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 1H NMR spectroscopy and X‐ray analysis. The complexes involve the inherently chiral octahedral cis‐α coordination motif, in which 8 serves as a tetradentate ligand. In the case of the ZnII complex 8‐ZnCl2, both Δcis‐α(S,S,λ) and Λcis‐α(R,R,λ) stereoisomers were found in the unit cell. For the CuII complex 8‐CuCl2, only one stereoisomer, namely Δcis‐α(S,S,λ) was found in the crystal under investigation. 1H NMR spectroscopy has shown that the same coordination motif is diastereoselectively formed in the chiral Zn2+ dendrimers 3‐ZnCl2 and 7‐ZnCl2. Likewise, the calculated CD spectrum of the Δcis‐α(S,S,λ) stereoisomer of the model complex 8‐CuCl2 shows good agreement with the experimental spectrum of the CuII dendrimers 3‐CuCl2 and 7‐CuCl2, allowing assignment of the absolute configurations of the preferred foldamers as Λcis‐α(R,R,λ) for 3‐CuCl2 and Δcis‐α(S,S,λ) for 7‐CuCl2. This work represents the first example of metal‐complexation‐mediated diastereoselective folding of chiral dendrimers with known absolute configuration. Diastereoselective folding of chiral dendrimers with known absolute configuration: Upon complexation of Cu2+ and Zn2+ ions, depsipeptide dendrimers containing an ethylenediaminetetraacetate‐derived central cavity stereoselectively adopt a chiral folding motif. The absolute configuration of, for example, 1‐CuCl2 around the core has been assigned by comparison of experimental and calculated CD spectra.