Facile synthesis of 2′-O-cyanoethyluridine by ring-opening reaction of 2,2′-anhydrouridine with cyanoethyl trimethylsilyl ether in the presence of BF3·Et2O

In this Letter, a facile method for the synthesis of 2′-O-cyanoethyluridine, which is a key intermediate in the synthesis of fully and partially 2′-O-cyanoethylated oligoribonucleotides as well as unmodified oligoribonucleotides, was developed by the ring-opening reaction of 2,2′-anhydrouridine with 2-cyanoethyl trimethylsilyl ether in the presence of BF3·Et2O in dimethylacetamide. The 2′-O-cyanoethyluridine 3′-phosphoramidite derivative was converted into the 2′-O-cyanoethyl-4-N-acetylcytidine 3′-phosphoramidite derivative by a series of reactions involving displacement of the 4-(1H-1,2,4-triazol-1-yl)uridine derivative with ammonia followed by acetylation.