Discovery of Bergamotanes against Hepatic Ischemia–Reperfusion Injury Based on DeepSAT Technology from Paraconiothyrium 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 Paraconiothyrium sp. H-B collected from Hypericum wilsonii N. Robson, 11 novel bergamotane-type sesquiterpenoids, paramotanes A-K (1-11), 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 via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Notably, compound 1 is the first reported 10-nor-bergamotane sesquiterpenoid. The pharmacodynamics assays demonstrated that compound 12 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.