Stelleroids A-C, Three Rearranged Guaiane Sesquiterpenoids with Caged Ring Systems from Stellera chamaejasme.

Three highly modified sesquiterpenoids, stelleroids A-C (1-3, respectively), were isolated from the roots of Stellera chamaejasme. Biosynthetically, these molecules are derived from the 5/7-fused bicyclic guaiane, involving a series of skeletal rearrangements, leading to the formation of an adamantane-like 12-oxa-tetracyclo[6.2.1.13,10.03,7]dodecane scaffold for 1, a tricyclo[6.2.1.02,6]undecane backbone for 2, and a tetracyclo[6.2.2.01,7.05,11]dodecane backbone for 3. The structures of 1-3 were elucidated through a combination of HR-ESI-MS, NMR, quantum chemical calculations, and X-ray diffraction. In the bioassay, compound 1 was identified as the most potent antipulmonary fibrosis lead structure because it significantly inhibited fibroblast proliferation and migration while downregulating the expression of fibrotic markers such as COL1A1 and α-SMA.