Derivatization/Functionalization:Natural Product(RMI)

衍生化/功能化：天然产物(RMI)

• 批准号: 7012060
• 负责人: MARVIN J MILLER
• 金额: $ 35.25万
• 依托单位: UNIVERSITY OF NOTRE DAME
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7012060
• 关键词: alkenes; biological products; biotechnology; chemical addition; chemical reaction; chemical registry /resource; chemical structure function; chemical synthesis; conformation; diene; method development; nitroso compounds

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).

描述（由申请人提供）：该提案是针对RFA-RM-05-013（天然产品化学的新方法）提交的。该提议的假设是，含二烯和烯烃的天然产物与硝基部分的反应得出的环载和ENE产品将提供新颖的衍生物，这些衍生物可以用作多功能的构建块（可转化的脚手架），以构成许多重要和通常的生物活性分子的合成。 具体目的是：1。通过简单的一个阶级环加成，从二烯和烯烃天然产物中产生新颖的脚手架，并与各种硝基化合物进行ENE反应，甚至具有广泛的额外功能。将描述溶液相化学和新型的“天然产物固相捕获”方法。 2。证明，新功能化的天然产品支架是“可进化的平台”，可以使用在所述合作者的实验室和PI的实验室中的实验室和PI的实验室中在PI的实验室和古典化学中开发的新型化学方法，并在PI的实验室和经典化学中开发，可以详细阐述构象限制和更灵活的库。 3。使用Hans-Knoll天然产品研究所（HKI）的广泛测定法（HKI）进行了广泛测试新颖化合物的脚手架和衍生的库。