Synthesis of Δ²⁰-Ginsenosides Rh₄, (20E)-Rh₃, Rg₆, and Rk₁: A General Approach To Access Dehydrated Ginsenosides

Abstract

Four representative Δ-ginsenosides, namely, ginsenosides Rh (1), (20E)-Rh (2), Rg (3), and Rk (4) from Panax Ginseng, were chemically synthesized for the first time. Dehydration of the naturally occurring 20(S)-protopanaxatriol and 20(S)-protopanaxadiol provided all types of Δ-sapogenins, which were separated due to a judicious choice of protecting groups. The Δ-sapogenins were then directly glycosylated with glycosyl ortho-alkynylbenzoate donors under the catalysis of PhPAuNTf as key steps. The neutral conditions of the glycosylations were crucial to prevent the acid-labile Δ double bond from isomerization.

Advances in the Semi-Synthesis of Triterpenoids

“…As a rare aglycone, 29 was subsequently glycosylated, and finally ginsenoside Rk1 was obtained after global deprotection. 22…”

“…27 With 32 as the starting material and (R)-(pyridine-2-yl)ethan-1-amine [(R)-DG] as the directing group, Schonecker-Baran's oxidation took place regioselectively and stereoselectively at C-22, yielding 33 after directing group cleavage (47%, 3 steps). The resulting C22-OH was then eliminated after triflylation to give ∆ 21 (22) derivative 34 (72%). Compound 34 was then subjected to 28-CHO reduction, and the resulting C28-OH was then used as a directing group to affect the -stereo-…”

“…regioisomers was finally accomplished by saponification of 26(E) and 27 under basic conditions to provide pure diols 28 and 29, respectively (65% and 28% yields). As a rare aglycone, 29 was subsequently glycosylated, and finally ginsenoside Rk1 was obtained after global deprotection 22. …”

Scalable Total Synthesis of Piceatannol-3′-O-β-d-glucopyranoside and the 4′-Methoxy Congener Thereof: An Early Stage Glycosylation Strategy

“…The mixture was allowed to warm to rt and reflux for 1 h. The solvent was then removed in vacuo. The crude product methyl 3,5-dihydroxybenzoic acid was used without further purification in the next step (an aliquot was purified for analytical purposes (10). The crude methyl 3,5-dihydroxybenzoate obtained in the last step was dissolved in DMF (400 ml, 1 M) together with imidazole (133 g, 5.0 eq) and cooled to 0 °C.…”

β-Selective Glycosylation Using Axial-Rich and 2-<i>O</i>-Rhamnosylated Glucosyl Donors Controlled by the Protecting Pattern of the Second Sugar

“…1a). These compounds exhibit various biological activities, [3][4][5][6][7] and the novel glycosides of flavones, [8][9][10][11][12] terpenes, [13][14][15][16][17] and steroids [18][19][20][21][22] are naturally occurring; therefore, they have attracted attentions of the pharmaceutical chemists. The synthesis of 2-O-α-L-rhamnosyl-β-O-glucosidic structure involves the rhamnosylation of 2-O in a glucosyl donor bearing an aglycon at the β-anomeric oxygen.…”