title: Efficient synthesis of trans- or cis-4(5)-(5-aminomethyltetrahydrofuran-2-yl)imidazoles via diazafulvene intermediates: synthetic approach toward human histamine H4)-ligands.
abstract: (+)-4(5)-[(2R,5R)-5-aminomethyltetrahydrofuran-2-yl]imidazole [(+)-1, imifuramine] and its 2R,5S-stereoisomer (+)-2 were expected as base compounds to develop selective human histamine H4-receptor ligands. The improved synthesis of (+)-1 was done via cyclization of a diazafulvene intermediate generated by Bu3P/N,N,N',N'-tetramethylazodicarboxamide (TMAD) treatment of a diol 17ab bearing an unsubstituted imidazole moiety in good yields. This methodology also afforded an alternative synthetic route to trans- and cis-ethyl 4(5)-(5-hydroxymethyltetrahydrofuran-2-yl)imidazole carboxylates (5 and 6), reported previously. Also, 4(5)-[(2R,5S)-5-aminomethyltetrahydrofuran-2-yl]imidazole (+)-2 was synthesized from ethyl 4(5)-(2-deoxy-beta-D-ribofuranosyl)imidazole-1-carboxylate (35) via the four steps involving deoxygenation.
authors.affiliation: Department of Synthetic Organic Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Harusawa
authors.forename: Lisa
authors.initials: L
authors.lastname: Araki
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Terashima
authors.forename: Makoto
authors.initials: M
authors.lastname: Kawamura
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Takashima
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Sakamoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamatodani
authors.forename: Takushi
authors.initials: T
authors.lastname: Kurihara
mesh_terms: D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000378:metabolism; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; D013237:Stereoisomerism
chemical_list: C418607:HRH4 protein, human; D007093:Imidazoles; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C113487:diazafulvene