2005 Fiscal Year Final Research Report Summary
Synthetic Studies of Polycyclic Natural Products with Unique Chemical Structures and Potent Biological Activities
| Project/Area Number |
16350049
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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 |
Synthetic chemistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
MIYASHITA Masaaki Hokkaido University, Graduate School of Science, Professor, 大学院・理学研究科, 教授 (50006326)
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| Co-Investigator(Kenkyū-buntansha) |
TANINO Keiji Hokkaido University, Graduate School of Science, Associate Professor, 大学院・理学研究科, 助教授 (40217146)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Norzoanthamine / Zoanthamine / Marine alkaloids / Antiosteoporotic agent / Total synthesis / Solanoeclepin A / Potato cyst nematodes / hatching agent |
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| Research Abstract |
(1)Aymmetric Total Syntheses of Norzoanthamine and Zoanthamine
Norzoanthamine can suppress the loss of bone weight and strength in ovariectomized mice and has been considered a promising candidate for an antiosteoporotic drug. On the other hand, zoanthamine has exhibited potent inhibitory activity toward phorbol myristate-induced inflammation in addition to powerful analgesic effects. The distinctive biological properties and novel chemical structures of this family of alkaloids make them extremely attractive targets for chemical synthesis. However, the chemical synthesis of the zoanthamine alkaloids has impeded by their densely functionalized complex stereostructures. We have achieved the first chemical syntheses of norzoanthamine and zoanthamine based on the synthetic strategy involving the three component coupling reactions, photosensitized oxidation of the furan, and the intramolecular Diels-Alder reaction, as the key steps. The total yield of norzoanthamine was 3.5% in 41 steps, an
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average of 92% yield each step, from 5-methylcyclohexenone. The present synthesis opens a completely chemical avenue to norozoanthamine, zoanthamine, and other zoanthamine alkaloids including synthetic zoanthamine derivatives.
(2)Synthetic Studies of Solanoeclepin A
Solanoeclepin A, isolated from a large quantity of potatoes as the most active hatching agent of potato cyst nematodes, possesses a unique heptacyclic structure containing all ring sizes from three to seven carbocycles with various oxygen functional groups. The synthetic challenges posed by solanoeclepin A include construction of the highly strained tricyclo[5.2.1.0^<1,6>]decane skeleton and the distinctive oxabicylclic system. We have developed an efficient and stereoselective synthetic methodology for the crucial tricyclo[5.2.1.0^<1,6>]decane skeleton based on a novel cyclopentene annulation reaction using 4-methoxy-3-butennitrile and a key intramolecular cyclization reaction of an epoxy nitrile to construct a four membred carbon ring. We also developed a novel coupling reaction of the oxabicylclic system and the tricyclo[5.2.1.0^<1,6>]decane core. Thus, we were able to solve all the synthetic challenges posed by solanoeclepin A. Less
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Research Products
(31 results)
