1449-05-4

Basic information

• Product Name: 18alpha-Glycyrrhetinic acid
• Synonyms: 3-beta-hydroxy-11-oxo-18-alpha-olean-12-en-30-oicaci;3-beta-hydroxy-11-oxo-18-alpha-olean-12-en-30-oicacid;beta-glycyrrhetinicacid;GLYCYRRHETINIC ACID, 18A-;3BETA-HYDROXY-11-OXO-18ALPHA,20BETA-OLEAN-12-EN-29-OIC ACID;18A-GLYCYRRHETINIC ACID;18ALPHA-GLYCYRRHETINIC ACID;Triterpene
• CAS NO: 1449-05-4
• Molecular Formula: C₃₀H₄₆O₄
• Molecular Weight: 470.68
• EINECS: 215-907-9
• Product Categories: Tri-Terpenoids;The group of Liquorice;sy;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;Inhibitors
• Mol File: 1449-05-4.mol
• Article Data: 11

Chemical Properties

• Melting Point: 331-333°C
• Boiling Point: 492.11°C (rough estimate)
• Flash Point: 323.651 °C
• Appearance: /
• Density: 0.9967 (rough estimate)
• Vapor Pressure: 2.71E-16mmHg at 25°C
• Refractive Index: 1.4800 (estimate)
• Storage Temp.: 2-8°C
• PKA: 4.71±0.70(Predicted)
• CAS DataBase Reference: 18alpha-Glycyrrhetinic acid(CAS DataBase Reference)
• NIST Chemistry Reference: 18alpha-Glycyrrhetinic acid(1449-05-4)
• EPA Substance Registry System: 18alpha-Glycyrrhetinic acid(1449-05-4)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• Safety Statements: ection
• WGK Germany: 3
• RTECS: RK0190000
• Hazardous Substances Data: 1449-05-4(Hazardous Substances Data)

Usage

Description

18alpha-Glycyrrhetinic acid (18α-GA) is a bioactive triterpenoid compound derived from licorice. It is known for its selective inhibition of 11-HSD1 (11-hydroxysteroid dehydrogenase 1) and exhibits anti-proliferative and apoptotic effects on hepatic stellate cells (HSCs). This white crystalline powder with a sweet taste is approximately 200 times sweeter than sucrose, making it a potential candidate for the sweetener industry. Its unique sweetness profile, which is sensed after a few moments and has a long retention time, allows for a combination with sucrose to save up to 20% of the sugar without affecting the overall sweetness. Additionally, 18alpha-Glycyrrhetinic acid has an incense effect and a melting point (decomposition) of 220 °C. Its aqueous solution is weakly acidic and can be treated with acid.

Uses

1. Used in the Food Industry:
18alpha-Glycyrrhetinic acid is used as a sweetener for its intense sweetness, which is about 200 times that of sucrose. It is particularly useful in dairy products, cocoa products, egg products, and mutton, where it acts as a flavor enhancer. It also functions well as a flavoring agent, especially when used in combination with salt, and is commonly used in sauces, sauce products, and pickled goods in Chinese folk cuisine.
2. Used in the Pharmaceutical Industry:
18alpha-Glycyrrhetinic acid is used as a starting material for the synthesis of various compounds, such as 3-keto-18alpha-glycyrrhetinic acid, methyl esters of 18alpha-glycyrrhetinic acid, and methyl esters of 3-keto-18alpha-glycyrrhetinic acid. These synthesized compounds have potential applications in the development of new drugs and therapies.
3. Used in the Chemical Industry:
18alpha-Glycyrrhetinic acid's unique chemical properties, including its weakly acidic aqueous solution and high melting point (decomposition) of 220 °C, make it a valuable compound for various chemical applications and processes.

InChI:InChI=1/C30H46O4/c1-25(2)21-8-11-30(7)23(28(21,5)10-9-22(25)32)20(31)16-18-19-17-27(4,24(33)34)13-12-26(19,3)14-15-29(18,30)6/h16,19,21-23,32H,8-15,17H2,1-7H3,(H,33,34)/p-1/t19-,21-,22-,23+,26+,27-,28-,29+,30+/m0/s1

Synthetic route

methyl 3-benzoyl-18α-glycyrrhetinate (650140-36-6) → 18-α-glycyrrhetinic acid (1449-05-4)

Conditions	Yield
With sodium hydroxide In water; ethylene glycol; isopropyl alcohol for 2h; Heating;	84%

18α-glycyrrhizic acid → 18-α-glycyrrhetinic acid (1449-05-4)

Conditions	Yield
With hydrogenchloride In water; acetic acid at 100℃; for 1h;	72%

enoxolone (471-53-4) → 18-α-glycyrrhetinic acid (1449-05-4)

Conditions	Yield
With potassium tert-butylate for 8h; Reagent/catalyst; Reflux;	68.5%
With potassium hydroxide In diethylene glycol for 2h; Reflux;	46%
With potassium hydroxide In diethylene glycol at 220℃; for 2h;	45%
With potassium hydroxide In diethylene glycol at 100 - 220℃;	43.7%
With hydrogenchloride; acetic acid

methyl 18α,b-glycyrrhetinate → 18-α-glycyrrhetinic acid (1449-05-4)

Conditions	Yield
With sodium hydroxide In water; ethylene glycol; isopropyl alcohol for 2h; Heating;	20%
Multi-step reaction with 2 steps 1: pyridine / 14 h / 20 °C 2: 84 percent / sodium hydroxide / H2O; propan-2-ol; ethane-1,2-diol / 2 h / Heating View Scheme

glycyrrhetinoic acid methyl ester → 18-α-glycyrrhetinic acid (1449-05-4)

Conditions	Yield
With potassium hydroxide

18α-glycyrrhizic acid → 18-α-glycyrrhetinic acid (1449-05-4) + glycyrrhetic acid 3-O-mono-β-D-glucuronide

Conditions	Yield
With β-glucuronidase Kinetics; Reagent/catalyst; Enzymatic reaction;

glycyrrhetic acid 3-O-mono-β-D-glucuronide → 18-α-glycyrrhetinic acid (1449-05-4)

Conditions	Yield
With β-glucuronidase for 10h; Enzymatic reaction;

diazomethane (186581-53-3, 908094-01-9) + 18-α-glycyrrhetinic acid (1449-05-4) → (3β,18α)-methyl 3-hydroxy-11-oxoolean-12-30-oate (5092-01-3)

Conditions	Yield
In diethyl ether	100%
In diethyl ether; dichloromethane	76.3%

18-α-glycyrrhetinic acid (1449-05-4) + methyl iodide (74-88-4) → (3β,18α)-methyl 3-hydroxy-11-oxoolean-12-30-oate (5092-01-3)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 2h;	86%

18-α-glycyrrhetinic acid (1449-05-4) + diazodiphenylmethane (908093-98-1) → (3β,18α,20β)-3-hydroxy-11-oxoolean-12-en-29-oic acid diphenylmethyl ester (441759-67-7)

Conditions	Yield
In methanol; diethyl ether at 45℃;	84%

18-α-glycyrrhetinic acid (1449-05-4) → 3,11-dioxo-18α-olean-12-en-30-oic acid (6184-16-3)

Conditions	Yield
With chromium trioxide-pyridine complex In dichloromethane at 20℃; for 1h;	80%

18-α-glycyrrhetinic acid (1449-05-4) + N-(3S-amino-2R-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitro-benzenesulfonamide hydrochloride (251105-80-3) → (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-10-hydroxy-N-((2S,3R)-3-hydroxy-4-(N-isobutyl-4-nitrophenylsulfonamido)-1-phenylbutan-2-yl)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxamide

Conditions	Yield
Stage #1: 18-α-glycyrrhetinic acid; N-(3S-amino-2R-hydroxy-4-phenylbutyl)-N-isobutyl-4-nitro-benzenesulfonamide hydrochloride With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 1.16667h; Inert atmosphere; Stage #2: With dmap at 20℃; for 11h; Inert atmosphere;	69%

18-α-glycyrrhetinic acid (1449-05-4) + N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide (159005-71-7) → (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-10-hydroxy-N-((2S,3R)-3-hydroxy-4-(N-isobutyl-4-methoxyphenylsulfonamido)-1-phenylbutan-2-yl)-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxamide

Conditions	Yield
Stage #1: 18-α-glycyrrhetinic acid; N-((2R,3S)-3-amino-2-hydroxy-4-phenylbutyl)-N-isobutyl-4-methoxybenzenesulfonamide With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 1.16667h; Inert atmosphere; Stage #2: With dmap at 20℃; for 11h; Inert atmosphere;	65%

18-α-glycyrrhetinic acid (1449-05-4) + 4-amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide (169280-56-2) → (2S,4aS,6aS,6bR,8aR,10S,12aS,12bR,14bS)-N-((2S,3R)-4-(4-amino-N-isobutylphenylsulfonamido)-3-hydroxy-1-phenylbutan-2-yl)-10-hydroxy-2,4a,6a,6b,9,9,12a-heptamethyl-13-oxo-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-2-carboxamide

Conditions	Yield
Stage #1: 18-α-glycyrrhetinic acid; 4-amino-N-(2R,3S)(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide With benzotriazol-1-ol; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride In N,N-dimethyl-formamide at 0 - 20℃; for 1.16667h; Inert atmosphere; Stage #2: With dmap at 20℃; for 11h; Inert atmosphere;	65%

18-α-glycyrrhetinic acid (1449-05-4) → (3β,18α)-methyl 3-hydroxy-11-oxoolean-12-30-oate (5092-01-3)

Conditions	Yield
With diazomethane; methanol; diethyl ether

18-α-glycyrrhetinic acid (1449-05-4) + acetic anhydride (108-24-7) → 3β-acetoxy-11-oxo-18α-oleanen-(12)-oic acid-(30) (18305-96-9)

Conditions	Yield
With pyridine

diazomethane (186581-53-3, 908094-01-9) + succinic acid anhydride (108-30-5) + 18-α-glycyrrhetinic acid (1449-05-4) → Methyl 3-O-(β-carboxypropionyl)-18α-glycyrrhetat (17175-23-4)

Conditions	Yield
(i) MeOH, Et2O, (ii) /BRN= 108441/, Py; Multistep reaction;

18-α-glycyrrhetinic acid (1449-05-4) → 11-oxo-18α-olean-12-ene-3β,30-diol (60209-40-7)

Conditions	Yield
With manganese(IV) oxide; lithium aluminium tetrahydride 1.) THF, 60 deg C, 1 h, 2.) CHCl3, THF, 25 h; Yield given. Multistep reaction;

18-α-glycyrrhetinic acid (1449-05-4) → (18α)-methyl 3,11-dioxoolean-12-en-30-oate (6588-91-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / CrO3-Py / CH2Cl2 / 1 h / 20 °C 2: 100 percent / diethyl ether View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 25 °C View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → methyl β-D-galactopyranosyl-(1->4)-β-D-glucopyranosyl-3-O-18α-glycyrrhetinate

Conditions	Yield
Multi-step reaction with 5 steps 1: 31.1 percent / Ag2O; I2 / CHCl3 / 48 h / 20 °C 2: 405 mg / sodium methylate / CHCl3 / 1.5 h / -20 °C 3: 85 mg / H2 / 10 percent Pd/C / methanol / 20 °C / 2587.71 Torr 4: 65.5 percent / diethyl ether; methanol / 1 h View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → β-D-galactopyranosyl-(1->4)-β-D-glucopyranosyl-3-O-18α-glycyrrhetic acid (22596-24-3)

Conditions	Yield
Multi-step reaction with 4 steps 1: 31.1 percent / Ag2O; I2 / CHCl3 / 48 h / 20 °C 2: 405 mg / sodium methylate / CHCl3 / 1.5 h / -20 °C 3: 85 mg / H2 / 10 percent Pd/C / methanol / 20 °C / 2587.71 Torr View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → C55H76O14

Conditions	Yield
Multi-step reaction with 3 steps 1: 31.1 percent / Ag2O; I2 / CHCl3 / 48 h / 20 °C 2: 405 mg / sodium methylate / CHCl3 / 1.5 h / -20 °C View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → diphenylmethyl 2',3',6',2'',3'',4'',6''-heptaacetyl-β-D-galactopyranosyl-(1->4)-β-D-glucopyranosyl-3-O-18α-glycyrrhetinate (441759-70-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: 31.1 percent / Ag2O; I2 / CHCl3 / 48 h / 20 °C View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → (3β,18α)-methyl 3-acetoxy-11-oxoolean-12-en-30-oate (10301-82-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: pyridine 2: diazomethane; diethyl ether View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 25 °C 2: pyridine / dichloromethane / 2 h / 25 °C View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → (3α,18α)-methyl 3-amino-11-oxoolean-12-en-30-oate + (3β,18α)-methyl 3-amino-11-oxoolean-12-en-30-oate

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 25 °C 3: ammonium acetate; sodium cyanoborohydride / methanol / 24 h / 25 °C View Scheme

18-α-glycyrrhetinic acid (1449-05-4) → (3β)-methyl 3-acetoxy-13-carboxy-19-hydroxy-11-oxo-C-norolean-18-en-30-oate-12,19-lactone + (3β,18β)-3-acetoxy-18-hydroxy-11-oxoolean-12-en-30-oic acid-30,18-lactone

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 2 h / 25 °C 2: pyridine / dichloromethane / 2 h / 25 °C 3: acetic acid; selenium(IV) oxide / 4 h / 145 °C / Microwave irradiation View Scheme

18-α-glycyrrhetinic acid (1449-05-4) + 3-ethoxycarbonyl-7-oxabicyclo[2.2.1]heptane-2-carbonyl chloride → 3β-(2-formyl-7-oxabicyclo[2.2.1]heptane-3-carbethoxy)oxy-18α-glycyrrhetinic acid

Conditions	Yield
With dmap In dichloromethane for 10h; Reflux;

[2-(2,6-dichloroanilino)phenyl]acetic acid (15307-86-5) + 18-α-glycyrrhetinic acid (1449-05-4) → DC

Conditions	Yield
With pyridine; dmap In dichloromethane at 30℃;

18-α-glycyrrhetinic acid (1449-05-4) + UDP-glucuronic acid (2616-64-0) → 18α-glycyrrhetinic acid 30-O-β-D-glucoside

Conditions	Yield
With recombinant Glycyrrhiza uralensis glycosyltransferase UGT73F17; magnesium(II) In aq. phosphate buffer at 45℃; for 12h; pH=7.5; regiospecific reaction;

Upstream product

• 6184-16-3 3-oxo-18α-glycyrrhetic acid 
• 6184-16-3 3-oxo-18β-glycyrrhetinic acid 
• 1405-86-3 Glycyrrhizic acid 
• 650140-36-6 methyl 3-benzoyl-18α-glycyrrhetinate 
• 471-53-4 enoxolone 
• 471-53-4 3β-hydroxy-18α-GA 
• 147218-57-3 glycyrrhetic acid 3-O-mono-β-D-glucuronide 

Downstream Products

• 471-53-4 3α-hydroxy-18β-GA 
• 1477-44-7 methyl 3α-hydroxy-18β-glycyrrhetate 
• 471-53-4 3α-hydroxy-18α-GA 
• 1477-44-7 methyl 3α-hydroxy-18α-glycyrrhetate 
• 1477-44-7 methyl 3β-hydroxylglycyrrhetinate 
• 1477-44-7 18β-glycyrrhetinic acid methyl ester 
• 1477-44-7 Glycyrrhetinsaeure-methylester 
• 441759-70-2 diphenylmethyl 2',3',6',2'',3'',4'',6''-heptaacetyl-β-D-galactopyranosyl-(1->4)-β-D-glucopyranosyl-3-O-18α-glycyrrhetinate 
• 441759-67-7 (3β,18α,20β)-3-hydroxy-11-oxoolean-12-en-29-oic acid diphenylmethyl ester 
• 6184-16-3 3-oxo-18α-glycyrrhetic acid 
• 6184-16-3 3-oxo-18β-glycyrrhetinic acid 

Relevant articles and documents

18α-Glycyrrhetinic acid monoglucuronide as an anti-inflammatory agent through suppression of the NF-κB and MAPK signaling pathway

Based on the SAR analysis of glycyrrhizin, 18α-glycyrrhetinic acid monoglucuronide (18α-GAMG) with strong inhibition against LPS-induced NO and IL-6 production in RAW264.7 cells was discovered. Western blotting and immunofluorescence results showed that 18α-GAMG reduced the expression of iNOS, COX-2, and MAPKs, as well as activation of NF-κB in the LPS-stimulated RAW264.7 cells. Further in vivo results showed that 18α-GAMG could significantly improve the pathological changes of CCl4-induced hepatic fibrosis.

Glycyrrhetinic acid derivative synthesis and use thereof

The invention designs and synthetizes a lead compound by using a glycyrrhetinic acid derivative as a carrier and being connected with norcantharidin and a derivative thereof through ester bonds, the obtained lead compound expects to have the advantages of having liver targeting action, prolonging action time, reducing toxic and side effects and improving the curative effect of resisting liver cancer, and a model compound is provided for the research of a liver targeting medicine for the liver cancer. Firstly, two positions of C11 and C30 in glycyrrhetinic acid molecules are reduced and synthetized respectively, methyl ester is chemically modified into glycyrrhetinic acid (GA) and 18 alpha-glycyrrhetinic acid as well as a derivative thereof, the glycyrrhetinic acid (GA) and 18 alpha-glycyrrhetinic acid as well as the derivative thereof are used as framework molecules, through a series of reactions, the framework molecules and the norcantharidin (NCTD) as well as a derivative thereof are condensed to form ester as a prodrug, a cell activity screening test is performed on 5 object compounds, 13 object compounds in 3 series are synthetized, and structural characterization is performed on a carbon spectrum, a hydrogen spectrum and a mass spectrum; the influence of different concentrations of 5 object compounds on HepG2 cell proliferation of the liver cancer is inspected by a method, results show that inhibitory action presents time-dose dependence, and the suppression ratio of 14 mu g/mL is the highest.

Synthesis of glycyrrhetinic acid derivatives for the treatment of metabolic diseases

The effect of glycyrrhetinic acid (GA) and GA-derivatives towards 11β-hydroxysteroid dehydrogenase (11β-HSD) was investigated. Novel compounds with modifications at positions C-3, C-11 and C-29 of the GA skeleton were prepared. Single crystal X-ray diffraction data of selected substances are reported and discussed.