This project addresses the total synthesis of halohistophan alkaloids, including the securines, securamines, chartellines, and chartellamides. A biogenetic hypothesis is used to interrelate these natural products, each of which contains an indole core connected by one or more rings. A 1,2-aza-migration will be exploited to construct the spiro beta-lactam functionality. The mechanism of an unusual oxidative rearrangement discovered in the course of these synthetic ventures will be explored. Given the exceedingly strained and compactly functionalized architectures of the chartellamides, isomeric structures will be prepared in order to identify unambiguously the structures of the natural products. A web-based resource for researchers in heterocyclic chemistry will be developed, and outreach programs to local high schools will be pursued.
With the support of this CAREER award from the Organic and Macromolecular Chemistry Program, Professor Phil S. Baran, of the Department of Chemistry at the Scripps Research Institute, is exploring the synthesis of a series of complex organic molecules. The target molecules, derived from marine organisms, are members of a structurally unique class of molecules containing exotic groupings of atoms. While other natural products isolated from related organisms have demonstrated intriguing biological activity, the targeted compounds have not been explored in bioassays, perhaps due to their isolation in vanishingly small amounts. By carrying out the synthesis of these complex molecules, Professor Baran will permit unambiguous determination of their molecular structures and make available sufficient quantities for biological testing. In addition, given their great complexity, new methods for the synthesis of nitrogen-containing organic compounds (heterocycles) will be developed. Professor Baran will develop a new online resource in heterocyclic chemistry, free and accessible to the entire chemical community, designed train students in the essence of heterocyclic chemistry and to demonstrate the chemical aspects of modern drug discovery. A high school outreach program will also been developed in order to inspire students at a young age to pursue a career in the art and science of synthetic organic chemistry.