A Trapped Intermediate in the Copper(II)-Mediated Template Synthesis of an Amino Acid-Containing Ligand.
A transition metal ion-templating reaction that has been widely exploited for the synthesis of nitrogen macrocycles, sepulchrates, and linear tetradentate ligands is the template-directed Mannich condensation of carbon acid and aldehyde equivalents with amines. In the course of investigating the copper(II) template-directed synthesis of linear tetradentate amino acid-containing ligands for the design and synthesis of double-strand DNA cleavage agents, we have trapped and characterized an intermediate in the templating reaction. Condensation of bis(phenylalaninato)copper(II) with formaldehyde and nitroethane led to a nitro-substituent-bearing precursor complex that upon reduction is crystallographically characterized as ((2S)-5-amino-2-benzyl-6-hydroxy-5-methyl-3-azahexanoate)copper(II) (space group P2(1)2(1)2(1), a = 9.0066(5) Å, b = 11.1040(6) Å, c = 16.009(2) Å, alpha = beta = gamma = 90.0 degrees, Z = 4, R(1) = 0.0265, wR(2) = 0.0612). NMR investigation of the precursor complex and the precursor and product ligands shows that the templated ligands each contain only a single phenylalanine unit, not the two phenylalanine units expected on the basis of similar synthetic procedures. The structure of the reduced product confirms this conclusion and provides structural characterization of a template intermediate trapped during ligand assembly.
Villanueva
Nydia D.
ND
Departments of Chemistry, The University of Connecticut, Storrs, Connecticut 06269, and University of California, Irvine, California 92697.
Bocarsly
Jeffrey R.
JR
Ziller
Joseph W.
JW