Aculeatones A and B, epimeric lovastatin derivatives with a 6/6/3-tricyclic carbon skeleton from Aspergillus aculeatus and their chemical transformation

Lovastatin and its derivatives are well-known as a class of lipid-lowering drugs in the medicinal chemistry of natural products, and they typically feature a rigid decalin core structure with almost no other carbon rings. Herein, aculeatones A (1) and B (2), two highly modified lovastatin derivatives with an unreported 6/6/3-tricyclic carbon skeleton, in addition to four undescribed lovastatin derivatives aculeatones C-F (3-6), were isolated from the fungus Aspergillus aculeatus. Their structures with absolute configurations were characterized by comprehensive spectroscopic, quantum chemical calculation, electronic circular dichroism (ECD), modified Mosher's method, and single-crystal X-ray diffraction studies. The plausible biosynthetic pathway for 1 and 2 was proposed, and the biomimetic formation of 1 was achieved starting from 3. Biologically, compounds 3, 5, and 6 significantly inhibited the accumulation of lipid in an oleic acid-treated HepG2 cell model.