title: Biomimetic total synthesis of cyanosporaside aglycons from a single enediyne precursor through site-selective p-benzyne hydrochlorination.
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.
authors.affiliation: Department of Chemistry, Graduate School of Science, Tohoku University, Aza Aramaki, Aoba-ku, Sendai 980-8578 (Japan).
authors.forename: Kei
authors.initials: K
authors.lastname: Yamada
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Lear
authors.forename: Takaya
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Ilya D
authors.initials: ID
authors.lastname: Gridnev
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hirama
mesh_terms: D001555:Benzene Derivatives / Q000737:chemistry*; D032701:Biomimetics; D002713:Chlorine / Q000737:chemistry*
chemical_list: D001555:Benzene Derivatives; D002713:Chlorine
keywords: benzenoids; cyclization; diradicals; enediynes; monochlorination