Cu-CATARMs · Asymmtric Copper(I) Catalysis in Artificial Metalloenzymes

The proposal that Cu-CATARMs (Asymmetric Copper(I) Catalysis in Artificial Metalloenzymes) aims to design and develop a proficient artificial metalloenzyme which contains a low oxidation state copper (Cu(I)) center, enabling a series of enantioselective new-to-nature transformations in a protein environment.The Roelfes group has been engaged in creation of LmrR based ARMs for the asymmetric copper-catalyzed new-to-nature reactions. Reliable approaches have been developed by the Roelfes group to efficiently recruited the copper(II) species to the LmrR pore, either introducing metal binding unnatural amino acids through in vivo stop codon suppression or supramolecular assembly via the stacking interaction between tryptophan moieties and metal complex. Our approach is enabled by reducing the copper(II) center which is chelated by anchoring moiety of LmrR to copper(I) center with mild and efficient reductants in situ (objective 1). This design of copper(I) catalysis in LmrR based artificial metalloenzyme will be exploited to develop the following objectives: Objective 2. Asymmetric conjugate addition of alkynes; Objective 3. Asymmetric intramolecular cyclopropanation; Objective 4. Apart from developing the novel methodologies, we will also devote ourselves to reveal the detailed mechanism, aiming to provide theoretical guidance for future works. Overall, the successful development of Cu-CATARMs project will represent a proficient strategy to apply low oxidation state transition metals in enzyme catalysis. The results of the project will inspire the development of C-C/C-N bond formation reactions through copper(I) catalysis in ARMs and offer new strategy for the organic chemistry and material communities when planning a synthetic route for a specific target.