Xie Yancheng, Bao Jiajing, Wang Yu, Shen Yi, Liang Zexuan, Tian Hailong, Gui Jinghan
State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
J Am Chem Soc. 2025 Mar 5;147(9):7875-7885. doi: 10.1021/jacs.4c18292. Epub 2025 Feb 17.
Rubriflordilactone B is a bisnortriterpenoid with a unique 5/5/7/6/5/5-hexacyclic framework that includes a characteristic tetrasubstituted aromatic ring. Herein, we report a convergent, enantioselective total synthesis of this natural product by a bioinspired skeletal reorganization approach. Key transformations include a chelation-controlled [2,3]-Wittig-Still rearrangement to assemble the western cyclohexenyl fragment with complete diastereocontrol, a Cu(II)-catalyzed tandem acyloin acylation-Wittig olefin to build the eastern butanolide fragment, a Friedel-Crafts cyclization to construct the seven-membered ring, and an E1cB reaction/transesterification/oxa-Michael addition cascade to forge the pivotal 5/5-fused bicyclic lactone. This work vividly demonstrates that bioinspired skeletal reorganization is a useful strategy for simplifying the retrosynthetic analysis of structurally complex natural products.
红毛椴内酯B是一种双降三萜类化合物，具有独特的5/5/7/6/5/5-六环骨架，其中包括一个特征性的四取代芳环。在此，我们报道了通过仿生骨架重排方法对该天然产物进行汇聚式对映选择性全合成。关键转化包括螯合控制的[2,3]-维蒂希-斯蒂尔重排，以完全非对映选择性地组装西部环己烯基片段；铜（II）催化的串联偶姻酰化-维蒂希烯烃反应，以构建东部丁内酯片段；傅克环化反应，以构建七元环；以及E1cB反应/酯交换/氧杂-迈克尔加成串联反应，以形成关键的5/5-稠合双环内酯。这项工作生动地表明，仿生骨架重排是简化结构复杂天然产物逆合成分析的一种有用策略。
