Synthetic studies on polycavernosides A and D aiming at the identification of their biological target
| Project/Area Number |
18K05450
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 38040:Bioorganic chemistry-related
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| Research Institution | Akita University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 全合成研究 / 有機合成化学 / 不斉合成 / 海藻毒 / 細胞毒性 / 神経毒性 / 標的生体分子探索 / 天然物全合成 / プローブ分子 / 毒性発現機構解明 / 標的分子探索 / 合成供給法開拓 / マクロライド配糖体 / 天然物合成 / 合成供給法開発 / 分子プローブ / 毒性機構解明 |
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| Outline of Final Research Achievements |
Polycavernoside A and D, isolated from a red algae as a lethal toxin and from a cyanobacterium as a cytotoxin, respectively, are structurally similar macrolide glycosides. The mode of toxic action of them is unclear in detail due to difficulty in the supply of them from natural source. Therefore, the synthetic supply of them was planned and examined. Polycavernoside D, which has not been synthesized so far, was planned to be assembled from a sugar chain and a macrolide moiety. The macrolide would be constructed from the upper-half unit and the bottom-half tetrahydropyran (THP) unit. Both the units were successfully synthesized from (R)-pantolactone. For the THP unit, a new synthetic method was developed based on the Hosokawa asymmetric vinylogous Mukaiyama aldol reaction. The late stage of the synthesis would be finished according to the procedure previously developed for polycavernoside A by the author, and, therefore, the completion of the synthesis of polycavernoside D is in sight.
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| Academic Significance and Societal Importance of the Research Achievements |
ポリカバノシドAは食用カタオゴノリの突然毒化の際の致死毒として単離された。毒化は一時的であり、その後カタオゴノリから毒素は検出されなくなったため、ポリカバノシドAの天然供給は絶たれている。最近藍藻から構造の酷似したポリカバノシドDが細胞毒として単離され、ポリカバノシドAとの毒性の特徴の差異が注目された。もし、ポリカバノシド類の毒性の背後に存在する生体分子標的や作用機序を解明できれば、生命維持に重要な新たな生物学的知見が得られると期待される。この毒性に関わる研究の遂行には、ポリカバノシド類の供給が不可欠である。本研究は人工合成でその供給を実現する意義を持ち、簡便供給につながる知見を得た。
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Report
(4 results)
Research Products
(5 results)
