Asymmetric reduction of cyclic imines by a new hybrid catalyst based on an iridium-vancomycin system

The so-called hybrid catalysts, derived from the combination of transition metal catalysts embedded within a biological environment have recently risen up as a promising approach able to merge the attractive properties of both metal-based catalysis and biocatalysis1-2. Dalbapeptides3, such as vancomycin, teicoplanin, ristocetin, are variously substituted heptapeptides whose antibiotic activity stems from their binding to the D-Ala-D-Ala dimer of peptidoglycan precursors thus resulting in the inhibition of cell wall biosynthesis. In this system, indeed, the source of chirality is due not only to the presence of the aminoacidic chain but also from the atropoisomerism of their structure. This interaction is marked by such a low dissociation constant (KD = ~10-17 M) that it makes dalbapeptides an innovative alternative to the classical biotin/(strept)avidin second sphere coordination system4-5. In this context, aminoethylbenzensulfonamide ligands functionalized with the D-Ala-D-Ala dimer at different positions of the phenyl ring were employed for the synthesis of the hybrid catalysts (HyCat) in association with an iridium centre leading to reductases applied to the asymmetric transfer hydrogenation of cyclic imines. An encouraging 48% (S) e.e. was obtained in the asymmetric reduction of the salsolidine precursor using the meta-Hycat in NaOAc 0.1 M buffer at pH 5. In the case of the most demanding isoquinoline substrates, the meta-HyCat afforded the product in an appreciable 70% (S) e.e. in the reduction of quinaldine.