中文摘要
大环内酯和大环内酰胺是一类重要的抗生素。本课题以2004年由我国科学工作者首先报道的大环内酯类化合物Bafilomysin A1和大环内酰胺类化合物Ansamitocinoside P-2作为目标分子，以RCM反应作为关键步骤，寻找和探索一条具有普适性的合成策略来合成Bafilomycin和Maytansine的母核结构。通过对RCM反应在大环体系中适用型的详细研究，我们得出一系列的经验规律，为此类反应在大环体系中的应用奠定了基础。同时，基于上述经验规律，我们设计并实现了19元大环内酰胺骨架的构建，通过不对称vinylogous Mukaiyama aldol反应，大大缩短了Ansamycin家族类化合物合成的步骤，并成功实现了N-Methylmaysenine的全合成，为此类化合物及其类似物构建提供了理论依据，为今后合成一系列以Bafilomycin和Maytansine母核结构为骨架的天然产物和类天然产物及构建对药物筛选极具实际意义的聚焦库奠定了基础。
英文摘要
The macrolactones and macrolactams are important antibiotics in natural products. Bafilomysin A1 and Ansamitocinoside P-2, which were first isolated in 2004 by Prof. Shen from Kunming Institute of Botany, CAS, belong to the macrolactone Bafilomycin family and the macrolactam Ansamycin family. A RCM reaction was ultilized as a key reaction in our group's research for the total synthsis of the Bafilomysin A1 and Ansamitocinoside P-2, searching for a universal strategy to achieve the construction of the core structure of Bafilomysin and Maytansine family compounds. After systematically screening of the RCM reaction in macro ring system, our group achieved the total synthesi of N-Methylmaysenine, a member of the Ansamycin family, by using asymetric Mukaiyama aldol reaction and RCM reaction as key steps. Meanwhile, a general theoretic principle of the RCM reaction in macro ring system has been well developed and summaried, which provide an opportunity for the further synthetic study of Bafilomycin family compounds, Ansamycin family compounds, and even their analogs, and also well for the further pharmaceutical study of Bafilomycin and Ansamycin family compounds in the future.
结题摘要
大环内酯和大环内酰胺是一类重要的抗生素。本课题以2004年由我国科学工作者首先报道的大环内酯类化合物Bafilomysin A1和大环内酰胺类化合物Ansamitocinoside P-2作为目标分子，以RCM反应作为关键步骤，寻找和探索一条具有普适性的合成策略来合成Bafilomycin和Maytansine的母核结构。通过对RCM反应在大环体系中适用型的详细研究，我们得出一系列的经验规律，为此类反应在大环体系中的应用奠定了基础。同时，基于上述经验规律，我们设计并实现了19元大环内酰胺骨架的构建，通过不对称vinylogous Mukaiyama aldol反应，大大缩短了Ansamycin家族类化合物合成的步骤，并成功实现了N-Methylmaysenine的全合成，为此类化合物及其类似物构建提供了理论依据，为今后合成一系列以Bafilomycin和Maytansine母核结构为骨架的天然产物和类天然产物及构建对药物筛选极具实际意义的聚焦库奠定了基础。