Metal-directed synthesis of a chiral acyclic pentaamine and pendant-arm macrocyclic hexaamine derived from an amino acid

l-3-Phenylpropane-1,2-diamine (dapp) was prepared by a three-step synthesis based on l-phenylalanine and characterized, including determination of stability constants with M2+ ions (Ni, Cu, Zn, Cd). The reaction of L-3-phenylpropane-1,2-diamine as the [Cu(dapp)2]2+ complex ion with formaldehyde and nitroethane in basic solution yields the acyclic (5-methyl-5-nitro-1,9-diphenyl-3,7-diazanonane-1,9-diamine)copper(II) complex ion, [Cu(1)]2+, as the major product. In addition, small amounts of the macrocyclic complex ion (2,10-diphenyl-6,13-dimethyl-6,13-dinitro-1,4,8,11-tetraazacyclotetradecane)copper(II), [Cu(2)]2+, form. Reduction of the [Cu(1)]2+ ion with zinc in aqueous acid yields the acyclic polyamine 5-methyl-1,9-diphenyl-3,7-diazanonane-1,5,9-triamine (3), an analogue of the previously reported pentaamine 5-methyl-3,7-diazanonane-1,5,9-triamine. Using the bis(l-3-phenylpropane-1,2-diamine)palladium(II) as precursor and an excess of other reagents, the macrocyclization reaction to produce [Pd(2)]2+ proved more successful. Reduction and recomplexation to copper(II) allowed isolation of the 2,9-dibenzyl-6,13-diammonio-6,13-dimethyl-1,4,8,11-tetraazacyclotetradecane)copper(II) ion, [Cu(4H22+)]4+. The acyclic complex [Cu(1)]2+ promotes the hydrolytic cleavage of plasmid DNA modestly; a mechanism to support this observation is presented.