Di-Boc-protected L-lysine p-nitrophenyl active ester (I) was coupled to spermine (II), yielding the primary amide (III) along with some by-products. The crude reaction mixture was fully protected using an excess of di-tert-butyl dicarbonate, and the desired compound (IV) was then isolated by column chromatography. Finally, the Boc-protecting groups of (IV) were removed by acidic treatment to provide the title spermine lysinamide.
The N-hydroxysuccinimide ester of di-carbobenzyloxy-L-lysine (IV) was coupled to spermine (II), yielding amide (V). The N- carbobenzyloxy groups were then deprotected by catalytic hydrogenolysis in the presence of Pearlman抯 catalyst.