2020 Fiscal Year Final Research Report
Synthesis of Biologically Active Alkaloids Based on a Novel Method for Constructing Bicyclic Skeletons and thier Structure-Activity Relationship
| Project/Area Number |
18K06548
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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 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Kyoto University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 天然物合成 / アルカロイド / 橋頭位イオン / ベンザイン |
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| Outline of Final Research Achievements |
Tubingensin B is a hexacyclic indole diterpenoid isolated from the marine fungus and reported to be cytotoxic to Hela cells and herpes simplex virus. From a structural viewpoint, this compound showcases an exquisite molecular architecture, i.e., an indole-fused benzobicyclo[3.2.2]nonene core, a rare scaffold in natural products.
We have achieved the total synthesis of tubingensin B by our novel synthetic route, including 1) intramolecular [4+2] cycloaddition between benzyne and cyclohexadiene connected by a Si-O bond, 2) alkyl-selective ring expansion followed by iodination of intermediary bridgehead cation species, and 3) C-C bond formation at the bridgehead position by exploiting bridgehead anion species generated by iodine-lithium exchange.
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| Free Research Field |
有機合成化学
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| Academic Significance and Societal Importance of the Research Achievements |
近年、創薬に関連する化合物は、平面的なものより立体的なものの方が重要であることが指摘されている。本研究の対象化合物であるツビンゲンシンＢもまた、より単純で平面性の高い類縁体より高い生物活性を示すことが知られている。本研究を通じて開発した合成手法を活用することにより、ビシクロ骨格上の置換基改変に基づく柔軟な構造展開が可能になる。将来的には、より詳細な構造活性相関研究を通じた優れた生物活性を有する新規有用物質の創製につながるものと期待される。
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