Atractylodimers A-D, unprecedented sesquiterpenoid dimers with cage-like skeletons from Atractylodes macrocephala and their neuroprotective activities

Atractylodimers A-D (1-4), sesquiterpenoid dimers fusing a unique cage-like structure, were isolated from the rhizomes of Atractylodes macrocephala. The most striking feature of these isolates was the highly twisted “cap” structure based on highly twisted five-mebered oxygen heterocyclic rings. Particularly, compound 1 possessed a furo2,3bfuran ring, a caged 3,10-oxa-tricyclo5.2.1.0^4,9decane moiety and 6/6/5/5/5/5/6/6 octocyclic skeleton. Compounds 2-3 featured a spiro-tetrahydrofuran ring, and compound 4 contained a caged spiro-2,5,9-oxa-tricyclo5.2.1.0^4,10decane scaffold for units linkage. Their structures were unambiguously established by spectroscopic methods and X-ray diffraction experiments. Plausible biosynthetic pathways of compounds 1-4 were proposed. Compounds 1 and 2 showed significant neuroprotective effects against serum-deprivation induced PC12 cell damage.