Cyathstrines A–K, Structurally Diverse Polycyclic Polyoxygenated Cyathane Diterpenoid Xylosides with Antibacterial and Neuroprotective Activities from the Fungus <i>Cyathus striatus</i>

A chemical investigation of the basidiomycete <i>Cyathus striatus</i> led to the isolation of 17 polyoxygenated cyathane diterpenoid xylosides, cyathstrines A-K (<b>1</b>-<b>17</b>), including 11 new ones sharing five distinct ring skeletons, two sesquiterpenoids (<b>18</b> and <b>19</b>), and two lupane triterpenoids (<b>20</b> and <b>21</b>), as well as three sterols (<b>22</b>-<b>24</b>), based on the OSMAC (One Strain-Many Compounds) strategy. Among them, compound <b>5</b> represents the first example of cyathane diterpenoids with an undescribed 5/6/7/6/5/6/6-fused ring skeleton incorporating an extra 2<i>H</i>-pyran moiety, and compound <b>7</b> bears an unconventional 9/7/6/5/6-fused pentacyclic ring skeleton. The structures of these compounds were elucidated by means of NMR spectroscopic analyses, HRESIMS and ECD calculations. Compounds <b>7</b> and <b>9</b> exhibited moderate antibacterial effects against six human pathogenic bacteria, with MIC values ranging from 8 to 32 μg/mL. Meanwhile, compound <b>8</b> showed significant neuroprotective activity at 20 μM, with cell viability improved to 82.4% from the MPP⁺-treated cell viability of 51.20%, which was comparable to the positive control. Additionally, compounds <b>3</b>, <b>13</b>, <b>15</b>, and <b>17</b> demonstrated notable neuroprotective effects, with cell viabilities of more than 70%. These findings expanded the chemical space of cyathane diterpenoids and provided the new template molecules for the development of anti-infective and neuroprotective drugs.