Synthetic studies on structurally complex natural products based on the development of innovative cascade reaction processes
| Project/Area Number |
18H02549
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Tohoku 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 |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
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| Keywords | 連続反応 / 全合成 / アルカロイド / ラジカル反応 / ベンザイン / 含窒素複素芳香環 / アザスピロ骨格 / ピロロキノリン骨格 / ピロロインドール骨格 / スピロ環 / 酸化反応 / アザスピロ環 / 不斉合成 / Mannich反応 / カスケード反応 / ワンポット反応 / パラジウム触媒 / 1,3-ジケトン / ラジカル環化反応 |
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| Outline of Final Research Achievements |
We have developed creative cascade reaction processes and demonstrated their synthetic utility by accomplishment of total syntheses of structurally complex natural products. A total synthesis of (-)-lepadiformin A having an aza-spiro skeleton was achieved by a radical translocation/cyclization reaction. A total synthesis of isobatzelline A and B possessing a pyrroloquinoline skeleton and the first total synthesis of plakinidine D were achieved via benzyne-mediated cyclization/functionalization cascade process. A construction of the main framework of discorhabdin V possessing pyrroloquinoline skeleton fused with a piperidine ring was achieved via oxidation/aza-Michael/oxidation cascade and intramolecular Heck reaction. The shortest total synthesis of (-)-deoxoapodine was achieved via C-H alkylation of the indole 2-position by the Catellani-type reaction and formation of hexacyclic skeleton by oxidative transannular reaction.
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| Academic Significance and Societal Importance of the Research Achievements |
近年、sp3炭素に富む縮環構造や多置換複素環構造などを有する天然物の創薬における重要性が再認識されているが、合成困難さのため十分研究されていない。今回開発した連続反応プロセスは、これらの複雑な化合物の高効率的な合成に有用であることを、いくつかの天然物の全合成を達成することで実証した。これらの結果は、含窒素多置換複素環化合物や高度に縮環したアザスピロアルカロイドなど、従来合成が困難であった化合物群に対して新たな合成指針を示す意味で学術的に意義深いだけでなく、それらの合成を通じて、医薬リード化合物として期待されながら合成困難さのために埋もれていた化合物の開発促進につながり、社会的な意義も大きい 。
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Report
(4 results)
Research Products
(96 results)
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[Journal Article] Identification of Emetine as a Therapeutic Agent for Pulmonary Arterial Hypertension: Novel Effects of an Old Drug.2019
Author(s)
Siddique MAH, Satoh K, Kurosawa R, Kikuchi N, Elias-Al-Mamun M, Omura J, Satoh T, Nogi M, Sunamura S, Miyata S, Ueda H, Tokuyama H, Shimokawa H.
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Journal Title
Arterioscler Thromb Vasc Biol
Volume: 39
Issue: 11
Pages: 2367-2385
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A Cell-Targeted Non-Cytotoxic Fluorescent Nanogel Thermometer Created with an Imidazolium-Containing Cationic Radical Initiator.2018
Author(s)
Uchiyama, S., Tsuji, T., Kawamoto, K., Okano, K., Fukatsu, E., Noro, T., Ikado, K., Yamada, S., Shibata, Y., Hayashi, T., Inada, N., Kato, M., Koizumi, H., and Tokuyama, H.
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Journal Title
Angewandte Chemie
Volume: 57
Issue: 19
Pages: 5413-5417
DOI
Related Report
Peer Reviewed / Open Access
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