2006 Fiscal Year Final Research Report Summary
Synthesis and Structure-Function Relationship Studies of Polycyclic Ether Natural Products
| Project/Area Number |
16310145
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Living organism molecular science
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| Research Institution | Tohoku University |
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Principal Investigator |
SASAKI Makoto Tohoku University, Graduate School of Life Sciences, Professor, 大学院生命科学研究科, 教授 (80235267)
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| Co-Investigator(Kenkyū-buntansha) |
OIKAWA Masato Tohoku University, Graduate School of Life Sciences, Associate Professor, 大学院生命科学研究科, 助教授 (70273571)
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| Project Period (FY) |
2004 – 2006
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| Keywords | Polycyclic ethers / Gambierol / Gymnocin-A / Gymnocin-B / Brevenal / Structural Revision / Gambieric acids / Structure-activity relationship |
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| Research Abstract |
1.We have synthesized 18 structural variants of gambierol, potent neurotoxic polycyclic ether, and evaluated their biological activity. The structure-activity relationship (SAR) studies revealed the crucial structural elements necessary for exhibiting potent neurotoxicity.
2.The structural features required for cytotoxicity of gymnocin-A were investigated by the total synthesis and evaluation of the structural analogues. The SAR studies indicated that the enal functionality of the side chain as well as the molecular length were necessary for cytotoxicity of gymnocin-A. A synthetic route to the LMNOring fragment of gymnocin-B was also established.
3.Total synthesis of the proposed structure of brevenal was achieved. However, the ^1H and ^<13>C NMR spectra did not match those for the natural sample. The revised structure, the C26-epmier, was proposed based on the detailed NMR analysis along with the proposed biosynthetic pathway of marine polycyclic ethers and finally validated through total synthesis. The present studies also led to determination of the absolute configuration.
4.A highly convergent synthesis of the nonacyclic polyether skeleton of gambieric acids A and C, potent antifungal polycyclic ethers, was accomplished for the first time. Stereoselective synthesis of the AB-ring fragment of gambieric acid A was also achieved.
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