| Budget Amount *help |
¥3,710,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
As our continuous studies on development of new synthetic methodologies for organofluorine compounds toward to the preparation of fluoro analogs of biologically important substances or to introduction of fluorine or fluoroalkyl substituent into newly designed molecules based on the characteristic features of fluorine related to biological responses, we have investigated the following research projects during these three years with the financial support in part from the Ministry of Education, Culture, Sports, Science and Technology, Japan. Our achievements are summarized as follows.
(1) Concerning the development of efficient synthetic method for fluorine-substituted functionalized olefins related to the chemical modification of amide bond in biologically active peptides, we have established a completely stereo-controlled method, which involves defluorinative allylic alkylation reaction. This reaction has been applied to the preparation of fluoroolefin analog of pepstatin, aspartyl prote
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ase inhibitory active naturally occurring peptide. As an alternative new synthetic method for fluoroolefinic compounds, we have found that reaction of dibromofluoroalkylated substrates with low valent chromium provides the corresponding fluoroolefinic compounds in stereoselective and functional group selective manner. An efficient preparation of fluoroalkenyl ester compounds has been achieved by this reaction.
(2) For the synthesis of conformationally restricted glutamate analogs to find out selective agonist or antagonist for group II mGluR, we have applied radical addition reaction offluoroiodoacetate to olefin leading to fluorocyclopropane carboxylate, which was developed by us before.
(3) Trifluoromethyl group is widely recognized as an important substituent in drug design, and thus development of new and efficient methods for heterocyclic compounds having trifluoromethyl group using easily available building blocks is of great importance. We have achieved that a variety of quinoline and related derivatives having trifluoromethyl group at 2 position can be prepared by the reaction of 2-aminostyrene derivatives with trifluoroacetaldehyde hemiacetal.
(4) We have developed several bidentate Lewis acids, which can promote the intramolecular cycloaddition reactions of ester tethered substrates, in particular the Diels- Alder reaction of 1,7,9-decatrienoale derivatives involving 2-fluoroacrylate derivatives.
(5) Although application to the fluorine containing substrates will be a future subject, we have successfully developed a highly effective method for the preparation of atropisomeric amide compounds via enantioselective catalytic aromatic amination reaction. Some asymmetric syntheses using these chiral molecules have been also explored. Less
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