| Project/Area Number |
10671984
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | NARA INSTITUTE OF SCIENCE AND TECHNOLOGY (1999-2000)
The University of Tokyo (1998) |
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Principal Investigator |
SHIRAI Ryuichi RESEARCH AND EDUCATION CENTER FOR MATERIALS SCIENCE, NARA INSTITUTE OF SCIENCE AND TECHNOLOGY, ASSOCIATE PROFESSOR, 物質科学教育研究センター, 助教授 (80183838)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | dysidiolide / sesterterpene / cdc25A / dual phosphatase / cell cycle / asymmetric totalsynthesis / Diels-Alder reaction / structure-activity relationship / セスタテルペン |
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| Research Abstract |
Dysidiolide is a novel inhibitor of the protein phosphatase cdc25A that promotes the G1/S transition of the cell cycle by dephosphorylation of the cyclin-cyclin dependent kinase complex. Asymmetric synthesis of dysidiolide was achieved via intennolecular Diels-Alder reaction of the chiral triene with crotonaldehyde and successive methylation of the exocyclic aldehyde enolate. The unnatural stereoisomers of dysidiolide was also synthesized.
Synthesis of the potent stereoisomers of dysidiolide and novel cdc25A inhibitors utilizing Vitamin D_3 framework was *so investigate. Some isomers exhibited stronger inhibitory activity against cdc25A dephosphorylation of 4-nitrophenol phosphate than dysidiolide. The beta-hydroxybutenolide moiety cuold be converted to simple carboxylic acid. The hydrophilic substructure of dysidiolide may have a property of the mimic of phosphate group. This research project opened the new possibility of cdc25A inhibitor by the fusion of hydrophobic substructures with hydrophilic phosphate mimics.
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