C-C bond forming reactions catalyzed by artificial metalloenzymes based on the biotin-streptavidin technology

Abstract

The research in Ward group is merging organometallic chemistry with Biotechnology. With the aim of exploiting most attractive and complementary features of catalysts, it is proposed to merge homogeneous and enzymatic catalysis to yield artificial metalloenzymes. In the past, the incorporation of an active metal moiety within a protein environment afforded hybrid catalysts with very promising properties, including high activities and selectivity, reminiscent of both homogeneous and enzymatic catalysts. Herein we discovered an artificial metalloenzymes for enantioselective Suzuki-Miyaura cross-coupling reaction. For this purpose, we synthesized a variety of biotinylated N-heterocycliccarbene- (NHC) and bulky phosphine ligands and tested these in the presence of a Pd-source combined with various streptavidin isoforms. We were able to achieve 90% ee with artificial suzukiase for the synthesis of a variety of axially chiral biaryl compounds. We discovered an artificial metathesase which, in the presence of streptavidin displayed remarkable ring-closing metathesis activity either in the periplasm or on untreated cell-free extracts. The olefin functionality is underrepresented functional group in cellular media and displays only modest reactivity towards the various reactants present in complex media. This property makes it ideal for biorthogonal chemistry. Different biotinylated “Hoveyda-Grubbs” type catalysts were synthesized, characterized and screened for ring-closing metathesis. In order to speed up screening efforts, ring-closing metathesis leading to umbelliferone was used. Efforts to implement the asymmetric C-H activation relying on rhodium (III) complexes bearing Cp* ligand in streptavidin in the presence of cellular extracts were also described herein.