Robins M J, Lee A S
J Med Chem. 1975 Nov;18(11):1070-4. doi: 10.1021/jm00245a005.
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).
用重氮甲烷处理4-羟基-1-β-D-呋喃核糖基-2-吡啶酮（3-脱氮尿苷，1）的甲醇溶液，得到2-甲氧基-1-β-D-呋喃核糖基-4-吡啶酮（2）和4-甲氧基-1-β-D-呋喃核糖基-2-吡啶酮（3a），其比例约为1:2。在二水合氯化亚锡存在下，用重氮甲烷对1进行类似处理，得到8种检测到的产物，包括2、2-甲氧基-1-(2-O-甲基-β-D-呋喃核糖基)-4-吡啶酮（4）、2-甲氧基-1-(3-O-甲基-β-D-呋喃核糖基)-4-吡啶酮（5）、3a、4-甲氧基-1-(2-O-甲基-β-D-呋喃核糖基)-2-吡啶酮（6a）、4-甲氧基-1-(3-O-甲氧基-β-D-呋喃核糖基)-2-吡啶酮（7a）、2'-O-甲基-3-脱氮尿苷（6b）和3'-O-甲基-3-脱氮尿苷（7b）。作为比较，通过氯化亚锡催化2和3a的甲基化反应，分别以良好的总收率制备了2（4和5）和3a（6a和7a）的2'-O-甲基衍生物。用苄基溴处理1得到4-苄氧基-1-β-D-呋喃核糖基-2-吡啶酮（3b）。4-新戊酰氧基-1-β-D-呋喃核糖基-2-吡啶酮（3c）的氯化亚锡催化甲基化反应得到相应的2'-O-甲基衍生物6c。这些化合物在白血病L1210培养物中以及针对三种细菌菌株进行了测试，发现均无活性。这提供了一个核苷结构特异性的显著例子，也为4-(金刚烷-1-羰氧基)-1-β-D-呋喃核糖基-2-吡啶酮（3d）的抗白血病活性的储存-酶促裂解模式提供了支持。
