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

Research output: Contribution to journalArticle

6 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 leptolyngbyolideC. 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
JournalChemistry - A European Journal
DOIs
Publication statusAccepted/In press - 2017

Fingerprint

Macrolides
Bioactivity
phosphine
Actins
Thioamides
Depolymerization
Stereochemistry
Cell death
Copper
Ligands
Nuclear magnetic resonance
Apoptosis
Molecules
Cyanobacteria

Keywords

  • Asymmetric catalysis
  • Cytotoxicity
  • Macrocycles
  • Natural products
  • Total synthesis

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp. Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis. / Cui, Jin; Morita, Maho; Ohno, Osamu; Kimura, Tomoyuki; Teruya, Toshiaki; Watanabe, Takumi; Suenaga, Kiyotake; Shibasaki, Masakatsu.

In: Chemistry - A European Journal, 2017.

Research output: Contribution to journalArticle

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AU - Morita, Maho

AU - Ohno, Osamu

AU - Kimura, Tomoyuki

AU - Teruya, Toshiaki

AU - Watanabe, Takumi

AU - Suenaga, Kiyotake

AU - Shibasaki, Masakatsu

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AB - 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 leptolyngbyolideC. 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.

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