146236-29-5

Upstream product

• 471-53-4 enoxolone 
• 410097-37-9 18β-glycyrrhetinic acid 
• 1449-05-4 3β-hydroxy-18β-GA 
• 471-53-4 3β-hydroxy-18α-GA 
• 1405-86-3 glycyrrhizin 

Downstream Products

• 157519-03-4 tert-Butyl-diphenyl-((2S,4aR,8aR)-1,1,4a,6-tetramethyl-1,2,3,4,4a,7,8,8a-octahydro-naphthalen-2-yloxy)-silane 
• 157519-06-7 (1R,4aS,6S,8aS)-6-(tert-Butyl-diphenyl-silanyloxy)-2,5,5,8a-tetramethyl-1,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-ol 
• 157519-05-6 tert-Butyl-diphenyl-((1aR,3aS,5S,7aS,7bS)-1a,4,4,7a-tetramethyl-decahydro-1-oxa-cyclopropa[a]naphthalen-5-yloxy)-silane 
• 157519-07-8 (4aS,6S,8aS)-6-(tert-Butyl-diphenyl-silanyloxy)-2,5,5,8a-tetramethyl-4a,5,6,7,8,8a-hexahydro-4H-naphthalen-1-one 
• 1321990-56-0 3,11-dioxo-18β-oleanane-12-ene-30-carboxylic acid benzyl ester 

Relevant academic research and scientific papers

Bioactive microbial metabolites from glycyrrhetinic acid

Biotransformation of 18β-glycyrrhetinic acid, using Absidia pseudocylinderospora ATCC 24169, Gliocladium viride ATCC 10097 and Cunninghamella echinulata ATCC 8688a afforded seven metabolites, which were identified by different spectroscopic techniques (1H, 13C NMR, DEPT, 1H-1H COSY, HMBC and HMQC). Three of these metabolites, viz. 15α-hydroxy-18α-glycyrrhetinic acid, 13β-hydroxy-7α,27-oxy-12-dihydro-18β-glycyrrhetinic acid and 1α-hydroxy-18β-glycyrrhetinic acid are new. The 13C NMR data and full assignment for the known metabolite 7β, 15α-dihydroxy-18β-glycyrrhetinic acid are described here for the first time. The major metabolites were evaluated for their hepatoprotective activity using different in vitro and in vivo models. These included protection against FeCl3/ascorbic acid-induced lipid peroxidation of normal mice liver homogenate, induction of nitric oxide (NO) production in rat macrophages and in vivo hepatoprotection against CCl4-induced hepatotoxicity in albino mice.

Structurally modified glycyrrhetinic acid derivatives as anti-inflammatory agents

With the aim of finding new anti-inflammatory drugs, a series of new Glycyrrhetinic acid derivatives (1–34) have been designed and synthesized by structural modification, and their anti-inflammatory activities in vitro have been evaluated. The anti-inflammatory activities assay demonstrated that compound 5b suppressed the expression of pro-inflammatory cytokines including IL-6, TNF-α and NO, it also suppressed the expression of iNOS and COX-2 in LPS-induced RAW264.7 cells in a dose-dependent manner. Additionally, western blot results indicated that the suppressing effect of compound 5b on pro-inflammatory cytokines were correlated with the suppression of NF-κB and MAPK signaling pathways. The results attained in this study indicated that compound 5b had the potential to be developed into an anti-inflammation agent and it may be applied to the prevention and treatment of inflammatory diseases.

Influence of honey on the gastrointestinal metabolism and disposition of glycyrrhizin and glycyrrhetic acid in rabbits.

To investigate the effects of honey on the pharmacokinetics of glycyrrhizin and glycyrrhetic acid, administration of glycyrrhizin or glycyrrhetic acid with and without honey was carried out in rabbits in a randomized crossover design. An in vitro study using rabbit fecal flora was employed to elucidate the mechanism of the interaction. HPLC methods were used for the determination of glycyrrhizin, glycyrrhetic acid and 3-dehydroglycyrrhetic acid concentrations in serum and feces. Paired and unpaired Student's t-tests were used for statistical comparisons for in vivo and in vitro studies, respectively. Our study indicated that the area under the curve (AUC0-t) of glycyrrhetic acid was significantly enhanced by 53% when honey was concomitantly given with glycyrrhizin, whereas that of glycyrrhizin was not significantly altered. Nevertheless, lack of effect was observed when honey was concurrently given with glycyrrhetic acid. Fecal study indicated that both the hydrolysis of glycyrrhizin to glycyrrhetic acid and subsequent oxidation of glycyrrhetic acid to 3-dehydroglycyrrhetic acid were significantly affected in the presence of honey to result in more glycyrrhetic acid available for absorption. It could be concluded that honey significantly affected the gastrointestinal metabolism of glycyrrhizin and resulted in the increased glycyrrhetic acid exposure. Therefore, honey might enhance the efficacy and adverse effects of glycyrrhizin.

Simultaneous determination of glycyrrhizin metabolites formed by the incubation of glycyrrhizin with rat feces by semi-micro high-performance liquid chromatography

A method for semi-micro high-performance liquid chromatography (HPLC) has been established for the simultaneous determination of 3α- hydroxyglycyrrhetic acid and 3-dehydroglycyrrhetic acid together with glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid mono-glucuronide formed by incubation of glycyrrhizin with rat feces. The analysis was accomplished within 25 min with a TSKgel ODS-80TsQA (150 x 2.0 mm i.d.) column by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile at a flow rate of 0.2 ml·min-1, a thermostatic oven at 25°C, and detection at 254 nm. The detection limits of these compounds were 0.2 pmol per injection (5 μl). The metabolites of glycyrrhizin, by anaerobic or aerobic incubation with rat fecal suspension over 48 h, were determined. Glycyrrhizin was almost completely converted to metabolite glycyrrhetic acid, and metabolites 3α-hydroxyglycyrrhetic acid and 3-dehydroglycyrrhetic acid in negligible amounts in anaerobic conditions. However, the metabolic time courses of 3-dehydroglycyrrhetic acid when incubated in aerobic conditions revealed that it apparently continued increasing during the whole incubation period.

Indole-and pyrazole-glycyrrhetinic acid derivatives as ptp1b inhibitors: Synthesis, in vitro and in silico studies

Regulating insulin and leptin levels using a protein tyrosine phosphatase 1B (PTP1B) inhibitor is an attractive strategy to treat diabetes and obesity. Glycyrrhetinic acid (GA), a triter-penoid, may weakly inhibit this enzyme. Nonetheless, semisynthetic derivatives of GA have not been developed as PTP1B inhibitors to date. Herein we describe the synthesis and evaluation of two series of indole-and N-phenylpyrazole-GA derivatives (4a–f and 5a–f). We measured their inhibitory activity and enzyme kinetics against PTP1B using p-nitrophenylphosphate (pNPP) assay. GA derivatives bearing substituted indoles or N-phenylpyrazoles fused to their A-ring showed a 50% inhibitory concentration for PTP1B in a range from 2.5 to 10.1 μM. The trifluo-romethyl derivative of indole-GA (4f) exhibited non-competitive inhibition of PTP1B as well as higher potency (IC50 = 2.5 μM) than that of positive controls ursolic acid (IC50 = 5.6 μM), claramine (IC50 = 13.7 μM) and suramin (IC50 = 4.1 μM). Finally, docking and molecular dynamics simulations provided the theoretical basis for the favorable activity of the designed compounds.

Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors

A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 μM and 0.86 μM respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3,30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 μM and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 μM, 32.7 μM and 12.3 μM respectively.

Synthesis and evaluation of A-seco type triterpenoids for anti-HIV-1protease activity

2,3-Seco-dioic acids derived from four different triterpene skeletons were prepared and evaluated for their anti-HIV-1 protease activity. Two A-seco derivatives showed potent inhibitory activity against HIV-1 protease (3c and 3e, IC50 5.7 and 3.9 μM, respectively), while four other derivatives showed moderate to weak inhibition (3a, 3b, 3d and 3f, IC50 15.7-88.1 μM). The combination of a 2,3-seco-2,3-dioic acid functional group in ring A and a free acid group at C-28 or C-30 significantly enhanced HIV-1 protease inhibitory activity (3a, 3c-3e, IC50 3.9-17.6 μM). On the other hand, all A-seco derivatives were found to be very weak inhibitors of HCV, renin and trypsin proteases (IC50 > 80 μM). These findings indicate that A-seco triterpenes with a carboxyl group at C-28 or C-30 are novel and highly selective HIV-1 protease inhibitors.

Synthesis and biological evaluation of pentacyclic triterpenoid derivatives as potential novel antibacterial agents

A series of ursolic acid (UA), oleanolic acid (OA) and 18β-glycyrrhetinic acid (GA) derivatives were synthesized by introducing a range of substituted aromatic side-chains at the C-2 position after the hydroxyl group at C-3 position was oxidized. Their antibacterial activities were evaluated in vitro against a panel of four Staphylococcus spp. The results revealed that the introduction of aromatic side-chains at the C-2 position of GA led to the discovery of potent triterpenoid derivatives for inhibition of both drug sensitive and resistant S. aureus, while the other two series derivatives of UA and OA showed no significant antibacterial activity even at high concentrations. In particular, GA derivative 33 showed good potency against all four Staphylococcus spp. (MIC = 1.25–5 μmol/L) with acceptable pharmacokinetics properties and low cytotoxicity in vitro. Molecular docking was also performed using S. aureus DNA gyrase to rationalize the observed antibacterial activity. This series of GA derivatives has strong potential for the development of a new type of triterpenoid antibacterial agent.

Glycyrrhetinic acid derivative Z-type isomer and preparation method thereof

The invention discloses a glycyrrhetinic acid derivative Z-type isomer and a preparation method thereof. The method comprises the following steps: dissolving a glycyrrhetinic acid derivative E-type isomer in a mixed solvent of an organic solvent and water, and stirring under 254-380nm light to obtain the glycyrrhetinic acid derivative Z-type isomer. According to the method, through a green and healthy mode, no catalyst is used, and isomerization from the glycyrrhetinic acid derivative E-type isomer to the glycyrrhetinic acid derivative Z-type isomer is caused only in the mixed solution of the organic solvent and water by utilizing distortion and relaxation of a central double bond of the isomer under induction of a clean light energy source. The glycyrrhetinic acid derivative E-type isomer provided by the invention has relatively good stability and antibacterial property.

A versatile tailoring tool for pentacyclic triterpenes of Penicillium griseofulvum CICC 40293

In the biosynthetic pathway of pentacyclic triterpenes (PTs), tailoring reactions can produce a wide range of end products from a small number of common scaffolds and the microbial transformation has also been established as an alternative technique for this purpose. In this study, we explored the tailoring reactions involved in the microbial transformation of pentacyclic triterpenes by Penicillium griseofulvum CICC 40293. Preparative biotransformation of eight different PTs from three scaffolds resulted in the isolation of thirteen metabolites. The structures of metabolites were elucidated by HR-ESI-MS, 1D, and 2D NMR spectroscopy. We discovered the highly efficient regio- and stereo-selective hydroxylation of inactivated sp3 CH2 and CH3 on the position of 2α, 7β, 15α, 21β, 23(angular methyl), and 30?COOH glycosylation, this versatile tailoring system for PTs would provide an effective method for expanding their structural diversities. In addition, all compounds were subjected to the bioassay on the model of lipopolysaccharide (LPS)-stimulated RAW 264.7 cells to evaluate their anti-inflammatory activity through nitric oxide (NO) inhibition activity. Compounds 2a and 5a exhibited excellent NO inhibitory activity with IC50 values of 8.35 ± 2.81 μM and 19.60 ± 4.25 μM, respectively.