Synthesis and properties of a novel nucleoside derivative possessing a 2,3,5,6-tetraazabenzo[cd]azulene skeleton

We describe herein the synthesis and properties of the novel nucleoside derivative, 4,7-diamino-2-(2-deoxy-β-d-erythro-pentofuranosyl)-2,6-dihydro-7H-2,3,5,6-tetraazabenzocd]azulene (1). The palladium catalyzed cross-coupling reaction of 2,4-diamino-5-iodo-7-(2-deoxy-β-d-erythro-pentofuranosyl)pyrrolo2,3-d]pyrimidine (9) with acrylonitrile afforded 2,4-diamino-5-(E)-1-cyano-2-ethenyl]-7-(2-deoxy-β-d-erythro-pentofuranosyl)pyrrolo2,3-d]pyrimidine (10) in 77% yield, which was treated with NaOMe in MeOH in the presence of NaSPh to give the desired 1 in 64% yield. Whereas 1 was stable in concentrated ammonia at room temperature, it was gradually hydrolyzed in water to give 4-amino-2-(2-deoxy-β-d-erythro-pentofuranosyl)-2,6-dihydro-7H-2,3,5,6-tetraazabenzocd]azulen-7-one (12). Density functional calculations indicated that 12 was 20 kcal/mol more thermodynamically stable than 1 in a model study.