With this CAREER Award, the Chemical Synthesis Program of the NSF Division of Chemistry is supporting the research of Professor Alexander J. Grenning at the University of Florida. His group is streamlining how bioactive terpenoid natural products, organic molecules commonly derived from plants with important biological activity, are prepared in the laboratory. There are several reasons why this modern challenge needs to be addressed: first, nature often only produces minute quantities of natural products and significant amounts of the chemical are needed for study and use in society. From a given natural product, a limited set of similar compounds can be prepared via what chemists call "semi-synthesis". Semi-synthesis refers to specific limited changes to a natural product. When performing studies designed to understand the way these molecules interact with biological systems, access to a variety of similar compounds is crucial for understanding and improving the reactivity of the parent molecule. Second, the laboratory synthesis of highly complex molecules ("total synthesis") forming large quantities in efficient ways is inherently challenging. Although targeted for decades, there are few general strategies to make the complex terpene molecules. The Grenning lab is studying the laboratory terpene synthesis to better understand the function of this molecule in the body and to enable the advanced manufacturing of the best molecules in large quantities. Educational aspects of this project are aimed at informing the public about the natural products. The Grenning lab is designing freely available "infographics" on terpenes for distribution to the general public. The Grenning lab is also organizing events and conferences ranging from the "Chemathon," a day-long celebration of chemistry for high-school students, to the "Florida Heterocyclic and Synthetic Conference (FloHet)," a specialized international meeting that gathers synthetic organic chemistry leaders to disseminate their research findings. Additional benefits include the recruitment of underrepresented groups, both at the undergraduate and graduate student level, for participation in the projects outlined in this CAREER Award.
The Grenning lab is focusing on the synthesis of polycycloalkane natural products bearing tricyclic motifs. This is a common terpenoid architecture that is difficult to access due to its inherent structural complexity. Ketones, malonic acids, and allylic electrophiles serve as starting materials and through an operationally simple and generalized reaction sequences consisting of deconjugative allylations, sigmatropic rearrangements, and ring-closing metathesis, a variety of "terpene scaffolds" are accessible. These terpene scaffolds then serve as platforms for reaction development aimed at preparing terpenoid targets and target-analogs. Select molecules are subject to biological evaluation to validate our chemical advancements. The molecules targeted include the tigliane, daphnane and rhamnofolane families of natural products and their analogs. Broader Impacts include the increased interaction with Santa Fe Community College. By educating the local community on organic chemistry and natural products, Professor Grenning and his group create a dialogue and inspire students to consider careers in chemistry. The team also designs terpenoid infographics and organizes events and conferences for educating students and disseminating results.
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.
