10.1021/ol048649m
The study investigates the Mannich-type C-nucleosidation reactions of 2,6-(oxo or amino)-disubstituted 5,8-diaza-7,9-dicarba-purines, a family of nucleobase analogues that are isomeric to natural purine nucleobases like adenine and guanine. The researchers synthesized various purinoids (1-4) and their adenine analogue using different chemical methods. For instance, the guanine analogue (2) was synthesized from N-formyl-glycyl-guanidine and trichloroacetonitrile through a series of reactions including hydrolysis and cyclization. The isoguanine analogue (3) and xanthine analogue (4) were prepared from 5-aminoimidazole using different reagents and reaction conditions. The study found that all these purinoids can undergo Mannich-type C-nucleosidation reactions with cyclic iminium salts, such as pyrroline derivatives (12 and 15), under mild conditions to form C-nucleosides. These C-nucleosides are isosteric with conventional N-nucleosides of natural purines. The reactivity of the purinoids in these C-nucleosidation reactions varies, with the 2,6-diamino derivative (1) being the most reactive and the 2-deamino derivative (adenine analogue) being the least reactive. The study also explored the stability and configuration of the resulting nucleosides, as well as the potential tautomerism in the isoguanine analogue (3). The findings suggest that these purinoids could be useful in studying the chemical etiology of nucleic acid structure and have potential applications in informational chemistry, medicinal chemistry, and chemical biology.
