| Project/Area Number |
10672088
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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 |
医薬分子機能学
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| Research Institution | Osaka University |
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Principal Investigator |
TANAKA Tetsuaki Graduate School of Pharmaceutical Sciences, Osaka University Professor, 薬学研究科, 教授 (40116059)
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| Co-Investigator(Kenkyū-buntansha) |
MAEZAKI Naoyoshi Graduate School of Pharmaceutical Sciences, Osaka University Associate Professor, 薬学研究科, 助教授 (00229296)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Macrocarpal / Synthesis / Arene chromium complex / Benzyl cation / Samarium iodide / Ketyl radical / Radical reaction / ipso-Substitution reaction / キレーション制御 / 炭素炭素結合形成反応 / メトキシ基 / 置換基効果 / マクロカルパアール / アレンクロミウム錯体 / ペンジルカチオン / 立体化学制御 / 脱メチル化 / 炭素炭素形成反応 |
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| Research Abstract |
Macrocarpals exhibiting interesting biological activities such as inhibitory activity of HIV RTase is a coupling at C11 position of the hydrophobic sesquiterpene aromadendrane skeleton and at the benzylic position of the hydrophilic isopentyl phloroglucinol dialdehyde. Totally, they are water-soluble. The key step of the synthesis is the coupling reaction of a cyclic dienol ether corresponding to the aromadendrane part with a hexasubstituted benzene chromium complex as a chiral benzyl cation equivalent. The reaction proceeded with an extremely high stereoselective manner. The synthetic method developed here would be applicable to various compounds bearing different alkyl group from isobutyl group, and furthermore, demethylation procedure could control the deprotection step.
On the way of the total synthesis of macrocarpal C, we found a new radical ipso-substitution reaction of an aromatic methoxy group. This new C-C bond formation reaction would have great possibilities in the filed of synthetic studies. Therefore, the scope and limitations were investigated with model compounds. In this reaction, the distance of the radical and the aromatic ring was found to be crucial. The limitation could be overcome by the chelation control with Sm (II) iodide. Namely, SmIィイD22ィエD2 generates a ketyl radical, and then is chelating intramolecularly to the oxygen atom of the methoxyl group. Therefore, the radical is easily approaching to the aromatic ring, thereby causing C-C bond formation. From these results, it was found that this new reaction takes place by making the radical close to the methoxy group on an aromatic ring.
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