Glycosylation of panaxadiol

Abstract

One of the methods for studying the relationship between the chemical structure of compounds and their biological activity consists of the synthesis of compounds with a given structure and an investigation of their biological properties. In order to evaluate the influence of an additional 6D-OH group in panaxatriol on the biological activity of its semi-synthetic glycosides [1, 2], it became necessary to synthesize the corresponding panaxadiol monoglucosides. Panaxadiol (3E,12E-dihydroxy-20R,25-epoxydammarane) (1) is the acid-hydrolysis product of the glycoside fraction of Panax ginseng C. A. Meyer root. Its molecule has no C-6 hydroxyl, in contrast with panaxatriol [3][4][5]. Exhaustive glycosylation of 1 was performed previously under conditions of the ortho-ester method [6]. However, proof of the structures and purities of the isomeric monoglucosides was not given. 1: R 1 = R 2 = H; 4: R 1 = Ac, R 2 = H; 5: R 1 = GlcAc 4 , R 2 = H 6: R 1 = H, R 2 = GlcAc 4 ; 7: R = GlcAc 4 ; 8: R 1 = Glc, R 2 = H 9: R 1 = H, R 2 = Glc; 10: R = Glc O Br AcOThe molecule of 1 has two hydroxyls on C-3 and C-12, the reactivity of which depends on the glycosylation conditions. A strong intramolecular H-bond (IMHB) between the 12E-OH proton and the O atom of the tetrahydropyran ring [3][4][5] increases the nucleophilicity of the 12E-OH O atom and makes it possible to glycosylate it regioselectively [7,8].

Synthesis of [3‐3H]20(S)‐protopanaxadiol

“…The 1 H NMR data for the product were consistent with those of unlabeled 3 reported in the literature. 6 This suggested that 2 was selectively reduced by NaBH 4 at the 3-carbonyl position, as this position was more reactive than the 12-carbonyl position. 6 The radiochromatogram of the reaction mixture (30 h) also showed that 3 was the main radiolabeled product.…”

“…6 This suggested that 2 was selectively reduced by NaBH 4 at the 3-carbonyl position, as this position was more reactive than the 12-carbonyl position. 6 The radiochromatogram of the reaction mixture (30 h) also showed that 3 was the main radiolabeled product. The 3 and [3, H]PPD accounted for 75 and 5% of the total radioactivity, respectively, based to their peak areas.…”

Synthesis of 20S-protopanaxadiol β-D-galactopyranosides

“…A previous attempt by us to perform regio-and stereoselective glycosylation of the C-20 tertiary hydroxyl in 20S-protopanaxadiol 3,12-diacetate was unsuccessful [15,16]. Condensation of 20S-protopanaxadiol 3,20-diketone with D-acetobromoglucose with subsequent reduction of both C-3 and C-12 ketones also did not give the desired result [14]. We studied condensation of 12E,20S-dihydroxydammar-24-en-3-one (5) with 2 in order to prepare dammarane tetracyclic triterpenoids containing C-12 and C-20 galactopyranosides.…”

“…The biological properties and mechanism of action of 20S-protopanaxadiol 3-O-E-D-glucopyranoside (ginsenoside Rh 2 ) [3-9] and 20S-protopanaxadiol 20-O-E-D-glucopyranoside, one of the principal metabolites of P. ginseng glycosides (compound K, M1) [1, 4,7,10,11], have been continuously studied for the last several years. We developed semi-synthetic preparative methods for preparing these compounds [12][13][14] that were based on chemical transformation of betulafolientriol, a dammarane triterpenoid and one of the constituents extracted from birch leaves (Betula pendula Roth., B. platyphylla Sukacz).Herein we continue research on the synthesis of glycosides of dammarane tetracyclic triterpenoids. We considered it advantageous to synthesize 20S-protopanaxadiol E-D-galactopyranosides that are close structural analogs of ginsenoside Rh 2 and metabolite M1 (compound K) in order to obtain new data on the structure-activity relationship of dammarane glycosides.…”

Synthesis of panaxatriol glucosides

“…These are glycosides of 20S-protopanaxadiol and those of 20S-protopanaxatriol, which differs from the former by having an additional hydroxyl on C-6. We prepared semisynthetic glycosides of 20S-protopanaxadiol and their analogs by chemical transformation of betulafolientriol, a component of the extract of birch (Betula) leaves [11][12][13][14]. Then, they were tested biologically [15][16][17][18][19][20].…”