| This dissertation presents a full account of studies toward the total synthesis of the polyketide natural product, (-)-kendomycin. The synthetic literature on kendomycin is reviewed. First and second generation approaches that both culminated in formal total syntheses are detailed. Prins cyclization methodology was developed in the first generation approach as a highly convergent means to assemble the fully substituted C-aryl tetrahydropyran of kendomycin. After securing a formal synthesis, this success formed the foundation of an efficient second generation approach, in which a Prins cyclization was designed to close the complex tetrahydropyran ring and 16-membered macrocycle of kendomycin in a single step. Combined with the development of the powerful Duff formylation and Hoffmann dimethallylation methods, this unprecedented Prins-mediated macrocyclization strategy generated a known, complex macrocycle in 18 linear steps and 6.2% overall yield from economically available starting materials. |
