Synthetic study of natural antibacterial agents for the purpose of determination of their stereochemistry
| Project/Area Number |
16K07713
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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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| Research Field |
Bioorganic chemistry
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| Research Institution | Tokyo University of Agriculture (2017-2018)
The University of Tokyo (2016) |
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Principal Investigator |
ISHIGAMI Ken 東京農業大学, 生命科学部, 教授 (70292787)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 天然物化学 / 有機化学 / 立体化学 / 構造決定 / 抗菌活性 / 抗ピロリ菌活性 / glabramycin / セスキテルペン / 光学分割 / 抗ピロリセスキテルペン / 有機合成化学 / 構造訂正 / Glabramycin / ラジカル環化 / 構造改訂 / 天然物有機化学 / 抗菌物質 / 絶対立体配置 |
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| Outline of Final Research Achievements |
Even today discovery of new antibiotics is very important, because the treatment against drug-resistant bacteria has remained largely unmet. We selected natural antibacterial substances with remarkable activity, whose structure remained unknown, and carried out structure determination including absolute configuration by synthetic studies.
Structural revision of glabramycin B was achieved by enantioselective synthesis of our proposed structure. By this study, we were able to correct the reported structural misassignment, and to confirm the relative configuration of glabramycin B.
We also succeeded in the synthesis of both enantiomers of a sesquiterpene, potent anti-H. pylori agent, employing radical cyclization. Both enantiomers were prepared via optical resolution of racemic intermediate. By this synthesis, we were able to determine the absolute configuration of the natural product.
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| Academic Significance and Societal Importance of the Research Achievements |
新規薬剤の探索研究において、活性物質の構造を完全に決定することが研究の礎となるが、新規薬剤としての可能性を有しながら真の構造が未解明であり、その後の応用研究が進展しない天然生物活性物質は数多く存在する。
今回、黄色ブドウ球菌に対する抗菌物質であるGlabramycinと、薬剤耐性ピロリ菌に対し抗菌活性を示すセスキテルペンの全合成研究を通じて、立体化学を含めた真の構造を改訂・決定できた。これらの新規薬剤としての可能性を検討する上で重要な知見である。
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Report
(4 results)
Research Products
(12 results)
