Synthesis of 2-Phenylaminoadenosine from Imidazole Nucleosides

Abstract

Three methods for the synthesis of 2-phenylaminoadenosine (1, CV-1808), a potent coronary vasodilator with prolonged action, were exploited. 1) The reaction of 5-amino-4-cyano-1-(β-D-ribofuranosyl) imidazole (7) with phenyl isothiocyanate gave 7-imino-5-phenylamino-3-(β-D-ribofuranosyl) imidazo [4, 5-d] [1, 3]-thiazine (11), which, on alkaline treatment, rearranged to 6-mercapto-2-phenylamino-9-(β-D-ribofuranosyl) purine (12). On methylation, 12 gave the 6-methylmercapto derivative (14), which was converted to 1 by treatment with ammonia. 2) 5-Amino-4-cyano-1-(β-D-ribofuranosyl) imidazole (7) reacted with phenyl cyanamide in methanolic ammonia, giving 1 and 2-aminoadenosine as a by-product. 3) Ethyl 5-amino-1-(β-D-ribofuranosyl)-4-carboximidate (21b) was directly obtained by treatment of 5-amino-1-(2, 3, 5-tri-O-propionyl-β-D-ribofuranosyl) imidazole-4-carboxamide (4) with Meerwein's reagent followed by deacylation, and this was led to 1 by the reaction with phenyl cyanamide.