The objective of this proposal is to obtain funding for the purchase a Varian 400 MHz multi-nuclear NMR spectrometer as a replacement for an aging Varian Gemini 200 MHz instrument. The current spectrometer has been in continuous service since September 1988. Varian will no longer support the Gemini series of instruments. The new instrument will be the only NMR spectrometer in the Ernest Mario School of Pharmacy and will serve the needs of approximately 35-40 researchers from the Graduate Programs in Medicinal Chemistry, Pharmaceutical Science, and Pharmacology and Toxicology. These researchers have no routine access to other NMR facilities on campus. This instrument will be used to support research efforts on 13 NIH funded projects. These projects are focused largely on the design and synthesis of novel heterocyclic and macrocyclic anticancer agents, the development of new methodology for the synthesis of pharmaceutical agents, the isolation and structure elucidation of natural products having potential as anticancer or chemopreventive agents, and on the determination of the mechanisms of action of chemopreventive agents. All of these projects require ready access to a high resolution NMR spectrometer for structure determination. The Varian 400 MHz multi-nuclear NMR spectrometer for which funding is being requested will greatly enhance the cutting edge research efforts of the major users of this instrument in the areas of novel anticancer drug design, synthesis, and discovery. The research projects described in this proposal are largely targeted towards the synthesis and identification of novel anticancer agents with the potential for development into clinically-useful drugs, the isolation and structure elucidation of bioactive compounds from plants, and the determination of metabolites and activation pathways of naturally-occurring cancer-preventive agents. The availability of a high resolution multi-nuclear NMR spectrometer is an essential tool for determining the chemical structures of these compounds and advancing these research efforts. ? ? ?
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