Indole S-glycosides: from natural product discovery to chemical synthesis.

Indole S-glycosides are a class of natural products in which an indole scaffold is connected to a glycosyl unit via a sulfur atom, forming a rare C-S glycosidic bond. These compounds have attracted considerable attention due to their unique chemical properties and diverse biological activities, including antiviral, anti-inflammatory, and anti-photoaging activities. This review systematically summarizes the discovery history, structural characteristics, and chemical synthesis of naturally occurring indole S-glycosides. We outline the trajectory from the discovery of calanthoside to the systematic isolation of indole S-glycosides from Isatis indigotica, classify three structural types based on the original literature nomenclature-isatindigotindolosides (Type I), isatindigobisindoloside (Type II), and isatigotindolediosides (Type III)-and discuss their bioactivities. We then focus on advances in C-S bond construction strategies for thioglycosylated indoles, including copper-catalyzed, TMSOTf-catalyzed, iodine-catalyzed, nickel-catalyzed, and photoredox-catalyzed methods. Finally, we describe the application of these methods to the total syntheses of calanthoside and isatindigotindolosides I-III and isatigotindoledioside E.