Synthesis of imidazo-fused bridgehead-nitrogen C-nucleosides via dehydrative coupling reactions of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid

Abstract

A short, efficient synthesis of novel imidazo-fused bridgehead-nitrogen C-nucleosides has been developed. Dehydrative coupling of 2,5-anhydro-3,4,6-tri-O-benzoyl-D-allonic acid (14) with a series of aminoalkyl-substituted heterocycles (6)–(8) gives the amides (15)–(17). The latter are subsequently converted into novel imidazo[1,5-a]pyridine, imidazo[1,5-a]pyrazine, imidazo[1,5-b]pyridazine, and imidazo[5,1-f]-1,2,4-triazine C-nucleosides (20) and (21). The synthesis of a novel adenosine isostere, 8-amino-3-β-D-ribofuranosylimidazo[1,5-a]pyrazine (32), is described.