New synthetic methods and strategies: Enabling natural product drug discovery

Natural products are chemicals produced by living organisms that encompass a fascinating range of structural diversity and potentially useful pharmaceutical activities. Some of the better-known natural products include anti-bacterial compounds derived from fungi (e.g., penicillin), analgesics such as salicylic acid, derived from the bark of willow trees, and paclitaxel, an anti-cancer compound isolated from the Pacific Yew tree. In fact, over half of the drugs approved by the FDA in the past 25 years are derived from or inspired by natural products, and the near-doubling of the average Canadian’s life expectancy in the 20th century is largely attributed to medical advances based on these compounds.

Recent advances in biochemistry and molecular biology have guided the discovery of many new natural products. However, the limited quantities of natural source materials and environmental concerns associated with harvesting the producing organism highlight the importance of using alternate methods to synthesize these biologically active compounds in the laboratory. Thus, through a total synthesis approach, organic chemists are able to provide a renewable source of the natural product and generate sufficient quantities for extensive biological testing.

The focus of Dr. Robert Britton's Natural Product Research Program is the total synthesis of natural products that represent potential lead candidates for the treatment of human diseases. In particular, his group is focusing on developing novel synthetic pathways to manufacture sufficient quantities of eleutherobin and biselide A, two natural products that hold potential for the treatment of cancer, as well as a family of imminosugars that represent leads for the treatment of diabetes, viral diseases, and lyposomal storage disorders. The work of his team involves the development of innovative synthetic reactions that will allow them to construct complex natural products in a straightforward manner from simple chemical building blocks. The synthesis of these molecules will also enable the discovery of new substances that are similar in structure to these natural products but with potentially improved pharmaceutical properties.