Cross-metathesis reactions of amino acids

摘要

Metathesis chemistry is now firmly established as a particularly important and general technique in synthetic organic chemistry.One variant of this general class of reaction,known as cross metathesis(CM),is a powerful reaction that can join together two alkene groups from different target molecules to form a new conjugate.In terms of peptide chemistry,the ability to link or conjugate a molecule to the side chain of lysine or cysteine,be it as a separate amino acid or as part of a peptide or protein,is fundamental to a number of important natural and non-natural processes.Examples include the biosynthesis of glycoproteins,the definition of protein structure,the preparation of haptens for monoclonial antibody production,and the cross-linking of proteins associated with the formation of blood clots,collagen and food-stuffs.Synthetic chemists are often limited to the formation of an amide bond as a general method of conjugating an organic molecule to a lysine side chain and mimicking disulfide bond formation with cysteine.This restriction greatly limits the choice of conjugation partners to those bearing acid or thiol functionalities.Presented here is a simple sequence whereby an olefin tether is attached to the side chain of either lysine or cysteine to allow cross metathesis(CM)conjugation with an target olefin partner to be carried out.