2010 Fiscal Year Final Research Report
Preparation of functionalized organofluorine compounds toward drug discovery
| Project/Area Number |
20590013
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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 and Life Science |
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Principal Investigator |
TAGUCHI Takeo Tokyo University of Pharmacy and Life Science, 薬学部, 教授 (00016180)
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| Co-Investigator(Kenkyū-buntansha) |
YANAI Hikaru 東京薬科大学, 薬学部, 助教 (10408685)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 有機フッ素化学 / フルオロアルケン / ペプチドイソスター / トリフルオロメチル / トリフリル基 / 炭素酸 |
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| Research Abstract |
On the basis of characteristic features of fluorinated organic molecules our research project consists of the following two parts ; (1) development of versatile synthetic methods for organo fluorine compounds directed to medicinal chemistry and (2) new carbon acid chemistry toward efficient catalysis of common synthetic reactions. Concerning the former subject we have successfully achieved the following reactions : (1)Regio and stereoselective synthesis of fluorinated olefins through the defluorinative allylic alkylation of difluorohomoallylic alcohols by copper mediated Grignard reaction or by copper free alkylaluminium reaction, and the further elaboration for the preparation of the corresponding dipeptide isosteres. (2)An efficient preparation of 1-fluoroalkenyl ester utilizing low valent chromium chemistry and the investigation of their reactivity as double acylating reagents. (3)Preparation of α,α-difluoroketone derivatives through the unique reaction of trifluoroacetaldehyde N,O-acetals with alkyllithium reagents. In the latter subject, we found that tetrakis(1,1,3,3-trifluoromethanesulfonyl)propane works as an extremely effective catalyst for the carbon-carbon bond forming reactions of enol silyl ethers as nucleophiles with carobonyl compounds such as α,β-unsaturated ketones, α,β-unsaturated aldehydes and sterically hindered ketones.
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