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

5 years ago

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

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

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. Absolutely right: Four new macrolactones, leptolyngbyolides A–D, were isolated from the cyanobacterium Leptolyngbya sp. collected in Okinawa, Japan. The absolute stereochemistry of leptolyngbyolide C was elucidated by catalytic asymmetric total synthesis (see scheme).

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/chem.201701183