Collect. Czech. Chem. Commun. 2009, 74, 1035-1059
Published online 2009-07-07 15:15:08

Synthesis of (purin-6-yl)acetates and their transformations to 6-(2-hydroxyethyl)- and 6-(carbamoylmethyl)purines

Zbyněk Hasník, Radek Pohl, Blanka Klepetářová and Michal Hocek*

Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, v.v.i., Gilead Sciences & IOCB Research Center, Flemingovo nám. 2, CZ-166 10 Prague 6, Czech Republic


A novel approach to the synthesis of (purin-6-yl)acetates was developed based on Pd-catalyzed cross-coupling reactions of 6-chloropurines with a Reformatsky reagent. Their reduction with NaBH4 and treatment with MnO2 gave 6-(2-hydroxyethyl)purines, while reactions with amines in presence of NaCN afforded 6-(carbamoylmethyl)purines. Mesylation of the 6-(2-hydroxyethyl)purines followed by nucleophilic substitutions gave rise to several 6-(2-substituted ethyl)purines. This methodology was successfully applied to the synthesis of substituted purine bases and nucleosides for cytostatic and antiviral activity screening. None of the compounds exerted significant activity.

Keywords: Purines; Nucleosides; Organozinc reagents; Cross-coupling; Reformatsky reagent; Functionalized organometallics.

References: 46 live references.