Biomimetic Total Synthesis of Cyanosporaside Aglycons from a Single Enediyne Precursor through Site‐Selective p‐Benzyne Hydrochlorination1. Issue 50 (8th October 2014)

• Record Type: Journal Article
• Authors: Yamada, Kei; Lear, Martin J.; Yamaguchi, Takaya; Yamashita, Shuji; Gridnev, Ilya D.; Hayashi, Yujiro; Hirama, Masahiro
• Is Part Of: Angewandte Chemie international edition. Volume 53:Issue 50(2014)
• Page Start: 13902
• Page End: 13906
• Publication Date: 2014-10-08
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201408416
• Languages: English
• ISSNs: 1433-7851

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The cyanosporasides A–F are a collection of monochlorinated benzenoid derivatives isolated from the marine actinomycetes <italic>Salinispora</italic> and <italic>Streptomyces</italic> sp. All derivatives feature one of two types of cyanocyclopenta[<italic>a</italic>]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 <italic>p</italic>‐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 <italic>p</italic>‐benzyne, calculated to be a ground‐state triplet diradical, to hydrogen, chlorine, and chloride sources are revealed.</p> </abstract>