A 2-Iminohydantoin from the Oxidation of Guanine

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• 作者：Wenjie Ye ; R. Sangaiah ; Diana E. Degen ; Avram Gold ; K. Jayaraj ; Karl M. Koshlap ; Gunnar Boysen ; Jason Williams ; Kenneth B. Tomer ; and Louise M. Ball
• 刊名：Chemical Research in Toxicology
• 出版年：2006
• 出版时间：April 2006
• 年：2006
• 卷：19
• 期：4
• 页码：506 - 510
• 全文大小：81K
• 年卷期：v.19,no.4(April 2006)
• ISSN：1520-5010

文摘

The nucleobase guanine was oxidized with dimethyldioxirane (DMDO) to explore the role of epoxidizingagents in oxidative DNA damage. Treatment of guanine with 10% molar excess DMDO in aqueoussolution at 0 mages/entities/deg.gif">C and pH 7.5 followed by workup under mild conditions gave 5-carboxamido-5-formamido-2-iminohydantoin (1) as the sole isolable product in 71% yield. The structure of 1 was established on thebasis of mass spectrometry and NMR studies on 1 and its isotopomers generated by the oxidation of[4-¹³C] and [7-¹⁵N]guanine, which yield [5-¹³C]1 and [7-¹⁵N]1. The distribution of ¹³C and ¹⁵N labels inthe isotopomeric products supports initial epoxidation of the C4-C5 bond of guanine followed by a1,2-acyl migration of guanine C6. Compound 1 is suggested as a possible primary DNA lesion fromputative epoxidizing agents, including hydroperoxides present during biological processes such as lipidperoxidation.