Sustainable chemistry, synthesis and structure-activity relationship studies of biologically important small molecules

With growing concerns for the environment, dwindling amounts of fossil fuels available for worldwide consumption and more resistant strains of diseases and infections becoming a reality, organic chemistry plays a vital role in the improvement and sustainability of modern society. Industrial chemicals from renewable sources has become an important area of research in recent years, while the synthesis and study of biologically active small molecules and their analogues leads to advancements which can help improve overall human health. In this dissertation, we explore methods to create important industrial molecules from biorenewable sources, extend a novel cyclization to make heterocyclic compounds, and develop a new route towards a natural product that is active against tumor cells which resist current cancer treatments. Chapter 1 discusses the synthesis of an important industrial compound, terephthalic acid, from malic acid, which can be obtained from biorenewable feedstocks. This work was performed in collaboration with chemical engineers at the Center for Biorenewable Chemicals. Chapter 2 describes the extension of the Kraus indole synthesis to biologically important natural products such as isocryptolepine and the indolo[2,1-a]isoquinoline series. Chapter 3 discusses advances made towards the total synthesis of a marine alkaloid, oroidin, including a novel cyclization to install the important 2-aminoimidazole portion of the molecule