SYNTHESIS OF (PURIN-6-YL)ACETATES AND THEIR TRANSFORMATIONS TO 6-(2-HYDROXYETHYL)- AND 6-(CARBAMOYLMETHYL)PURINES

Dedicated to Dr. Alfred Bader for his generous support of chemical research and education. 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 re-actions 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