A total synthesis of the aglycone of IB-00208 was accomplished in 22 steps using a newly developed approach towards polycyclic 1,4-dioxygenated xanthones from benzocyclobutenones. The generality of this entry to xanthones was initially established on several model systems before it was successfully applied to the construction of the hexacyclic core of the natural product. A new and potentially general approach towards angularly-fused benzocyclobutenones using ring-closing metathesis (RCM) was also developed.
Keywords: Moore rearrangement; cyclobutenediones; natural products; polycyclic xanthones; total synthesis.