Total synthesis of dysidiolide and cacospongionolide F: A general approach to the synthesis of labadane, isolabadane and clerodane polyterpenes

This thesis details the total synthesis of the anti-cancer natural product dysidiolide and the first total synthesis of the anti-inflammatory natural product cacospongionolide F. In addition, it describes the syntheses of the core structures of the parent cacospongionolide and cacospongionolide E as well as synthetic studies towards the cytotoxic agent dysidotronic acid and cyclolinteinone.; The above mentioned natural products, with the exception of cyclolinteinone, are terpenoids that share a hydrophobic bicyclic decalin core. This investigation has established a general synthetic route for their preparation and its utility was demonstrated by the total syntheses of the sesterterpenes dysidiolide and cacospongionolide F. The divergency of the synthetic route was demonstrated by the preparation of the clerodane cores of cacospongionolide E and cacospongionolide.; The syntheses described herein are characterized by highly diastereoselective relay of transformations that take full advantage of the conformations of synthetic intermediates and demonstrate efficient amplification of chiral information. This approach has enabled the divergent syntheses of the natural products form a novel bicyclic enone template, which is developed as an alternate to the Wieland-Miescher ketone for the preparation of the isolabadane skeletal class.