Synthesis of allopurinol and 4-amino-1H-pyrazolo[3,4-d]pyrimidine N1- and N2-(β-D-arabinofuranosides)

✍ Scribed by Seela, Frank ;Winter, Holger

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 547 KB
• Volume: 1991
• Category: Article
• ISSN: 0947-3440
• DOI: 10.1002/jlac.199119910120

✦ Synopsis

Abstract

Allopurinol and 4‐amino‐1H‐pyrazolo[3,4‐d]pyrimidine N^1^‐and N^2^‐(D‐arabinofuranosides) have been synthesized. Nucleobase anion glycosylation of 4‐methoxy‐1H‐pyrazolo[3,4‐d]‐pyrimidine (7) with the α‐D‐arabinofuranosyl chloride 6a proceeds stereoselectively and affords the N^1^‐(β‐D‐nucleoside) 8 as the main product (43% yield) together with the N^2^ isomer 10 (25% yield). The formation of the α anomer 9 (6% yield) results from the β‐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 N^1^‐and N^2^‐(arabinonucleosides) 1b, 2b, 3, and 4b. The anomeric configuration and the position of glycosylation have been established by 1D ^1^H‐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.