Novel Derivatization/Functionalization of Natural Produc

描述（由申请人提供）：本提案是根据RFA-RM-05-013（天然产物化学新方法）提交的。该提案的假设是，由含二烯和烯烃的天然产物与亚硝基部分反应产生的环加合物和烯产品将提供新的衍生物，可以作为合成许多重要且通常是新的生物活性分子的通用构建块（可进化的支架）。

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).