Barbin A, Friesen M, O'Neill I K, Croisy A, Bartsch H
Chem Biol Interact. 1986 Jul-Aug;59(1):43-54. doi: 10.1016/s0009-2797(86)80054-0.
Pyrimidine nucleosides were treated with chloroethylene oxide (CEO) and 2-chloroacetaldehyde (CAA) in methanol and, following trimethylsilylation, the products were analysed by combined gas chromatography-mass spectrometry (GC-MS). Reaction of CEO with 2'-deoxycytidine gave 3,N4-etheno-2'-deoxycytidine and diadduct isomers in which a 1-hydroxy-2-chloroethyl group was substituted for hydrogen on either deoxyribose hydroxyl group. When the N-3-position of 2'-deoxycytidine was blocked by a methyl group, CEO or CAA added a 2-chlorovinyl group at the exocyclic N4 amino nitrogen, as evidenced by a pair of cis/trans isomers. Reaction of 3-methylcytidine and CEO also gave the cis/trans 2-chlorovinyl base adducts, as well as six isomers with a 1-hydroxy-2-chloroethyl group attached to ribose and nine isomeric diadducts, which are possibly positional and optical isomers. Although CEO and CAA were less reactive towards uracil in 3-methyluridine than to cytosine in 3-methyl(deoxy)-cytidine, both electrophiles were able to alkylate 3-methyluridine on ribose, yielding 1-hydroxy-2-chloroethyl derivatives. These data suggest that CEO and CAA may also yield non-cyclic adducts with cytosine in double-stranded DNA where the N-3 position is of low accessibility. Such adducts are of interest in view of their potential promutagenic properties. The data also imply a new mechanism of reaction of CEO with nucleophiles.
嘧啶核苷在甲醇中用环氧氯乙烷（CEO）和2-氯乙醛（CAA）处理，经三甲基硅烷化后，产物用气相色谱-质谱联用仪（GC-MS）进行分析。CEO与2'-脱氧胞苷反应生成3,N4-乙烯基-2'-脱氧胞苷和二加合物异构体，其中1-羟基-2-氯乙基取代了脱氧核糖羟基上的氢。当2'-脱氧胞苷的N-3位被甲基封闭时，CEO或CAA在环外N4氨基氮处添加一个2-氯乙烯基，这由一对顺式/反式异构体证明。3-甲基胞苷与CEO反应也生成顺式/反式2-氯乙烯基碱基加合物，以及六种核糖连接有1-羟基-2-氯乙基的异构体和九种可能是位置异构体和旋光异构体的二加合物。尽管CEO和CAA对3-甲基尿苷中的尿嘧啶的反应性比对3-甲基（脱氧）胞苷中的胞嘧啶的反应性低，但两种亲电试剂都能够使3-甲基尿苷在核糖上烷基化，生成1-羟基-2-氯乙基衍生物。这些数据表明，CEO和CAA也可能与双链DNA中N-3位难以接近的胞嘧啶生成非环状加合物。鉴于其潜在的促诱变特性，此类加合物令人关注。数据还暗示了CEO与亲核试剂反应的新机制。
