Selective synthesis of polyamine derivatives: Efficient derivatization of the secondary amino group of N-monosubstituted 1,3-diamines

N-Monosubstitute 1,3-diamines were selectively functionalized at the secondary N-atom via 2-Ph-substituted hexahydropyrimidine intermediates. Reaction of the diamines with benzaldehyde, followed by treatment with an electrophile and hydrolysis, provided the desired products with excellent selectivity and in high yields. N-4,N-9-bis[3-phenylprop-2-enoyl]spermine (4a), which was further converted to N-1,N-12-bis[3-phenylprop-2-enoyl]spermine (15) by a transamidation reaction, was prepared by this way in 82% yield from spermine (1). Compound 4a was alternatively synthesized in 83% yield, equally from 1, by a sequence involving intermediary protection of the terminal amino groups.