Harusawa S, Moriyama H, Murai Y, Imazu T, Ohishi H, Yoneda R, Kurihara T, Hata H, Sakamoto Y
Osaka University of Pharmaceutical Sciences, Japan.
Chem Pharm Bull (Tokyo). 1997 Jan;45(1):53-61. doi: 10.1248/cpb.45.53.
The reaction of 2,3,5-tri-O-benzyl-D-ribose with the lithium salt of an imidazole derivative gave an adduct 17RS. Treatment of 17RS with 1.5N HCl in refluxing tetrahydrofuran gave the beta-4(5)-ribofuranosylimidazole 19 (35%) and the ribosylimidazole 18 (51%). The latter was converted into beta-19 in 86% yield by the Mitsunobu cyclization. This synthetic method produced only the desired beta-anomer. Protection of the imidazole nitrogen of 19 with an ethoxycarbonyl group followed by debenzylation gave 21, which was successively derived to the 5'-amino derivative 1 via the 5'-substituted phthalimide 23, followed by hydrazine degradation in excellent yield. Compound 1 was then converted into the 5'-cyanoguanidine 2 in 79% yield. The 5'-amino derivatives 3-9 lacking a methyl group were efficiently synthesized. Among them, the cyanoguanidine 5 and phenylthiourea 8 exhibited antiulcer activities with half the efficacy of cimetidine. The molecular conformation of 5 was determined by X-ray structure analysis.
2,3,5-三-O-苄基-D-核糖与咪唑衍生物的锂盐反应生成加合物17RS。在回流的四氢呋喃中用1.5N盐酸处理17RS，得到β-4(5)-呋喃核糖基咪唑19（产率35%）和核糖基咪唑18（产率51%）。后者通过光延环化以86%的产率转化为β-19。这种合成方法仅产生所需的β-异头物。用乙氧羰基保护19的咪唑氮，然后脱苄基得到21，21通过5'-取代的邻苯二甲酰亚胺23依次衍生为5'-氨基衍生物1，随后用肼降解，产率优异。然后将化合物1以79%的产率转化为5'-氰基胍2。高效合成了缺少甲基的5'-氨基衍生物3-9。其中，氰基胍5和苯硫脲8表现出抗溃疡活性，效力为西咪替丁的一半。通过X射线结构分析确定了5的分子构象。
