Biomimetic total synthesis of cyanosporaside aglycons from a single enediyne precursor through site-selectivep-benzyne hydrochlorination

Yamada, Kei and Lear, Martin J. and Yamaguchi, Takaya and Yamashita, Shuji and Gridnev, Ilya D. and Hayashi, Yujiro and Hirama, Masahiro (2014) Biomimetic total synthesis of cyanosporaside aglycons from a single enediyne precursor through site-selectivep-benzyne hydrochlorination. Angewandte Chemie International Edition, 53 (50). pp. 13902-13906. ISSN 1433-7851

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Abstract

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.

Keywords:chemistry, JCNotOpen
Subjects:F Physical Sciences > F100 Chemistry
Divisions:College of Science > School of Chemistry
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ID Code:22706
Deposited On:18 Mar 2016 15:18

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