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Abstract
Grant Number: 1R01GM075855-01 Project Title: Derivatization/Functionalization:Natural Product(RMI)
PI Information: Name Title MILLER, MARVIN J. mmiller1@nd.edu GEORGE AND WINIFRED CLARK PROFESSOR AND Abstract: DESCRIPTION (provided by applicant): This proposal is being submitted in response to RFA-RM-05-013 (New Methodologies for Natural Products Chemistry). The hypothesis of this proposal is that cycloadducts and ene products derived from reactions of diene- and alkene-containing natural products with nitroso moieties, will provide novel derivatives that can serve as versatile building blocks (evolvable scaffolds) for syntheses of a number of important and often new bioactive molecules. Specific Aims Are: 1. Generate novel scaffolds from diene and alkene-containing natural products by simple one step cycloaddition and ene reactions with a variety of nitroso compounds, even those that contain extensive additional functionality. Both solution phase chemistry and novel "natural product solid phase capture" methods will be described. 2. Demonstrate that the newly functionalized natural product scaffolds are "evolvable platforms" that can be elaborated to both conformationally restricted and more flexible libraries using novel chemistry developed in the PI's laboratory and classical chemistry in the labs of the described collaborators as well as in the PI's labs. 3. Broadly test the scaffold and derived libraries of novel compounds using the extensive set of assays in place at the Hans-Knoll Institute for Natural Products Research (HKI).
Public Health Relevance:
This Public Health Relevance is not available.Thesaurus Terms:
biological product, chemical structure function, chemical synthesis, method development
alkene, chemical addition, chemical reaction, chemical registry /resource, conformation, diene, nitroso compound
biotechnology
Institution: UNIVERSITY OF NOTRE DAME 511 MAIN BLDG NOTRE DAME, IN 46556 Fiscal Year: 2005 Department: CHEMISTRY AND BIOCHEMISTRY Project Start: 23-SEP-2005 Project End: 31-JUL-2008 ICD: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES IRG: ZRG1