Biomimetic Synthetic Studies on the Bruceol Family of Meroterpenoid Natural Products
Biomimetic Synthetic Studies on the Bruceol Family of Meroterpenoid Natural Products
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DOI：
10.1021/acs.joc.9b02862
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发表时间：
2020-02-21
影响因子：
3.6
通讯作者：
George, Jonathan H.
中科院分区：
文献类型：
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作者：
Day, Aaron J.;Sumby, Christopher J.;George, Jonathan H.
全合成的仿生方法可以提供几个好处，包括级联反应的发展，以快速生成分子复杂性，并指导旧的天然产物的结构修改和新的预测。在这里，我们描述了如何仿生合成鸦胆子醇，五环meroterpenoid，导致的预期，分离和合成的isobruceol。通过富电子色烯脱芳构化生成的邻醌甲基化物的分子内杂Diels-桤木反应是马钱子酚和异马钱子酚合成的关键步骤。难以捉摸的生物合成中间体的合成也允许通过光化学[2 + 2]环加成简洁地合成Eriobrucinol。此外，对异戊烯化马钱子醇衍生物的生物合成的一些推测启发了Claisen/科普/Diels-Alder级联反应的发展。我们还报道了利用单线态氧烯反应生成卤代马钱子醇衍生物和合成几种原马钱子醇天然产物。
A biomimetic approach to total synthesis can offer several benefits, including the development of cascade reactions for the rapid generation of molecular complexity, and guidance in the structure revision of old natural products and the anticipation of new ones. Herein, we describe how a biomimetic synthesis of bruceol, a pentacyclic meroterpenoid, led to the anticipation, isolation, and synthesis of isobruceol. The key step in the synthesis of both bruceol and isobruceol was an intramolecular hetero-Diels-Alder reaction of an o-quinone methide that was formed by dearomatization of an electron-rich chromene. The synthesis of an elusive biosynthetic intermediate also allowed a concise synthesis of eriobrucinol via a photochemical [2 + 2] cycloaddition. Furthermore, some speculation on the biosynthesis of prenylated bruceol derivatives inspired the development of a Claisen/Cope/Diels-Alder cascade reaction. We also report the generation of halogenated bruceol derivatives and the synthesis of several protobruceol natural products using singlet oxygen ene reactions.