2010 Fiscal Year Final Research Report
Synthetic studies on antitumor active molecules utilizing of sequential cyclizations
| Project/Area Number |
20590018
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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 | Meiji Pharmaceutical University |
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Principal Investigator |
NAGAOKA Hiroto Meiji Pharmaceutical University, 薬学部, 教授 (30155915)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 抗腫瘍活性物 / ヨウ化サマリウム / 連続環化 / δ-トコトリエノール / コリオリン / パクリタキセル / シクロペンタノン誘導体 / 光学活性シクロペンタノン |
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| Research Abstract |
The synthetic studies on several antitumor active compounds including δ-tocotrienol, coriolin and paclitaxel were performed. The following results, 1) to 4), were provided by this study. 1) A novel and short step synthetic route for δ-tocotrienol was developed. 2) In the course of the synthetic studies on coriolin, samarium (II) iodide-induced cascade reaction involving reductive coupling-Dieckmann condensation of bis-α, β-unsaturated esters bearing tert-butyldimethylsilyloxy group at δ-position to highly diastereo- and regioselectively produce bicyclo [3. 3. 0] octane ring systems in optically active form. 3) A stereoselective and efficient synthetic route for the C ring system of paclitaxel was developed. 4) Cascade reaction involving reductive cyclization, Dieckmann condensation, and lactonization of E- and Z-dimethyl 2-methyl-8-oxoundec-2-enedioates and Z-dimethyl 2-methyl-7-oxodec-2-enedioate with samarium (II) iodide was found to stereospecifically produce cis and trans bicyclo [4. 4. 0] decane ring systems and trans bicyclo[4.3.0]nonane ring system each consisting of γ-lactone, respectively.
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