2015 Fiscal Year Final Research Report
Development of New Means of Asymmetric Halogenation and Total Synthesis of Bioactive Halogenated Natural Products
| Project/Area Number |
24590008
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Chemical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
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| Project Period (FY) |
2012-04-01 – 2016-03-31
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| Keywords | ジクロロ化 / 不斉合成 / 全合成 / 有機ハロゲン化合物 / 抗生物質 / ナピラジオマイシンン / 創薬 |
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| Outline of Final Research Achievements |
The chemical synthesis of organohalogens has become a focal point of intensive studies in organic synthesis. In the present study, we established a synthetic route to napyradiomycin A1, a chlorinated antibiotic isolated from the culture broth of Chainia rubra MG802-AF1. Extensive screening of amine ligands in combination with Willgerodt reagent (PhICl2) led to the development of a C2-symmetric catalyst applicable to asymmetric dichlorination of allylic alcohols. We have also found that an enantioenriched dichloride is produced from a dehydro-α-lapachone derivative in some, albeit small, degree of asymmetric induction under the Nicolaou conditions using (DHQD)2PHAL-PhICl2, paving the way to asymmetric synthesis of the natural antibiotic. In addition, biological evaluation of the synthetic intermediates has culminated in the discovery of a new analogue useful for further medicinal studies.
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| Free Research Field |
化学系薬学
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