Date of Award
Doctor of Philosophy
George A. Kraus
Natural products with interesting unique structures and special biological activities possess great potential in the development of novel pharmaceuticals. However, the evaluation of biological activity is always limited due to the low yield and difficulty of separation from plants and microorganisms. Synthetic organic chemistry provides an alternative tool to create such natural products from accessible materials. A huge mission for organic chemists is to develop novel strategies to produce natural products and their analogs in lab, as well as in quantitative scales. With this in mind, we have designed small molecule inhibitors towards Porcine reproductive and respiratory syndrome virus (PRRSV) and developed the synthetic routes to natural products psoracorylifols and furomollugin. In addition, a novel palladium nanoparticle catalyst was evaluated with the Suzuki-Miyaura reaction of aryl chloride.
Chapter one describes the design and synthesis of small molecule inhibitors of PRRSV. Natural 1-(E)- Atractylodinol was successfully produced in a seven-step direct route. More analogs with antiviral activity were synthesized based on this natural product. The goal to design a cost effective antiviral drug towards PRRSV was achieved.
The design of an approach to the unique 6,8-dioxabicyclo[3.2.1]octane skeleton in psoracorylifols B and C is discussed in chapter two. This special core structure was constructed via ketal formation in five steps.
The novel direct synthetic route to furomollugin is introduced in chapter 3. Furomollugin was synthesized by utilizing the Hauser-Kraus annulation as a key step.
The last chapter focuses on the evaluation and application of a novel palladium catalyst developed by Datye and co-workers. The utility of Datye catalyst was demonstrated in the Suzuki-Miyaura reaction of aryl chlorides and boronic acids. This catalyst showed great catalytic activity when aryl chlorides and aryl bromides were used for the Suzuki coupling in water media.
Dong, Pengfei, "Synthesis of natural product analogs as small molecule inhibitors" (2016). Graduate Theses and Dissertations. 15692.