The modification of nucleoties and nucleosides: XI. A modification of cytosine derivatives with succinic anhydride

Abstract

Acylation of cytosine derivatives with succinic anhydride in an 85% aqueous dimethyl sulfoxide solution was investigated. 1.1. When I-methylcytosine was reacted with succinic anhydride, two products were obtained as crystals. The major product was identified as N4-(β-carboxypropionyl)-1-methylcytosine and the minor one as N4,N4′-succinyl-bis-(1-methylcytosine).2.2. The reaction of cytidine with succinic anhydride gave two main products. The major product was isolated as crystals and identified as N4-(β-carboxypropionyl)cytidine. On incubation at 38° for 3h, the N-acylated nucleoside was practically stable at pH 6 to 8, while 50% of the nucleoside was deacylated at pH 2.5 and 10.5.3.3. N4-(β-Carboxypropionyl)cytidine 2′,3′-cylic phosphate was prepared by acylation of cytidine 2′,3′-cyclic phosphate, resulting in the introduction of an anionic group into the base moiety. It is noted that this compound was much more rapidly hydrolyzed by pancreatic ribonuclease A than N4-acetylcytidine 2′,3′-cyclic phosphate, the rate of hydrolysis being almost identical with that of cytidine 2′,3′-cyclic phosphate.4.4. The possibility of an application of this reaction to the selective modification of particular nucleoside residues in nucleic acids is discussed.