Natural products and privileged structures

天然产品和特权结构

• 批准号: 7553319
• 负责人: KEITH R. BUSZEK
• 金额: $ 9.67万
• 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/7553319
• 关键词: biological products; chemical synthesis; combinatorial chemistry; lactones; stereochemistry; technology /technique development

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.

该项目的主要目标是基于 对映体纯、立体化学结构明确、新颖、多功能且有趣的分子 源自天然产品和特殊结构或受其启发的脚手架。该项目的具体目标是： 1. 制备基于八元内酯天然产物的示范文库和 通过闭环复分解 (RCM) 化学研究强大的抗肿瘤剂八内酯 A，并评估类似物对人类癌细胞系的细胞毒活性。 2. 开发一类用于组合化学的新型离子降冰片烯基连接体。 3.使用固相和溶液相技术通过组合方法制备三烯霉素A类似物。 4. 聚合物负载鏻盐的利用、烯烃交叉复分解、低聚手性 构建大环核心过程中的助剂和 PEG 支持的二氧戊环 三烯霉素A 5. 开发新型化学来制备独特的含氮支架。 6. 开发用于固相不对称合成的新型无痕连接方法。