Natural products and privileged structures

该项目的主要目标是基于 对映体纯的、立体化学定义明确的、新颖的、多用途的和有趣的分子 衍生自天然产品或特殊结构的支架。该项目的具体目标是： 1.以八元内酯类天然产物为基础， 通过闭环复分解（RCM）化学，对强力抗肿瘤剂奥克拉菌素A进行了研究，并评估了类似物对人类癌细胞系的细胞毒活性。 2.开发用于组合化学的新型离子型双烯基连接体。 3.利用固相和液相技术的组合方法制备三烯霉素A类似物。 4.聚合物负载的鳞盐、烯烃交叉复分解、低聚手性 助剂和PEG支撑的二氧戊环在大环核心的建设过程中， 三烯霉素A 5.开发新的化学方法以制备独特的含氮支架。 6.固相不对称合成中新型无痕连接体方法的发展。

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.