Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp. Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis

Jin Cui, Maho Morita, Osamu Ohno, Tomoyuki Kimura, Toshiaki Teruya, Takumi Watanabe, Kiyotake Suenaga, Masakatsu Shibasaki

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7 Citations (Scopus)

Abstract

Four new macrolactones, leptolyngbyolides A–D, were isolated from the cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The planar structures of leptolyngbyolides were determined by extensive NMR studies, although complete assignment of the absolute configuration awaited the catalytic asymmetric total synthesis of leptolyngbyolide C. The synthesis took advantage of the catalytic asymmetric thioamide-aldol reaction using copper(I) complexed with a chiral bidentate phosphine ligand to regulate two key stereochemistries of the molecule at the outset. The present total synthesis demonstrates the utility of this reaction for the construction of complex chemical entities. In addition to the total synthesis, this work reports that leptolyngbyolides depolymerize filamentous actin (F-actin) both in vitro and in cells. Detailed biological studies suggest the probable order of F-actin depolymerization and apoptosis caused by leptolyngbyolides.

Original languageEnglish
Pages (from-to)8500-8509
Number of pages10
JournalChemistry - A European Journal
Volume23
Issue number35
DOIs
Publication statusPublished - 2017 Jun 22

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Keywords

  • asymmetric catalysis
  • cytotoxicity
  • macrocycles
  • natural products
  • total synthesis

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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