Natural products and privileged structures

天然产品和特权结构

• 批准号: 7553324
• 负责人: KEITH R. BUSZEK
• 金额: $ 22.61万
• 依托单位: UNIVERSITY OF KANSAS LAWRENCE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7553324
• 关键词: Alkenes; Biological Factors; Cancer cell line; Chemistry; Class; Development; Dioxolanes; Facility Construction Funding Category; Human; Lactones; Libraries; Methodology; Methods; Molecular; Nitrogen; Phase; Polymers; Preparation; Salts; Solid; Structure; Technology; analog; antitumor agent; base; combinatorial; combinatorial chemistry; cytotoxic; formal glycol; interest; novel; scaffold; solid solution; trienomycin A

The main objective of this project is the synthesis of compound libraries based on enantiomerically pure, stereochemically well-defined, novel, versatile, and interesting molecular scaffolds that are derived from or inspired by natural products and privileged structures. The specific aims of this project are: 1. Prepare a demonstration library based on the eight-membered lactone natural product and powerful antitumor agent octalactin A via ring-closing metathesis (RCM) chemistry and evaluate the analogues for cytotoxic activity against human cancer cell lines. 2. Develop a new class of ionic norbornenyl linkers for combinatorial chemistry. 3. Preparation of trienomycin A analogues by combinatorial methods using both solid- and solution-phase technologies. 4. Utilization of polymer-supported phosphonium salts, olefin cross-metathesis, oligomeric chiral auxiliaries and PEG-supported dioxolanes during the construction of the macrocyclic core of trienomycin A. 5. Development of novel chemistry to prepare unique nitrogen-containing scaffolds. 6. Development of novel traceless linker methodology for solid phase asymmetric synthesis.

本项目的主要目的是在合成复合库的基础上