Efficient synthesis of trans- or cis-4(5)-(5-aminomethyltetrahydrofuran-2-yl)imidazoles via diazafulvene intermediates: synthetic approach toward human histamine H4)-ligands.
(+)-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.
Harusawa
Shinya
S
Department of Synthetic Organic Chemistry, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan.
Araki
Lisa
L
Terashima
Hirotaka
H
Kawamura
Makoto
M
Takashima
Seiichiro
S
Sakamoto
Yasuhiko
Y
Hashimoto
Takeshi
T
Yamamoto
Yumiko
Y
Yamatodani
Atsushi
A
Kurihara
Takushi
T
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
C418607:HRH4 protein, human; D007093:Imidazoles; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C113487:diazafulvene