Collect. Czech. Chem. Commun. 2006, 71, 788-803

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

Peter Šilhár, Radek Pohl, Ivan Votruba, Blanka Klepetářová and Michal Hocek*

Centre for New Antivirals and Antineoplastics, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 16610 Prague 6, Czech Republic


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.

Keywords: Purines; Nucleosides; Cross-coupling reactions; Hydroxymethylation; Palladium; Functionalized organozinc reagents; Cytostatic activity; X-Ray diffraction.

References: 38 live references.