Lignan-phloroglucinol hybrids with an unprecedented beadlike core from the leaves of Melicope chunii

(±)-Melichuniiones A and B (1 and 2), two novel enantiomeric pairs of lignan-phloroglucinol hybrids with an unprecedented beadlike core were isolated from the leaves of Melicope chunii, together with new analogues 3-6. Compounds 1 and 2 possess a unique dispiro [furan-2,5'-cyclopenta[b]furan-2',3''-furan] 5/5/5/5 tetracyclic skeleton. Their structures were established by extensive spectroscopic analyses, single crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound 2 significantly reduces GPX4 levels, leading to the accumulation of lipid reactive oxygen species (lipid ROS) in HT-1080 cells, suggesting its potential to induce ferroptosis for anti-tumor activity.