Efficient and β-stereoselective synthesis of 4(5)-methyl-5(4)-(5- amino-5-deoxy-β-D-ribofuranosyl)imidazole and related compounds exhibiting antiulcer activity

Article abstract of 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 1.5 n HCl in refluxing tetrahydrofuran gave the β-4(5)-ribofuranosylimidazole 19 (35%) and the ribosylimidazole 18 (51%). The latter was converted into β-19 in 86% yield by the Mitsunobu cyclization. This synthetic method produced only the desired β-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.

Full text of DOI:10.1248/cpb.45.53

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