Biomimetic total synthesis of cyanosporaside aglycons from a single enediyne precursor through site-selective p-benzyne hydrochlorination.
Biomimetic total synthesis of cyanosporaside aglycons from a single enediyne precursor through site-selective p-benzyne hydrochlorination.
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DOI：
10.1002/anie.201408416
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发表时间：
2014-12
影响因子：
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通讯作者：
Kei Yamada;M. J. Lear;T. Yamaguchi;Shuji Yamashita;I. Gridnev;Y. Hayashi;M. Hirama*
中科院分区：
文献类型：
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作者：
Kei Yamada;M. J. Lear;T. Yamaguchi;Shuji Yamashita;I. Gridnev;Y. Hayashi;M. Hirama*
cyanosporasides a - f是从海洋放线菌Salinispora和Streptomyces sp中分离出来的单氯苯类衍生物。所有衍生物都具有两种类型的氰环五[a]独立框架中的一种，它们在单氯原子的位置是区域异构体。提出这些氯取代苯是通过双环九元烯二炔前体的环芳构化生物合成而成的。在这里，我们报道了这种双环前体的合成，它的自发转环成对苯，以及它在有机氯或氯盐条件下的不同1,4氢氯化反应活性。我们的生物启发方法在首次区域发散性全合成中达到高潮，合成了糖基A/F和B/C，以及氰孢苷D和e。此外，我们还揭示了一种类似天然的对苯（计算为基态三重态双自由基）对氢、氯和氯源的选择性。
The cyanosporasides A-F are a collection of monochlorinated benzenoid derivatives isolated from the marine actinomycetes Salinispora and Streptomyces sp. All derivatives feature one of two types of cyanocyclopenta[a]indene frameworks, which are regioisomeric in the position of a single chlorine atom. It is proposed that these chloro-substituted benzenoids are formed biosynthetically through the cycloaromatization of a bicyclic nine-membered enediyne precursor. Herein, we report the synthesis of such a bicyclic precursor, its spontaneous transannulation into a p-benzyne, and its differential 1,4 hydrochlorination reactivity under either organochlorine or chloride-salt conditions. Our bioinspired approach culminated in the first regiodivergent total synthesis of the aglycons A/F and B/C, as well as cyanosporasides D and E. In addition, empirical insights into the site selectivity of a natural-like p-benzyne, calculated to be a ground-state triplet diradical, to hydrogen, chlorine, and chloride sources are revealed.