Bis-14-membered ring diketal diamines: synthesis and evaluation of their anti-HIV and anti-tumoral activities

Chiral and achiral macrocyclic bis-diketal diamines, analogs of bicyclam AMD 3100, were synthesized in three steps from the previously obtained 14-membered ring diketal dilactams. Their monoreduction with lithium aluminium hydride gave the corresponding diketal aminolactams. Coupling these with dibromo-p-xylene led to xylyl dimer compounds. A second reduction step yielded the expected bis-diketal diamines in the methyl and unsubstituted series. Biological tests on the unreduced and reduced dimers showed both weak anti-HIV and anti-proliferative activities for the bis-diphenyl diketal aminolactam 13b, with a mode of action probably different from that of AMD 3100.