Natural Products for Drug and Supplement Development

We use natural products for drug discovery and dietary supplement development. The fields of medicinal chemistry, synthetic organic chemistry, molecular modeling, and natural product chemistry, and fluorine chemistry are combined in our laboratory. We design analogues of natural products to identify new structure-activity relationships or expand existing ones. Our group develops therapeutics for diseases that have no or few existing treatment options, including neurodegenerative disorders, drug addiction, and cancer. Each research project starts with natural products as the initial inspiration for drug discovery.

Currently, our research is focused on flavonoids, in which we directly modify their structures, develop strategies for the total synthesis of novel analogues, and explore their activities. We have designed and synthesized a fluorinated derivative of 3’,4’,5’-trihydroxyflavone, which showed enhanced antioxidant activity. Additionally, quantitative 19F NMR analysis is a method that is frequently utilized in our projects, which we use in monitoring antioxidant activities, prodrug conversion, and reaction progression.

Synthetic Methodology

The second research area is developing novel synthetic methods for direct and efficient modification of organic molecules and to install fluorine atoms. Carbon-carbon bond cleavage for compound remodeling is also investigated in our research group. The field of synthetic organic chemistry and fluorine chemistry are blended in our laboratory. Methods developed by our group can be used in the synthesis of biologically important molecules.

We have discovered that the release of trifluoroacetate is a powerful approach to break carbon–carbon bonds and generate difluoroenolates and other fluorinated intermediates. Our method has opened new avenues in synthetic chemistry for the creation of fluorinated organic molecules and includes reactions such as halogenation, deuteration, and aldol, and imino-aldol reactions. We employed this strategy to develop a novel class of selective agonist for the GABAB receptor, the β-hydroxy difluoromethyl ketones and β-amino difluoromethyl ketones.

Reagents

Our research group is also interested in translating discoveries from the laboratory to the private sector and partnering with industry. We have two reagents that are commercialized with MilliporeSigma through Aldrich Chemistry. The first reagent is the Colby trifluoromethylation reagent, which we invented in 2013. The second is morpholine 3,3,3-trifluoropropanamide which can be used to construct (E)-β-fluoro-α,β-unsaturated amides, developed in 2020.