Methods for and Synthesis of Natural Product Hybrids for Medicinal Chemistry Applications

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This proposal deals with chemistry related to the science of synthetic organic chemistry. The science of organic chemistry is the science that examines the construction of organic (meaning built mostly of carbon, hydrogen, nitrogen and oxygen atoms) molecules. Similar to an architect designing a building, and engineers and construction workers building it based on that design, synthetic organic chemists design routes to, and build, organic molecules. Because of the complexity of organic molecules that Nature makes, synthetic organic chemists require new methods (the tools) to build these new molecules. Once these tools are designed, they are tested in the course of a complex molecule synthesis. This research program embraces the development of new methodology that can be harnessed to produce compounds with a goal for increased understanding, or treatment, of human disease. Fundamental questions in catalysis include the study of catalyzed alkyne-diene Diels-Alder processes (Rh or Ni), interception of organometallic fragments using Csp nucleophiles (Pd), tandem activations of bisindoles (Rh) and tandem formations of bisindoles (Pd). Functional natural product like molecules (based on highly bioactive natural products) will be used to explore biological constructs related to human health, specifically malaria and cancer. The described research will provide crucial advanced training for HQP interested in academic, industrial and biotechnology positions. HQP trained in these techniques traditionally end up working in fields related to the discovery of new medicines and new materials. Consequently, society receives many benefits through the efforts of HQP trained in the field of synthetic organic chemistry.