Gulypyrones A and B and Phomentrioloxins B and C Produced by <i>Diaporthe gulyae</i>, a Potential Mycoherbicide for Saffron Thistle (<i>Carthamus lanatus</i>)

A virulent strain of <i>Diaporthe gulyae</i>, isolated from stem cankers of sunflower and known to be pathogenic to saffron thistle, has been shown to produce both known and previously undescribed metabolites when grown in either static liquid culture or a bioreactor. Together with phomentrioloxin, a phytotoxic geranylcyclohexenetriol recently isolated from a strain of <i>Phomopsis</i> sp., two new phytotoxic trisubstituted α-pyrones, named gulypyrones A and B (<b>1</b> and <b>2</b>), and two new 1,<i>O</i>- and 2,<i>O</i>-dehydro derivatives of phomentrioloxin, named phomentrioloxins B and C (<b>3</b> and <b>4</b>), were isolated from the liquid culture filtrates of <i>D. gulyae</i>. These four metabolites were characterized as 6-[(2<i>S</i>)­2-hydroxy-1-methylpropyl]-4-methoxy-5-methylpyran-2-one (<b>1</b>), 6-[(1<i>E</i>)-3-hydroxy-1-methylpropenyl]-4-methoxy-3-methylpyran-2-one (<b>2</b>), 4,6-dihydroxy-5-methoxy-2-(7-methyl-3-methylene­oct-6-en-1-ynyl)­cyclohex-2-enone (<b>3</b>), and 2,5-dihydroxy-6-methoxy-3-(7-methyl-3-methylene­oct-6-en-1-ynyl)­cyclohex-3-enone (<b>4</b>) using spectroscopic and chemical methods. The absolute configuration of the hydroxylated secondary carbon of the 2-hydroxy-1-methylpropyl side chain at C-6 of gulypyrone A was determined as <i>S</i> by applying a modified Mosher’s method. Other well-known metabolites were also isolated including 3-nitropropionic, succinic, and <i>p</i>-hydroxy- and <i>p</i>-methylbenzoic acids, <i>p</i>-hydroxybenzaldehyde, and nectriapyrone. When assayed using a 5 mM concentration on punctured leaf disks of weedy and crop plants, apart from 3-nitropropionic acid (the main metabolite responsible for the strong phytotoxicity of the culture filtrate), phomentrioloxin B caused small, but clear, necrotic spots on a number of plant species, whereas gulypyrone A caused leaf necrosis on <i>Helianthus annuus</i> plantlets. All other compounds were weakly active or inactive

Higginsianins A and B, Two Diterpenoid α‑Pyrones Produced by <i>Colletotrichum higginsianum</i>, with <i>in Vitro</i> Cytostatic Activity

Two new diterpenoid α-pyrones, named higginsianins A (<b>1</b>) and B (<b>2</b>), were isolated from the mycelium of the fungus <i>Colletotrichum higginsianum</i> grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)­dodecahydro­naphtho­[2,1-<i>b</i>]­furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)­decahydro­naphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (<b>1</b>) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (<b>2</b>), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. <b>1</b> and <b>2</b> were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of <b>1</b> and <b>2</b> for antiproliferative activity against a panel of six cancer cell lines revealed that the IC₅₀ values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 μM). Finally, three hemisynthetic derivatives of <b>1</b> were prepared and evaluated for antiproliferative activity. Two of these possessed IC₅₀ values and differential sensitivity profiles similar to those of <b>1</b>

Higginsianins A and B, Two Diterpenoid α‑Pyrones Produced by <i>Colletotrichum higginsianum</i>, with <i>in Vitro</i> Cytostatic Activity

Two new diterpenoid α-pyrones, named higginsianins A (<b>1</b>) and B (<b>2</b>), were isolated from the mycelium of the fungus <i>Colletotrichum higginsianum</i> grown in liquid culture. They were characterized as 3-[5a,9b-dimethyl-7-methylene-2-(2-methylpropenyl)­dodecahydro­naphtho­[2,1-<i>b</i>]­furan-6-ylmethyl]-4-hydroxy-5,6-dimethylpyran-2-one and 4-hydroxy-3-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)­decahydro­naphthalen-1-ylmethyl]-5,6-dimethylpyran-2-one, respectively, by using NMR, HRESIMS, and chemical methods. The structure and relative configuration of higginsianin A (<b>1</b>) were confirmed by X-ray diffractometric analysis, while its absolute configuration was assigned by electronic circular dichroism (ECD) experiments and calculations using a solid-state ECD/TDDFT method. The relative and absolute configuration of higginsianin B (<b>2</b>), which did not afford crystals suitable for X-ray analysis, were determined by NMR analysis and by ECD in comparison with higginsianin A. <b>1</b> and <b>2</b> were the C-8 epimers of subglutinol A and diterpenoid BR-050, respectively. The evaluation of <b>1</b> and <b>2</b> for antiproliferative activity against a panel of six cancer cell lines revealed that the IC₅₀ values, obtained with cells reported to be sensitive to pro-apoptotic stimuli, are by more than 1 order of magnitude lower than their apoptosis-resistant counterparts (1 vs >80 μM). Finally, three hemisynthetic derivatives of <b>1</b> were prepared and evaluated for antiproliferative activity. Two of these possessed IC₅₀ values and differential sensitivity profiles similar to those of <b>1</b>