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

Kei Yamada, Martin James Lear, Takaya Yamaguchi, Shuji Yamashita, Ilya D. Gridnev, Yujiro Hayashi, Masahiro Hirama

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)

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 cyclo-aromatization 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 orga-nochlorine 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.

Original languageEnglish
Pages (from-to)13902-13906
Number of pages5
JournalAngewandte Chemie - International Edition
Volume53
Issue number50
DOIs
Publication statusPublished - 2014 Oct 8

Keywords

  • Benzenoids
  • Cyclization
  • Diradicals
  • Enediynes
  • Monochlorination

ASJC Scopus subject areas

  • Chemistry(all)
  • Catalysis
  • Medicine(all)

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