Synthesis and characterization of $N^1$-alkylisoguanosine (doridosine derivative)

Abstract

$N^1$-Alkylisoguanosines, doridosine derivatives, were prepared. Reaction of 4-cyano-5-amino-1-(2``,3``,5``-tri-O-acetyl-$\beta$-D-ribofuranosyl)-imidazole with alkylisocyanate gave the bis carbamoyl derivatives. Cyclization at ca. $4^\circ C$ in methanolic ammonia solution afforded $N^1$-alkylisoguanosine. The structure of $N^1$-alkylisoguanosine was determined to be $N^1$-alkyl-6-amino-2-oxo-9-$\beta$-D-ribofuranosyl purine in water, dioxane, acetonitrile and dimethylsulfoxide solution. The biological activity of $N^1$-ethylisoguanosine was run on the guinea pig atria. $N^1$-ethylisoguanosine showed the same type of activity as $N^1$-methylisoguanosine (Doridosine), but ca. half that of doridosine.