Calendar of Events

Organic Synthesis for Biological Investigation: From Neurotoxin Total Synthesis to Quorum Sensing Inhibition

Natural products and small molecules can be useful tool compounds for the investigation of complex biological systems. My research has focused on the synthesis of several classes of such compounds. I will first describe my work towards the total synthesis of the natural product zetekitoxin AB (ZTX). ZTX is a potent neurotoxin isolated from the endangered Panamanian golden frog, Atelopus zeteki, and is a potent inhibitor of voltage-gated sodium ion channels. Given that the total isolate supply of ZTX is 300 μg, chemical synthesis of ZTX is the only way to enable structure- activity studies. To this end, I developed a route to the tricyclic core of ZTX to enable access to the natural product. This route also provides access to the related bis-guanidinium toxins saxitoxin and the gonyautoxins.

I will then describe my work on the development of small molecule inhibitors of bacterial communication in Staphylococcus aureus. The accessory gene regulator (agr) quorum sensing (QS) system is used by S. aureus to coordinate group behaviors, including virulence, in response to changes in cell population density. Small molecules that inhibit agr QS have the potential to be used as therapeutics to combat S. aureus infection. Our lab has developed a new class of small molecule agr inhibitors. I have designed a new synthetic route to a best-in-class small molecule inhibitor. This synthesis enables facile functional group variation for structure-activity studies to improve compound potency, solubility, and stability.

**This seminar counts towards the chemistry major seminar attendance requirement