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| Paper |
David Mabe
University of North Carolina at Asheville
Subject Listing - Chemistry
Advisor: Dr. Herman L. Holt, Jr.
Thursday, Oral Session 1, Presentation 1, Karpen Hall 038
STUDIES TOWARDS IMPROVING THE SYNTHESIS OF THE MITOMYCIN FAMILY OF ANTITUMOR AGENTS
The mitomycins are a family of anticancer compounds that are currently in widespread clinical use because they are effective in halting growth and reducing the size of malignant tumors. Mitomycin C is the most common drug in the mitomycin family used. It binds to a cell's DNA (guanine specifically), rendering the cell incapable of replication and of protein synthesis. The synthesis of mitomycin compounds is typically costly and involves many intermediate compounds that are produced in moderate yields. A novel synthesis of the four fused ring system that is the backbone of all the mitomycins has been developed. Our research utilizes a novel A-B-C-D approach to the synthesis of the ring system, beginning with a vinyl azide rearrangement to the indole backbone that proceeds in close to quantitative yield. In order to determine the best method of initiating formation of the C-ring, several different types of reactions were investigated. Intramolecular Claisien-Schmitt condensations utilizing different combinations of reagents were examined, as well as a Grubbs catalyzed sequence. Subsequent steps towards the formation of the D-ring of the mitomycin skeleton involve aziridination of the resulting alkene by a nitrene source or by utilizing a triazole intermediate. Progress towards the mitomycin skeleton and other model systems will be presented.
Advisor: Dr. Herman L. Holt, Jr., Assistant Professor, Department of Chemistry, University of North Carolina at Asheville, Asheville, NC