An Artificial Metalloenzyme for Atroposelective Metathesis**

Abstract

Atropisomers – separable conformers that arise from restricted single-bond rotation – are frequently encountered in medicinal chemistry. However, preparing such compounds with the desired configuration can be challenging. Herein, we present a biocatalytic strategy for achieving atroposelective synthesis relying on artificial metalloenzymes (ArMs). Based on the biotin-streptavidin technology, we constructed ruthenium-bearing ArMs capable of producing atropisomeric binaphthalene compounds through ring-closing metathesis in aqueous media. Further, we show that atroposelectivity can be fine-tuned by engineering two close-lying amino acid residues within the streptavidin host protein. The resulting ArMs promote product formation with enantiomeric ratios of up to 81 : 19, while small-molecule catalysts for atroposelective metathesis under aqueous reaction conditions are yet unknown. This study represents the first demonstration that stereoselective metathesis can be achieved by an artificial metalloenzyme.