1998 Fiscal Year Final Research Report Summary
Synthetic Studies of Imidazole C-nucleosides aimed at Novel Histomine Ligands
| Project/Area Number |
08672462
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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 | Osaka University of Pharmaceutical Sciences |
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Principal Investigator |
KURIHARA Takushi Osaka University of Pharmaceutical Sciencies, Professor, 薬学部, 教授 (90067281)
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| Project Period (FY) |
1996 – 1998
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| Keywords | histamine / H_3 / receptor / agonist / antagonist / imidazole / C-nucleoside / conformation |
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| Research Abstract |
We recently reported the beta-stereoselective synthesis of C-4 linked imidazole nucleosides, On the basis of what we have now, we became interested in the synthesis of the four possible stereoisomerers of a novel imidazole C-nucleoside (ICN) analogues in which the imidazole and amino groups were restricted across a tetrahydrofuran ring. A synthetic route to the four possible stereoisomers of a novel 2' 3' dideoxyimidazole C-nucleoside derivative was at first developed via the efficient use of PhSe group from L-glutamic acid. The key intermediates selenolactols were successively derived to the respective 5 arnino-2', 3' -dideoxy-ICN derivatives in excellent yields Their enantiomers were provided via nucleosides from D-glutarnic acid by the same methodology. The four isomers of 5' Amino-2', 3' didehydro-2' 3' dideoxy-ICN were also synthesized via oxidative elimination the C2'-phenylselenyl group of the intermediates. Further, 4(5)-(5-aminomethylfuran-2-yl)-1H-imidazole (5) was synthesized starting from D-ribose. Of particular interest, only (+)-4(5)-{(2R,5R)-5-(aminomethyl)-tetrahydrofuran-2-yl}imidazole named imifuramine, was identified as a H_3 agonist by in vivo brain microdialysis.
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