2006 Fiscal Year Final Research Report Summary
Medicinal Chemistry Based on the Rational Design of the Chemical Reactions
| Project/Area Number |
17590087
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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 |
Drug development chemistry
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| Research Institution | Nagoya Institute of Technology |
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Principal Investigator |
SHIBATA Norio Nagoya Institute of Technology, Chemistry, Associate Professor, 工学研究科, 助教授 (40293302)
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| Co-Investigator(Kenkyū-buntansha) |
TORU Takeshi Nagoya Institute of Technology, Chemistry, Professor, 工学研究科, 教授 (00163957)
NAKAMURA Shuichi Nagoya Institute of Technology, Chemistry, Assistant Professor, 工学研究科, 助手 (20335087)
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| Project Period (FY) |
2005 – 2006
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| Keywords | fluorine / catalyst / cinchona alkaloids / bis (oxazoline) / nickel / asymmetric synthesis / biologically active |
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| Research Abstract |
The selective construction of carbon-fluorine bonds is of great interest to medicinal chemists because the replacement of hydrogen and oxygen atoms with fluorine atom in biologically active molecules can confer molecules with improved physicochemical properties and biological activities. Since the first discovery of enantioselective fluorination using N-fluorocamphorsultam, our synthetic interests have been focused on the development of chiral N-fluorosulfonamide derivatives capable of enantioselective fluorination. However, these initial efforts revealed several limitations in both chemical yields and enantioselectivities of the fluorinated products. We developed the novel enantioselective fluorination reactions and applied of the methods to the design and synthesis of fluoroisosteres of biologically active natural products. Two novel approaches using the cinchona alkaloids/Selectfluor【○!R】 combination and bis(oxazoline)-Ph have been pursued respectively. Cinchona alkaloid/Selectfluor【○!R】 combination, i.e., N-fluoroammonium salts of cinchona alkaloids, was found to be an effective enantioselective fluorinating reagent for a wide range of substrates such as silyl enol ethers, beta-keto esters, arylcyanoesters, and oxindoles without any additives. The bis(oxazoline)-Ph was found to be an efficient and unique catalyst for enantioselective fluorination in the presence of a catalytic amount of metal salts. An interesting phenomenon, "elective" enantioselectivity, has been observed in the fluorination of beta-keto esters. Switching the metal catalyst from copper to nickel in the presence of the same bis(oxazoline)-Ph gave a complete reversal of enantioselectivity.
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Research Products
(26 results)
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[Journal Article] Efficient Synthesis of Bicyclic α-Hydroxy-α-trifluoromethyl-γ-lactams2006
Author(s)
Shibata, Norio, Fujimoto, Hiroyuki, Mizuta, Satoshi Ogawa, Shinichi, Ishiuchi, Yumi, Nakamura, Shuichi Toru, Takeshi
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Journal Title
Synlett (20)
Pages: 3484-3488
Description
「研究成果報告書概要(欧文)」より
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