Exploiting Neglected Reactivity to Develop New Tools for Organic Synthesis and Medicinal Chemistry

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Our research focuses on finding new and improved ways of making value-added organic molecules from simple chemical feedstocks. Although the new technology we develop will most directly impact the discovery and development of pharmaceuticals, the fundamental knowledge gained in the process will be broadly useful. Specifically, we aim to take poorly understood and undeveloped chemical processes and transform them into practical methods to make useful organic compounds. With this as a guiding principle we will tackle the following challenges: I Develop New Silver Catalysts for Heterocycle Synthesis. Nitrogen heterocycles are cylic structures made of carbon and at least one nitrogen atom, and are particularly important in pharmaceutical discovery, with most drugs having at least one such ring. Often, making these heterocycles can be challenging, slowing down drug development. We will use recent discoveries in my group to make new silver catalysts that will facilitate the synthesis of nitrogen heterocycles, allowing the rapid generation of small molecule libraries for biological testing, and thereby accelerating drug discovery and development. II Develop New Antibiotics. Antibiotics underpin modern medicine. Unfortunately, while antibiotic resistance continues to rise unabated, only two new classes of antibiotics have been developed in the last twenty years. We will use our previous research in highly strained organic molecules to develop new antibiotics. This will require the development of new methods to prepare innovative organic molecules that will interfere with cell-wall biosynthesis in bacteria. To test their antibiotic activity we will collaborate with experts in bacterial research, who will provide valuable data on active compounds. Using this feedback mechanism, we will design and prepare new molecules to arrive at new and desperately needed antibiotics. III Develop a New Way of Making Cycloheptanes. Cycloheptanes are seven-membered rings composed of carbon and are found in many naturally occurring compounds with very useful biological activity. Unfortunately, there are not many effective ways to prepare these rings, and therefore they are not widely used in drug discovery. We will develop a new reaction to make these rings in one step from simple building blocks, and demonstrate its utility by making new molecules approaching the complexity of those found in nature. Overall, our research stands to make valuable contributions to fundamental organic chemistry and will find application in the pharmaceutical sector, potentially leading to new intellectual property and new therapeutics. In addition, this research will be an integral part of the training of over 20 young scientists.