Derivatization of Amino Acids

Development of methods for the arylation of the side chain of amino acids

Access to methods that facilitate the modification of amino acids through the installation of small organic groups is important in synthetic organic chemistry and particularly in medicinal chemistry where peptides occupy an increasing place in drug development. Many methods exist to arylate the side chain of amino acids but some of them show limitations such as the necessity of heating to high temperatures or restrictions in terms of aryl groups that can be transferred. Therefore, there is still a need for efficient methods that allow the installation of aryl moieties on amino acids. These amino acids can then be used as building blocks in the construction of peptides where specific residues are modified. Our group works on the development of arylation procedures that target the side chain of amino acids such as cysteine, tyrosine and tryptophan and that involve organobismuth reagents. Our methods are inspired from our work on the arylation of indoles, phenols and thiols and also from methods from the literature.

Amino acid without histidine.tiff

Recently, we developed conditions for the chemoselective N-arylation of the indolic function of tryptophan. Our method operates under mild conditions under air and shows excellent functional group compatibility. Work is in progress to determine the hierarchy of reactivity between all amino acids. The determination of the intrinsic reactivity of each amino acids under our conditions will permit the transposition of our protocol to peptides possessing multiple reactive amino acids.

Arylation tryptophan.tiff