Selective protection of polyamines: synthesis of model compounds and spermidine derivatives

A general procedure for the selective protection of mixed primary-secondary (poly)amines, based on t-butoxycarbonylation of carbamate groups (exhaustive t-butoxycarbonylation) derived from the primary amino functions only, is reported. In most cases to be described, benzyl (poly)carbamates are used for this purpose. Subsequent removal of all benzyloxycarbonyl (Z) groups from the resulting intermediates by catalytic hydrogenolysis liberates the secondary amino functions, while t-butoxycarbonyl (Boc) is retained on the primary ones. Alternatively, selective removal of Z only from amino functions protected by both Z and Boc, which can be accomplished by base-catalysed methanolysis, results in protected (poly)amines with Boc and Z on their primary and secondary amino groups, respectively. The new reactions have been studied with two unsymmetrical derivatives of ethylene- and p-phenylene-diamine as model substances. The yields of most intermediates and the products were high. Additional experiments have been performed with spermidine to give N1,N8-Boc2-spermidine. Finally, by virtue of the non-equivalence of the two primary amino groups in this molecule, the synthesis of N8-Boc-N1-Z-spermidine by the same approach is presented.