The use of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in the selective N4-acylation of cytidine and its derivatives

Abstract

Cytidine and its nucleoside derivatives reacted with an excess of carboxylic acid and of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) in dimethyl-formamide as solvent to form the corresponding N 4-acyl derivatives. In this way, the N 4-benzoyl, -acetyl, and tert.-butyloxycarbonyl- l-phenylalanyl derivatives of 2′- O-tetrahydropyranyl cytidine, 2′-deoxycytidine, and cytidine, respectively, were formed and isolated in yields of 75–90 %. No significant O-acylation was detected. Reaction of 2′,3′- O-isopropylidene cytidine with anisic acid and EEDQ led to appreciable O-acylation and the isolated yield of N 4-anisoyl-2′,3′- O-isopropylidene cytidine was only 40 %. None of the nucleosides of adenine and guanine tested under the same conditions gave appreciable amounts of their N-acetyl derivatives so the method is restricted to cytidine and its derivatives.