An efficient protocol for the synthesis of diverse diosgen-3-yl glycoconjugates, a class of novel synthetic analogs of natural saponins of biological significance, has been developed. The method relies on gold(I)-catalyzed etherification of diosgen-3-yl ortho-hexynylbenzoate with stoichiometric sugar alcohols to afford the corresponding glycoconjugates in 38%–99% yields. The reaction involves the preferential attack of hydroxyl groups to the C3 position of homoallylic carbocation intermediate and displays a broad substrate scope and a good functional group tolerance.

As an important step to total synthesis of philinopside E with important antitumor activities (Ed50 0.75–3.50 μg mL−1), we described herein convergent synthesis of a triterpene glycoside composed of the sulfated tetrasaccharide residue identical to that of philinopside E and the aglycone of lanost-7-en-3β-ol. The stereocontrolled synthesis of the aglycone from 24,25-dihydrolanosterol was accomplished relying on the stereoselective reductions of the 2,3-unsaturated-1,4-diketone system assisted by a C3-tert-butyldimethylsilyloxy group and convenient installation of the required 7(8)-double bond via syn elimination of triflate. Sequencial convergent coupling of monoglycoside, prepared by reacting the aglycone with orthogonally protected xylosyl thioglycoside, with trisaccharide thioglycoside originated from glucose, xylose and quinovose derivatives, incorporation of sulfation and deprotection afforded the target molecule. The features of our work are that the four 1,2-trans glycosidic bonds were stereoselectively constructed and the precious aglycone was introduced in the late-stage synthesis, which would facilitate the total synthesis of philinopside E and related natural products.

A mild and convenient protocol for direct synthesis of β-mannosides has been developed. Glycosylation of 4,6-O-benzylidene-protected mannosyl ortho-hexynylbenzoates with various alcohol acceptors catalyzed by gold(I) complex proceeded smoothly at 0 °C to room temperature and afforded the corresponding β-mannoside in high yield and satisfactory stereoselectivity. This reaction was applied to the total synthesis of acremomannolipin A and its analogue.

•Glycosyl 3,3-dimethyl-4,5-allenoates as donors are easily prepared.•Oligosaccharides are obtained by treating glycosyl allenoates with alcohols.•The glycosylations proceed smoothly under the promotion of BDMS/AgOTf.•Allenic group is critical for the glycosylation of glycosyl allenoate.A series of novel glycosyl allenoates were prepared by condensions of hemiacetals with 3,3-dimethyl-4,5-allenoic acid. Their glycosylations with various alcohols under the promotion of bromodimethylsulfonium bromide/silver triflate smoothly proceeded to produce disaccharides. Studies reveal that allenic group is crucial for the efficient glylcosylation of glycosyl allenoate.

Recently, a novel glycosylated diphyllin derivative 11 which exhibiting potent anticancer activity by targeting topoisomerase IIα was reported by our group. In order to provide more molecules for structure-activity relationship (SAR) studies, 12 new glycosylated diphyllin analogs have been designed, synthesized, and evaluated for their biological activities. The SAR analysis revealed that (i) the sugar moiety on the diphyllin is essential for the anticancer activity; (ii) equatorial C4′–OH on the sugar is superior to the axial one, and (iii) a proper cyclic lipophilic group at the C4′ and C6′ of sugar might enhance the anticancer activity.A series of glycosylated diphyllin derivatives were designed for anti-tumor activity and SAR studies were revealed.Highlights► 12 new glycosylated diphyllin derivatives were designed for anti-tumor activity. ► The sugar moiety on the C4 is a key element for its bioactivity. ► Glycosides with equatorial C4′–OH are more active than those with axial one. ► Acetal glucosides showed outstanding cytotoxicity and Topo II inhibitory activity.

An efficient, chemoselective, and environment-friendly method for the deprotection of tert-butyldiphenylsilyl ethers mediated by triflic acid supported on silica gel is reported. A wide range of tert-butyldiphenylsilyl ethers derived from carbohydrate and saponin residues can be smoothly cleaved in the presence of various types of other protecting groups in good to excellent yields in acetonitrile. This heterogeneous reaction does not require aqueous workup, and the supported catalyst can be readily recycled.

•A highly stereoselective protocol for 1,2-trans glycosylation of chacotriosyl imidate has been developed.•26-Thio- and selenodioscin have been accomplished by convergent block synthesis.•26-Thio- and selenodioscin have comparable antitumor activities with dioscin at μM concentrations.Convergent block syntheses of 26-thio- and selenodioscin have been achieved by developing the highly stereoselective 1,2-trans glycosylations of chacotriosyl imidate without recourse to neighboring group assistance. Both thiodioscin and selenodioscin possess cytotoxic activities similar to dioscin, a natural spirostanol glycoside.Download full-size image

•An array of oleanolic acid-type saponins were synthesized.•One-by-one glycosylation strategy was applied to synthesize saponins 1–7.•One-pot sequential glycosylation strategy was adopted to synthesize saponins 8–11.•These saponins showed different cytotoxicities against 3 cancer lines.•Terminal monosaccharides and linkage positions affected their cytotoxicities.An array of oleanolic acid-type saponins based on β-hederin has been synthesized in a linear or one-pot manner. The cell viability assays indicate that synthetic saponins show antiproliferation activities in three cancer cell lines with IC50 values of 2.4–15.1 μM and hederacolchiside A1 being the most potent. The results demonstrate that the type of terminal monosaccharides and linkage position have apparent effects on cytotoxicities and selectivities of these saponins against cancer cell lines tested. This study is helpful for future development of more potent anticancer leads.

A convenient approach to the synthesis of furostanol glycosides has been developed with the features of both highly efficient incorporation of a 26-O-β-D-glucopyranosyl unit and ready formation of hemiketal ring E. The total syntheses of seven furostanol saponins including funlioside B, lilioglycoside, protobioside I, protodioscin, pallidifloside I, coreajaponins A and parisaponin I are efficiently achieved using an easily available 16β-acetoxy-22-oxo-26-hydroxy-cholestanic derivative as a powerful building block. The α-glucosidase inhibitory activity of the synthesized saponins is also evaluated, which reveals that funlioside B is a highly potential lead for developing α-glucosidase inhibitors.