Vignette: Extending the Application of Metathesis in Chemical Biology - The Development of Site-Selective Peptide and Protein Modifications

Olefin metathesis (OM) is one of the most versatile methods used to create carbon-carbon bonds in molecules. The synthetic strategies that it offers have enabled the construction of biologically active natural products. OM is exploited in various ways in chemical biology. Advances in aqueous metathesis, including the development of water-soluble metathesis catalysts and use of organic co-solvents or surfactants to aid solubility of conventional metathesis catalysts, have laid the groundwork enabling OM on proteins together with earlier work carried out on amino acids and peptides. This chapter describes the laboratory research efforts toward enabling the application of OM to site-selective protein modification. The cross-metathesis (CM) of unsaturated amino acids with allyl alcohol is analyzed. The enhanced reactivity of allyl sulfides (and other allyl chalcogenides) in aqueous metathesis has enabled OM on protein surfaces, and there are increasing numbers of applications in chemical biology and synthetic chemistry.