1999 Fiscal Year Final Research Report Summary
Development of asymmetric synthetic method for organofluorine compounds of biological interests
| Project/Area Number |
09672163
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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, School of Pharmacy, Professor, 薬学部, 教授 (00016180)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Hisanaka Tokyo University of Pharmacy and Life Science, School of Pharmacy, Assistant (70287457)
KITAGAWA Osamu Tokyo University of Pharmacy and Life Science, School of Pharmacy, Lecturer, 薬学部, 講師 (30214787)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Difluorocyclopropane / Glutamic acid / Cyclopropylglycine / Methylenecyclopropane / Clasen rearrangement / Asymmetric synthesis / Diels-Alder reaction / lodoaminocyclization / Atropisomers |
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| Research Abstract |
As our continuous studies on development of new synthetic methods for organofluorine compounds directed to the synthesis of fluoro analogs of biologicaly interesting substrates, we have focused develop asymmetric synthetic methods for organofluorine compounds during these three years with the financial support in part from the Ministry of Education, Science, Sports and Culture.
Our achievements are summarized as follows.
(1) We have synthesized fuctionalized difluorocyclopropane derivatives in optically active form from glyceraldehyde as a chiral precursor, which are used for the preparation of conformationlly restricted glutamate analogs (FィイD22ィエD2CCGs). Pharmacological evaluation of FィイD22ィエD2CCGs was also investigated.
(2) We have succeeded in establishing the efficient synthetic methods for methylenedifluorocyclopropanes, which are revealed to have unique properties such as highly reactive Michael acceptor.
(3) For the construction of a fluorine substituted chiral tertiary carbon in optically pure form, we have examined the asymmetric Diels-Alder reaction of 2-fluoroacrylate and we applied our results to the preparation of conformationally restricted glutamate analog having norbornane structure.
(4) We have found an efficient enantioselective Claisen rearrangement promoted by the chiral borane complex as a Lewis acid, which opened a new synthetic method for optically active functionalized difluoromenthylene compounds. We have also achieved N-selective iodocyclization reaction of amide derivatives controlled by metallic reagent. As a new class of asymmetric reactions, we have developed several reactions using atropisomeric anilide derivatives.
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