Pestalotiopens A and B: Stereochemically Challenging Flexible Sesquiterpene‐Cyclopaldic Acid Hybrids from Pestalotiopsis sp.

From the endophytic fungus Pestalotiopsis sp. isolated from the leaves of the Chinese mangrove, Rhizophora mucronata, two novel hybrid sesquiterpene‐cyclopaldic acid metabolites with an unusual carbon skeleton, named pestalotiopens A and B, were obtained, together with the already known phytotoxin altiloxin B. Pestalotiopen B even contains a third, triketide‐derived module. The constitutions and the absolute configurations of the new metabolites and of altiloxin B were unambiguously determined by a combination of spectroscopic methods and quantum‐chemical optical‐rotatory dispersion (ORD) and circular dichroism (CD) calculations. A biosynthetic pathway to pestalotiopens A and B is proposed with altiloxin B as one of the suggested precursors. Pestalotiopen A shows moderate antimicrobial activity against Enterococcus faecalis.     

Two New Octahydronaphthalene Derivatives from Trichoderma spirale,an Endophytic Fungus Derived from Aquilaria sinensis

Two new octahydronaphthalene derivatives, trichodermic acid A ( 1 ) and trichodermic acid B ( 2 ), along with a known analog, trichodermic acid ( 3 ), and a known modified dipeptide, trichodermamide A ( 4 ), were isolated from the extract of Trichoderma spirale, an endophytic fungus present in the medicinal plant Aquilaria sinensis. The structures of these compounds were established by extensive analysis of their spectroscopic data including 1D‐ and 2D‐NMR and MS data.     

Alkaloid and Anthraquinone Derivatives Produced by the Marine‐Derived Endophytic Fungus Eurotium rubrum

Cultivation of the fungal strain Eurotium rubrum, an endophytic fungus that was isolated from the inner tissue of the semi‐mangrove plant Hibiscus tiliaceus, resulted in the isolation of one new dioxopiperazine alkaloid, 12‐demethyl‐12‐oxo‐eurotechinulin B ( 1 ), and one new anthraquinone derivative, 9‐dehydroxyeurotinone ( 2 ), together with ten known compounds including variecolorin J ( 3 ), eurotechinulin B ( 4 ), variecolorin G ( 5 ), alkaloid E‐7 ( 6 ), cryptoechinuline G ( 7 ), isoechinulin B ( 8 ), 7‐isopentenylcryptoechinuline D ( 9 ), 2‐O‐methyl‐9‐dehydroxyeurotinone ( 10 ), emodin ( 11 ), and emodic acid ( 12 ). The structures of the isolated compounds were determined by extensive analysis of their spectroscopic data as well as by comparison with literature reports. Some of the purified compounds were evaluated for antibacterial, antifungal, and cytotoxic activities.     

New phomalone derivatives from the endolichenic fungus Cochliobolus kusanoi in Ny‐Alesund Arctic

Natural products from endolichenic fungi, isolated from different lichen species, have been attracting much attention because of their potential to produce metabolites with activities and/or new structures. The filamentous fungus M227‐2 isolated from lichen in Ny‐Alesund Arctic showed significant anti‐microbial activity and was identified as Cochliobolus kusanoi based on 18S rDNA. Secondary metabolites of M227‐2 were investigated in order to exploit them as lead compounds for new antibiotics. Chemical investigation on M227‐2 led to the isolation of three phomalone derivatives (products 1 – 3) . Their structures were elucidated on the basis of their NMR and MS spectral data. Product 2 was new, whereas products 1 and 3 were isolated for the first time from the species. The biosynthetic pathway is also proposed.     

An endophytic fungus from Trichoderma harzianum SWUKD3.1610 that produces nigranoic acid and its analogues

The objective of this study was to determine whether endophytic fungi, isolated from Kadsura angustifolia produce nigranoic acid and its highly oxygenated derivatives. From the 426 endophytic fungi screened, Trichoderma harzianum SWUKD3.1610 was detected to have a component with the same TLC R _f value and HPLC retention time as authentic nigranoic acid. This component was further confirmed as nigranoic acid by investigating the chemical composition of the fungal extracts. Besides (1), one new triterpenoid, 7β- schinalactone C (2), and two known minor compounds were isolated and characterized by HRESIMS, 1D and 2D NMR spectroscopic methods. Our study indicates that endophytic fungus may play an important role in increasing the quality of the crude drugs from Chinese medicinal plant K. angustifolia. This study is the first to isolate, characterize, and identify schitriterpenes-producing Trichoderma spp.     

Two New Secoanthraquinone Derivatives from the Marine‐Derived Endophytic Fungus Aspergillus wentii EN‐48

Two new secoanthraquinone derivatives, wentiquinones A ( 1 ) and B ( 2 ), together with the eight known compounds 3 – 10 , were isolated from the culture extracts of Aspergillus wentii EN‐48, an endophytic fungus derived from an unidentified marine brown algal species of the genus Sargassum. The structures of these compounds were elucidated on the basis of extensive spectroscopic analysis.     

A New Glycine Derivative and a New Indole Alkaloid from the Fermentation Broth of the Plant Endophytic Fungus Pestalotiopsis podocarpi Isolated from the Chinese Podocarpaceae Plant Podocarpus macrophyllus

A new glycine derivative, podocarpiamide ( 1 ), a new indole alkaloid, 1‐methoxy‐1H‐indol‐3‐ethanol ( 2 ), together with two known compounds, 1‐methoxy‐1H‐indole‐3‐acetic acid ( 3 ) and methyl 1‐methoxy‐1H‐indole‐3‐acetate ( 4 ), were isolated from the fermentation broth of the plant endophytic fungus Pestalotiopsis podocarpi. Their structures were elucidated by extensive spectroscopic analysis including 1D‐ and 2D‐NMR (HSQC, HMBC, and COSY) and MS experiments. Compound 1 has an interesting unusual carbamic acid structure.     

Two new compounds of Penicillium polonicum,an endophytic fungus from Camptotheca acuminata Decne

Abstract

To discover novel structural compounds which are producted by endophytic fungi, a primary chemical profiling of Camptotheca acuminata Decne derived endophytic fungus Penicillum polonicum had been taken. Two new compounds β-lactone polonicin A (1) and enoic acid polonicin B (2) together with seven known compounds 3-9 were isolated from Penicillum polonicum obtained from C. acuminata. The structures of the new compounds 1 and 2 were identified by modern spectrum technology including detailed 1D, 2D NMR and MS data analyses. When tested against HepG2 hepatocellular carcinoma (HCC) cell lines, compounds 4-8 showed moderate anti-HCC activity. In addition, compound 1-3 have effects on increasing GLUT4 translocation and glucose uptake in vitro. Compound 1 showed the strongest glucose uptake and GLUT4 translocation activities in rat skeleton (L6) myoblast cell line with enhancements of 1.8 and 2.1 folds respectively compared to the control.     

Chloropupukeanolides C-E: cytotoxic pupukeanane chlorides with a spiroketal skeleton from Pestalotiopsis fici

Chloropupukeanolides C–E ( 8 – 10 ), three highly functionalized secondary metabolites featuring a novel spiroketal skeleton derived from the chlorinated tricyclo‐[4.3.1.0^{3, 7}]‐decane (pupukeanane) and the 2,6‐dihydroxy‐4‐methylbenzoic acid moieties, were isolated from the scale‐up fermentation extract of the plant endophytic fungus Pestalotiopsis fici. The constitutions of compounds 8 – 10 were elucidated primarily by NMR experiments. Their relative configurations were deduced by analogy to metabolites 4 – 6 , which were previously isolated from the same fungus. The absolute configuration of 8 was assigned by X‐ray crystallography and those of 9 and 10 by quantum‐chemical CD calculations. Biogenetically, chloropupukeanolides C–E ( 8 – 10 ) are presumably derived from the same oxidation‐induced Diels–Alder reaction pathway as compounds 1 and 4 – 7 , via the putative biosynthetic precursors 2 and 3 . The opposite configurations of the complete “Southern parts” of 8 and 9 suggests that this Diels–Alder reaction is stereochemically not very selective. Compounds 8 – 10 showed significant cytotoxicity against a small panel of human tumor cell lines and weak activities against the pathogens of tropical diseases.     

Sesquiterpenes produced by Pestalotiopsis microspora HF 12440 isolated from Artocarpus heterophyllus

Abstract

A drimane-type sesquiterpene, (+)-dendocarbin L (1) together with two bisabolane-type sesquiterpenes, (+)-sydonic acid (2) and (+)-sydowic acid (3) were isolated from the mycelium of Pestalotiopsis microspora HF 12440, an endophytic fungus from the stem of Artocarpus heterophyllus. The structures of all compounds were elucidated using spectroscopic methods and by comparison with the literature. Compound 1 was isolated from the fungi for the first time, compounds 2 and 3 were firstly obtained from this endophytic fungus. Compound 3 showed cytotoxicity (IC₅₀ 2.56?μg/mL) against murine leukemia P-388 cells.     

Biotransformation of ursolic acid by an endophytic fungus from medicinal plant Huperzia serrata

Endophytic fungi were used not only for their producing bioactive products but also for their ability to transform natural compounds. An endophytic fungus, isolated from medicinal plant Huperzia serrata, was identified as Umbelopsis isabellina based on the internal transcribed spacer of ribosomal DNA (rDNA-ITS) region. It was used to transform ursolic acid (1), a pentacyclic triterpene. Incubation of ursolic acid with U. isabellina afforded three products, 3β-hydroxy-urs-11-en-28,13-lactone (2), 3β,7β-dihydroxy-urs-11-en-28,13-lactone (3), 1β,3β-dihydroxy-urs-11-en-28,13-lactone (4). Although product 2 was a known compound, it was first obtained by microbial transformation. Products 3 and 4 were new compounds. The structural elucidation of the three compounds was achieved mainly by the 1D- and 2D-NMR, MS, IR data. The endophytic fungus U. isabellina can hydroxyate the C12-C13 double bond at position 13 of ursolic acid 1 and form a five-member lactone effectively. In the meantime, this fungus can also introduce the hydroxyl group at C-1 or C-7 of ursolic acid 1.     

Nigerasterols A and B,Antiproliferative Sterols from the Mangrove‐Derived Endophytic Fungus Aspergillus niger MA‐132

Two new 6,8(14),22‐hexadehydro‐5α,9α‐epidioxy‐3,15‐dihydroxy sterols, nigerasterols A and B ( 1 and 2 , resp.), together with two known cyclopentapeptides, malformins A₁ and C ( 3 and 4 , resp.), were identified in the culture extract of Aspergillus niger MA‐132, an endophytic fungus isolated from a fresh healthy sample of the mangrove plant Avicennia marina. The structures and relative configurations of these compounds were established on the basis of extensive spectroscopic analyses. The absolute configuration of compound 1 was determined by application of a modified version of Mosher's method. Nigerasterols A and B ( 1 and 2 , resp.) represent the first 5,9‐epidioxy‐sterol compounds of marine origin, and they displayed potent activity against tumor cell lines HL60 and A549 in a preliminary bioassay.     

Structure elucidation of three diphenyl ether derivatives from the mangrove endophytic fungus SBE‐14 from the South China Sea

Two new natural products, tenelate A ( 1 ) and B ( 2 ), together with the known compound, tenellic acid C ( 3 ), were isolated from the mangrove endophytic fungus Talaromyces sp. (SBE‐14), from the South China Sea. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR techniques. Copyright © 2009 John Wiley & Sons, Ltd.     

Withanolide production by fungal endophyte isolated from Withania somnifera

Withanolides, the secondary metabolite from Withania species is used in Ayurvedic medicine and now proved to have potential use in treating cardiovascular, Alzheimer’s disease, etc. Its production in plants varies between genotypes with very low yield. For improved industrial commercialisation, there is a need to increase its production. Endophytic fungi are symbiotically associated with plants and can synthesise the same bioactive compounds and natural products as their host plant. There are no reports available on withanolide-producing (endophytic) fungi. The present study identified an endophytic fungus (Taleromyces pinophilus) from leaves of Withania somnifera which produces withanolides in the medium. The structure of withanolide was confirmed by ¹H NMR, LC-MS analyses and quantified by HPLC analysis. The fungus produces high amount of withanolide when compared to leaf and root of W. somnifera. The fungus can be exploited to produce the withanolide to meet its demand.     

Chemical Constituents of the Endophytic Fungus Phomopsis sp. A240 Isolated from Taxus chinensis var. mairei

A new sesquiterpene, eremophil‐9‐ene‐11,12,13‐triol ( 1 ), a new oxazole, 4‐(2‐hydroxyethyl)‐5‐methyloxazole ( 2 ), and the two known lactones, 5′‐hydroxyalternariol ( 3 ) and alternariol ( 4 ), were isolated from the extract of Phomopsis sp. A240, an endophytic fungus isolated from the bark of Taxus chinensis var. mairei. The structures of the isolated compounds were determined by analyses of their spectroscopic data, as well as by comparison with literature reports. The isolated compounds were evaluated for their cytotoxic and antioxidant activities.     

Sesterterpenes and 2H‐Pyran‐2‐ones (=α‐Pyrones) from the Mangrove‐Derived Endophytic Fungus Fusarium proliferatum MA‐84

Two new tricyclic sesterterpenes, fusaprolifins A and B ( 1 and 2 ), and three new 2H‐pyran‐2‐one derivatives, prolipyrones A – C ( 3 – 5 ), were isolated and characterized from Fusarium proliferatum MA‐84, an endophytic fungus obtained from the fresh tissue of the marine mangrove plant Bruguiera sexangula. In addition, two known sesterterpenes, terpestacin ( 6 ) and fusaproliferin ( 7 ), and one known 2H‐pyran‐2‐one derivative, gibepyrone D ( 8 ), were also identified. The structures of these compounds were elucidated by detailed spectroscopic analyses. Fusaprolifin A ( 1 ) showed moderate activity against brine shrimp (Artemia salina), with a lethality rate of 49.5% at 100 μg/ml, while fusaprolifin B ( 2 ) showed weak activity.     

A new helvolic acid derivative from an endophytic Fusarium sp. of Ficus carica

A new helvolic acid derivative named helvolic acid methyl ester (1), together with two known helvolic acid compounds, helvolic acid (2) and hydrohelvolic acid (3), were isolated from the fermentation of endophytic fungus Fusarium sp. in Ficus carica leaves. Their structures were elucidated and identified by spectroscopic methods. Compounds 1–3 showed potent antifungal and antibacterial activities.     

Oleanane‐Type Triterpenoids from the Endophytic Fungus Pestalotiopsis clavispora Isolated from the Chinese Mangrove Plant Bruguiera sexangula

Three new triterpenoid derivatives, named (15α)‐15‐hydroxysoyasapogenol B ( 1 ), (7β,15α)‐7,15‐dihydroxysoyasapogenol B ( 2 ), and (7β)‐7,29‐dihydroxysoyasapogenol B ( 3 ), were isolated from cultures of the plant endophytic fungus Pestalotiopsis clavispora. Their structures and relative configurations were elucidated by extensive spectroscopic analysis and X‐ray crystallography.     

A New Cyclic Peptide and a New Steroid from the Fungus Penicillium sp. GD6 Isolated from the Mangrove Bruguiera gymnorrhiza

A rare new cyclic tetrapeptide, 5,5′‐epoxy‐MKN‐349A ( 1 ), featured by a MKN‐349A ( 5 ) skeleton and containing an uncommon ether bridge between C(5) and C(5′), and a new steroid, named 11‐O‐acetyl‐NGA0187 ( 2 ), together with two known steroids, 3 and 4 , were isolated from an endophytic fungus Penicillium sp. GD6 associated with the Chinese mangrove Bruguiera gymnorrhiza. The structures of the new compounds were elucidated on the basis of extensive spectroscopic analyses and by comparison with the data of related compounds reported in literature. Neither of the compounds 3 and 4 , isolated in this study, showed obvious bioactivities in the antibacterial bioassay experiments.     

Tuberculariols A – C,New Sesquiterpenes from the Mutant Strain M‐741 of Tubercularia sp. TF5

Three new sesquiterpenes, tuberculariols A–C ( 1 – 3 , resp.), were isolated from the mutant strain M‐741 of Tubercularia sp. TF5, an endophytic fungus of Taxus mairei. Their structures were elucidated by spectroscopic analyses including 1D‐ and 2D‐NMR experiments, and HR‐Q‐TOF‐MS. Antitumor and antibacterial properties of these compounds were evaluated.