Vancomycin-Iridium (III) Interaction: An Unexplored Route for Enantioselective Imine Reduction

Abstract

The chiral structure of antibiotic vancomycin (Van) was exploited as an innovative coordination sphere for the preparation of an IrCp* based hybrid catalysts. We found that Van is able to coordinate iridium (Ir(III)) and the complexation was demonstrated by several analytical techniques such as MALDI-TOF, UV, Circular dichroism (CD), Raman IR, and NMR. The hybrid system so obtained was employed in the Asymmetric Transfer Hydrogenation (ATH) of cyclic imines allowing to obtain a valuable 61% e.e. (R) in the asymmetric reduction of quinaldine 2. The catalytic system exhibited a saturation kinetics with a calculated efficiency of Kcat/KM = 0.688 h−1mM−1.

Alternative Strategy to Obtain Artificial Imine Reductase by Exploiting Vancomycin/D-Ala-D-Ala Interactions with an Iridium Metal Complex

“…After cleavage from the resin, m-l and p-l ligands were isolated with 40% overall yield. Considering the demonstrated capability of Van to coordinate directly with the iridium metal centre, thus producing an effectively functioning catalyst, 33 band at almost 390 nm should underline the interaction between Van and the amino acid moiety of the complex observed both using 1:1 and 2:1 ratios. This shift should be attributable to the noncovalent interactions (hydrogen bonding, π-π stacking, electrostatic, hydrophobic, and van der Waals interactions) that occurred between the metal centre and the second coordination sphere generated by Van around the catalytic active portion of the complex.…”

“…B and with ethyl acetate for substrate C. The organic layers were dried with anhydrous Na2SO4 and filtered, and the solvent was removed under vacuum for analysis by an HPLC equipped with a chiral column to determine conversion and enantiomeric excess. 24 Corresponding Author *Isabella.rimoldi@unimi.it *sara.pellegrino@unimi.it Author Contributions ± These authors contributed equally.…”

A diversity of recently reported methodology for asymmetric imine reduction

“…44). 51 Quinaldine was reduced in a MES (2-(4-morpholino)ethanesulfonic acid) 1.2 M buffer at pH 5 with a impressing 61% ee, whereas inversion of configuration was observed in the case of 3-methylbenzo[d]isothiazole 1,1-dioxide where a product of 42% ee was observed in phosphate buffer 0.1 M pH 8.…”

Exploring the copper binding ability of Mets7 hCtr‐1 protein domain and His7 derivative: An insight in Michael addition catalysis

“…[2][3][4] Enzymes active sites possess unique architectures determined by the nature and the position of the amino acid residues involved in metal ion coordination. 5 This intricate three-dimensional network of interactions creates an asymmetric environment around the metal centre allowing an efficient substrate recognition and orientation. It is thus not surprising that chemists have been exploring the advantageous properties of peptides as ligands for metal ions for asymmetric catalysis.…”

“…Commonly, amino acids bind metal ions through the formation of stable five‐membered chelates, but the presence of different side chains, comprising more than one set of donor atoms, greatly increases coordination geometries variability and thermodynamic stability 2–4 . Enzymes active sites possess unique architectures determined by the nature and the position of the amino acid residues involved in metal ion coordination 5 . This intricate three‐dimensional network of interactions creates an asymmetric environment around the metal centre allowing an efficient substrate recognition and orientation.…”