Dysidavarone A presents a structurally unique, but scarce marine natural product that was very recently isolated from the sponge Dysidea avara.The 3D architecture of this quinone sesquiterpene is characterized by an unprecedented, challenging tetracyclic core that is presumably derived from a rearranged drimane skeleton.Based on a convergent approach, the first total synthesis of Dysidavarone A was achieved in a highly concise route in 10 steps (longest linear sequence) with a total yield of 11%, which unequivocally confirms the unique 3D structure of this class of quinone sesquiterpenes. Key transformations of the concise synthesis include a stereoselective reductive alkylation of a Wieland-Miescher type ketone under Birch conditions and an advantageous a-arylation of a highly hindered elaborate ketone using the Buchwald ligand. The route enabled access to sufficient material for further biological evaluation of this scarce metabolite, revealing potent antibacterial and antiproliferative activities by specifically changing the morphology of treated cells. Present studies are now directed to further analyse and potentially use this promising biological potency.

First total synthesis of Dysidavarone A via an intramolecular palladium-catalyzed a-arylation

248th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.