Spratt T E, Peterson L A, Confer W L, Hecht S S
Division of Chemical Carcinogenesis, American Health Foundation, Valhalla, New York 10595.
Chem Res Toxicol. 1990 Jul-Aug;3(4):350-6. doi: 10.1021/tx00016a013.
N'-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), two potent tobacco-specific carcinogens, have been previously found to pyridyloxobutylate DNA. The adducts were found to be unstable and have not been fully characterized. In order to gain an understanding of the chemistry of the pyridyloxobutylating species, five model pyridyloxobutylating agents have been solvolyzed and the products identified. 4-[(Acetoxymethyl)-nitrosamino]-1-(3-pyridyl)-1-butanone (3), 4-(carbethoxynitrosamino)-1-(3-pyridyl)-1-butanone (4), 4-oxo-4-(3-pyridyl)-1-butyl p-toluenesulfonate (16), 2-chloro-2-(3-pyridyl)-2,3,4,5-tetrahydrofuran (17), and 4-[(acetoxymethyl)nitrosamino]-1-(3-pyridyl)-1-butanol (20) were solvolyzed in buffer and in buffer containing 20% MeOH. The solvolyses of 16 and 17 in H2O produced only 4-hydroxy-1-(3-pyridyl)-1-butanone (7). In the presence of 20% MeOH, 7 and 2-methoxy-2-(3-pyridyl)-2,3,4,5-tetrahydrofuran (12) were produced from 16 and 17 in a 4:1 ratio. The solvolysis of 3 and 4 in the presence of esterase gave similar products. 4-Methoxy-1-(3-pyridyl)-1-butanone (8) was not detected as a product. In the absence of MeOH, compound 7, 3-pyridyl cyclopropyl ketone (10), and 1-(3-pyridyl)-but-2-en-1-one (18) were observed. In the presence of MeOH, 12 was also formed and the ratio of 7 to 12 was again about 4:1. The esterase-catalyzed hydrolysis of 20 yielded 1-(3-pyridyl)-1,4-butanediol (22), 1-(3-pyridyl)-1,3-butanediol (27), 1-(3-pyridyl)-but-3-en-1-ol (25), 1-(3-pyridyl)but-2-en-1-ol (26), and 2-(3-pyridyl)-2,3,4,5-tetrahydrofuran (24).(ABSTRACT TRUNCATED AT 250 WORDS)
N'-亚硝基降烟碱（NNN）和4-（甲基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（NNK）是两种强效的烟草特有致癌物，此前已发现它们会使DNA发生吡啶氧基丁酰化。已发现这些加合物不稳定且尚未得到充分表征。为了了解吡啶氧基丁酰化物种的化学性质，对五种吡啶氧基丁酰化模型试剂进行了溶剂解并鉴定了产物。4-[(乙酰氧基甲基)-亚硝基氨基]-1-（3-吡啶基）-1-丁酮（3）、4-（乙氧羰基亚硝基氨基）-1-（3-吡啶基）-1-丁酮（4）、4-氧代-4-（3-吡啶基）-1-丁基对甲苯磺酸盐（16）、2-氯-2-（3-吡啶基）-2,3,4,5-四氢呋喃（17）和4-[(乙酰氧基甲基)亚硝基氨基]-1-（3-吡啶基）-1-丁醇（20）在缓冲液和含20%甲醇的缓冲液中进行了溶剂解。16和17在水中的溶剂解仅产生4-羟基-1-（3-吡啶基）-1-丁酮（7）。在20%甲醇存在下，16和17产生了比例为4:1的7和2-甲氧基-2-（3-吡啶基）-2,3,4,5-四氢呋喃（12）。3和4在酯酶存在下的溶剂解产生了类似的产物。未检测到4-甲氧基-1-（3-吡啶基）-1-丁酮（8）作为产物。在没有甲醇的情况下，观察到化合物7、3-吡啶基环丙基酮（10）和1-（3-吡啶基）-丁-2-烯-1-酮（18）。在甲醇存在下，也形成了12，7与12的比例再次约为4:1。20的酯酶催化水解产生了1-（3-吡啶基）-1,4-丁二醇（22）、1-（3-吡啶基）-1,3-丁二醇（27）、1-（3-吡啶基）-丁-3-烯-1-醇（25）、1-（3-吡啶基）丁-2-烯-1-醇（26）和2-（3-吡啶基）-2,3,4,5-四氢呋喃（24）。（摘要截断于250字）
