Synthesis of 4(5)-[5-(aminomethyl)tetrahydrofuran-2-yl- or 5-(aminomethyl)-2,5-dihydrofuran-2-yl]imidazoles by efficient use of a PhSe group: Application to novel histamine H-3-ligands

(+)-4(5)-[(2R,5S)-(5-Aminomethyl)tetrahydrofuran-2-yl]imidazole 1 and its C 2' epimer (-)-2, which are the 5'-amino derivatives of a novel imidazole C- nucleoside, were synthesized via beta- and alpha-2'-phenylselenenyl nucleos ides 15 and 16. The anomers 15 and 16 were provided by a new synthetic meth od for C-nucleosides via the elimination of PhSeCl and selenocyclization fr om diol intermediates 12 and 14, starting from L-glutamic acid. Their ent-1 and ent-2 (imifuramine), the latter of which was indicated as a novel type of histamine H-3-agonist confirmed by an in vivo brain microdialysis metho d, were synthesized by the same methodology from D-glutamic acid. The four isomers (3, 4, ent-3, and ent-4) of a 4(5)-[(5-aminomethyl)-2,5-dihydrofura n-2-yl]imidazole were also synthesized via the oxidative elimination of-the PhSe group of the key intermediates (15, 16, ent-15, and ent-16). In conne ction with this study, 4(5)-(5-aminomethylfuran-2-yl)-1H-imidazole (5) was also synthesized starting from D-ribose.