Derivatization/Functionalization of Natural Product(RMI)

天然产物衍生化/功能化(RMI)

基本信息

批准号：
7270478
负责人：
MARVIN J MILLER
金额：
$ 31.98万
依托单位：
UNIVERSITY OF NOTRE DAME
依托单位国家：
美国
项目类别：
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/7270478
关键词：
Acylation Address Alkenes Alkylation Amides Amines Biochemistry Biological Biological Assay Biological Factors Cell physiology Chemicals Chemistry Collaborations Collection Commercial Sources Development Diels Alder reaction Disease Drug Delivery Systems Evaluation Future Generations Germany Goals Health Hydroxyl Radical Individual Institutes Investigation Laboratories Lead Letters Libraries Methodology Methods Microbe Microbiology Modification Natural Products Chemistry Nature Nitroso Compounds Numbers One-Step dentin bonding system Pharmaceutical Preparations Phase Polyenes Principal Investigator Productivity Proteins Publishing Range Reaction Research Resources Scheme Screening procedure Solid Solutions Source Structure Testing United States National Institutes of Health adduct analog antimicrobial drug base chemical synthesis combinatorial chemistry cycloaddition design diene functional group high throughput screening hydroxamate interest method development novel programs response scaffold size small molecule solid solution

项目摘要

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）：本提案是为了回应 RFA-RM-05-013（天然产物化学新方法）而提交的。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衍生的环加合物和烯产物，将提供新的衍生物，可作为通用构建单元（可进化支架）用于合成许多重要和重要的化合物。通常是新的生物活性分子。具体目标是： 1.通过简单的一步环加成和烯与各种亚硝基化合物（甚至是那些含有大量附加功能的化合物）的反应，从含二烯和烯烃的天然产物中生成新型支架。将描述溶液相化学和新颖的“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 PI 实验室开发的新型化学和所述合作者实验室以及PI 的实验室。 3. 使用 Hans-Knoll 天然产物研究所 (HKI) 现有的大量检测方法广泛测试新型化合物的支架和衍生文库。