59870-68-7

Basic information

• Product Name: Glabridin
• Synonyms: 1,3-Benzenediol, 4-(3,4-dihydro-8,8-diMethyl-2H,8H-benzo(1,2-b:3,4-b')dipyran-3-yl)-, (R)-;(R)-4-(3,4-Dihydro-8,8-dimethyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-3-yl)-1,3-benzenediol;4-[(3R)-3,4-Dihydro-8,8-dimethyl-2H,8H-benzo[1,2-b:3,4-b′]dipyran-3-yl]-1,3-benzenediol;Glabridin, >=98%;Glabridin/Propylene Glycol;4-[(3R)-8,8-dimethyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromen-3-yl]benzene-1,3-diol;GLABRIDIN;4-[(3R)-8,8-Dimethyl-3,4-dihydro-2H-pyrano[6,5-f]chromen-3-yl]benzene-1,3-diol
• CAS NO: 59870-68-7
• Molecular Formula: C₂₀H₂₀O₄
• Molecular Weight: 324.37
• EINECS: 1308068-626-2
• Product Categories: Miscellaneous Natural Products;Natural Plant Extract;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract
• Mol File: 59870-68-7.mol
• Article Data: 7

Chemical Properties

• Melting Point: 154～155℃
• Boiling Point: 518.555 °C at 760 mmHg
• Flash Point: 267℃
• Appearance: white to light brown/
• Density: 1.257 g/cm³
• Vapor Pressure: 2.26E-11mmHg at 25°C
• Refractive Index: 1.622
• Storage Temp.: room temp
• Solubility: DMSO: soluble5mg/mL, clear (warmed)
• PKA: 9.66±0.40(Predicted)
• Stability: Hygroscopic
• BRN: 7141956
• CAS DataBase Reference: Glabridin(CAS DataBase Reference)
• NIST Chemistry Reference: Glabridin(59870-68-7)
• EPA Substance Registry System: Glabridin(59870-68-7)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 59870-68-7(Hazardous Substances Data)

Usage

Chemical Properties

White to tan powder

Uses

Glabridin is a compound extracted from Licorice (root) shows properties that are cytotoxic, antimicrobial, estrogenic and anti-proliferative.

Definition

ChEBI: A member of the class of hydroxyisoflavans that is (R)-isoflavan substituted by hydroxy groups at positions 2' and 4' and a 2,2-dimethyl-2H-pyran group across positions 7 and 8 respectively.

Biochem/physiol Actions

Glabridin is a bio-available isoflavan isolated from licorice (Glycyrrhiza glabra L.) root extract. Glabridin has been reported to posses varies biological activities including strong antioxidant activity, antioxidant against LDL oxidation, anti-Helicobacter pylori properties, estrogen-like activity and antinephritic and radical scavenging activities. Also it appears to inhibit serotonin re-uptake, melanogenesis, inflammation and cytochrome P450 3A4, 2B6, and 2C9.

InChI:InChI=1/C20H20O4/c1-20(2)8-7-16-18(24-20)6-3-12-9-13(11-23-19(12)16)15-5-4-14(21)10-17(15)22/h3-8,10,13,21-22H,9,11H2,1-2H3/t13-/m0/s1

Synthetic route

2',4'-dimethylglabridin → (±)-glabridin (59870-68-7)

Conditions	Yield
With boron tribromide In dichloromethane at -78 - 20℃; for 2h;	84%
With boron tribromide In dichloromethane at -78℃; for 2h; Inert atmosphere;	79%

2',4'-di(methoxymethyl)glabridin → (±)-glabridin (59870-68-7)

Conditions	Yield
With hydrogenchloride In water; isopropyl alcohol at 20℃; for 5h;

1,3-Dimethoxybenzene (151-10-0) → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 2.1: sulfur; morpholine / 12 h / 130 °C 2.2: 12 h / Reflux 3.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 3.2: 0.33 h / 55 °C 3.3: 3 h / 80 °C 4.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 5.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 6.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 2.1: sulfur; morpholine / 12 h / 130 °C 2.2: 12 h / Reflux 3.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 3.2: 0.33 h / 55 °C 3.3: 3 h / 80 °C 4.1: acetic acid; hydrogen; 5%-palladium/activated carbon / ethanol; water / 12 h / 20 °C 5.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 6.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 2.1: sulfur; morpholine / 12 h / 130 °C 2.2: 12 h / Reflux 3.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 3.2: 0.33 h / 55 °C 3.3: 3 h / 80 °C 4.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 5.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 6.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 7.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 2.1: sulfur; morpholine / 12 h / 130 °C 2.2: 12 h / Reflux 3.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 3.2: 0.33 h / 55 °C 3.3: 3 h / 80 °C 4.1: hydrogen / N,N-dimethyl-formamide / 0.5 h / 22 °C / 760.05 Torr 5.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 6.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 7.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

2',4'-dimethoxyacetophenone (829-20-9) → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: sulfur; morpholine / 12 h / 130 °C 1.2: 12 h / Reflux 2.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 2.2: 0.33 h / 55 °C 2.3: 3 h / 80 °C 3.1: acetic acid; hydrogen; 5%-palladium/activated carbon / ethanol; water / 12 h / 20 °C 4.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 5.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: sulfur; morpholine / 12 h / 130 °C 1.2: 12 h / Reflux 2.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 2.2: 0.33 h / 55 °C 2.3: 3 h / 80 °C 3.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 4.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 5.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: sulfur; morpholine / 12 h / 130 °C 1.2: 12 h / Reflux 2.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 2.2: 0.33 h / 55 °C 2.3: 3 h / 80 °C 3.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 4.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 5.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 6.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 6 steps 1.1: sulfur; morpholine / 12 h / 130 °C 1.2: 12 h / Reflux 2.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 2.2: 0.33 h / 55 °C 2.3: 3 h / 80 °C 3.1: hydrogen / N,N-dimethyl-formamide / 0.5 h / 22 °C / 760.05 Torr 4.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 5.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 6.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

recorcinol (108-46-3) → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: sodium hydroxide / water / 3 h / 0 - 70 °C 2.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 3.1: sulfur; morpholine / 12 h / 130 °C 3.2: 12 h / Reflux 4.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 4.2: 0.33 h / 55 °C 4.3: 3 h / 80 °C 5.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 6.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 7.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 7 steps 1.1: sodium hydroxide / water / 3 h / 0 - 70 °C 2.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 3.1: sulfur; morpholine / 12 h / 130 °C 3.2: 12 h / Reflux 4.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 4.2: 0.33 h / 55 °C 4.3: 3 h / 80 °C 5.1: acetic acid; hydrogen; 5%-palladium/activated carbon / ethanol; water / 12 h / 20 °C 6.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 7.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: sodium hydroxide / water / 3 h / 0 - 70 °C 2.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 3.1: sulfur; morpholine / 12 h / 130 °C 3.2: 12 h / Reflux 4.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 4.2: 0.33 h / 55 °C 4.3: 3 h / 80 °C 5.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 6.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 7.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 8.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 8 steps 1.1: sodium hydroxide / water / 3 h / 0 - 70 °C 2.1: aluminum (III) chloride / dichloromethane / 1 h / 0 - 20 °C 3.1: sulfur; morpholine / 12 h / 130 °C 3.2: 12 h / Reflux 4.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 4.2: 0.33 h / 55 °C 4.3: 3 h / 80 °C 5.1: hydrogen / N,N-dimethyl-formamide / 0.5 h / 22 °C / 760.05 Torr 6.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 7.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 8.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

2,4-dimethoxyphenylacetic acid (6496-89-5) → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 1.2: 0.33 h / 55 °C 1.3: 3 h / 80 °C 2.1: acetic acid; hydrogen; 5%-palladium/activated carbon / ethanol; water / 12 h / 20 °C 3.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 4.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 1.2: 0.33 h / 55 °C 1.3: 3 h / 80 °C 2.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 3.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 4.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 1.2: 0.33 h / 55 °C 1.3: 3 h / 80 °C 2.1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 3.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 4.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 5.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: boron trifluoride diethyl etherate / 0.17 h / 100 °C 1.2: 0.33 h / 55 °C 1.3: 3 h / 80 °C 2.1: hydrogen / N,N-dimethyl-formamide / 0.5 h / 22 °C / 760.05 Torr 3.1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 4.1: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 5.1: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

3-(2,4-dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one (1891-01-6) → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; hydrogen; 5%-palladium/activated carbon / ethanol; water / 12 h / 20 °C 2: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 3: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 2: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 3: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: acetic acid; hydrogen; platinum on carbon / 12 h / 100 °C 2: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 3: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 4: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: hydrogen / N,N-dimethyl-formamide / 0.5 h / 22 °C / 760.05 Torr 2: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 3: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 4: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

3-(2,4-dimethoxyphenyl)-chroman-7-ol → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 2: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

3-(2,4-dimethoxyphenyl)-7-hydroxychroman-4-one (51106-84-4) → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: acetic acid; phenylboronic acid / toluene / 12 h / Reflux; Inert atmosphere 2: lithium aluminium tetrahydride / diethyl ether / 6 h / Reflux 3: boron tribromide / dichloromethane / 2 h / -78 - 20 °C View Scheme

7-hydroxy-2H-chromen-2-one (93-35-6) → (±)-glabridin (59870-68-7)

Conditions

Yield

Multi-step reaction with 7 steps 1: 1,8-diazabicyclo[5.4.0]undec-7-ene; copper(II) choride dihydrate / acetonitrile / 10 h / 20 °C 2: bromine / N,N-dimethyl-formamide / 2 h / Cooling with ice 3: 1.5 h / 180 °C 4: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide; water / 2 h / 90 °C 5: lithium borohydride / tetrahydrofuran / 20 °C 6: triphenylphosphine; di-isopropyl azodicarboxylate / dichloromethane / 10 h / Cooling with ice 7: boron tribromide / dichloromethane / 2 h / -78 °C / Inert atmosphere View Scheme

7-((2-methylbut-3-yn-2-yl)oxy)-2H-chromen-2-one (27421-18-7) → (±)-glabridin (59870-68-7)

Conditions

Yield

Multi-step reaction with 6 steps 1: bromine / N,N-dimethyl-formamide / 2 h / Cooling with ice 2: 1.5 h / 180 °C 3: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide; water / 2 h / 90 °C 4: lithium borohydride / tetrahydrofuran / 20 °C 5: triphenylphosphine; di-isopropyl azodicarboxylate / dichloromethane / 10 h / Cooling with ice 6: boron tribromide / dichloromethane / 2 h / -78 °C / Inert atmosphere View Scheme

C14H11BrO3 → (±)-glabridin (59870-68-7)

Conditions

Yield

Multi-step reaction with 5 steps 1: 1.5 h / 180 °C 2: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide; water / 2 h / 90 °C 3: lithium borohydride / tetrahydrofuran / 20 °C 4: triphenylphosphine; di-isopropyl azodicarboxylate / dichloromethane / 10 h / Cooling with ice 5: boron tribromide / dichloromethane / 2 h / -78 °C / Inert atmosphere View Scheme

C14H11BrO3 → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium carbonate; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride / N,N-dimethyl-formamide; water / 2 h / 90 °C 2: lithium borohydride / tetrahydrofuran / 20 °C 3: triphenylphosphine; di-isopropyl azodicarboxylate / dichloromethane / 10 h / Cooling with ice 4: boron tribromide / dichloromethane / 2 h / -78 °C / Inert atmosphere View Scheme

C22H20O5 → (±)-glabridin (59870-68-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: lithium borohydride / tetrahydrofuran / 20 °C 2: triphenylphosphine; di-isopropyl azodicarboxylate / dichloromethane / 10 h / Cooling with ice 3: boron tribromide / dichloromethane / 2 h / -78 °C / Inert atmosphere View Scheme

(±)-glabridin (59870-68-7) + 1-(2-chloroethyl)-2-methyl-5-nitro-1H-imidazole (13182-81-5) → C26H27N3O6

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 75℃; for 10h;	66%

(±)-glabridin (59870-68-7) + N,N-dimethyl-formamide (68-12-2, 33513-42-7) → 3-(8,8-dimethyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromen-3-yl)-2,6-dihydroxybenzaldehyde

Conditions	Yield
With trichlorophosphate at 100℃; for 3h; Cooling with ice;

Upstream product

• 93-35-6 7-hydroxy-2H-chromen-2-one 
• 27421-18-7 7-((2-methylbut-3-yn-2-yl)oxy)-2H-chromen-2-one 
• 17715-69-4 1-Bromo-2,4-dimethoxybenzene 
• 92741-82-7 1,3-diethyl 2-(2,4-dimethoxyphenyl)propanedioate 
• 31042-20-3 7-(benzyloxy)chroman-4-one 
• 124093-43-2 Acetic acid 7-benzyloxy-2H-chromen-4-yl ester 
• 76240-27-2 7-hydroxy-2,3-dihydro-4H-chromen-4-one 
• 59870-70-1 (R)-3-(2,4-dimethoxyphenyl)-8,8-dimethyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromene 

Downstream Products

• 68978-03-0 hispaglabridin A 
• 59870-70-1 (R)-3-(2,4-dimethoxyphenyl)-8,8-dimethyl-3,4-dihydro-2H,8H-pyrano[2,3-f]chromene 
• 1217305-76-4 5'-formylglabridin 

Relevant articles and documents

Method for synthesizing optically pure glabridin

The invention relates to a method for synthesizing optically pure glabridin. According to the method, chiral carbon of optically pure glabridin is constructed through biological enzyme catalysis, optically pure glabridin is prepared in combination with an organic synthesis method, and the key steps are that a chiral intermediate compound III is generated by using a lipase catalysis compound II, and an important intermediate compound IV is obtained through a bromination reaction. According to the method for synthesizing optically pure glabridin, raw materials are cheap and easy to obtain, and the total yield is high.

Method for asymmetrically synthesizing glabridin with optical purity

The invention discloses a method for asymmetrically synthesizing glabridin with optical purity, belonging to the field of organic synthesis. According to the invention, 7-hydroxychroman-4-one is usedas a raw material and is subjected to seven successive reactions including a protecting group protection reaction, an enol esterification reaction, an asymmetric addition reaction, a carbonyl reduction reaction, a phenolic hydroxyl protecting group removal reaction, a cyclization reaction and a demethylation reaction so as to finally prepare glabridin with optical purity. The optically pure glabridin is obtained by asymmetrically introducing a chiral center by using a palladium catalyst and an organophosphorus ligand; reaction conditions are mild; operation is convenient; and the method is suitable for industrial application. The raw material is easy to obtain and low in cost, and the product is good in yield and high in stereoselectivity.

Method for asymmetrically synthesizing glabridin with optical purity under catalysis of ruthenium compound

The invention relates to a method for asymmetrically synthesizing glabridin with optical purity under catalysis of a ruthenium compound. The method comprises the following steps: 1) taking isoflavoneprotected by a protection group as a raw material and carrying out dynamic kinetic asymmetric hydrogen transfer reaction under the catalysis effect of a ruthenium trichloride compound and the action of an acid-alkali buffering system to obtain chiral isoflavol with an absolute configuration being (3R, 4R); 2) removing hydroxyl of the chiral isoflavol under the action of triethylsilane and trifluoroacetic acid to obtain a product with an absolute configuration being (R); 3) removing a protection group of the product with the configuration being (R) in step 2) under an acidic or alkaline condition to obtain the glabridin with the configuration (R) and the optical purity. The method provided by the invention can be used for synthesizing the glabridin with the optical purity in a high-yield and high-stereoselectivity manner; the obtained product is completely the same as that of the glabridin extracted from glycyrrhiza glabra and can be used for replacing the glabridin derived from naturalplants to be industrially applied.