Synthesis and Transformation of Certain Pyridazine Cyclonucleosides

Article abstract of DOI:10.1021/jo00169a032

Reaction of 4-hydroxy-1-β-D-ribofuranosylpyridazin-6(1H)-one (1) with acetyl bromide has afforded the cyclonucleoside 6,2'-anhydro-6-hydroxy-1-(3,5-di-O-acetyl-β-D-arabinofuranosyl)pyridazin-4(1H)-one (3).Removal of the acetyl blocking groups from 3 furnished 6,2'-anhydro-6-hydroxy-1-β-D-arabinofuranosylpyridazin-4(1H)-one (5).Basic hydrolysis of the ether linkage in 5 afforded 4-hydroxy-1-β-D-arabinofuranosylpyridazin-6(1H)-one (6).Treatment of 3 with liquid ammonia furnished 6-amino-1-β-D-arabinofuranosylpyridazin-4(1H)-one (4).The nucleoside 1 was transformed into 6,5'-anhydro-6-hydroxy-1-β-D-ribofuranosylpyridazin-4(1H)-one (11) via a 4,5'-di-O-tosyl derivative. 4-Amino-1-β-D-ribofuranosylpyridazin-6(1H)-one (2) was reacted with α-acetoxyisobutyryl chloride to give 6,2'-anhydro-6-hydroxy-4-imino-1-β-D-arabinofuranosylpyridazine hydrochloride (14) which was converted into 4-amino-1-β-D-arabinofuranosylpyridazin-6(1H)-one (15).Opening of the anhydro linkage of 14 with azide yielded 4-amino-1-(2-azido-2-deoxy-β-D-ribofuranosyl)pyridazin-6(1H)-one (16), while reaction with benzyl mercaptide furnished 4-amino-1-(2-benzylthio-2-deoxy-β-D-ribofuranosyl)pyridazin-6(1H)-one (17).Desulfurization of 17 afforded 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)pyridazin-6(1H)-one.