| Abstract
| - 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-β-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).
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