Synthetic analogues of polynucleotides. Part IV. Carboxymethyl derivatives of uridine and of thymidine

Abstract

5′-O-Carboxymethyl-2′,3′-O-isopropylideneuridine (I) was obtained by treatment of the disodio-derivative of isopropylideneuridine with sodium chloroacetate. Small amounts of 3-carboxymethyl and 3-carboxymethyl-5′-O-carboxymethyl derivatives of isopropylideneuridine were also formed. The monosodio-derivative of isopropylideneuridine gave 3-carboxymethyl-2′,3′-O-isopropylideneuridine. Acid hydrolysis of (I) produced 5′-O-carboxymethyluridine. Condensation of (I) with 5′-O-tritylthymidine in the presence of dicyclohexylcarbodi-imide and removal of the protecting groups gave 3′-O-(uridin-5′-O-ylacetyl)thymidine.

Reaction of the disodio-derivative of 5′-O-tritylthymidine with sodium chloroacetate gave 3′-O-carboxymethyl-5′-O-tritylthymidine (V) as the major product. 3-Carboxymethyl-5′-O-tritylthymidine and small amounts of more highly substituted thymidines were also formed. Acid hydrolysis of (V) gave 3′-O-carboxymethylthymidine (X).

Polymerisation of (X) in the presence of (V)(0·1 mol.) by the action of dicyclohexylcarbodi-imide and removal of the terminal trityl group gave poly-(3′-O-carboxymethylthymidine), about 40% of which had mol. wt. > 4000. The polymer interacted with polyadenylic acid in water and in salt solutions but did not interact with polyuridylic acid or with denatured deoxyribonucleic acid.