An enantioselective and diastereoselective approach toward the synthesis of the polycyclic norditerpenoid ineleganolide is presented. A palladium-catalyzed enantioselective allylic alkylation is employed to stereoselectively construct the requisite chiral tertiary alcohol. Careful substrate design enabled the convergent assembly of the ineleganolide [6,7,5,5]-tetracyclic scaffold by a diastereoselective cyclopropanation-Cope rearrangement cascade under unusually mild conditions. This work represents the first successful synthesis of the core structure of any member of the furanobutenolide-derived polycyclic norcembranoid diterpene family of natural products. Advanced synthetic manipulations generated a series of natural product-like compounds that were shown to possess selective secretory antagonism of either interleukin-5 or interleukin-17.

Enantioselective, convergent synthesis of the ineleganolide core by a tandem annulation cascade

253rd National Meeting (2017)

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