| Project/Area Number |
09557199
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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 | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | Kanazawa University |
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Principal Investigator |
HANAOKA Miyoji Faculty of Pharmaceutical Sciences, Kanazawa University Professor, 薬学部, 教授 (80028844)
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| Co-Investigator(Kenkyū-buntansha) |
EKIMOTO Hisao Nippon Kayaku, Division of Antitumor Drug, Chief Researcher, 制癌剤創薬部門, 主任研究員
KATAOKA Osamu Faculty of Pharmaceutical Sciences, Kanazawa University Research Associate, 薬学部, 助手 (40303292)
MUKAI Chisato Graduate School of Natural Science and Technology, Kanazawa University Professor, 大学院・自然科学研究科, 教授 (70143914)
杉本 雄一 金沢大学, 薬学部, 助手 (90226465)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1997: ¥8,100,000 (Direct Cost: ¥8,100,000)
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| Keywords | benzophenanthridine / protoberberine / marine alkaloid / biomimetic synthesis / total synthesis / anititumor activity / ニチジン / 抗腫瘍性化合物 / 交叉耐性 / ベンゾフェナンスリジンアルカロイド / プロトベルベリンアルカロイド / コリノリン / アンビニン / 生合成経路 / パラジウム錯体 / カップリング反応 |
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| Research Abstract |
1. A simple and general synthesis of protoberberines and 13-methylprotoberberines via the same synthetic intermediates was newly developed. This method was applied to a new synthesis of protoberberine alkaloids.
2. A novel biomimetic synthesis of benzophenanthridines form protoberberines through the enamine intermediates was developed. Benzophenanthridine alkaloids such as chelerythrine and nitidine were synthesized by this method.
3. A new and simple synthesis of isocoumarins was developed employing palladium-catalyzed cyclization of o-alkenylbenzoic acids. This method was applied to a synthesis of a benzophenanthridine.
4. Synthesis of hexahydrobenzophenanthridine alkaloids, corynoline and its stereoisomeric alkaloids from corresponding 13-methylprotoberberine alkaloid, corysamine was succeeded through a newly developed biomimetic route. An alkaloid having a unique substitution pattern, ambinine was totally synthesized by this method.
5. A pyridoacridine skeleton was synthesized by a coupling reaction of quinoline derivative with phenylboric acid or phenyltin compound. Synthesis of antitumor marine alkaloids, cystodytin J and deplamine, was successfully realized by this method.
6. We found a benzophenanthridine compound having high antitumor activity as well as activity against drug-resistant tumor cell.
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