Herqupenoid\nA, an Unparalleled Sesquiterpene-Quinone\nHybrid Featuring a Multicyclic Caged 2,7-Dioxatetracyclo[5.4.0.0<sup>4,11</sup>.0<sup>5,9</sup>]Hendecane Fragment from <i>Penicillium\nherquei</i>

Herqupenoid A (<b>1</b>), a sesquiterpene-quinone\nhybrid\nwith an unparalleled 5/5/6/5-fused ring skeleton based on a multicyclic\ncaged 2,7-dioxatetracyclo[5.4.0.0<sup>4,11</sup>.0<sup>5,9</sup>]hendecane\nfragment, was isolated from fungus <i>Penicillium herquei</i>. Its structure was assigned by extensive spectroscopic analyses,\nDP4+ computational method, and single-crystal X-ray diffraction. Further\npharmacology research has established that compound <b>1</b> exhibited significant anti-inflammatory activity via inhibiting\nNF-κB-NLRP3 axis with an IC<sub>50</sub> value of 2.63 μM,\nwhich was stronger than the positive control dexamethasone. A putative\nbiosynthetic pathway involving the key hemiacetal and aldol condensation\nreactions for <b>1</b> was also discussed.