The synthesis of ring-expanded imidazo[4,5-c]azepine nucleosides (3-6) is described. Treatment of 5-iodoimidazole derivative 9 with methyl acrylate in the presence of a palladium catalyst gave (E)-5-(2-carbomethoxyvinyl)-1-(2,3,5-tri-O-acetyl-β-d-ribofuranosyl)imidazo le-4-carboxamide (10), appropriate manipulation of which gave 1-β-d-ribofuranosyl-1,5-dihydroimidazo[4,5-c]azepin-4,6-dione (3). The ring-expanded guanosine derivative 4 was prepared in a manner similar to the synthesis of 3. The ring-expanded inosine derivatives 5 and 6 were obtained from 6-acetoxy-1-(2,3,5-tri-O-acetyl-β-d-ribofuranosyl)-5,6-dihydroimidazo[4,5-c ]azepin-4(1H)-one (21) through palladium-catalyzed hydrogenolysis. The cytotoxicity of these ring-expanded nucleosides is also described.