Recent advances in the thioglycosylation of indoles and tryptophan: strategies and applications in natural product synthesis.

Thioglycosylated indoles and tryptophan derivatives represent an important class of sulfur-containing compounds with increasing significance in natural product synthesis, medicinal chemistry, and chemical biology. The development of efficient and selective C-S bond-forming methods has enabled access to structurally diverse thioglycosides and expanded their applications in the synthesis of biologically relevant molecules. The recent discovery of isatindigotindolosides I-IV from Radix isatidis, which exhibit anti-inflammatory and antiviral activities, has further stimulated interest in thioglycosylation strategies for the synthesis of biologically relevant indole derivatives. This review summarizes recent advances in the C2- and C3-thioglycosylation of indoles, tryptophan, and tryptophan-containing peptides. Particular attention is given to the use of N-(thioglycosyl)succinimides, glycosyl thiosulfonates, and glycosyl thiols as sulfenylating agents, with emphasis on reaction design, substrate scope, regioselectivity, mechanistic aspects, and synthetic applications. Representative applications in natural product synthesis, including the total synthesis of isatindigotindolosides I-IV, are also highlighted. Overall, these advances demonstrate the current state of thioglycosylation as a powerful approach for accessing structurally diverse and pharmaceutically relevant sulfur-containing indole derivatives and provide insights into future opportunities for the development of more efficient, selective, and broadly applicable thioglycosylation methods.