A new artificial reductase based on the D-Ala-D-Ala/Vancomycin supramolecular interaction and its applications in the enantioselective reduction of cyclic imines

The widespread presence of metal ions in biological systems and the possibility to use nature-framed structures as ligands in transition metal complexes have prompted different research groups to investigate new artificial systems based on the combination of the reactive metals with different biological scaffolds[1]. Dalbapeptides[2], such as vancomycin, teicoplanin, ristocetin, are variously substituted heptapeptides whose antibiotic activity stems from their ability to tightly bind the D-Ala-D-Ala dimer of peptidoglycan precursor thus resulting in the inhibition of cell wall biosynthesis. This interaction is marked by such a low dissociation constant (KD = ~10-17 M) that it makes dalbapeptides an innovative and yet unexplored alternative to the classical biotin/(strept)avidin second coordination sphere system[3]. In this context, D-Ala-D-Ala functionalized diamines were employed as ligands for the synthesis of iridium(III) hybrid catalysts in presence of vancomycin and applied to the asymmetric transfer hydrogenation of cyclic imines, known for being important pharmaceutical precursors. An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor in sodium acetate 0.1 M buffer at pH 5. In the case of the most demanding isoquinoline substrates, an appreciable 71% (S) e.e. in the reduction of quinaldine[4].