With this award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Thomas Snaddon of Indiana University. Professor Snaddon is developing new tools and chemical reactions for the synthesis of organic compounds with an emphasis on a family of complex molecules found in nature called epidithiodioxopiperazines (ETPs). The ETPs show important biological activity as anticancer agents. They share a common core structure that contains carbon, nitrogen, oxygen, and sulfur atoms in a precise 3-dimensional arrangement. ETPs are challenging to prepare and modify, and Professor Snaddon is designing new chemical transformations to facilitate their synthesis. His approach is enabling the synthesis of new ETP derivatives such that their reactivity with biological systems can be rigorously explored and understood. Professor Snaddon's research group is also involved in various outreach activities. Specific to this award, and in collaboration with Professor Deborah Snaddon, graduate and undergraduate students are involved in the production of "Inspirational Interviews". These interviews comprise short videos of faculty members explaining their life, education, and science backgrounds, why they chose to study chemistry, and what their research involves. The interviews serve as a broad resource for high school students interested in careers in science, but who have no direct contact with STEM-involved students or researchers.
Professor Snaddon is pursuing novel reactions and strategies that will facilitate the efficient construction of medicinally-important diketopiperazine-containing molecules. In particular, he is studying new and modular ways to synthesize the epidithiodiketopiperazines (ETPs), disulfide-bridged diketopiperazines, by exploiting the unusual bifunctional reactivity of triketopiperazines. These hetereocycles undergo controlled, sequential reactions with electrophiles and nucleophiles, respectively, leading to general synthetic routes to ETPs. In addition to naturally-occurring ETPs with therapeutically-relevant biological properties, the experiments underway in Professor Snaddon's laboratory is also enabling new unnatural ETPs to be designed and synthesized for use as probes to elucidate and evaluate biological processes. Students working on this project receive rigorous training in chemical synthesis, preparing them for future careers in STEM fields.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
