Photoassisted Synthesis of Complex Molecular Motifs

The use of photochemistry in organic synthesis has enable chemists to build structural complexity into molecules that is either difficult or impossible to achieve using traditional thermal methods. Using light as a reagent is a desirable, cost-effective, and green tactic for constructing molecules, and is an attractive alternative to expensive catalysts or harsh reaction conditions. Over the years, our lab has developed several methods that exploit the synthetic utility of photochemistry in complex molecule synthesis. Chapter 1: The ophiobolins are naturally sesterterpenes that contain a 5-8-5 fused carbocyclic core. Many of these molecules have been shown to possess potent and interesting biological activities, making them attractive targets for synthetic organic chemists. There have been many synthetic efforts and approaches towards these natural products, however, only four total syntheses are reported to date. Ophiobolin A, the first isolated and reported ophiobolin, is especially of interest to both chemists and biochemists due to its potent anti-cancer activity. In recent studies, the primary biological mechanism of action for this sesterterpene was reported and has sparked an interest in the scientific community in synthesizing ophiobolin derivatives to gain better insight into their biological activities and structure-activity relationships. Chapter 2: Our group has developed a method that utilizes a tandem diastereoselective photochemical [2+2] cycloaddition and Cope rearrangement to access complex, functionalized 5-8-5 fused ring systems. Rapid and modular access into this class of molecules can enable future efforts for synthetic endeavors into natural products containing this carbocyclic framework or biological structure-activity relationship studies. We further elaborated our method in efforts towards the synthesis of the ophiobolin pharmacophore. Chapter 3: Indoles are a class of molecules that are commonly found in nature and in a variety of FDA approved drugs. The synthesis and reactivity of indoles has been extensively studied and reported in literature, however some indole scaffold that have been notoriously difficult to efficiently synthesize include 1H-indole-2-acetamides. Our lab has developed an efficient, modular route to access a variety of functionalized 1H-indole-2-acetamide derivatives. This method could prove useful for future biological studies as well as offer new synthetic utility for entry into structurally diverse indole targets.