Facile Synthesis of the Naturally Cytotoxic Triterpenoid Saponin Patrinia-Glycoside B-II and Its Conformer

Abstract

Abstract:The first chemical synthesis of the natural triterpenoid saponin Patrinia-glycoside B-II, namely oleanolic acid]-α-L-arabinopyranoside, has been accomplished in a linear 11-step sequence 11 with 9.4% overall yield. The abnormal 1 C 4 conformation of the arabinose residue was found to occur via conformational fluctuation during preparation of the intermediates. Molecular mechanism and quantum chemistry calculations showed that Patrinia-glycoside B-II and its conformer 1 cannot interconvert under normal conditions. Preliminary structure-activity relationships studies indicated that the 4 C 1 chair conformation of the arabinose residue in the unique α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl disaccharide moiety is one of the chief positive factors responsible for its cytotoxic activity against tumors.

The Herba Patriniae (Caprifoliaceae): A review on traditional uses, phytochemistry, pharmacology and quality control

“… NO. Compound Name Molecular Formula Species Reference Triterpenoid aglycones and triterpenoid saponins 1 3- O -β-D-xylopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl oleanolic acid C 46 H 74 O 15 PS Li and Lou (2007) 2 Giganteaside D C 41 H 66 O 11 PS Li and Lou (2007) 3 3- O -β-D-glucopyranosyl-(1 → 3)-α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl oleanolic acid C 47 H 76 O 16 PS Choi and Woo (1987) 4 Patrinia-glycosides B-II C 47 H 76 O 16 PS Ren et al (2013) 5 Conformer of Patrinia-glycoside B-II C 47 H 76 O 16 PS Ren et al (2013) 6 3- O -β-D-glucopyranosyl-(1 → 3)-α-L-arabinopyranosyl oleanolic acid C 41 H 66 O 12 PS Jiang et al (2003) 7 3- O -α-L-rhamnopyranosyl-(1 → 2)-α-L-arabinopyranosyl oleanolic acid C 41 H 66 O 11 PS Nakanishi et al (1993) 8 Oleanolic acid C 30 H ...…”

“…); administration 48 h Patrinia-glycosides B-II showed powerful inhibitory activity against eight tumor cell lines at micromolar concentrations (3.4–28.7 μM). PS Ren et al (2013) AGS, SGC-7901, BV-2, 5-FU/HCT-8, HepG2, HT-29, HeLa and MDA-MB-231cells (negative control: culture solution) essential oil extract (The dried whole plant of PS (500 g) was distilled with double distilled water of 5000 mL for 4 h, and the yellow essential oil of 0.2 mg/g (w/w) was obtained. ); 50–200 μg/mL for 24 h The essential oil of PS exhibited remarkable dose-dependent growth inhibition in the dilution range of 50–200 μg/mL.…”

“…Moreover, at the dose of 50 mg/kg and 100 mg/kg, it also effectively reduced the weight of U14 cervical tumor in vivo (35.1% and 57.1%, respectively), which was closely related to the increase of apoptosis and G0/G1 tumor cells and the decrease of mutant P53 and Bcl-2 protein expression ( Zhang et al, 2008 ). Patrinia-glycoside B-II from PS showed strong cytotoxic activities against HeLa (human cervical carcinoma cells), HepG2, HT1080 (human fibrosarcoma cells), A549 (human lung adenocarcinoma cells), A375-S2 (human melanoma cells), K562 (human erythroleukemic cells), HL60 (human leukemia cells), and U937 (Human leukemic monocyte lymphoma cells) with an IC 50 of 5.4, 4.2, 18.0, 27.9, 15.8, 6.2, 6.6, and 5.5 μM, respectively ( Ren et al, 2013 ). Therefore, terpenoids in Herba Patriniae can be used as an anti-cancer potential component for in-depth research in vivo and in vitro .…”

Serjanic Acid Glycosides from Chenopodium hybridum L. with Good Cytotoxicity and Selectivity Profile against Several Panels of Human Cancer Cell Lines

“…Numerous reports confirmed that a rhamnose unit in the sugar chain attached at C-3 is a structural feature that enhances cytotoxicity of triterpene saponins [ 15 ]. Moreover, a sugar chain that incorporates a monosaccharide unit composed of α- l -rhamnopyranosyl-(1→2)-α- l -arabinopyranosyl located at C-3 is also considered to be a key factor for cytotoxic activity of oleanane type saponins [ 14 , 16 ]. Such a unique disaccharide sequence located at C-3 of serjanic acid may be responsible for the observed activity of compound 1 towards cells grouped in the skin panel (HTB-140, A375, WM793) where the activity of compound 1 was higher as compared to 2 , which is devoid of the terminal rhamnose unit.…”

Novel Steroidal Glycosides from the Bulbs of Lilium pumilum

“…These interesting steric behaviors of arabinopyranose cannot be explained by steric hindrance only. In a recent study, there are reports of the inner substituted 1 C 4 conformation of α- l -arabinopyranosyl moiety in triterpene glycoside [14,15]. Many more examples and data need to be collected in future work.…”