Large steric effect in the substitution reaction of amines with phosphoimidazolide-activated nucleosides

Kinetic studies of the reaction of different aliphatic amines with phosphoimidazolide-activated of guanosine and cytidine (ImPN) derivatives reveal that kinetic barrier for the reaction increases with the size of the alkyl group in the aliphatic secondary amines. Kinetic data support the higher reactivity of the primary amino groups than the secondary amino groups toward ImPN. The slow reactivity accounts for the absence of substitution products of the secondary amino groups of the polyamines.