EFFICIENT AND BETA-STEREOSELECTIVE SYNTHESIS OF 4)-(5-AMINO-5-DEOXY-BETA-D-RIBOFURANOSYL)IMIDAZOLE AND RELATED-COMPOUNDS EXHIBITING ANTIULCER ACTIVITY

The reaction of 2,3,5-tri-O-benzyl-D-ribose with the lithium salt of a n imidazole derivative gave an adduct 17RS. Treatment of 17RS with 1.5 N HCl in refluxing tetrahydrofuran gave the beta-4(5)-ribofuranosylimi dazole 19 (35%) and the ribosylimidazole 18 (51%). The latter was conv erted into beta-19 in 86% yield by the Mitsunobu cyclization. This syn thetic method produced only the desired beta-anomer. Protection of the imidazole nitrogen of 19 with an ethoxycarbonyl group followed by deb enzylation gave 21, which was successively derived to the 5'-amino der ivative I via the 5'-substituted phthalimide 23, followed by hydrazine degradation in excellent yield. Compound I was then converted into th e 5'-cyanoguanidine 2 in 79% yield. The 5'-amino derivatives 3-9 lacki ng a methyl group were efficiently synthesized. Among them, the cyanog uanidine 5 and phenylthiourea 8 exhibited antiulcer activities with ha lf the efficacy of cimetidine. The molecular conformation of 5 was det ermined by X-ray structure analysis.