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。这一提议的假设是，含有二烯和烯烃的天然产物与亚硝基反应生成的环加成物和烯产物将提供新型的衍生物，这些衍生物可以用作多种构筑材料(可进化的支架)，用于合成一些重要的、通常是新的生物活性分子。 具体目标是：1.从含有二烯和烯烃的天然产物中通过简单的一步环加成反应和与各种亚硝基化合物的烯反应生成新型支架，即使是那些含有广泛附加官能团的化合物。将描述溶液相化学和新的“天然产物固相捕获”方法。2.证明新功能化的天然产物支架是“可进化的平台”，可以使用在PI的实验室中开发的新化学和在所述合作者的实验室中以及在PI的实验室中开发的经典化学来细化到构象受限和更灵活的库。3.使用汉斯-诺尔天然产品研究所(HKI)现有的一套广泛的分析方法，广泛测试新化合物的支架和衍生库。

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).