Terpendole C

AsexualEpichloësp. endophytes in association with pasture grasses produce agronomically important alkaloids (e.g., lolitrem B, epoxy-janthitrems, ergovaline, peramine, and lolines) that exhibit toxicity to grazing mammals and/or insect pests. Novel strains are primarily characterised for the presence of these compounds to ensure they are beneficial in an agronomical setting. Previous work identified endophyte strains that exhibit enhanced antifungal activity, which have the potential to improve pasture and turf quality as well as animal welfare through phytopathogen disease control. The contribution of endophyte-derived alkaloids to improving pasture and turf grass disease resistance has not been closely examined. To assess antifungal bioactivity, nineEpichloërelated compounds, namely peramine hemisulfate,n-formylloline-d3,n-acetylloline hydrochloride, lolitrem B, janthitrem A, paxilline, terpendole E, terpendole C, and ergovaline, and fourClaviceps purpureaergot alkaloids, namely ergotamine, ergocornine, ergocryptine, and ergotaminine, were tested at concentrations higher than observed in planta in glasshouse and field settings using in vitro agar well diffusion assays against three common pasture and turf phytopathogens, namelyCeratobasidiumsp.,Drechslerasp., andFusariumsp. Visual characterisation of bioactivity using pathogen growth area, mycelial density, and direction of growth indicated no inhibition of pathogen growth. This was confirmed by statistical analysis. The compounds responsible for antifungal bioactivity ofEpichloëendophytes hence remain unknown and require further investigation.

Structures of terpendoles A, B, C and D, novel acyl-CoA: cholesterol acyltransferase (ACAT) inhibitors, were determined by spectroscopic studies. All terpendoles consist of diterpene and indole moieties in common. Terpendoles A, C and D possess an additional isoprenyl unit via oxygen atom(s) of their diterpene moieties. The relative stereochemistries of terpendoles C and D were confirmed by NOE experiments and X-ray crystallographic analysis.

Indole diterpene alkaloids have been isolated from Ipomoea asarifolia and I. muelleri and are associated with a tremorgenic syndrome in livestock. To better characterize the tremorgenic activity of the major indole diterpene alkaloids in these two plants, terpendole K (1), 6,7-dehydroterpendole A (2), 11-hydroxy-12,13-epoxyterpendole K (3), terpendole C (5), paxilline (6), and a new compound, 6,7-dehydro-11-hydroxy-12,13-epoxyterpendole A (4), were isolated and evaluated for tremorgenic activity in a mouse model. Compounds 1, 2, 5, and 6 all showed similar and significant signs of tremorgenic activity. In contrast, the 11-hydroxy-12,13-epoxy compounds, 3 and 4, showed no significant tremorgenic activity.