Eder E, Hoffman C
Institute of Toxicology, University of Würzburg, Germany.
Chem Res Toxicol. 1992 Nov-Dec;5(6):802-8. doi: 10.1021/tx00030a012.
Crotonaldehyde, a chemically reactive alpha,beta-unsaturated carbonyl compound, is an important industrial chemical and a ubiquitous environmental pollutant. It has been shown to be carcinogenic and mutagenic. We have studied the reaction of crotonaldehyde with nucleosides and 5'-mononucleotides and found three different types of adducts with deoxyguanosine and 2'-deoxyguanosine 5'-monophosphate. No adducts could be isolated either with nucleosides other than deoxyguanosine or with nucleotides other than 2'-deoxyguanosine 5'-monophosphate. With crotonaldehyde, deoxyguanosine produced 1,N2 and 7,8 adducts as well as 1,N2/7,8 bis-adducts. The 1,N2 adducts were mixtures of diastereomers: one pair in which the substituents in the newly formed ring were trans [adduct Ia (6S,8S) and (6R,8R)], about 94%, and another pair Ib in which they were cis. In the case of the 7,8-adducts IIa,b, the ribose was cleaved and a mixture of isomers in which the substituents were cis-IIa and trans-IIb (2:1) in the newly formed tetrahydropyrrole ring was observed. A 3:2 cis-IIIa and trans-IIIb mixture of 1,N2,7,8 bis-adducts was found with the isomerism in the newly formed tetrahydropyrrole ring in analogy to the 7,8 adducts IIa,b. The corresponding bis-adduct with the cis form in the newly formed tetrahydropyrimidine ring was not observed.
巴豆醛是一种具有化学反应活性的α,β-不饱和羰基化合物，是一种重要的工业化学品，也是一种普遍存在的环境污染物。它已被证明具有致癌性和致突变性。我们研究了巴豆醛与核苷及5'-单核苷酸的反应，发现与脱氧鸟苷和2'-脱氧鸟苷5'-单磷酸形成了三种不同类型的加合物。除脱氧鸟苷以外的核苷或2'-脱氧鸟苷5'-单磷酸以外的核苷酸均未分离出加合物。巴豆醛与脱氧鸟苷反应生成1,N2和7,8加合物以及1,N2/7,8双加合物。1,N2加合物是非对映异构体的混合物：一对新形成环中取代基为反式的加合物[加合物Ia (6S,8S)和(6R,8R)]，约占94%，另一对Ib中取代基为顺式。对于7,8-加合物IIa,b，核糖被裂解，观察到新形成的四氢吡咯环中取代基为顺式-IIa和反式-IIb (2:1)的异构体混合物。发现1,N2,7,8双加合物的顺式-IIIa和反式-IIIb混合物比例为3:2，新形成的四氢吡咯环中的异构现象与7,8加合物IIa,b类似。未观察到新形成的四氢嘧啶环中具有顺式形式的相应双加合物。
