Rapid discovery of novel spirobenzylisoquinoline alkaloids from Hypecoum erectum and their hepatoprotective activities.

Spiro-benzylisoquinoline alkaloids (spiroBIAs) have sparked substantial interest due to their unique structures and biological significance. Phytochemical investigations on the whole plants of Hypecoum erectum guided by an integrated non-targeted metabolomics workflow led to the isolation of seven novel spiroBIAs erectumines A-G (1-7), one unusual spiroBIA erectumine H (8), and one rare BIA hypeisoxazole B (9), involving five intriguing skeletal types. Their structures were determined via extensive spectroscopic and spectrometric analyses, X-ray crystallography, and computational methods. Compound 1 features a distinctive spiro [1,2-dihydronaphthalene-isoindolinone] ring system; compounds 2-5 possess an undescribed spiro [2,3-dihydroisoquinoline-1,4-dione-1,2,3,4-tetrahydroisoquinoline] skeleton; compounds 6 and 7 bear a unique spiro [2,3,4,5-tetrahydro-1H-benzo[d]azepin-1-one-1,3-dihydroisobenzofuran] framework; compound 8 possesses an uncommon spiro [benzofuranone-benzazepine] structural architecture, and compound 9 has a diindeno[2,1-c:2',1'-d]isoxazole scaffold. The plausible biosynthetic pathways for 1-8 are proposed. Compound 9 is a potent hepatoprotective agent that exerts synergistic effects by activating TFEB-mediated autophagy and mitochondrial biogenesis.