Modifications of peptides using Palladium mediated C-H activation

Palladium mediated C-H bond activation has become a popular tool used by many organic chemists. Whilst there are many different types of C-H activation processes, the methods used for biologically relevant molecules is relatively low, with most catalysis on biological molecules being on cysteine residues (thiol functionalisation), and lysine residues (amine functionalisation).
The work presented in this thesis continues the use of tryptophan as the residue of choice for functionalisation. Tryptophan contains an indole ring lending itself to C-H bond activation, due to its intrinsic reactivity. A big question regarding peptide and protein modification is whether modification is feasible for more complex peptides, where selectivity (site of functionalisation) becomes a challenge. The aim of the project is to explore the scope of tryptophan arylation using Pd catalysis and aryl diazonium salts, to determine whether the arylation procedure caused any erosion of the chiral information at tryptophan through racemisation, and to what extent does the procedure work on peptides and what effect it has on the conformation.
The procedure used is typically used on L-tryptophan due to the biological usability, but does the procedure arylate both enantiomers? Using chiral HPLC, it can be seen that di-protected racemic tryptophan can be arylated and that two peaks will be observed next to each other. Overlaying the L-enantiomer onto the graph shows that the procedure works for both enantiomers meaning that it is not enantiomerically selective. The procedure worked on peptides and the conformational changes were monitored using ROESY NMR spectroscopy.