Metathesis in peptides and peptidomimetics

This review is intended to cover the applications of olefin metathesis, with its variations, to the synthesis and manipulation of peptides and peptidomimetics. The examples presented here emphasize the use of metathesis in several aspects of peptides and peptidomimetics, from amino acid synthesis, design and synthesis of secondary structure elements, and manipulation of pharmaceutically active peptides and peptidomimetics to improve their stability and activity. These examples testify to the power of the ruthenium-based catalysts, which are particularly useful in the synthesis of complex molecules such as peptides, due to their high stability in various media, high chemoselectivity, and tolerance to a variety of functional groups that decorate the peptide side chains. Another observation one could make from surveying these studies is that ring-closing metathesis (RCM) is the most used variation of olefin metathesis in these fields. Finally, metathesis, which leads to the formation of carbon-carbon bonds with various hybridization states, i.e., alkyne, alkene, and alkane allows for great diversity and flexibility in the synthesis leading to novel structures and function properties. Unarguably, metathesis is a fascinating reaction that continues to have its impact in various fields including peptides and peptidomimetics. 1 Introduction 2 Metathesis in the Synthesis of Unusual Amino Acids 3 β-Turn Mimic via RCM 4 Cross-Linked Peptide Helices by RCM 5 Disulfide Bond Surrogates by RCM 6 Modifying Pharmaceutically Relevant Peptides and Peptidomimetics using RCM 7 Metathesis in Miscellaneous Peptidic Systems 8 Summary and Outlook.