Cinnamigones A–C, three highly oxidized guaiane-type sesquiterpenes with neuroprotective activity from Cinnamomum migao

Cinnamigones A–C, three undescribed highly oxidized guaiane-type sesquiterpenes were isolated from the fruits of Cinnamomum migao. Cinnamigone A (1), structurally artemisinin-like, is a natural 1,2,4-trioxane caged endoperoxide with an unprecedented tetracyclic 6/6/7/5 ring system. Compounds 2–3 are classic guaiane sesquiterpene featuring different epoxy units. Guaiol (4) is considered to be the precursor of 1–3 in the biosynthesis pathway hypothesis. The planar structures and configurations of cinnamigones A–C were elucidated by spectral analysis, HRESIMS, X-ray crystallography and ECD calculations. Evaluation of the neuroprotective activity of 1–3 on N-methyl-ᴅaspartate (NMDA) toxicity was demonstrated that compounds 1–2 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity.