Development of convergent synthtic strategy for novel polycyclic exhibiting inhibit activity for 11b-HSD1
| Project/Area Number |
20K06949
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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 | Tokyo University of Pharmacy and Life Science |
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Principal Investigator |
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 有機合成化学 / メロテルペノイド / マンギノイド / 全合成 / マンギノイド類 / 合成化学 / 有機化学 / 天然有機化合物 |
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| Outline of Research at the Start |
マンギノイド類の収束的合成経路を確立し、その合成経路を基に様々な誘導体の合成研究も併せて行う。収束的合成経路の確立においては、独自に開発したキラル合成素子を利用する。それらマンギノイド類の合成中間体や誘導体の生物活性試験を行い、構造活性相関を明らかにしたい。最終的には生活習慣病治療薬の新たなシード化合物創出を目指すともに、蛍光標識基や光アフィニティー基を導入したツール分子の開発も目指し、酵素阻害機構解明に向けた研究にも貢献したい。
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| Outline of Final Research Achievements |
In 2017, manginoids, which are novel polycyclic meroterpenoids containing a spiro ring, were isolated and revealed to have 11β-HSD1 inhibitory activity. Therefore, with the aim of providing samples for more detailed biological activity tests of manginoids and creating compounds with better activity than natural products, we are conducting research with the aim of establishing a convergent synthetic route that can be adapted to derivative synthesis. As a result, we succeeded in establishing a method for constructing tricyclic compounds containing a spiro ring, which is the key skeleton of manginoids. Next, using this established synthetic route, we expanded our research into the synthesis of manginoid E, which has the most complicated structure among manginoids, and were one step closer to establishing a skeleton construction method.
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| Academic Significance and Societal Importance of the Research Achievements |
マンギノイド類は11β-HSD1阻害活性を有する多環式メロテルペノイドである。11β-HSD1阻害剤は二型糖尿病などの生活習慣病に対する治療薬として注目されている化合物である。本研究の研究成果は、これまでにない新規骨格の構築法の確立という学術的意義および新たな生活習慣病治療薬のシード化合物創出という社会的意義を有する。
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Report
(4 results)
Research Products
(1 results)
