Purines. LI. Synthesis and Biological Activity of Hypoxanthine 7-N-Oxide and Related Compounds

抄録

A detailed account is given of the first chemical synthesis of hypoxanthine 7-N-oxide (5), which started from coupling of 6-chloro-5-nitro-4(3H)-pyrimidinone (7) with N-(4-methoxybenzyl)phenacylamine, generated in situ from the hydrochloride (8), and proceeded through cyclization of the resulting phenacylaminopyrimidinone (9) and removal of the 4-methoxybenzyl group. The results of catalytic hydrogenolysis, methylation followed by catalytic hydrogenolysis, and rearrangement under acidic conditions of 5 supported the correctness of the assigned structure. An ultraviolet spectroscopic approach suggested that the neutral species of 5 exists in H₂O mainly as the N(7)-OH tautomer (21). In the in vitro bioassay of antileukemic activity against murine L5178Y cells, 5 was weakly cytotoxic, with IC₅₀ of 100μg/ml. It did not show any antimicrobial activity even at 1000μg/ml. None of the 9-(4-methoxybenxyl) (11) and O-methyl (12, 13, and 14) derivatives was found to be antiieukemic or antimicrobial.