Synthesis of spirostanol saponins via gold(I)-catalyzed glycosylation in the presence of Ga(OTf)3, In(OTf)3, or HOTf

An effective approach relying on a Lewis acid- or Bronsted acid-assisted gold(I)-catalyzed glycosylation has been reported in the synthesis of a panel of the representative natural spirostanol saponins, namely polyphyllin D (1), polyphyllin V (2), dioscin (3), formosanin C (4), and a derivative of polyphyllin D bearing a terminal azide group (5). This approach highlights the engagement of low loadings of Ph3AuPOTf (<= 0.5 mol%) in the presence of Ga(OTf)(3), In(OTf)(3), or HOTf (similar to 10mol%) as a co-catalyst, at practical reaction rates as an alternative to the conventional similar to 10 mol% loadings of the gold(I) catalyst in the glycosylation. Polyphyllin D (1) was obtained in 41% overall yield over six steps compared to the maximum 30% yield in previous syntheses where conventional donors and promoters were used. By exploiting a regioselective rhamnosylation, a "one-pot" approach was adopted to assemble 1 and 5, thus further strengthening the efficiency of the gold(I)-catalyzed glycosylation.