The proposed research focusses on the total synthesis of two classes of natural products, the cyathins and the viridins. Construction of key intermediates via an electrochemical ring closure will be investigated in both cases. The cyathins have been shown to upregulate the synthesis of nerve growth factor while the viridins are inhibitors of phosphatidylinositol 3-kinase, a key signaling enzyme linked to cell growth and cancer. The design and synthesis of analogs of both classes of natural product will be carried out and their biological activity will be evaluated by collaborators of Professor Wright. Professor Wright will organize his undergraduate organic chemistry class into "learning communities" of 5-8 students. These groups will meet for one hour per week outside of lecture for problem-solving workshops. A further innovation will be to have the student groups design a short (3-5 step) synthesis of a potential drug candidate that would then be carried out for Professor Wright's research group.
With this CAREER award, the Organic Synthesis program is supporting the research of Professor Dennis Wright of the Department of Chemistry at the University of Florida. Professor Wright's studies are directed towards the synthesis of two classes of natural products, the cyathins and the viridins. The cyathins (and possibly their analogs) stimulate nerve growth factor (NGF) synthesis and could potentially be used in place of exogenous NGF administration. The viridins (and possibly their analogs) inhibit an enzyme associated with cell growth and could potentially be used as antitumor agents. The education component of the project will introduce problem-solving and synthesis design sessions into the undergraduate organic chemistry course.
