The Total Synthesis of (+)-Ineleganolide, the Lycojapomine Alkaloids, and a New Strategy for Radical Deoxygenation

Organic chemistry is an enabling science, that has given scientist the ability to construct and manipulate small molecules. The relationship that bridges the classic study of chemical reactivity and synthesis at the molecular level with the broader field of the life sciences continues to flourish and has expanded its impact tremendously. The study of complex, bioactive small molecules, their synthesis, and the development of new reactions has laid the foundation for many of these advancements to build upon. The contents of this thesis contribute to this goal and hope to be of use for future generations and the development of the field. The first chapter describes the total synthesis of the furanobutenolide-derived norcembranoid diterpenoid ineleganolide, a secondary metabolite produced by sinularia soft corals. Displaying cytotoxic bioactivity, the chemical structure has intrigued chemists for several decades. We describe a successful synthesis of the natural product in 14 steps, enabled by several unique cascade reactions. The second chapter details the total synthesis of Lycojapomine A and B, two members of the lycopodium alkaloids. To achieve a practical and concise synthetic route, we developed a photoreaction for the stepwise dearomatization of a pyrrole heterocycle. Building off the simple and easily accessible starting material, we can synthesize each of the complex target molecule in 13 steps. Inspired by the previously utilized photochemistry, the third chapter details a new catalytic method for the generation of alkyl radicals directly from alcohols. We achieved this transformation by photo irradiation of a titanium porphyrin catalyst and showcase its ability to deoxygenate several different alcohols, by generation of the carbon-centered radical.