Cyclic Peptide Synthesis Via Pd-Catalyzed C-H Activation

Peptide and peptidomimetics are emerging as an important class of clinic therapeutics due to their diverse bioactivity,high target specificity and low toxicity.Despite their promising bioactivities,the application of linear peptides as clinic drugs is hindered by their poor proteolytic stability and cell permeability.Macrocyclization has been viewed as an efficient method to improve the stability and bioactivity of peptides.In this thesis,we utilize palladium catalysts to perform chemical modification and macro cyclization of peptides:In the first part,we developed a peptide-guided method for the functionalization and macrocyclization of bioactive peptidosulfonamides by Pd(II)-catalyzed late-stage C-H activation.In this protocol,the substrates are easily prepared and the reaction is efficient.Furthermore,peptides act as internal directing groups and enable site-selective olefination of benzylsulfonamides and cyclization of benzosulfonamides to yield benzosultam-peptidomimetics.In the second part,we synthesized cyclic peptides containing phosphinamide via dissymmetric C-H activation.A series of dipeptides with different configurations were prepared to exam the influence of substrates of cyclic peptides.Moreover,this protocol allows facile chemical ligation between two peptides via a linker.