Synthesis of a mutagenic nucleoside, 2'-deoxy-2-(p-nitrophenyl)-adenosine

The reaction of 2-amino-6-chloropurine riboside with i-amyl nitrite in benzene in the presence of Cu2O, followed by treatment with NH3/MeOH gave 2-phenyladenosine (1). The crude sample of 1 was found to be mutagenic to bacteria (Salmonella typhimurium TA 98 and TA 100, without metabolic activation). When this material was subjected to high pressure liquid chromatography, the mutagenic activity was found only in contaminating minor components, whose structures were assigned as 2-(m- and p-nitrophenyl)-adenosines (2m,p). In order to study structure-activity relationships, several nucleoside and base analogues were synthesized. Among them, 2'-deoxy-2-(p-nitrophenyl)-adenosine (8) was the most potent mutagen as tested either with TA 98 or TA 100.