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

Abstract

Summary of main observation and conclusion An effective approach relying on a Lewis acid‐ or Brønsted 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 (~10mol%) as a co‐catalyst, at practical reaction rates as an alternative to the conventional ~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.

Synthesis and Antiproliferative Activities of OSW‐1 Analogues Bearing 2”‐O‐p‐Acylaminobenzoyl Residues†

“…On the other hand, the conversion of hemiacetal 7 into shelf‐stable alkynylbenzoate donor 15 was highly efficient upon treatment with o ‐hexynylbenzoic acid ( 14 ) and EDCI in the presence of DIPEA and DMAP. [ 54‐61 ] Similar results were obtained in the transformation of hemiacetal 12 into the corresponding trichloroacetimidate 16 and alkynylbenzoate 17 .…”

Optimization of Catalysts and Conditions in Gold(I) Catalysis—Counterion and Additive Effects

“…164 The same group recently exploited this acid-assisted gold(I)-catalyzed glycosylation approach in the synthesis of a series of natural spirostanol saponins. 165 Shi and co-workers reported the first gold-catalyzed Nakamura reaction by synergistic Au(I)/Ga(III) catalysis (Scheme 38). This catalytic system is very efficient, boosting the reaction at room temperature with the gold catalyst loading as low as 0.05% as well as up to 93% yield.…”

“…0.5 mol %) . The same group recently exploited this acid-assisted gold­(I)-catalyzed glycosylation approach in the synthesis of a series of natural spirostanol saponins …”

Total Synthesis of the Potent and Broad-Spectrum Antibiotics Amycolamicin and Kibdelomycin

“…In pursuit of this, various triflate sources were examined as additives for promoting the formation of the proposed α-triflate intermediate (Table S4). Using In­(OTf) 3 or Gd­(OTf) 3 led to 1:1 ratios of 36 and 37 (entries 5–6). To our delight, Gd­(OTf) 3 exerted an improved effect when CH 3 CN was employed as a cosolvent (entries 7–8, 36 / 37 = 1:3.3) .…”