2020 Fiscal Year Final Research Report
Total synthesis of 10-14 membered ring fused dimacrolides, potent narrow antimicrobial activities
| Project/Area Number |
18K06586
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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 | Kitasato 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 | Luminamicin / 全合成 / 微生物発酵 / ラクトン / シスデカリン / 構造活性相関 |
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| Outline of Final Research Achievements |
Luminamicin, is not found in other natural products, has a 14-membered lactone that contains an enol ether conjugated to maleic anhydride, and also possess a cis-decalin skeleton containing an oxygen bridge structure connecting to a 10-membered lactone with a trisubstituted olefin. Therefore, Luminamicin is an attractive target from the viewpoint of organic synthetic chemistry.
As a result, we completed the synthesis of the key intermediate for the total synthesis was completed from a commercially available starting material. On the other side, the key intermediate was also obtained by degradation of the natural product, which was supplied by the mass cultivation of a luminamicin-producing strain. Finally,the total synthesis of luminamicin was achieved by the reconstruction of the Luminamicin-skeleton from key intermediate.
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| Free Research Field |
天然物合成化学
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| Academic Significance and Societal Importance of the Research Achievements |
現在までに承認された医薬品の約6割が天然物由来であるという事実からも、天然物をシード化合物とする創薬研究は依然として重要な研究領域である。このことから新規な骨格をターゲットとする本研究は天然物創薬において意義がある。
これまで他の研究グループによるLuminamicinをターゲットにした全合成研究、創薬研究は報告は無く、世界的に細菌感染症の耐性化が問題視されている現状から、Luminamicinの有する一部の細菌のみへの選択的な抗菌活性の作用メカニズムを解明することは、耐性菌発現を誘導しない抗菌剤創製に繋がる。本研究成果を基盤として、その創薬研究が加速するものと期待できる。
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