New Mets7 motif metallopeptide catalysts for Cu(I)-catalyzed asymmetric Henry reaction

Homogeneous catalysis by transition metals containing chiral bidentate ligands has been often considered a valid strategy to obtain high productivity, stereoselectivity and atom economy for the synthesis of optically pure compounds. The same attraction has been reserved to enzymatic catalysis based on the fact that biocatalysis has many benefits to offer in the context of green chemistry. Considering the ability of macromolecules to selectively discriminate substrates and the number of chemical transformations catalysed by transition metals, which have not been observed to occur enzymatically, in the last decade several research groups reasoned that a hybrid catalyst may combine some of the most attractive features of metal and enzymatic catalysts. This hybrid system results from the incorporation of a catalytically competent organometallic moiety within a macromolecule.1 A valid approach to design hybrid metal-peptide catalysts could be based on the identification of natural protein domains known for their ability to bind a specific metal ion and modulate their properties. An example is represented by the methionine (Met)-rich motifs located in the N-terminal domain and known for their ability to bind ion Cu(I). The octapeptide MTGMKGMS, Mets7, mimicking the seventh Met-rich motif in the N-terminal domain of the yCtr-1, was taken into consideration as lead peptide ligand, knowing its ability to interact with Cu(I) and Pt(II) forming a β-turn type structure around the metal centre.2, 3 In this work we studied the possibility to use this complex as catalyst in the asymmetric Henry condensation under green reactions condition. Mimicking Mets7, different peptides were designed by inserting optimized non-natural amino acids or peptidomimetic scaffold4 and evaluated as ligands. As expected good results in terms of enantioselectivity were obtained with complexes. in which peptide ligands possessed stable β-turn conformation.