Modifications of Nucleosides and Nucleotides. II. Reaction of Ethylene Oxide with 1-Methylcytosine

Abstract

The reaction of aqueous ethylene oxide, a biologically important alkylating agent, with 1-methylcytosine (I) was investigated. At pH above 5, a hydroxyethylation was found to take place at N³-position of I to yield 1-methyl-3-(2-hydroxyethyl)cytosine (II). When the pH of the reaction mixture was higher than 7, the reaction was followed by a further alkylation at the N⁴-position of II to give 1-methyl-N, 3-bis(2-hydroxyethyl)-cytosine (III) and was also followed by hydrolysis of these products, II and III, to 1-methyl-3-(2-hydroxyethyl) uracil (IV). Mechanisms of these reactions are discussed in the light of reaction-rate differences at various pH's. At pH 14, II underwent Dimroth rearrangement to give 1-methyl-N-(2-hydroxyethyl)cytosine (V).