Selective Suecinylation of Adenosine Catalyzed by 4-Morpholine-N,N' -dicyclohexylcarboxamidine

Succinyl derivatives of adenosine are synthesized by direct reaction with succinic anhydride catalyzed by 4-morpholine N,N'-dicyclohexylcarboxamidine under kinetic or thermodynamic conditions and partial hydrolysis. Derivatives obtained were N6-succinyl adenosine, N6,5'-0-disuccinyl adenosine, 3'(2')-0-succinyl adenosine, N6,3'(2')-0-disuccinyl adenosine and 3'(2'),5'-0-disuccinyl adenosine. The last three derivatives were crystallized and gave equilibrium mixtures of 2'-0and 3'-0-isomers in aqueous solvents with the 3'-0-isomer prevailing. Differentiation of isomers was done by PMR. A mechanism for isomerisation is proposed. The products were purified by anion exchange chromatography and desalting. The procedures are useful for pharmacological applications because of the purity and yield of products.