Oxidation of 2'-Deoxycytidine to Four Interconverting Diastereomers of N1-Carbamoyl-4,5-dihydroxy-2-oxoimidazolidine Nucleosides

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• 作者：Sé ; bastien Tremblay ; Tsvetan Gantchev ; Luc Tremblay ; Pierre Lavigne ; Jean Cadet ; J. Richard Wagner
• 刊名：Journal of Organic Chemistry
• 出版年：2007
• 出版时间：May 11, 2007
• 年：2007
• 卷：72
• 期：10
• 页码：3672 - 3678
• 全文大小：132K
• 年卷期：v.72,no.10(May 11, 2007)
• ISSN：1520-6904

文摘

Modification of 2'-deoxycytidine (dCyd) by hydroxyl radicals and direct ionization leads to the formationof various oxidation products, including dCyd 5,6-glycols, 5-hydroxy-2'-deoxycytidine, and ringfragmentation products. The mechanism of oxidation is complex and poorly understood. In the presentwork, we have prepared four cis- and trans-diastereomers of N¹-(2-deoxy--D-erythro-pentofuranosyl)-1-carbamoyl-2-oxo-4,5-dihydroxyimidazolidine by bromination of dCyd followed by peroxidation of theresulting dCyd bromohydrins. The structure and stereochemistry of each product were determined by ¹HNMR, ¹³C NMR, and 2D NOE analyses. The formation of imidazolidine products involves rearrangementof initial 5(6)-hydroxy-6(5)-hydroperoxides to C6-C2 endoperoxides, which subsequently decomposeby a concerted pathway to imidazolidine products. A remarkable feature of the four diastereomers wastheir ability to interconvert via single and successive cycles of ring-chain tautomerism at N1-C5 andN3-C4, leading to epimerization of C5 and C4, respectively. The rate of isomerization was greater forcis-diastereomers compared to trans-diastereomers, and the rate sharply increased with pH (pH 9.0 >7.0 > 5.5).