| Project/Area Number |
13672207
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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 | CHIBA UNIVERSITY |
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Principal Investigator |
NISHIDA Atsushi CHIBA UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, PROFESSOR, 大学院・薬学研究院, 教授 (80130029)
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| Co-Investigator(Kenkyū-buntansha) |
ARISAWA Mitsuhiro CHIBA UNIVERSITY, GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, ASSISTANT PROFESSOR, 大学院・薬学研究院, 助手 (40312962)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Asymmetric Diels-Alder reactions / BINAMIDE / Yb(OTf)_3 / sarkomycin / TXA2 antagonist / allylic halogenation / Pictet-Spengler reaction / サルコマイシン / トロンボキサンA_2拮抗剤 / NBS / Fischerインドール合成 / ピロロインドール / シロキシジエン / 軸不斉配位子 / 2,2'-diaminobinaphthalene / 不斉Diels-Alder反応 / Sarkomycin / Yb(Otf)_3 / 閉環メタセシス / Poctet-Spengler反応 / テトラヒドローβ-カルボリン |
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| Research Abstract |
1) Asymmetric Diels-Alder reactions of cyclopentadiene and several dienophiles catalyzed by a chiral ytterbium complex prepared by a noble axially asymmetric chiral ligand, BINAMIDE and Yb(OTf)_3 were investigated.
The reaction with bromoacryloyl amide afforded cyclo-adduct in 97% yield with 98% de and with 93% ee. The adduct was converted cyclosarkomycin, a key intermediate for the synthesis of antitumor antibiotics sarkomycin (overall 6%, 10 steps). Although a diastereoselective synthesis of optically active cyclosarkomycin has been reported, this is the first catalytic enentioselective synthesis cyclosarkomycin.
The reaction with a fumaric acid derivative gave a mixture of adduct in 83% yield with 52% de and with 84% ee. The adduct was converted to a key intermediate for the synthesis of TXA2 antagonist, ONO-8809 which was developed by Ono company. This fumaric acid derivative also reacted with siloxydiene to give a cyclohexene derivative with low enantioselectivity (13% ee).
2) A new allylic halogenation and Pictet-Spengler reaction of imines, both catalyzed by Yb(OTf)_3 were developed. Asymmetric version of these reactions will be developed in future.
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