2010 Fiscal Year Final Research Report
Synthesis and binding sites of new compounds which bind to the sodium channels
| Project/Area Number |
20611002
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SATAKE Masayuki The University of Tokyo, 大学院・理学系研究科, 准教授 (90261495)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 環状エーテル / 鈴木カップリング / 渦鞭毛藻 / ナトリウムチャネル |
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| Research Abstract |
A polycyclic ether brevisin was isolated from the red tide dinoflagellate Karenia brevis, which produces a variety of polycyclic ethers such as brevetoxins, brevenal, and a mono cyclic ether amide brevisamide. Its unique structure consists of two fused tricyclic ether ring assemblies bridged by a methylene carbon and a conjugated aldehyde side chain, which is similar to brevenal and brevisamide. Its separated polycyclic ether skeleton in the center of the molecule is unusual in the marine polycyclic ethers. Interestingly, even though its skeletal structure is divided into two tricyclic ether units by the methylene, brevisin inhibits the binding of tritiated 42-dihydrobrevetoxin B (PbTx-3) to the voltage sensitive sodium channels (VSSC). In order to confirm its aberrant chemical structure, elucidate its interaction with VSSC, and evaluate its other biological activities, chemical synthesis for its supply was essential. Here the total synthesis of brevisin based on highly convergent strategy using Suzuki-Miyaura cross coupling and aldol reaction as the key reactions was achieved in 29 steps (the longest linear sequence).
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