MODIFICATIONS OF NUCLEOSIDES AND NUCLEOTIDES. I. REACTION OF ETHYLENE OXIDE WITH URIDINE AND URIDYLIC ACID.

Abstract

The reaction of ethylene oxide with uridine derivatives in an aqueous solution at room temperature was investigated. 1-Methyluracil gave 1-methyl-3-(2-hydroxyethyl)-uracil (II) quantitatively upon reaction with ethylene oxide at pH 10. The reaction of uridine with ethylene oxide at neutral pH results in the formation of 3-(2-hydroxyethyl)-uridine (IV) quantitatively. These products, II and IV, were isolated as crystals and the structure well defined. The rate of N3-alkylation of uridine increases with the increase of pH value. This indicated that the reaction proceeds through the dissociated form of uridine. At a high-pH region, alkylation of the hydroxyl group(s) of ribose moiety took place concomitantly with the N3-alkylation and gave multiply 2-hydroxyethylated derivatives of uridine. In the reaction of uridine 5'-phosphate with ethylene oxide, besides the N3-hydroxyethylation, phosphodiester formation was also observed. In a high-pH solution, the hydroxyethylation of sugar-hydroxyl group(s) took place as in the case of uridine. Synthesis of uridine 5'-phosphate 2-hydroxyethyl ester by the reaction of uridine 5'-phosphate with ethylene glycol in the presence of dicyclohexyl carbodiimide was described.