Synthesis and Structure Analysis of Natural Products

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With the support of the Chemical Synthesis (SYN) Program in the Division of Chemistry, Professor Scott Rychnovsky of the University of California, Irvine is developing new strategies to assign the structure and handedness of molecules. Molecules may exist in two possible mirror-image forms, which are commonly described as right-handed or left-handed structures. New molecules are isolated from plants and animals, and are created in the lab by chemists. The structure of molecules determine their physical properties such as their physical form, liquid or solid, and how they interact with living systems. Odor and taste come from the shape and structure of a molecule. More significantly, molecular drugs are effective because their shapes interact with proteins to alleviate diseases. The Rychnovsky group is using osmium complexes to simplify the determination of structure of new molecules, as well as computer modeling. In difficult cases, the final step to proving a structure consists of constructing the molecule in a lab from simpler components—chemical synthesis. Undergraduate and graduate students will carry out the research for this project. UC Irvine is a Hispanic Serving Institution, providing ample opportunities to recruit talented Hispanic (and other minority) students to participate in this project. Professor Rychnovsky works with the faculty at Santiago Community College to help their students develop their research skills and expertise. This project is expected to have a strong impact on student training, helping to build the future STEM (science, technology, engineering and mathematics) workforce for both careers in industry and in academia.The award supports the development of osmate derivatives to improve the crystallinity of complex molecules. Osmates are often highly crystalline, and the density of the osmium metal facilitates the determination of structure and handedness by X-ray crystallography (anomalous dispersion). Chemical synthesis tools are also being developed, including a new intramolecular Diels-Alder reaction that builds new six-membered rings with easily predicted geometries. Computational modeling of spectroscopic properties is used to test plausible structure to determine if they correctly match the newly isolated molecular structures. Comparing the computer-predicted properties with the measured properties is a powerful technique to determine molecular structure. A final test is to build the best proposed structure from simpler fragments to prove that it matches the newly isolated molecule. The research is well suited for the training of undergraduate and graduate scientists, and students with diverse backgrounds are recruited to participate in this project. Santiago Community College has many students who transfer to the UC system, but they rarely have the opportunity to participate in research projects. Professor Rychnovsky works with the faculty there to recruit summer students to take part in this research program, thus providing an avenue for community college students to develop research skills and experience.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.