Development of Enabling Methods for Natural Product and Medicinal Chemistry

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Over 50% of drugs approved by the FDA in the past 25 years are natural products or were inspired by a natural product lead in the therapeutic area. While the importance of natural products to human health is clear, oftentimes the limited amounts of material available from the natural source, or environmental concerns associated with harvesting the producing organism prevent their development into drugs. Additionally, the structural complexity of many naturally occurring compounds can further complicate their development. Thus, the full realization of natural product discoveries often relies on simultaneous breakthroughs in synthetic organic chemistry necessary to prepare useful quantities of these compounds in the laboratory, and explore the relationship between their structure and biological activity. Bearing this in mind, the long term goal of this Research Program is to address fundamental challenges in natural product and medicinal chemistry by focusing on the following discovery themes: i) new methods that can be applied to the rapid synthesis of 'privileged' molecular structures that are common to both natural products and pharmaceuticals; ii) directed synthesis of scarce natural products that have potentially useful biological activity; and iii) development of new fluorination reactions that can be exploited for the purpose of nuclear medicine. In particular, we plan to develop syntheses of eleutherobin and biselide A, two natural products that hold potential for the treatment of cancer, and two separate families of iminosugars and carbohydrate mimics that may enable future breakthroughs in the treatment of bacterial infections and Alzheimer's disease. In addition, we will investigate new reactions that replace hydrogen atoms in various organic molecules with fluorine. Ultimately, these fluorination reactions should lead to the discovery of improved radiotracers for positron emission tomography (PET) imaging of tumors. This Research Program should impact the practices of the wider community by providing enabling technologies and convenient methods for researchers engaged in natural products and drug discovery, and nuclear medicine. Through the downstream development of drugs and improved radiotracers for early detection of cancer, the anticipated outcomes of this research will have a significant and positive impact on the health of Canadians.