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

Yamada, Kei, Lear, Martin J., Yamaguchi, Takaya, Yamashita, Shuji, Gridnev, Ilya D., Hayashi, Yujiro and Hirama, Masahiro (2014) Biomimetic total synthesis of cyanosporaside aglycons from a single enediyne precursor through site-selective p-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 mono chlorinated 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:benzenoids, cyclization, diradicals, enediynes, monochlorination, NotOAChecked
Subjects:F Physical Sciences > F165 Biomolecular Chemistry
F Physical Sciences > F160 Organic Chemistry
F Physical Sciences > F163 Bio-organic Chemistry
Divisions:College of Science > School of Chemistry
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ID Code:17095
Deposited On:16 Apr 2015 13:40

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