A series of fluoroalkylated cyclic λ3‐iodanes and their hydrochloride salts was prepared and used in a combination with sodium ascorbate in buffer or aqueous methanol mixtures for radical fluoroalkylation of a range of substituted indoles, pyrroles, tryptophan or its derivatives, and Trp residues in peptides. As demonstrated on several peptides, the aromatic amino acid residues of Trp, Tyr, Phe, and His are targeted with high selectivity to Trp. The functionalization method is biocompatible, mild, rapid, and transition‐metal‐free. The proteins myoglobin, ubiquitin, and human carbonic anhydrase I were also successfully functionalized.
Trifluoromethylated and fluoroalkylated cyclic λ 3-iodanes and their acyclic salts were used for visible light-driven fluoroalkylation of tryptophan and tryptophan-containing peptides in aqueous media. In comparison to previously reported fluoroalkylation using similar reagents and sodium ascorbate as reductant, the photochemical process did not require any additive or catalyst and was more selective for Trp versus other aromatic amino acids due to the gradual production of fluoroalkyl radicals over the whole irradiation period. However, in the presence of Cys residues, both methods were not selective and cysteine sulfhydryl groups were fluoroalkylated in side reactions. Spectroscopic and photochemical investigations as well as quantum chemical calculations provided insight into the reaction mechanism. The process was found to be photoinduced involving the formation of fluoroalkyl radical from the excited state of λ 3-iodane.
In an underwater sea scene, the key process of protein functionalization on tryptophan is shown. The follow‐up click reaction by using the pink reagent carrying a payload delivers the conjugate of choice. Realistic depiction of hypervalent iodine reagents includes the T‐shape geometry on the iodine atom and the azido‐containing fluoroalkyl group. On the seabed there are side products from the reagent after the reaction with the protein. More information can be found in the Full Paper by P. Novák, P. Beier, et al. on page 15779.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.