SYNTHESIS OF ALLOPURINOL AND 4-AMINO-1H-PYRAZOLO[3,4-D]PYRIMIDINE N1-(BETA-D-ARABINOFURANOSIDES) AND N2-(BETA-D-ARABINOFURANOSIDES)

Abstract

Allopurinol and 4-amino-1H-pyrazolo[3,4-d]pyrimidine N1- and N2-(D-arabinofuranosides) have been synthesized. Nucleobase anion glycosylation of 4-methoxy-1H-pyrazolo[3,4-d]-pyrimidine (7) with the alpha-D-arabinofuranosyl chloride 6a proceeds stereoselectively and affords the N1-(beta-D-nucleoside) 8 as the main product (43% yield) together with the N2 isomer 10 (25% yield). The formation of the alpha-anomer 9 (6% yield) results from the beta-D-arabinofuranosyl chloride 6b being formed upon chlorination of the nitrobenzoate 5. Compounds were deprotected (11-13) and subjected to nucleophilic displacement reactions affording allopurinol and 8-aza-7-deazaadenine N1- and N2-(arabinonucleosides) 1b, 2b, 3, and 4b. The anomeric configuration and the position of glycosylation have been established by 1D H-1-NOE difference spectroscopy. Compound 3 has proved to be a substrate of adenosine deaminase with a half-life 100-fold longer than that of ara-A.