Recent Advances in the Palladium‐Catalyzed Synthesis of Unnatural Tryptophans

Abstract

AbstractUnnatural tryptophans are introduced to explore and engineer the dynamics, function and properties of modified proteins because of intrinsic fluorescence decay, participation in various π‐system interactions, and high occurrences of tryptophan nucleolus in proteins. Due to its role in protein stability and utility as a fluorophore, it becomes a useful unit for protein studies. Several unnatural tryptophans including the oxygen and sulfur analogues have been constructed as endogenous tryptophan analogues to modify the fluorescent character with minimal perturbation to the native structure, while others have been synthesized to probe the cellular mechanisms of protein synthesis. A number of efficient methods for the construction of this important building block, including Larock indolisation, Heck coupling, Negishi coupling and Sonagashira coupling followed by cyclisation have been widely studied and patented as well, by different research groups. Surprisingly, there is a scarcity of any comprehensive reviews on palladium catalyzed synthesis of unnatural tryptophans. Therefore, we summarized the development of different palladium catalysts, ligands and synthetic approaches for the unnatural tryptophans from 2005 to the most recent results. To the best of our knowledge, this is the first review on the synthesis of unnatural tryptophans.