Synthesis of MeON-neoglycosides of digoxigenin with 6-deoxy- and 2,6-dideoxy- d -glucose derivatives and their anticancer activity

Biological and Pharmacological Effects of Synthetic Saponins

“…Tang and co-workers focused on the derivatization of the 3-O sugar moiety of digoxigenin to understand its influence on Nur77 protein induction, cytotoxicity, and apoptosis induction in NIH-H460 cancer cells. Applying oxyamine neoglycosylation to construct a series of 6-deoxy and 2,6-dideoxy-d-glucose derivatives of digoxin revealed that the induction of Nur77 protein expression was strong in some compounds but lacked sufficient cytotoxicity against cancer cells [135]. To further improve the cytotoxicity against NIH-H460 cancer cells, digoxigenin derivatives containing different carbohydrates at 3-OH were synthesized, and the O-linked saponins bearing D -ribose and L -rhamnose (38,39) exhibited nanomolar range cytotoxicity which was better than digoxin.…”

Introducing Oxo-Phenylacetyl (OPAc) as a Protecting Group for Carbohydrates

“…The starting material was synthesized from the literature protocol. 30 Isolated as a syrup (150 mg, 88% yield); 1 H NMR (400 MHz, CDCl 3 ) δ 8.02 (dd, J = 8.3, 1.1 Hz, 2H), 7.93 (dd, J = 8.3, 1.1 Hz, 2H), 7.66−7.57 (m, 2H), 7.47 (t, J = 7.8 Hz, 2H), 7.37−7.23 (m, 11H), 5.32−5.22 (m, 1H), 4.96 (d, J = 11.2 Hz, 1H), 4.80 (d, J = 12.1 Hz, 1H), 4.73−4.57 (m, 4H), 4.49 (dd, J = 12.1, 2.6 Hz, 1H), 4.20− 4.07 (m, 2H), 3.66 (dd, J = 9.6, 3.5 Hz, 1H), 3.40 (s, 3H). 13 Methyl-2,3-di-O-oxobenzoyl-4,6-O-benzylidene-α-D-glucopyranoside (5u).…”

“…The starting material was synthesized from the literature protocol. 30 Isolated as a syrup (167 mg, 86% yield); 1 H NMR (400 MHz, CDCl 3 ) δ 8.07−7.94 (m, 2H), 7.89−7.81 (m, 2H), 7.65 (t, J = 7.4 Hz, 1H), 7.57−7.48 (m, 5H), 7.41 (dd, J = 6.5, 3.6 Hz, 3H), 7.19 (t, J = 7.9 Hz, 2H), 6.00 (t, J = 9.9 Hz, 1H), 5.56 (s, 1H), 5.31 (dd, J = 9.9, 3.7 Hz, 1H), 5.22 (d, J = 3.7 Hz, 1H, H1), 4.38 (dd, J = 10.4, 4.9 Hz, 1H), 4.08 (td, J = 9.9, 4.9 Hz, 1H), 3.83 (td, J = 10.0, 4.7 Hz, 2H), 3.52 (s, 3H). 13 Methyl-3,4-di-O-oxobenzoyl-2,6-di-O-benzoyl-α-D-glucopyranoside (5v).…”

“…The organic layer was dried over Na 2 SO 4 and concentrated in vaccum, and the crude product was subjected to flash chromatography (20% ethyl acetate/hexane) to afford the product 29 (0.240 g, 89%) as a gummy solid. Methyl-6-O-oxobenzoyl-2,3-di-O-benzyl-4-O-(4-methoxybenzyl)-α-D-glucopyranoside (30). To a solution of 29 (0.1 g, 0.197 mmol) and PMBOC(=NH)CCl 3 (0.110 g, 0.392 mmol) in dry DCM was added triflic acid (2 drops) at 0 °C.…”

Synthesis of MeON-Glycoside Derivatives of Oleanolic Acid by Neoglycosylation and Evaluation of Their Cytotoxicity against Selected Cancer Cell Lines

“…Neoglycosylation is a mild chemoselective reaction between free reducing sugars and N -methoxyamino-substituted acceptors, which can produce the desired glycoconjugates of a selected target scaffold and thereby avoid the need for subsequent post-glycosylation modification/deprotection [ 12 ]. To date, a number of neoglycosides of natural products with potential anticancer activity against selective cancer lines were synthesized by neoglycosylation, such as perillyl alcohol [ 13 ], cyclopamine [ 14 ], and cardenolide [ 15 , 16 , 17 ]. In our previous work, we designed and synthesized four series of steroidal neoglycosides in D-ring and found that conjugation with the 2-deoxy- d -glucose could significantly enhance its anticancer activity, and compound 5k ((25 R )-3 β -hydroxy-26- N -methoxyaminofurost-5-en- β -2-deoxy- d -glucoside) exhibited IC 50 values even reaching 1.5 µM against HepG2 cells [ 18 ].…”