Efficient Synthesis of trans- or cis-4(5)-(5-Aminomethyltetrahydrofuran-2-yl)imidazoles via Diazafulvene Intermediates: Synthetic Approach toward Human Histamine H_4-Ligands

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(+)-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 H_4-receptor ligands.The improved synthesis of (+)-1 was done via cyclization of a diazafulvene intermediate generated by Bu_3,P/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-β-D-ribofuranosyl)imidazole-l-carboxylate (35) via the four steps involving deoxygenation.
公益社団法人日本薬学会の論文
2003-07-01