Milosavljevic Aleksa, Alachouzos Georgios, Frontier Alison J
Department of Chemistry, University of Rochester, 120 Trustee Rd, Rochester, New York 14627, United States.
J Am Chem Soc. 2025 Jul 2;147(26):23120-23127. doi: 10.1021/jacs.5c06475. Epub 2025 Jun 16.
The first successful fragment coupling/cationic cascade approach for the synthesis of a complex indoloditerpenoid tubingensin A is described. The synthesis is the first example of a novel disconnection strategy targeting a central quaternary carbon locus. A -Prins/-Nazarov cationic cascade sequence enabled the rapid preparation of a complex intermediate as a single diastereomer, containing the vicinal quaternary centers found in the backbone stereotriad. This approach installed much of the complex carbon skeleton of tubingensin A in one step from fragment coupling of two simple reactants. To complete the synthesis, the indane ring system is converted to the target decalin, preserving the integrity of the stereotriad. The isopropylidene fragment is appended in the endgame. The target is obtained in 15 fully diastereoselective steps from simple achiral materials. Investigation of the -Nazarov cyclization revealed fluxional behavior in the Friedel-Crafts termination step.
本文描述了首个成功用于合成复杂吲哚二萜类化合物tubingensin A的片段偶联/阳离子级联方法。该合成是针对中心季碳位点的新型切断策略的首个实例。一个-Prins/-Nazarov阳离子级联序列能够快速制备出一种单一非对映异构体的复杂中间体，该中间体包含主链立体三联体中发现的邻位季碳中心。这种方法通过两个简单反应物的片段偶联一步构建了tubingensin A的大部分复杂碳骨架。为完成合成，茚满环系被转化为目标十氢化萘，同时保留立体三联体的完整性。在合成的最后一步引入亚异丙基片段。目标产物从简单的非手性原料经15个完全非对映选择性步骤得到。对-Nazarov环化反应的研究揭示了傅-克终止步骤中的动态行为。
