| Abstract
| - X-ray crystal structures of several 6-(azolyl)purine base and nucleoside derivatives show essentiallycoplanar conformations of the purine and appended 6-(azolyl) rings. However, the planes of the purineand imidazole rings are twisted ∼57° in a 2-chloro-6-(4,5-diphenylimidazol-1-yl)purine nucleoside, anda twist angle of ∼61° was measured between the planes of the purine and pyrrole rings in the structureof a 6-(2,5-dimethylpyrrol-1-yl)purine nucleoside derivative. Shielding “above” N7 of the purine ring bya proximal C−H on the 6-azolyl moiety is apparent with the coplanar compounds, but this effect isdiminished in those without coplanarity. Syntheses of 6-(azolyl)purines from both base and nucleosidestarting materials are described. Treatment of 2,6-dichloropurine with imidazole gave 2-chloro-6-(imidazol-1-yl)purine. Modified Appel reactions at C6 of trityl-protected hypoxanthine and guanine derivativesfollowed by detritylation gave 6-(imidazol-1-yl)- and 2-amino-6-(imidazol-1-yl)purines. Imidazole wasintroduced at C6 of 2‘,3‘,5‘-tri-O-acetylinosine by a modified Appel reaction, and solvolysis of the glycosyllinkage gave 6-(imidazol-1-yl)purine. Guanosine triacetate was transformed into the protected 2,6-dichloropurine nucleoside, which was subjected to SNAr displacement with imidazoles at C6 followedby glycosyl solvolysis to provide 2-chloro-6-(substituted-imidazol-1-yl)purines. Potential applications ofthese purine derivatives are outlined.
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