Protoilludane, Illudalane, and Botryane Sesquiterpenoids from the Endophytic Fungus <i>Phomopsis</i> sp. TJ507A

To explore the chemical diversity of metabolites from endophytic fungi, the strain <i>Phomopsis</i> sp. TJ507A, isolated from the medicinal plant <i>Phyllanthus glaucus</i>, was investigated. A 2,3-<i>seco</i>-protoilludane-type sesquiterpenoid (<b>1</b>), eight protoilludane-type sesquiterpenoids (<b>2</b>–<b>9</b>), four illudalane-type sesquiterpenoids (<b>10a</b>/<b>10b</b>, <b>11</b>, and <b>12</b>), and a botryane-type sesquiterpenoid (<b>13</b>) in addition to seven known sesquiterpenoids (<b>14</b>–<b>20</b>) 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 [Rh₂(OCOCF₃)₄]-induced ECD spectra as well as X-ray crystallographic analyses. Compound <b>1</b> represents the first example of a naturally occurring sesquiterpenoid containing the unusual 2,3-<i>seco</i>-protoilludane scaffold. Compounds <b>1</b> (<i>p</i> < 0.001); <b>2</b>–<b>6</b>, <b>15</b>, and <b>18</b> (<i>p</i> < 0.01); and <b>7</b>, <b>9</b>, and <b>20</b> (<i>p</i> < 0.05) displayed β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities ranging from 19.4% to 43.8% at the concentration of 40 μM. LY2811376 was used as the positive control with an inhibitory activity of 38.6% (<i>p</i> < 0.01). Furthermore, none of these compounds showed obvious hepatotoxicity at concentration of 40 μM