Inubritantrimers A–D: Trimerized Sesquiterpenoid [4 + 2] Adducts Featuring a Distinctive Spiro-Polycyclic Scaffold from <i>Inula britannica</i>

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 IC50 values in the range of 5.84–12.01 μM.