Grant: Research Tools and Instruments - Category 1 (<$150,000)

The development of pharmacologically active agents that improve the quality and longevity of human life has had an enormous societal impact over the last 50 years. Nevertheless, the increasing cost of drug discovery, due to the low success rate of clinical candidates progressing through the various phases of drug development (<0.2%), has prompted serious analysis of the factors that contribute to the high failure rate. For example, the average cost to market a new drug is in excess of $1 billion, in which only three out of ten drugs generate enough revenue to cover the costs of the research and development. Natural products have historically proven reliable lead compounds for drug discovery. For example, these agents have inspired over 60% of the anticancer agents and 70% of the antibiotics entering clinical trials in the last 30 years. Nevertheless, many companies have abandoned natural products due to the perceived problems associated with the preparation of libraries of natural product analogues for detailed Structure Activity Relationship Studies. The advent of chemical genetics is exciting for drug development; however, the disconnection between the production of a protein and its function constitutes a considerable ""knowledge gap."" Hence, the solution of the human genome provides a chemical and biological conundrum, the extent to which has been dramatically underestimated by the pharmaceutical industry. The construction of architecturally challenging structural motifs in a predictable and expeditious manner remains a Grand Challenge for synthetic organic chemistry. This limitation has severely limited the ability to facilitate Structure-Activity Relationship Studies in a range of biologically interesting molecules, which has limited the ability to exploit many interesting and potentially useful lead compounds. The introduction of the Continuous Flow Reactor provides the potential to expand the scope and overcome the limitations with many processes. Hence, we will expand the current tool-kit of chemical reactions to include carbocyclization and directed lithiation reactions, which will provide cutting-edge HQP training.