Synthesis of polyprenylated acylphloroglucinols using bridgehead lithiation: The total synthesis of racemic clusianone and a formal synthesis of racemic garsubellin A
Synthesis of polyprenylated acylphloroglucinols using bridgehead lithiation: The total synthesis of racemic clusianone and a formal synthesis of racemic garsubellin A
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DOI：
10.1021/jo070388h
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发表时间：
2007-06-22
影响因子：
3.6
通讯作者：
Blake, Alexander J.
中科院分区：
文献类型：
--
作者：
Ahmad, Nadia M.;Rodeschini, Vincent;Blake, Alexander J.
聚异戊二烯化的间苯三酚天然产物，包括clusianone，nemorosone，garsubellin A的合成，是通过一个战略，涉及建设一个核心的双环[3.3.1]壬三酮结构和随后的阐述通过有机锂中间体。通过适当取代的环己酮烯醇醚或烯醇硅烷与丙二酰二氯的环化反应，得到了合适的桥核结构。然后通过区域选择性锂化反应引入额外的取代基，包括桥头烯醇化物的生成，从而使得能够全合成clusianone以及nemorosone的高级中间体。在garsubellin A的情况下，通过具有侧链环氧化物的烯醇醚（或烯醇）的仿生5-exo-tet环化来阐述另外的THF样环。这使得能够通过获得Danishefsky合成中的后期中间体之一来正式合成外消旋garsubellin A。
The synthesis of polyprenylated phloroglucinol natural products, including clusianone, nemorosone, and garsubellin A, was pursued by a strategy involving construction of a core bicyclo[3.3.1]nonanetrione structure and subsequent elaboration via organolithium intermediates. Appropriate bridged core structures were obtained through the cyclization of a suitably substituted cyclohexanone enol ether or enol silane with malonyl dichloride. Additional substituents were then introduced by means of regioselective lithiation reactions, including the generation of bridgehead enolates, thus enabling the total synthesis of clusianone and also of an advanced intermediate toward nemorosone. In the case of garsubellin A, an additional THF-like ring was elaborated by a biomimetic 5-exo-tet cyclization of an enol ether (or enol) with a side-chain epoxide. This enabled a formal synthesis of racemic garsubellin A by accessing one of the late intermediates in the Danishefsky synthesis.