Synthesis of N-glycoside analogs via thionolactones

Indolyl N-glycoside analogs were obtained by a two-step sequence via indole N-thioamides. Treatment of thionobutyrolactone with indolylmagnesium bromide provides the corresponding indole N-thioamide. The use of 10:1 toluene:THF as solvent is important in favoring N- over C3-acylation. Treatment of the omega-hydroxythioamide with 2 equiv of Meerwein's reagent followed by sodium borohydride gives the corresponding N-(tetrahydrofuranyl)indole. Addition of carbon nucleophiles gives access to ketose nucleoside analogs, while activation of the omega-hydroxyl group can give access to tetrahydrothiophene N-glycosides.