Synthesis and bio-functional analysis of marine polyketide natural product with potent cell proliferation-promoting activity.
| Project/Area Number |
16K13082
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Biomolecular chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
Sasaki Makoto 東北大学, 生命科学研究科, 教授 (80235267)
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| Research Collaborator |
Tsuda Masashi
Konoki Keiichi
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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 |
¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | アンフィリオニン－５ / 細胞増殖促進活性 / 全合成 / 立体配置決定 / 機能解析 / 機能解明 / アンフィリオニン－5 |
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| Outline of Final Research Achievements |
Amphirionin-5, a marine polyketide natural product, exhibits potent cell proliferation-promoting activity on murine bone marrow stromal cells and murine osteoblastic cells at nanomolar concentrations. Our efforts towards the total synthesis and complete configurational assignment of amphirionin-5 to clarify its biological activity were conducted. The relative configuration of the C1－C12 portion of amphirionin-5 was established by the stereodivergent synthesis of six diastereomeric model compounds and comparison of their NMR spectroscopic data with those reported for the natural product. This study led to the elucidation of the relative configuration between C4/C5 and C9/C12 and to the reassignment of the proposed configuration of the C9 position of amphirionin-5. Assignment of the unexplored relative configuration of C23/C26 was also attempted through a similar complementary use of organic synthesis and NMR analysis.
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| Academic Significance and Societal Importance of the Research Achievements |
アンフィリオニン-5 は、マウス骨髄由来間葉系幹細胞及び骨芽細胞の増殖を促進する生物機能を持つこれまでに前例のない海洋ポリケチド天然物である。アンフィリオニン-5 の構造を基盤とした新規細胞増殖促進分子の創製・機能解明のためには立体化学に関する情報は不可欠である。本研究では、適切に設計した部分構造の合成と天然物とのNMR データの比較によるC9/C12 及びC23/C26 位の相対配置を決定し、「不斉中心の立体配置の違いが、2 つのメチレン鎖を介した炭素のNMR 化学シフト値にもわずかではあるが明瞭に影響を及ぼす」ことを実証した。
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Report
(4 results)
Research Products
(34 results)
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[Journal Article] Tetracyclic Truncated Analogue of the Marine Toxin Gambierol Modifies NMDA, Tau, and Amyloid β Expression in Mice Brains: Implications in AD Pathology2017
Author(s)
Eva Alonso, Andres C. Vieira, Ines Rodoriguez, Rebeca Alvarino, Sandra Gegunde, Haruhiko Fuwa, Yuto Suga, Makoto Sasaki, Amparo Alfonso, Jose Mannuel Cifuentes, Luis M. Botana
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Journal Title
ACS Chemical Neuroscience
Volume: 8
Issue: 6
Pages: 1358-1367
DOI
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Peer Reviewed / Int'l Joint Research
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[Presentation] ポルチミンの合成研究2017
Author(s)
三好太朗、齋藤真輝、岩崎浩太郎、佐々木 誠
Organizer
日本化学会第97春季年会
Place of Presentation
慶應義塾大学（神奈川県横浜市）
Year and Date
2017-03-18
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[Book] 理科年表 20192018
Author(s)
佐々木 誠
Total Pages
17
Publisher
丸善出版株式会社
ISBN
9784621303320
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