Collect. Czech. Chem. Commun. 2005, 70, 1669-1695

Synthesis of 2-Substituted 6-(Hydroxymethyl)purine Bases and Nucleosides

Peter Šilhár, Radek Pohl, Ivan Votruba 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, CZ-166 10 Prague 6, Czech Republic


A facile and efficient methodology of the synthesis of 6-(hydroxymethyl)purine derivatives (bases and nucleosides) was developed based on Pd-catalyzed cross-coupling reactions of 6-halopurines or N-protected 2-amino-6-halopurines with (benzoyloxymethyl)zinc iodide followed by deprotection. Regioselective hydroxymethylations of 2,6-dihalopurines were also studied and used for the synthesis of 2-chloro-6-(hydroxymethyl)- or 2,6-bis(hydroxymethyl)purines. The 6-(hydroxymethyl)purine ribonucleoside 5f exerted high cytostatic effect and moderate inhibition of adenosine deaminase, while all the other derivatives were much less effective or entirely inactive.

Keywords: Purines; Nucleosides; Cross-coupling reactions; Hydroxymethylation; Palladium; Functionalized organozinc reagents; Cytostatic activity; Adenosine deaminase.

References: 48 live references.