| Project/Area Number |
10671999
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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 | Tokyo University of Pharmacy & Life Science |
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Principal Investigator |
KIBAYASHI Chihiro Tokyo University of Pharmacy & Life Science, School of Pharmacy, Professor, 薬学部, 教授 (80057330)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAZAKI Naoki Tokyo University of Pharmacy & Life Science, School of Pharmacy, Assistant Professor, 薬学部, 講師 (30277264)
AOYAGI Sakae Tokyo University of Pharmacy & Life Science, School of Pharmacy, Associate Professor, 薬学部, 助教授 (30212385)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | poison-dart alkaloids / pumiliotoxin A / pumiliotoxin 225F / asymmetric synthesis / exocyclic alkenyl group / palladium-catalyzed carbonylation / プミリオトキシン 229F |
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| Research Abstract |
A versatile general approach for preparing the pumiliotoxin alkaloids has been developed employing Pd-catalyzed cross-coupling reaction between a homoallylic organozinc and a vinyl iodide, which led to the convergent asymmetric synthesis of pumiliotoxin A and 225F.The (Z)-alkylideneindolizidine, which is a common organic part of the organozinc reagent in this approach, was synthesized with a high degree of stereocontrol using HfClィイD24ィエD2-mediated addition of the allenylsilane to (S)-2-acetylpyrrolidine and subsequent intramolecular lactonization by Pd-catalyzed carbonylation as key steps. In the course of this investigation, the synthesis of (-)-pumiliotoxin 225F was achieved for the first time. The homoallyl iodide thus obtained was converted via halogenmetal exchange with t-BuLi followed by transmetalation with ZnClィイD22ィエD2 into the homoallylic zinc derivative, which underwent homoallylalkenyl cross-coupling with the vinyl iodide using Pd(PhィイD23ィエD2)ィイD24ィエD2 catalyst to afford the 1, 5-diene product with complete retention of the configurations. Subsequent provided (+)-pumiliotoxin A in 6% overall yield from the dibromoolefin.
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