| Project/Area Number |
18590009
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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 | Gifu Pharmaceutical University |
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Principal Investigator |
SAJIKI Hironao Gifu Pharmaceutical University, Pharmaceutical Sciences, Professor (50275096)
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| Co-Investigator(Kenkyū-buntansha) |
MAEGAWA Tomohiro Gifu Pharmaceutical University, Pharmaceutical Sciences, Asociate Professor (40363890)
MONGUCHI Yasunari Gifu Pharmaceutical University, Pharmaceutical Sciences, Assistant Professor (40433205)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥4,020,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Organic Chemistry / Palladium / Deuteration / Deuterium Generation / Labeled by Stable-Isotope / 重水素ガス調製法 |
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| Research Abstract |
The Pd/C-catalyzed H_2-D_2 exchange reaction between D_2O and H_2 and its application to the preparation of deuterium labeled compounds have been demonstrated. H_2 sealed in the reaction flask was efficiently converted into pure D_2, which can be used for the one-pot reductive deuteration of a variety of reducible functionalities. Furthermore, the chemoselective deuterogenation of olefins and acetylenes was accomplished by the addition of a trace amount of Ph_2S with retention of the various other reducible functionalities. A method of capturing the generated D_2 gas was also developed. The significant features of the H_2-D_2 exchange reaction are efficiency, inexpensiveness, environmental-friendly and convenience. Furthermore, a simple, mild, and regioselective H-D exchange reaction at the benzylic sites using the heterogeneous Pd/C as a catalyst without expensive D_2 gas was developed. The present method can afford the corresponding deuterium-labelled compounds with excellent deuterium efficiency. The use of 10% Pd/C in the presence of a small amount of hydrogen gas could achieve an efficient H-D exchange using the less expensive D-2O as the deuterium source at room temperature for 72 h. Furthermore, this reaction is dramatically accelerated under mild heating (50℃) conditions, resulting in shortening the reaction time and expanding the applicability of the substrates. The H-D exchange reaction could also be used for the deuteration of benzyl ethers, which were generally unstable under Pd/C-catalyzed hydrogenation conditions, with a high deuterium efficiency using Pd/C(en) instead of Pd/C. Furthermore, the use of THE and D_2O mixed (7:3) solvent successfully suppressed the hydrogenolysis of the corresponding benzyl ether. The present method would also be very useful for the simplification of complex ^1H NMR charts.
The general utility of these methodologies will make such simple techniques an attractive addition to the wide range of deuteration procedures.
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