Nucleic acid related compounds. 17. 3-Deazauridine. Stannous chloride catalysis of cis-diol vs. phenolic base methylation with diazomethane

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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 present of stannous chloride dihydrate gave 8 detected products including 2, 2-methoxy-1-(2-O-methyl-.beta.-D-ribofuranosyl)-4-pyridinone (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-methyl-.beta.-D-ribofuranosyl)-2-pyridinone (7a), 2''-O-methyl-3-deazauridine (6b) and 3''-O-methyl-3-deazauridine (7b). For comparison, the 2''-O- and 3''-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-ribofuranoxyl-2-pyridinone (3b). Stannous chloride catalyzed methylation of 4-pivaloxy-1-.beta.-D-ribofuranoxyl-2-pyridinone (3c) gave the corresponding 2''-O-methyl derivative 6c. These compounds were tested in [mouse] leukemia L1210 culture and against 3 bacterial strains and were 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-ribofuranoxyl-2-pyridinone (3d).

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