Synthesis of 6-Amino-, 6-Methyl- and 6-Aryl-2-(hydroxymethyl)purine Bases and Nucleosides

Abstract

An efficient methodology of the synthesis of 6-substituted 2-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed. Regioselective Pd-catalyzed cross-coupling reactions of 6-chloro-2-iodopurines with [(benzoyloxy)methyl]zinc iodide gave 2-[(benzoyloxy)-methyl]-6-chloropurines that were converted to 2-(hydroxymethyl)adenines by reactions with ammonia and to 6-methyl- or 6-aryl-2-(hydroxymethyl)purines by cross-coupling reactions with trimethylaluminium or arylboronic acids followed by deprotection. The title 6-substituted 2-(hydroxymethyl)purine bases and nucleosides did not exhibit significant cytostatic or anti-HCV activity.