Towards site-specific protein labeling via Tsuji-Trost reaction

The use of palladium-catalyzed site-specific protein labeling has been extensively explored in the field of bioorthogonal chemistry. However, there is limited research on the application of the Tsuji-Trost reaction for protein labeling. In Chapter I, we developed a series of discrete palladium complexes with acetanilide ligands, striking a balance between reactivity and stability within living cells. Additionally, we designed and synthesized a bioorthogonal caged probe based on a potential tandem Heck/Tsuji-Trost mechanism for activation-deallylation. Chapter II saw the evaluation of our most promising palladium complexes for an N-terminus-guided site-specific protein labeling strategy. This strategy was successfully demonstrated on the Ala-Ala-Ala-NH2 tripeptide, showcasing the feasibility of N-terminus-guided labeling. Chapter III introduced a groundbreaking Tsuji-Trost affinity-guided protein labeling strategy, which employed a 'swimming' π-allyl palladium intermediate, obviating the need for linker adjustments to achieve selective histidine labeling near the binding site. Moreover, our introduction of the best palladium complex marked its maiden application in bioorthogonal chemistry, to the best of our knowledge. We have confidence that our endeavors to advance bioorthogonal chemistry through the Tsuji-Trost reaction for site-specific protein labeling will be acknowledged for their substantial value and contribution.