Development of new methods for the synthesis of biologically active natural products

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It is difficult to overstate the importance of natural products to human health. The near doubling of the life expectancy for the average Canadian in the 20th century is largely attributed to medical advances based on natural products and over 50% of drugs approved by the FDA in the past 25 years are, or their origins can be traced to, natural products. Recent advances in biochemistry and molecular biology, that includes the development of high-throughput assays for rapidly identifying biologically active compounds, has enabled the discovery of many new natural products with a fascinating range of biological activities and structural diversity. However, due to often-limited amounts of material available from the natural source or environmental concerns associated with harvesting the producing organism, the full realization of these discoveries relies on simultaneous breakthroughs in synthetic chemistry, or total synthesis, necessary to assemble the biologically active compound in the laboratory. Thus, through total synthesis organic chemists provide a renewable source of the natural product, and generate sufficient quantities for unambiguous structural assignment and thorough biological testing. Bearing this in mind, the major focus of our research program is the total synthesis of natural products that represent potential lead candidates for the treatment of human diseases, and insect sex pheromones that provide earth-friendly alternatives to insecticides. These studies rely heavily on the development of innovative reactions that will allow us to construct complex natural products in a straightforward manner from simple chemical building blocks. In particular, we plan to develop reactions that will provide rapid access to haterumalide, a potential anticancer agent; hyacinthacine A5, a potential antidiabetic agent; and chimonanthine, an analgesic natural product. Our flexible syntheses of these molecules will also allow us to generate new substances, similar in structure to these natural products but with potentially improved pharmaceutical properties. The successful implementation of this program will enable discoveries fundamental to our basic understanding of organic chemistry and the development of pharmaceuticals.