Studies of the genome-sequenced, flutimide-producing coprophilous fungus Delitschia confertaspora (ATCC 74209), originally obtained from a sample of rock hyrax (Procavia capensis) dung collected in Namibia, led to the discovery of three new highly aromatic natural products named delicoferones A–B (1–2) and fimetarone B (3). The new benzophenone derivatives 1 and 2 have a somewhat unusual skeleton that incorporates three aromatic rings linked via two ketone carbonyl groups, while 3 contains a spiro[chroman-3,7′-isochromene]-4,6′(8′H) skeleton reported only once previously. The structures of these compounds were assigned mainly by analysis of 2D NMR and HRESITOFMS data.

Glucocorticoid (GC) release into the environment has led to widespread detection of glucocorticoid receptor (GR) activity in water resources that has been shown to persist throughout conventional and some advanced wastewater treatment processes. Here, we used high performance liquid chromatography, high resolution mass spectrometry and nuclear magnetic resonance spectroscopy to explore the reaction of natural (cortisone, cortisol) and synthetic (prednisone, prednisolone, dexamethasone) GCs with free chlorine (HOCl) to simulate their fate during chemical disinfection of water and wastewater. Generally, GCs react slowly (t1/2 ∼ 7–200 h) with HOCl when compared to other steroid classes, but they yield complex mixtures of transformation products, with at times the majority of product mass comprising structurally identifiable and likely bioactive steroids. For example, we frequently observed chlorination at the C-9 position (e.g., 9-chloro-prednisone), a reaction known to increase GC activity 4-fold. We also identified reaction products in the adrenosterone family of androgens produced via cleavage of the C-17 side-chain on many GCs. Another common transformation pathway was the conversion of endogenous GCs to their more potent synthetic analogs via oxidation at the C-1/C-2 positions, with unsaturation reported to increase GR activity 4-fold (e.g., cortisol to prednisolone). Despite identification of such products, in vitro assays generally suggest GR activity decreases with extent of parent decay during chlorination. Cortisol was the exception, with GR activity only decreasing 2-fold in product mixtures (based on measured EC50 values) despite a 95% reduction in parent concentration, a result attributable to formation of the more potent prednisolone during chlorination. Furthermore, our assay likely underestimates product bioactivity as it did not account for the activity of several identified GC byproducts that first require in vivo activation via C-11 reduction, nor did it consider androgen receptor (AR) activity associated with byproducts from the adrenosterone family. To avoid formation of product mixtures with conserved bioactivity, advanced chemical oxidation processes may represent a more promising approach; we show that GCs react much more rapidly with ozone (t1/2 ∼ 0.4–1.3 min) and produce no observable UV-active products. This suggests disruption of the GC conjugated π-electron and ring systems, thereby likely mitigating biological activity.

Seven new polyketide metabolites (disseminins A–E, 1–5, and spiciferones D and E, 7 and 8) were obtained from cultures of a fungicolous isolate of Pestalotiopsis disseminata (NRRL 62562), together with a related compound (6) previously known only as a semisynthetic product. Structures were determined mainly by analysis of HRMS and NMR data. Biogenetically related compounds 1 and 2 possess uncommon bis-tetrahydrofuran and dioxabicyclo[3.2.1]octane ring systems, respectively. X-ray crystallographic analysis of the p-bromobenzoate derivative of 1 confirmed the structure and enabled assignment of its absolute configuration.

•Two fungicolous isolates of the fungal genus Pestalotiopsis were investigated.•Seven new punctaporonins (caryophyllene-derived sesquiterpenoids) were identified.•One of the isolates was identified as Pestalotiopsis disseminata.•The structures were assigned primarily by NMR and MS analysis.•Results include the first punctaporonins to bear substitution at the 13-position.Seven new caryophyllene sesquiterpenoids (5–11) were isolated during investigation of two fungicolous isolates of Pestalotiopsis sp. and identified as punctaporonin analogues. The structures of these compounds were mainly assigned by analysis of NMR and HRMS data. Compounds 5, 6, and 7 are 13-hydroxy analogues of 6-hydroxypunctaporonins A, B, and E, respectively, and compound 8 is a 6-hydroxy analogue of punctaporonin D. Compounds 9 and 11 are ketone-containing analogues of 6-hydroxypunctaporonin A and fuscoatrol A, respectively, and compound 10 is a 9-methoxy derivative of 8. The names punctaporonins N, O, and P are proposed for compounds 9, 10, and 11, respectively. Antibacterial activity associated with the extract was attributed to the presence of known punctaporonins as major metabolites.

Three amino acid-derived compounds, haenamindole (1) and 2'-epi-fumiquinazolines C (2) and D (3), were isolated from cultures of a fungicolous isolate of Penicillium lanosum (MYC-1813=NRRL 66231). Compound 1 was also encountered in cultures of P. corylophilum (MYC-418=NRRL 28126). Structure elucidation of these metabolites was based mainly on high resolution mass spectrometry and NMR data analysis. Haenamindole (1) was found to be a recently reported diketopiperazine-type metabolite that incorporates an unusual β-Phe unit. Analysis of X-ray crystallographic data and the products of acid hydrolysis of 1 enabled a conclusive, slightly modified stereochemical assignment for haenamindole. Fumiquinazoline analog 2 is a new natural product, while related compound 3 has been previously reported only as a product of an in vitro enzymatic step and of a genetically engineered fungal culture. Compounds 1 and 3 showed antiinsectan activity against the fall armyworm Spodoptera frugiperda.

Three new sesquiterpenoids (pestaloporonins A–C; 1–3) related to the caryophyllene-derived punctaporonins were isolated from cultures of a fungicolous isolate of Pestalotiopsis sp. The structures of 1–3 were determined by analysis of NMR and HRMS data, and the structure of 1, including its absolute configuration, was confirmed by X-ray crystallographic analysis. Compounds 1 and 2 contain new bicyclic and tricyclic ring systems, respectively.

Studies of the coprophilous fungus Hypocopra rostrata (TTI-0009, NRRL 66178) isolated from a sample of horse dung collected in Texas led to the isolation of three new sesquiterpenoids that we named hypocoprins A–C (1–3), together with the known fungal metabolite helvolic acid. The new metabolites have a distinctive ring system consisting of fused cyclopropane and cyclodecene units not previously reported from a fungal source. Compounds 1 and 3 moderately inhibited growth of Staphylococcus aureus. The structures of these metabolites were assigned mainly by analysis of 2D NMR and HRESITOFMS data. Relative and absolute configurations were assigned by interpretation of NMR J-values and NOESY data and by application of Mosher’s method. These results represent the first report of chemistry from any strain of the genus Hypocopra.

Seven new compounds (aflaquinolones A–G; 1–7) containing dihydroquinolin-2-one and terpenoid units have been isolated from two different fungal sources. Two of these metabolites (1 and 2) were obtained from a Hawaiian fungicolous isolate of Aspergillus sp. (section Flavipedes; MYC-2048 = NRRL 58570), while the others were obtained from a marine Aspergillus isolate (SF-5044) collected in Korea. The structures of these compounds were determined mainly by analysis of NMR and MS data. Relative and absolute configurations were assigned on the basis of NOESY data and 1H NMR J-values, comparison of calculated and experimental ECD spectra, and analysis of a Mosher’s ester derivative of 2. Several known compounds, including alantrypinone, aspochalasins I and J, methyl 3,4,5-trimethoxy-2((2-((3-pyridinylcarbonyl)amino)benzoyl)amino)benzoate, and trans-dehydrocurvularin were also encountered in the extract of the Hawaiian isolate.

Phomalevones A−C (1−3), three new com-pounds with bis-dihydroxanthone and bis-benzophenone systems, were isolated from cultures of a Hawaiian isolate of Phoma sp. (MYC-1734 = NRRL 39060; Cucurbitariaceae). The structures of 1−3 were determined by analysis of NMR and MS data. The absolute configurations of the sp3 stereocenters in the monomeric unit of 1 were assigned by application of Mosher's method, and overall absolute configurations were proposed on the basis of ECD data using both computational methods and comparisons with literature data for model compounds. All three compounds showed antibacterial activity, and compounds 2 and 3 also exhibited antifungal effects.

Hymenopsin A (1), hymenopsin B (2), and a new macrophorin analogue, 2′,3′-epoxy-13-hydroxy-4′-oxomacrophorin A (3), have been isolated from a fungicolous isolate of Hymenopsis sp. (MYC-1703; NRRL 37638). The structures and relative configurations of these compounds were assigned on the basis of 2D NMR and MS data, and the identity of 1 was confirmed by X-ray crystallographic analysis. The absolute configuration of 2 was proposed on the basis of CD analysis using both empirical and computational methods. Compounds 2 and 3 showed antibacterial activity against Staphylococcus aureus and Bacillus subtilis. Compound 3 was also active against Aspergillus flavus and Fusarium verticillioides.

Four new decarestrictine analogues (botryolides A−D; 1–4), a biosynthetically related γ-lactone (botryolide E; 5), and the known compounds decarestrictine D (6) and sterigmatocystin have been isolated from cultures of a fungicolous isolate of Botryotrichum sp. (NRRL 38180). The structures of these compounds were determined by analysis of 2D NMR and ESIMS data. The relative configurations of 1–5 were established on the basis of NMR data and/or X-ray diffraction analysis, while the absolute configuration of 1 was assigned using the modified Mosher method.

Cultures of a fungicolous isolate of Sporormiella minimoides afforded two new polyketide metabolites which we have named sporminarins A (1) and B (2). The planar structures of 1 and 2 were elucidated by analysis of NMR and MS data, and by chemical methods. 1 exhibited significant antifungal activity against Aspergillus flavus.

Glucocorticoid (GC) release into the environment has led to widespread detection of glucocorticoid receptor (GR) activity in water resources that has been shown to persist throughout conventional and some advanced wastewater treatment processes. Here, we used high performance liquid chromatography, high resolution mass spectrometry and nuclear magnetic resonance spectroscopy to explore the reaction of natural (cortisone, cortisol) and synthetic (prednisone, prednisolone, dexamethasone) GCs with free chlorine (HOCl) to simulate their fate during chemical disinfection of water and wastewater. Generally, GCs react slowly (t1/2 ∼ 7–200 h) with HOCl when compared to other steroid classes, but they yield complex mixtures of transformation products, with at times the majority of product mass comprising structurally identifiable and likely bioactive steroids. For example, we frequently observed chlorination at the C-9 position (e.g., 9-chloro-prednisone), a reaction known to increase GC activity 4-fold. We also identified reaction products in the adrenosterone family of androgens produced via cleavage of the C-17 side-chain on many GCs. Another common transformation pathway was the conversion of endogenous GCs to their more potent synthetic analogs via oxidation at the C-1/C-2 positions, with unsaturation reported to increase GR activity 4-fold (e.g., cortisol to prednisolone). Despite identification of such products, in vitro assays generally suggest GR activity decreases with extent of parent decay during chlorination. Cortisol was the exception, with GR activity only decreasing 2-fold in product mixtures (based on measured EC50 values) despite a 95% reduction in parent concentration, a result attributable to formation of the more potent prednisolone during chlorination. Furthermore, our assay likely underestimates product bioactivity as it did not account for the activity of several identified GC byproducts that first require in vivo activation via C-11 reduction, nor did it consider androgen receptor (AR) activity associated with byproducts from the adrenosterone family. To avoid formation of product mixtures with conserved bioactivity, advanced chemical oxidation processes may represent a more promising approach; we show that GCs react much more rapidly with ozone (t1/2 ∼ 0.4–1.3 min) and produce no observable UV-active products. This suggests disruption of the GC conjugated π-electron and ring systems, thereby likely mitigating biological activity.