Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis
Leptolyngbyolides, Cytotoxic Macrolides from the Marine Cyanobacterium Leptolyngbya sp.: Isolation, Biological Activity, and Catalytic Asymmetric Total Synthesis
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DOI：
10.1002/chem.201701183
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发表时间：
2017-06-22
影响因子：
4.3
通讯作者：
Shibasaki, Masakatsu
中科院分区：
文献类型：
--
作者：
Cui, Jin;Morita, Maho;Shibasaki, Masakatsu
从日本冲绳采集的蓝细菌Leptolyngbya sp.中分离得到4个新的大环内酯类化合物leptolyngbyolides A-D。通过广泛的NMR研究确定了leptolyngbyolides的平面结构，但绝对构型的完全归属有待leptolyngbyolides C的催化不对称全合成。该合成利用了催化的不对称硫代酰胺-羟醛缩合反应，使用与手性双齿膦配体络合的铜（I）在开始时调节分子的两个关键立体化学。本发明的全合成证明了该反应用于构建复杂化学实体的实用性。除了全合成外，本工作还报道了leptolyngbyolides在体外和细胞中降解丝状肌动蛋白（F-肌动蛋白）。详细的生物学研究表明，leptolyngbyolides引起的F-肌动蛋白解聚和细胞凋亡的可能顺序。
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.