Abstract
A large scale preparation of 2-haloadenosines (1) was attained by acetylation of 2-haloinosines (3), followed by chlorination and amination. 2-Alkoxyadenosines (5) were prepared in fairly good yields by protection of both 2'- and 3'-hydroxyl groups of 2-chloroadenosine (1a) or 2-chloroinosine (3a), followed by substitution of the chlorine atom with alkoxy group. In the reaction of 1a with sodium alkoxide, there were obtained some oligomers of 5, of which the structures were elucidated. The reaction of 5-amino-4-cyano-1-β-D-ribofuranosylimidazole with carbon disulfide afforded 2, 6-di-mercapto-9-β-D-ribofuranosylpurine (15), which was converted to 2-mercaptoadenosine (14e) and its S-substituted derivatives. 2-Phenylaminoadenosine (29e) was prepared with comparative ease via 2-phenylamino-2', 3', 5'-tri-O-acetylinosine (32), the synthesis of which was effected by acetylation of 2-phenylaminoinosine (30) with acetylchloride in acetic acid. Many 2-substituted adenosines including O-substituted 2-hydroxyadenosines, S-substituted 2-mercaptoadenosines, N2-substituted 2-aminoadenosines, 2-alkyl- and -aryl-adenosines were prepared, among which several compounds were found to have a remarkable coronary vasodilating potency. Compound (29e) showed not only a strong potency, but also a longer duration of the effect than that of 1a. The structure-coronary vasodilating activity relationship was also discussed.
