University Honors

Spiroalanfurantone A is an eudesmanolide-furan sesquiterpenoid adduct biosynthesized by Inula helenium, a plant occurring throughout Asia, Africa, and North America. Its medicinal properties are potentially highly valuable; specifically, spiroalanfurantone A is an inhibitor of nitric oxide production, which has implications in reducing the severity of memory loss and combating migraine headaches. Accessing this and related natural products must come from chemical synthesis because their isolation from the natural source is extremely low yielding and impractical. Importantly, the ability to synthesize these compounds enables further exploration of their nitric oxide synthase inhibition. This class of complex natural products has never been synthesized. Thus, developing a synthesis of spiroalanfurantone A is critical for future biomedical and chemical innovation. This project involves a seventeen-step synthesis employing two novel chemical reactions developed in the Kou lab: (1) a type-1 intramolecular Diels-Alder reaction of furan (IMDAF) to form a quaternary carbon center and (2) an oxabicycle ring- opening reaction to create the tricyclic lactone core structure. Currently, thirteen of the seventeen synthetic reactions have been completed, accessing natural products alantolactone, alloalantolactone, isoalantodiene, and epoxyalantolactone, which are biosynthetic precursors to spiroalanfurantone derivatives. My specific contributions focused on optimization of the first eight steps of the synthetic route, plus the large scale, five-step synthesis of the Weinreb amide fragment, an important reactant that is not commercially available, thus allowing access to the four aforementioned natural products. Additionally, I have experimental extensively on the optimization of an alternate Diels-Alder cycloaddition that could improve the overall synthesis. Ongoing studies will involve advancing the synthetic route to access spiroalanfurantone A, as well as access other derivatives of the pool of natural products we are targeting. The completion of spiroalanfurantone A would enhance accessibility of these complex natural products across the world, which I expect to be highly beneficial for future biochemical and biomedical evaluations.