Cephalodiones A–D: Compound Characterization and Semisynthesis by [6+6] Cycloaddition

Cephalodiones A–D (1–4), the first example of C19‐norditerpenoid dimers, were isolated and fully characterized from a Cephalotaxus plant. These new skeletal natural products shared a unique tricyclo[6.4.1.12,7]tetradeca‐3,5,9,11‐tetraene‐13,14‐dione core that was capped in both ends with rigid multicyclic ring systems either C2‐symmetrically or asymmetrically. Compounds 1–4 were proposed to be biosynthetically produced by the [6+6]‐cycloaddition of two identical C19‐norditerpenoid troponoids, which was validated by the semisyntheses of dimers 2–4. Moreover, some compounds showed significant inhibition on Th17 cell differentiation. Chemical study on a Cephalotaxus plant led to the characterization of four unprecedented C19‐norditerpenoid dimers, named cephalodiones A–D (1–4). These compounds were proposed to be biosynthetically formed through [6+6]‐cycloaddition of two C19‐norditerpenoid troponoids either C2‐symmetrically or asymmetrically, which was validated by the semisyntheses of 2–4. Some compounds showed significant inhibition on Th17 cell differentiation.