Progress Towards an Expedient Synthesis of the Core of Dihydro-β-agarofuran Natural Products

Dihydro-β-agarofurans are a class of polyester sesquiterpene secondary metabolites isolated from the Celastraceae plant family. Many compounds in this class have demonstrated biological activity and have therefore generated much synthetic interest. However, their trans-decalin/tetrahydrofuranyl ring system and high levels of oxidation make them synthetically challenging. The first chapter presents a discussion on the biological activity and various historical methods used to construct this ring system. The second chapter describes the new dearomative oxidation/cyclization method developed by our group to rapidly synthesize the tricyclic ring system in only 9 steps from commercially available 6-methoxy-1-tetralone. Other key steps include a MHAT reduction of a b,b-disubstituted dienone, stereospecific reduction of an enone, and hydroxyl-directed Simmons-Smith cyclopropanation. The large-scale synthesis of these advanced synthetic intermediates and the attempted elaboration to the dihydro-β-agarofuran core is described in detail.