NUCLEOSIDES AND NUCLEOTIDES 179 - RING-EXPANDED PURINE NUCLEOSIDES - THE SYNTHESIS AND CYTOTOXICITY OF IMIDAZO[4,5-C]AZEPINE NUCLEOSIDES

The synthesis of ring-expanded imidazo[4,5-c]azepine nucleosides (3-6) is described. Treatment of 5-iodoimidazole derivative 9 with methyl a crylate in the presence of a palladium catalyst gave vinyl)-1-(2,3,5-t ri-O-acetyl-beta-D-ribofuranosyl) imidazole-4-carboxamide (10), approp riate manipulation of which gave uranosyl-1,5-dihydroimidazo[4,5-c]aze pin-4,6-dione (3). The ring-expanded guanosine derivative 4 was prepar ed in a manner similar to the synthesis of 3. The ring-expanded inosin e derivatives 5 and 6 were obtained from ranosyl)-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 . (C) 1998 Elsevier Science Ltd. All rights reserved.