Discovery of Bergamotanes against Hepatic Ischemia–Reperfusion Injury Based on DeepSAT Technology from <i>Paraconiothyrium</i> sp. H–B

Hepatic ischemia-reperfusion injury (HIRI) is a common and inevitable complication of liver surgery that induces severe hepatic functional impairment and can trigger multiple organ dysfunction syndrome. From the rice culture of <i>Paraconiothyrium</i> sp. H-B collected from <i>Hypericum wilsonii</i> N. Robson, 11 novel bergamotane-type sesquiterpenoids, paramotanes A-K (<b>1</b>-<b>11</b>), along with three known congeners, were obtained by the guidance of the DeepSAT system (a neural network-based tool for HSQC spectrum analysis). The structures and configurations of these compounds were confirmed <i>via</i> spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Notably, compound <b>1</b> is the first reported 10-<i>nor</i>-bergamotane sesquiterpenoid. The pharmacodynamics assays demonstrated that compound <b>12</b> exhibits hepatoprotective effects and can ameliorate liver function in HIRI mice, positioning it as a promising leading compound for developing novel hepatoprotective agents for the clinical management of HIRI.