Natural products and privileged structures

天然产品和特权结构

• 批准号: 7553314
• 负责人: KEITH R. BUSZEK
• 金额: $ 9.39万
• 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/7553314
• 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合成基于 对映体纯净、立体化学定义明确、新颖、用途广泛和有趣的分子 源自自然产品和特权结构或受其启发的脚手架。该项目的具体目标是： 1.以八元内酯天然产物为基础制备示范库， 通过闭环歧化(RCM)化学合成高效抗肿瘤药物八角菌素A，并评估其对人类癌细胞株的细胞毒活性。 2.开发了一类用于组合化学的新型离子降冰片烯基连接剂。 3.采用固相技术和溶液相技术相结合的方法制备曲尼霉素A类似物。 4.聚合物负载的膦盐、烯烃交叉歧化、低聚手性的利用 大环核构建过程中的助剂和聚乙二醇二氧杂环己烷 三环菌素A 5.开发新的化学方法来制备独特的含氮支架。 6.开发固相不对称合成的新型无迹连接物方法。