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Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis
Author(s) -
Cui Jin,
Morita Maho,
Ohno Osamu,
Kimura Tomoyuki,
Teruya Toshiaki,
Watanabe Takumi,
Suenaga Kiyotake,
Shibasaki Masakatsu
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201701183
Subject(s) - isolation (microbiology) , chemistry , cytotoxic t cell , catalysis , stereochemistry , total synthesis , combinatorial chemistry , microbiology and biotechnology , biochemistry , biology , in vitro
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.