Ahmad Nadia M, Rodeschini Vincent, Simpkins Nigel S, Ward Simon E, Blake Alexander J
School of Chemistry, The University of Nottingham, University Park, Nottingham NG7 2RD, UK.
J Org Chem. 2007 Jun 22;72(13):4803-15. doi: 10.1021/jo070388h. Epub 2007 May 26.
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.
通过一种策略来开展多异戊烯基连苯三酚天然产物（包括clusianone、nemorosone和garsubellin A）的合成，该策略涉及构建一个核心双环[3.3.1]壬三酮结构，并随后通过有机锂中间体进行修饰。通过将适当取代的环己酮烯醇醚或烯醇硅烷与丙二酰二氯环化，得到了合适的桥连核心结构。然后通过区域选择性锂化反应引入额外的取代基，包括桥头烯醇盐的生成，从而实现了clusianone的全合成以及nemorosone的一个高级中间体的合成。对于garsubellin A，通过烯醇醚（或烯醇）与侧链环氧化物的仿生5-外向-四环化反应构建了一个额外的类似四氢呋喃的环。这通过获取Danishefsky合成中的一个后期中间体实现了外消旋garsubellin A的形式合成。
