Protoilludane, Illudalane, and Botryane Sesquiterpenoids from the Endophytic Fungus Phomopsis sp TJ507A

To explore the chemical diversity of metabolites from endophytic fungi, the strain Phomopsis sp. TJ507A, isolated from the medicinal plant Phyllanthus glaucus, was investigated. A 2,3-seco-protoilludane-type sesquiterpenoid (1), eight protoilludane-type sesquiterpenoids (2-9), four illudalane-type sesquiterpenoids (10a/10b, 11, and 12), and a botryane-type sesquiterpenoid (13) in addition to seven known sesquiterpenoids (14-20) were identified from the liquid culture of the fungus. Structures of the isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, a modified Mosher analysis, electronic circular dichroism (ECD) calculations, and [Rh-2(OCOCF3)(4)]-induced ECD spectra as well as X-ray crystallographic analyses. Compound 1 represents the first example of a naturally occurring sesquiterpenoid containing the unusual 2,3-seco-protoilludane scaffold. Compounds 1 (p < 0.001); 2-6, 15, and 18 (p < 0.01); and 7, 9, and 20 (p < 0.05) displayed beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities ranging from 19.4% to 43.8% at the concentration of 40 mu M. LY2811376 was used as the positive control with an inhibitory activity of 38.6% (p < 0.01). Furthermore, none of these compounds showed obvious hepatotoxicity at concentration of 40 mu M.