Asymmetric Total Synthesis of Heronamides A–C: Stereochemical Confirmation and Impact of Long-Range Stereochemical Communication on the Biological Activity

Naoki Kanoh, Shunya Itoh, Kohei Fujita, Kohei Sakanishi, Ryosuke Sugiyama, Yuta Terajima, Yoshiharu Iwabuchi, Shinichi Nishimura, Hideaki Kakeya

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Heronamides are biosynthetically related metabolites isolated from marine-derived actinomycetes. Heronamide C shows potent antifungal activity by targeting membrane phospholipids possessing saturated hydrocarbon chains with as-yet-unrevealed modes of action. In spite of their curious hypothesized biosynthesis and fascinating biological activities, there have been conflicts in regard to the reported stereochemistries of heronamides. Here, we describe the asymmetric total synthesis of the originally proposed and revised structures of heronamide C, which unambiguously confirmed the chemical structure of this molecule. We also demonstrated nonenzymatic synthesis of heronamides A and B from heronamide C, which not only proved the postulated biosynthesis, but also confirmed the correct structures of heronamides A and B. Investigation of the structure–activity relationship of synthetic and natural heronamides revealed the importance of both long-range stereochemical communication and the 20-membered macrolactam ring for the biological activity of these compounds.

Original languageEnglish
Pages (from-to)8586-8595
Number of pages10
JournalChemistry - A European Journal
Volume22
Issue number25
DOIs
Publication statusPublished - 2016 Jan 1

Keywords

  • configuration determination
  • macrocycles
  • natural products
  • structure–activity relationships
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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