Synthetic Studies of Imidazole C-nucleosides aimed at Novel Histomine Ligands

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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.