Preparation of conjugates of uridine with proteins by the imido ester condensation method

Abstract

Reaction of 5'-O-p-toluenesulfonyl-2',3'-O-isopropylideneuridine (I) with sodium 4-cyanophenoxide afforded 2',3'-O-isopropylidene-5'-O-(4-cyanophenyl)uridine (II) which was converted by acid hydrolysis into 5'-O-(4-cyanophenyl)uridine (IIIa). Acid-catalyzed addition of ethanol to compound IIIa gave the imido ester hydrochloride IIIb which on reaction with ammonia or ethylamine was transformed into the amidine derivatives IIIc and IIId. Compound IIIb reacted with human serum albumine or bovine gamma-globuline at pH 9.2 to give protein conjugates with uridine, bound covalently by an amidine bond (IIIe,f).