The Development of an Aza‐C‐Glycoside Library Based on a Tandem Staudinger/Aza‐Wittig/Ugi Three‐Component Reaction

We report the tandem Staudinger/aza‐Wittig/Ugi three‐component reaction mediated synthesis of a 64‐member compound library of aza‐C‐glycosides. The library is composed of four pyrrolidine and three piperidine scaffolds, onto which a number of functional groups is grafted to form seven sublibraries. Variation in the library is achieved by transformation of two pentoses and a hexose into the corresponding 4‐azidopentanal and 5‐azidohexanal derivatives as precursors for the Staudinger/aza‐Wittig process. Further variation is achieved by using different isocyanides as well as protective‐ and functional‐group manipulations on the fully protected Ugi‐3CR intermediates. Preliminary biological evaluation of the compound library revealed several low micromolar inhibitors of human acid glucosylceramidase.