Development of Lewis acid-polyoxometalate complexes as catalysts for peptide bond and phosphorylation reactions

This proposal aims to combine features of reaction design and catalyst design to expand the catalytic applications of Lewis acidpolyoxometalate complexes (LA-POMs) and develop highly desired catalytic, simple, safe, and selective peptide and X–P bond forming reactions. LA-POMs are a class of robust Lewis acid catalysts scarcely explored for the development of organic reactions. However, among other potential advantages, they present a remarkable stability to the presence of water, and bear the potential to greatly simplify reaction protocols. Considering the high relevance of peptide and phosphoester/amide bonds in bioactive molecules, and the limitations on current methods to form them, we propose the development of efficient and selective reactions to form peptide and X-P (X = O, N) bonds catalyzed by LA-POMs. Preliminary results on an atom-economic and water-tolerant amide bond formation catalyzed by Hf(IV)/Zr(IV)-POM complexes support the feasibility and the potential of the proposed investigation.