Diazonium ion derived products from the Ce(IV) oxidation of beta-hydroxy nitrosamines.
Diazonium ion derived products from the Ce(IV) oxidation of beta-hydroxy nitrosamines.
复制标题
β-羟基亚硝胺 Ce(IV) 氧化产生的重氮离子衍生产物。
DOI：
10.1021/tx00006a002
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发表时间：
1988
影响因子：
4.1
通讯作者：
Li,E
中科院分区：
文献类型：
--
作者：
Loeppky,RN;Li,E
Sir: Dialkylnitrosamines are known to undergo “biochemical activation” by cytochrome P-450 catalyzed hydroxylation at one of the-carbons (1). The resulting-hydroxy nitrosamine decomposes rapidly in aqueous solution at 25 C to an aldehyde and products derived from carbocations through the intermediacyof a diazonium ion (2). There are serious questions, however, as to whether this pathway is open to nitrosamines that possess/3-hy-droxyl groups or other/3-carbon functionalities (3). Carcinogenic/3-hydroxy nitrosamines are prevalent in the human environment (4, 5), and a knowledge of their ac-tivation chemistry is desirable. We report here model chemistry which demonstrates that/3-hydroxy nitros-amines can be “activated” through cerium (IV) one-electron oxidation at the hydroxyl group which is followed by rapid fragmentation, oxidation, and the formation of a diazonium ion, carbocations, and products derived from them. The results also reveal a prominent “detoxication” pathway which is inherent in the chemistry. The metabolic activation of some/3-hydroxy nitros-amines, as detected by DNA alkylation, involves alkyl chain shortening through scission of the N-proximalC-C (OH) or CC= 0 bonds (6-8). This process could occur through the/3-scission of an alkoxy radical produced by an appropriate metalloenzyme (9, 10). The Ce (IV) oxi-dation of alcohols is an effective method for the production of alkoxyradicals (11-18).The reaction of methyl (2-hydroxy-2-phenylethyl)-nitrosamine (1; see Chart I) with 2 equiv of ceric ammo-nium nitrate (CAN) in 50% aqueous acetonitrile resulted in the production of benzaldehyde and traces of methyl-(2-oxo-2-phenylethyl) nitrosamine but no other easily de-tected products. The formation of benzaldehyde is clearly indicative of scission through the alkoxy radical but the methylnitrosamino portion of the substrate apparently gives rise tolow molecular weight products that are dif-
