Inubritantrimers A-D: Trimerized Sesquiterpenoid [4 + 2] Adducts Featuring a Distinctive Spiro-Polycyclic Scaffold from Inula britannica .

Inubritantrimer A ( 1 ), a trace trimerized sesquiterpenoid [4 + 2] adduct featuring an unusual exo - exo type spiro-polycyclic scaffold, together with three new endo - exo [4 + 2] adducts, inubritantrimers B-D ( 2 - 4 ), were discovered from the flowers of Inula britannica . Their structures were elucidated using 1D/2D NMR, X-ray diffraction, and ECD approaches. 1 is characterized as a novel exo - exo trimer, synthesized biogenetically from three sesquiterpenoid monomers, featuring a unique linkage of C-11/C-1', C-13/C-3' and C-13'/C-3″, C-11'/C-1″ through a two-step exo [4 + 2] cycloaddition process. Compounds 1 - 4 exhibited modest cytotoxicity against breast cancer cells with IC 50 values in the range of 5.84-12.01 μM.