Metal-induced chiral folding of depsipeptide dendrimers

The synthesis and metal complexation of chiral depsipeptide dendrimers 3 and 7 containing an ethylenediaminetetraacetic acid (EDTA) ester-derived core is reported. The EDTA ester cavity of these dendrimers selectively complexes Zn2+ and Cu2+ ions leading to diastereoselective folding. To elucidate the coordination motif in the resulting "foldamers" of 3-ZnCl2, 7-ZnCl2, 3-CuCl2, and 7-CuCl2, the coordination behavior of the tetramethyl ester of EDTA (8) has been investigated as a model case. The corresponding complexes 8-ZnCl2 and 8-CuCl2 have been structurally characterized by H-1 NMR spectroscopy and X-ray analysis. The complexes involve the inherently chiral octahedral cis-alpha coordination motif, in which 8 serves its a tetradentate ligand. In the case of the Zn-II complex 8-ZnCl2, both Delta cis-alpha(SS lambda) and Delta cis-alpha(R,R,lambda) stereoisomers were found in the unit cell, For the Cu-II complex 8-CuCl2, only one stereoisomer, namely Delta cis-alpha(S,S,lambda) Was found in the crystal under investigation. H-1 NMR spectroscopy has shown that the same coordination motif is diastercoselectivcly formed in the chiral Zn2+ dendrimers 3-ZnCl2 and 7-ZnCl2. Likewise. the calculated CD spectrum of the Delta cis-alpha(S,S,lambda) stereoisomer of lite model complex 8-CuCl2 shows good agreement with the experimental spectrum of the Cu-II dendrimers 3-CuCl2 and 7-CuCl2. allowing assignment of the absolute configurations of the preferred foldamers as Delta cis-alpha(RA lambda) for 3-CuCl2 and Delta cis-alpha(SS lambda) for 7-CuCl2. This work represents (lie first example of diaster-coselective folding of chiral dendrimers with known absolute configuration.