2019 Fiscal Year Final Research Report
Efficient Synthesis of Important Bioactive Medium-Size Polycyclic Natural Products
| Project Area | Middle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis. |
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| Project/Area Number |
15H05841
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Science and Engineering
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| Research Institution | Waseda University |
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Principal Investigator |
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| Project Period (FY) |
2015-06-29 – 2020-03-31
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| Keywords | 有機化学 / 生物活性 / 反応集積化 / 中分子 / 不斉触媒 |
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| Outline of Final Research Achievements |
The first enantioselective total synthesis of anti-cancer drug candidate cotylenin A has been achieved. In the process of its synthesis, a new acyl radical cyclization and stereoselective reducing reagent have been developed. A compound expected to be converted to bruceanthin was synthesized via Au(I)-catalyzed ene-yne cycloisomerization. A novel chiral NHC ligand effective for ene-yne cycloisomerization has been developed. An immobilized asymmetric copper catalyst effective for catalytic asymmetric cyclopropanation has been developed. A derivative with higher biological activity than Scabronin G has been designed and synthesized. A Liebeskind-Srogl coupling/intramolecular Diels-Alder reaction cascade has been developed. The α-imidation of α,β-unsaturated cyclic amide was formed in 2% yield by the batch method, but the yield was significantly improved to 78% by the flow method.
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| Free Research Field |
有機合成化学
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| Academic Significance and Societal Importance of the Research Achievements |
コチレニンAは生産菌が増殖能を失っているため、培養による供給が途絶えている。今回の全合成の成功によりコチレニンAの供給が可能になったため、そのさらなる生物科学的研究や副作用のない誘導体開発への道が拓けたことは意義が大きい。スキャブロニンGよりも高活性な化合物の創製は有機合成の力を示すものである。新アシルラジカル環化、立体選択的還元試薬、固定化不斉銅触媒、連続反応、エンイン環化異性化に有効な新規キラルNHC配位子の開発は、他の化合物合成に適用可能であるため学術的意義がある。また、マイクロフローリアクターをイミドの形成に有効活用できたのは、本学術領域研究における共同研究の成果であり、意義が大きい。
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