A chemist at Florida State University has created a new method to assemble complex natural molecules, which could lead to advances in medicine and pharmaceuticals. James Frederich, Warner Herz Associate Professor of Chemistry and Biochemistry, and his team have synthesized fusicoccadiene for the first time. This molecule is a precursor to compounds being explored as cancer treatments. Their findings were published in the Journal of the American Chemical Society.
“The Frederich Laboratory specializes in the synthesis of architecturally complex natural products that we believe have special translational potential, especially in medicine, but are currently inaccessible in a practical manner,” Frederich said. “We build complex structures from scratch by extending existing chemical methods and developing entirely new ones.”
The function of biomolecules depends on their structure. By studying substances such as those produced by fungi like fusicoccum amygdali, researchers can alter these molecules for drug discovery.
Fusicoccadiene is a hydrocarbon that leads to fusicoccanes—a group of molecules with biomedical potential. Some fusicoccanes, including fusicoccin A and cotylenin A, have been shown to make cancer cells more susceptible to cell death.
The molecular structure of fusicoccadiene is particularly difficult to synthesize because it contains two five-membered rings joined with an eight-membered ring at its core.
“Realizing the synthetic blueprint to prepare fusicoccadiene was very challenging,” Frederich said. “This synthesis is the culmination of several doctoral thesis projects spanning almost a decade. Chemical synthesis requires great resolve from both students and principal investigators, and it requires a special creativity.”
Frederich’s team used light-driven chemical processes to convert one compound into another during synthesis. After forming the molecule, they made targeted modifications at specific sites on its structure.
“Instead of designing a molecule for target-specific endpoints, we envisioned an assembly scheme that could capture new, non-natural compositions of matter for future iterations of the molecule that can be used in medicine,” Frederich said. “Our approach focuses on direct construction of the 5-8-5 nucleus in the early stages of molecular formation. We then leverage a range of certain reactions to decorate the periphery of the structure with a range of functionality.”
Moving discoveries like this from lab research to patient-ready therapies often takes years. Labs such as Frederich’s perform essential early work by testing different structures and functionalities that could become future medicines.
“Dr. Frederich’s research catalyzes the inheritance of our department’s legacy and strengths in the areas of natural product and synthetic organic chemistry and bridges our rich history into the exciting new Initiative on Molecular BioDesign, leading to a vibrant and long-sought modern platform for FSU drug discovery,” said Wei Yang, chair of the Department of Chemistry and Biochemistry.
The project received funding from both federal sources through the National Institute of General Medical Sciences (a part of NIH) as well as private support from an endowed fund.
For more information about FSU Health initiatives visit https://fsuhealth.fsu.edu/. Details about ongoing research at FSU’s Department of Chemistry and Biochemistry are available at https://www.chem.fsu.edu/.
