Unified Total Syntheses of Benzenoid Cephalotane-Type Norditerpenoids: Cephanolides and Ceforalides
Unified Total Syntheses of Benzenoid Cephalotane-Type Norditerpenoids: Cephanolides and Ceforalides
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DOI：
10.1021/jacs.2c08803
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发表时间：
2022-10-05
影响因子：
15
通讯作者：
Sarpong, Richmond
中科院分区：
文献类型：
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作者：
Sennari, Goh;Gardner, Kristen E.;Sarpong, Richmond
本文详细介绍了C18-和C19-苯型头孢烷型去甲二萜的合成研究。在化学网络分析的指导下，使用迭代交叉偶联以简洁的方式构建了该天然产物家族的核心结构，然后进行了正式的逆电子需求[4 + 2]环加成。使用Mukaiyama水合和随后的烯化使[4 + 2]环加合物中的烯烃基团官能化的最初努力导致完整的C18-碳骨架。虽然有效，但这种方法被证明是漫长的，并促进了直接烯烃双官能化的发展，该直接烯烃双官能化依赖于硼铜化以将环加合物推进为天然产物。晚期外周C-H官能化促进了在6-10个步骤中获得所有已知的头孢内酯，以及在8-13个步骤中获得五种最近分离的头孢内酯。
Detailed herein are our synthetic studies toward the preparation of the C18- and C19-benzenoid cephalotane-type norditerpenoids. Guided by chemical network analysis, the core structure of this natural product family was constructed in a concise manner using an iterative cross-coupling, followed by a formal inverse-electron-demand [4 + 2] cycloaddition. Initial efforts to functionalize an alkene group in the [4 + 2] cycloadduct using a Mukaiyama hydration and a subsequent olefination led to the complete C18-carbon framework. While effective, this approach proved lengthy and prompted the development of a direct alkene difunctionalization that relies on borocupration to advance the cycloadduct to the natural products. Late-stage peripheral C-H functionalization facilitated access to all of the known cephanolides in 6-10 steps as well as five recently isolated ceforalides in 8-13 steps.