with 87.06% inhibition of human colon carcinoma (HCT-116) cell viability, decreased numbers of live cells/numbers of dead cells in a dose-dependent manner with the IC₅₀ values of 34.8–84.7?μM in a 3D culture model depending on durations of incubation. In addition, folipastatin dose-dependently inhibited forskolin-stimulated chloride secretion in human intestinal epithelial (T84) cells with an IC₅₀ value of 0.5?μM. These depsidones were considered to be inactive against noncancerous Vero Cells with the IC₅₀ values of >10?μM.     

Highly unsaturated pyranone derivatives from the basidiomycete Junghuhnianitida

Four new highly unsaturated pyranone derivatives A–D (1–4), together with one known compound 5 (−)-nitidon were isolated from cultures of the fungus Junghuhnianitida. Planar structures of the new compounds were elucidated on the basis of extensive NMR spectroscopic and mass spectrometric analyses. Absolute configurations of the new compounds were determined on the basis of biosynthetic considerations and quantum chemistry theory. Compound 1 exhibited almost the same cytotoxic activities as cis-platin.     

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).     

南海红树林内生真菌Cephalosporium sp．（2090#）次级代谢产物研究

海洋微生物是寻找海洋药物先导化合物的一个新的源泉,人们已经从海洋微生物的次级代谢产物中分离得到了很多结构新颖或强药理活性的化合物[1]。我们在对中国南海红树林内生真菌的研究中,发现了大量的生物活性化合物,这也揭示了我国南海海洋真菌具有极大的药用开发前景[2-5]。红     

Polyhydroxylated macrolide isolated from the endophytic fungus Pestalotiopsis mangiferae

A new polyhydroxylated macrolide, named mangiferaelactone (1) was isolated from a solid culture of the endophytic fungus Pestalotiopsis manguiferae, together with ten known compounds [(6S,1′S)-LL-P880α; (6S,1′S,2′R)-LL-P880β; (1′S,2′R)-LL-880γ; (1′R)-dehydropestalotin; (−)-5-carboxylmellein; (−)-5-methylmellein; (−)-5-hydroxylmethylmellein; arabenoic acid; 5,6-dihydro-4-methoxy-2H-pyran-2-one; and the (−)-2-hexylidene-3-methylsuccinic acid]. P. manguiferae was isolated from Hyptis dilatata, a small shrub common in the central region of Panama. The structure of compound 1 was elucidated by a combination of spectroscopic methods (IR, MS, optical rotation, 1D and 2D NMR spectroscopy). The absolute configuration of 1 was established as 4R,7R,8R,9S by application of vibrational circular dichroism (VCD). Compound 1 showed a minimum inhibitory concentration (MIC) of 1.6863 mg/mL against Listeria monocytogenes, and 0.5529 mg/mL against Bacillus cereus. No activity was observed for compound 1 against Plasmodium falciparum or Trypanosoma cruzi; likewise, no cytotoxic activity was observed against A2058 and H522-T1 cells.     

Absolute configuration of bioactive furanogermacrenones from Commiphora erythraea (Ehrenb) Engl. by computational analysis of their chiroptical properties

Absolute configurations (+)-(4S), (+)-(3S,4R), (−)-(2S,4S), and (−)-(1R,2R,4S) were assigned, for the first time, to bioactive furanogermacranes extracted from Commiphora erythraea resin by DFT computational analysis of their ORD curves and ECD spectra. This analysis established that all of these compounds share the same absolute configuration at the methyl-substituted carbon thus allowing us to hypothesize a biosynthetic relationship among these structurally related metabolites.