Research toward the development of microenvironment-responsive epidithiodiketopiperazines
| Project/Area Number |
18K14867
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47010:Pharmaceutical chemistry and drug development sciences-related
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 天然物合成 / フロー合成 / 網羅的合成 / 酸化的脱芳香環化 / トリコデルマミド / がん微小環境 / 構造活性相関 / 全合成 / 天然物 / 増殖阻害活性 / 一重項酸素 / 脱芳香環化 / 真菌 / DC1149B / グルコース飢餓環境選択的 |
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| Outline of Final Research Achievements |
During the course of our screening for growth inhibitors against the cancer cells, DC1149B was isolated along with its related compounds, trichodermamide A and aspergillazine A, from an Indonesian marine derived fungus, Trichoderma sp. These natural products exhibit potent bioactivity and possess a highly functionalized cis-1,2-oxazadecaline skeleton and therefore have attracted both of medicinal and synthetical interest. However, to date, two racemic and only a single enantioselective synthesis of trichodermamide A, B and C have been reported. In this study, we developed a new method for the construction of cis-1,2-oxazadecalin enone via tandem dearomatization/intramolecular oxy-Michael addition sequence of tyrosine derivatives. In addition, we also applied the method for natural products synthesis and achieved several enantioselective synthesis of trichodermamides.
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| Academic Significance and Societal Importance of the Research Achievements |
本課題では、DC1149Bおよび類縁化合物の網羅的合成研究に取り組んだ。その結果、共通重要骨格である光学活性なcis-1,2-オキサザデカリンエノンの効率的な新規構築法を開発した。また、本手法を基盤として、トリコデルマミドD,E及びFの統一的な初の不斉合成を達成した。本化合物群は副作用の少ない抗がん剤のリード化合物への可能性を秘めていることから、今回得られた成果は合成化学及び創薬化学の両領域への大きな波及効果が期待できる。
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Report
(3 results)
Research Products
(8 results)
