title: Nucleic acid related compounds. 17.3-Deazuridine. Stannous chloride catalysis of cis-diol vs. phenolic base methylation with diazomethane.
abstract: Treatment of a methanolic solution of 4-hydroxy-1-beta-D-ribofuranosyl-2-pyridinone (3-deazauridine, 1) with diazomethane gave 2-methoxy-1-beta-D-ribofuranosyl-4-pyridinone (2) and 4-methoxy-1-beta-D-ribofuranosyl-2-pyridinone (3a) in an approximate ratio of 1:2. Analogous treatment of 1 with diazomethane in the presence of stannous chloride dihydrate gave eight detected products including 2, 2-methoxy-1-(2-O-methyl-beta-D-ribofuranosyl)-4-phridinone (4), 2-methoxy-1-(3-O-methyl-beta-D-ribofuranosyl)-4-pyridinone (5), 3a, 4-methoxy-1-(2-O-methyl-beta-D-ribofuranosyl)-2-pyridinone (6a), 4-methoxy-1-(3-O-methoxy-beta-D-ribofuranosyl)-2-pyridinone (7a), 2'-O-methyl-3-deazauridine (6b), and 3'-O-methyl-3-deazauridine (7b). For comparison, the 2'-O-methyl derivatives of 2 )4 and 5) and of 3a (6a and 7a), respectively, were prepared in good overall yields by stannous chloride catalyzed methylation of 2 and 3a. Treatment of 1 with benzyl bromide gave 4-benzyloxy-1-beta-D-ribofuranosyl-2-pyridinone (3b). Stannous chloride catalyzed methylation of 4-pivaloxy-1-beta-D-ribofuranosyl-2-pyridinone (3c) gave the corresponding 2'-O-methyl derivative 6c. These compounds were tested in leukemia L1210 culture and against three bacterial strains and were found to be uniformly inactive. This provides a striking example of nucleoside structure specificity and also adds support to the depot storage-enzymic cleavage mode of antileukemic activity of 4-(adamantane-1-carbonyloxy)-1-beta-D-ribofuranosyl-2-pyridinone (3d).
mesh_terms: D015092:3-Deazauridine; D000818:Animals; D003978:Diazomethane; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006018:Glycols; D007939:Leukemia L1210 / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008745:Methylation; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology; D012263:Ribonucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014001:Tin; D014529:Uridine / Q000031:analogs & derivatives*
chemical_list: D006018:Glycols; D011728:Pyridones; D012263:Ribonucleosides; D015092:3-Deazauridine; D003978:Diazomethane; D014001:Tin; D014529:Uridine