2022 Fiscal Year Final Research Report
Structural elucidation of endogenous digitalis-like factor using theoretical calculation and chemical synthesis
| Project/Area Number |
20K05863
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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 | Iwate University (2021-2022)
Nagoya University (2020) |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 19-ノルブファリン / EDLF / MSスペクトル / 理論計算予測 / 強心ステロイド / 化学合成 / ジアステレオマー / 2-ピロン |
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| Outline of Final Research Achievements |
Endogenous digitalis-like substance (EDLF) is an important molecule from the clinical medicine perspective of prevention and treatment of various diseases. To elucidate the full structure of 19-norbufarin (19-NB), a candidate compound of EDLF, in this study we achieved 1) a synthetic method for stereoisomerism of 19-NB with respect to the A ring and a new method for the construction of 2-pyrone with 17-position 2-pyrone. We also established 2) synthetic methods for oxidized terpenoids by utilizing these developed methods. We are currently studying the improvement of the accuracy of MS spectral prediction, and we will examine the comparison with the actual measured data and verify which stereoisomers are promising as well as the validity of the proposed structure by comparing with the values in the original literature.
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| Free Research Field |
生物有機化学
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| Academic Significance and Societal Importance of the Research Achievements |
EDLFの構造解明は、正確な構造が得られることによって、i) 生合成酵素の探索、ii) EDLFをバイオマーカーとする検出技術の開発、iii) 発症メカニズムの解明等が大きく進展し、疾患予防や治療に直結すると期待される。また本研究は、未だ実現していないMS分野の究極的な課題である「MSフラグメントパターンからの構造導出」の技術基盤の確立につながる重要性を有する。本提案が実現できれば、医療・創薬・農業・食品分野などの各分野で代謝物の網羅的解析（メタボロミクス）によって多数発見されている新規化合物の構造推定が円滑に行えるだけでなく、未知の生物機能の解明にも繋がる発展的な研究展開が期待できる。
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