1447-88-7

Basic information

• Product Name: HISPIDULIN
• Synonyms: SCUTELLAREIN 6-METHYL ETHER;4',5,7-Trihydroxy-6-methoxyflavone;5,7-Dihydroxy-2-(4-hydroxyphenyl)-6-methoxy-4H-1-benzopyran-4-one;6-Methoxyapigenin;6-Methylscutellarein;Hispidulin(Dinatin);Methoxyapigenin;Dinatin
• CAS NO: 1447-88-7
• Molecular Formula: C₁₆H₁₂O₆
• Molecular Weight: 300.26
• Product Categories: Miscellaneous Natural Products
• Mol File: 1447-88-7.mol
• Article Data: 15

Chemical Properties

• Melting Point: 291-292 °C
• Boiling Point: 601.506 °C at 760 mmHg
• Flash Point: 230.135 °C
• Appearance: white to beige/
• Density: 1.512 g/cm³
• Vapor Pressure: 4.61E-15mmHg at 25°C
• Refractive Index: 1.697
• Storage Temp.: Desiccate at -20°C
• Solubility: DMSO: soluble20mg/mL, clear
• PKA: 6.51±0.40(Predicted)
• CAS DataBase Reference: HISPIDULIN(CAS DataBase Reference)
• NIST Chemistry Reference: HISPIDULIN(1447-88-7)
• EPA Substance Registry System: HISPIDULIN(1447-88-7)

Safety Data

• Hazard Codes: Xn
• Statements: 22
• WGK Germany: 3
• RTECS: DJ2996000
• Hazardous Substances Data: 1447-88-7(Hazardous Substances Data)

Usage

Uses

Hispidulin has been used as a calibration standard: in high-performance liquid chromatography (HPLC) for quantification of Clerodendrum petasites flavonoidsin liquid chromatography/electrospray ionization mass spectrometry (LC/ESI-MS) analysis in reverse-phase high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and high-performance thin-layer chromatography (HPTLC)

Definition

ChEBI: A monomethoxyflavone that is scutellarein methylated at position 6.

General Description

This substance is a primary reference substance with assigned absolute purity (considering chromatographic purity, water, residual solvents, inorganic impurities). The exact value can be found on the certificate. Produced by PhytoLab GmbH & Co. KG

Biological Activity

Partial positive allosteric modulator at the benzodiazepine receptor (IC 50 = 1.3 μ M for inhibition of flumazenil binding); natural sage flavone. Stimulates GABA-induced chloride currents in Xenopus oocytes expressing α 1?? α 2-, α 3-, α 5- or α 6- β 2 γ 2S GABA A receptors. Brain penetrant; oral administration reduces seizures in a gerbil model of epilepsy. Also has antifungal, antiproliferative, antioxidant and antithrombotic properties.

Biochem/physiol Actions

Hispidulin is a bioactive flavonoid with a variety of effects including antiproliferative, antifungal, anti-inflammatory, antioxidative and antiepileptic activity. Like EGCG, hispidulin appears to activate AMPK and inhibit the PI3K/Akt/mTOR pathway. The antiepileptic activity may be due to additional activity as a benzodiazepine (BZD) receptor ligand.

InChI:InChI=1/C16H12O6/c1-21-16-11(19)7-13-14(15(16)20)10(18)6-12(22-13)8-2-4-9(17)5-3-8/h2-7,17,19-20H,1H3

Synthetic route

7-(benzyloxy)-2-(4-(benzyloxy)phenyl)-5-hydroxy-6-methoxy-4H-chromen-4-one (28736-83-6) → hispidulin (1447-88-7)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; ethanol under 760.051 Torr; for 8h; Inert atmosphere;	96%
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; ethanol under 760.051 Torr; for 8h;	96%
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; ethanol for 8h;	96.1%
With palladium 10% on activated carbon; hydrogen In tetrahydrofuran; ethanol at 20℃; for 8h;	96%

5-hydroxy-6-methoxy-7-(methoxymethoxy)-2-(4-(methoxymethoxy)phenyl)-4H-chromen-4-one → hispidulin (1447-88-7)

Conditions	Yield
With hydrogenchloride In diethyl ether; dichloromethane at 0 - 25℃; for 1h;	92%
With hydrogenchloride In diethyl ether; dichloromethane; water at 0 - 25℃; for 1h;

hispidulin-7-O-β-D-methylglucuronopyranoside → hispidulin (1447-88-7)

Conditions	Yield
With sulfuric acid In ethanol; water at 20 - 100℃; Solvent; Temperature; Reagent/catalyst;	91%
With sulfuric acid In ethanol; water at 100℃; Inert atmosphere;	90%

4'-benzyloxy-6-methoxy-5-benzyloxy-7-hydroxyflavone → hispidulin (1447-88-7)

Conditions	Yield
With boron trichloride In dichloromethane at -78℃; for 1.33333h;	85%
With boron trichloride In dichloromethane at -78℃; for 1.33333h;	85%

4'-benzyloxy-6-methoxy-5,7-dihydroxyflavone → hispidulin (1447-88-7)

Conditions	Yield
With boron trichloride In dichloromethane at -78 - 20℃; for 1h; Inert atmosphere;	80%

tectoridin (17680-84-1) → D-Glucose (2280-44-6) + hispidulin (1447-88-7)

Conditions	Yield
With hydrolysis

5,7-dihydroxy-6-methoxy-flavone-4'-O-neohesperidoside → hispidulin (1447-88-7)

Conditions	Yield
With sulfuric acid for 8h;	95 mg

7-benzyloxy-2-(4-benzyloxy-phenyl)-5,6-dimethoxy-chromen-4-one → hispidulin (1447-88-7)

Conditions	Yield
With boron trichloride In dichloromethane at -65℃; for 1.5h;

2-hydroxy-4,6-dimethoxyacetophenone (90-24-4) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 8 steps 1: 60 percent / aluminium chloride / chlorobenzene / 1 h / Heating 2: 99 percent / K2CO3 / acetone / Heating 3: 29 percent / NaOH; K2S2O8; pyridine / H2O / 24 h / 20 °C 4: 59 percent / K2CO3 / acetone / Heating 5: pyridine / 3 h / 20 °C 6: KOH / pyridine / 4 h / 60 °C 7: sulfuric acid / acetic acid / 1.5 h / 60 °C 8: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

4-(benzyloxy)benzoic acid chloride (1486-50-6) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / 3 h / 20 °C 2: KOH / pyridine / 4 h / 60 °C 3: sulfuric acid / acetic acid / 1.5 h / 60 °C 4: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

2,4,6-trihydroxyacetophenone (480-66-0) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 9 steps 1: 92 percent / K2CO3 / acetone / 3 h / 65 °C 2: 60 percent / aluminium chloride / chlorobenzene / 1 h / Heating 3: 99 percent / K2CO3 / acetone / Heating 4: 29 percent / NaOH; K2S2O8; pyridine / H2O / 24 h / 20 °C 5: 59 percent / K2CO3 / acetone / Heating 6: pyridine / 3 h / 20 °C 7: KOH / pyridine / 4 h / 60 °C 8: sulfuric acid / acetic acid / 1.5 h / 60 °C 9: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme
Multi-step reaction with 9 steps 1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0 °C 2: silver trifluoroacetate; iodine / dichloromethane / 0 °C 3: potassium carbonate / N,N-dimethyl-formamide / 0 °C 4: potassium hydroxide; tris-(dibenzylideneacetone)dipalladium(0); tert-butyl XPhos / water; 1,4-dioxane / 90 °C 5: potassium carbonate / acetone / 5 h / 56 °C 6: potassium hydroxide / water; ethanol / 24.5 h / 0 - 20 °C 7: hydrogenchloride / methanol; tetrahydrofuran / 8 h / 0 - 20 °C 8: iodine / dimethyl sulfoxide / 2 h / 120 °C 9: boron trichloride / dichloromethane / 1.33 h / -78 °C View Scheme

1-(4-(benzyloxy)-6-hydroxy-2,3-dimethoxyphenyl)ethan-1-one (25892-95-9) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: pyridine / 3 h / 20 °C 2: KOH / pyridine / 4 h / 60 °C 3: sulfuric acid / acetic acid / 1.5 h / 60 °C 4: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

4,6-dihydroxy-2-methoxyacetophenone (3602-54-8) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: 99 percent / K2CO3 / acetone / Heating 2: 29 percent / NaOH; K2S2O8; pyridine / H2O / 24 h / 20 °C 3: 59 percent / K2CO3 / acetone / Heating 4: pyridine / 3 h / 20 °C 5: KOH / pyridine / 4 h / 60 °C 6: sulfuric acid / acetic acid / 1.5 h / 60 °C 7: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

p-(benzyloxy)benzoic acid (1486-51-7) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: oxalyl chloride / CH2Cl2 / 8 h / 20 °C 2: pyridine / 3 h / 20 °C 3: KOH / pyridine / 4 h / 60 °C 4: sulfuric acid / acetic acid / 1.5 h / 60 °C 5: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

1-(4-(benzyloxy)-3,6-dihydroxy-2-methoxyphenyl)ethan-1-one (25892-94-8) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 59 percent / K2CO3 / acetone / Heating 2: pyridine / 3 h / 20 °C 3: KOH / pyridine / 4 h / 60 °C 4: sulfuric acid / acetic acid / 1.5 h / 60 °C 5: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

1-(4-(benzyloxy)-2-hydroxy-6-methoxyphenyl)ethan-1-one (39548-89-5) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: 29 percent / NaOH; K2S2O8; pyridine / H2O / 24 h / 20 °C 2: 59 percent / K2CO3 / acetone / Heating 3: pyridine / 3 h / 20 °C 4: KOH / pyridine / 4 h / 60 °C 5: sulfuric acid / acetic acid / 1.5 h / 60 °C 6: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

4-hydroxy-benzoic acid (99-96-7) + acid → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: KOH / H2O; ethanol / 6 h / Heating 2: oxalyl chloride / CH2Cl2 / 8 h / 20 °C 3: pyridine / 3 h / 20 °C 4: KOH / pyridine / 4 h / 60 °C 5: sulfuric acid / acetic acid / 1.5 h / 60 °C 6: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

4-benzyloxy-benzoic acid 2-acetyl-5-benzyloxy-3,4-dimethoxy-phenyl ester → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: KOH / pyridine / 4 h / 60 °C 2: sulfuric acid / acetic acid / 1.5 h / 60 °C 3: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

1-(4-benzyloxy-6-hydroxy-2,3-dimethoxy-phenyl)-3-(4-benzyloxy-phenyl)-propane-1,3-dione → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid / acetic acid / 1.5 h / 60 °C 2: BCl3 / CH2Cl2 / 1.5 h / -65 °C View Scheme

scutellarin (27740-01-8) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 7 steps 1: hydrogenchloride / ethanol; water / 36 h / Inert atmosphere; Reflux 2: diphenylether / 0.5 h / 175 °C / Inert atmosphere 3: potassium carbonate / N,N-dimethyl-formamide / 14 h / 0 - 25 °C 4: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 5: potassium carbonate / N,N-dimethyl-formamide / 12 h / 0 - 25 °C / Inert atmosphere 6: potassium carbonate / N,N-dimethyl-formamide / 25 °C / Inert atmosphere 7: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr / Inert atmosphere View Scheme
Multi-step reaction with 7 steps 1: hydrogenchloride / water; ethanol / 36 h / Inert atmosphere; Reflux 2: diphenylether / 0.5 h / 175 °C / Inert atmosphere 3: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 4: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 5: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 6: potassium carbonate / N,N-dimethyl-formamide / 12 h / 25 °C / Inert atmosphere 7: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr View Scheme
Multi-step reaction with 4 steps 1: hydrogenchloride / water; ethanol / 36 h / Inert atmosphere; Reflux 2: potassium carbonate / acetone / 6 h / Reflux 3: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C 4: palladium 10% on activated carbon; hydrogen / ethanol; tetrahydrofuran / 8 h View Scheme

scutellarein (529-53-3) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 6 steps 1: diphenylether / 0.5 h / 175 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 14 h / 0 - 25 °C 3: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 4: potassium carbonate / N,N-dimethyl-formamide / 12 h / 0 - 25 °C / Inert atmosphere 5: potassium carbonate / N,N-dimethyl-formamide / 25 °C / Inert atmosphere 6: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr / Inert atmosphere View Scheme
Multi-step reaction with 6 steps 1: diphenylether / 0.5 h / 175 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 3: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 4: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 5: potassium carbonate / N,N-dimethyl-formamide / 12 h / 25 °C / Inert atmosphere 6: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / acetone / 6 h / Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 12 h / 20 °C 3: palladium 10% on activated carbon; hydrogen / ethanol; tetrahydrofuran / 8 h View Scheme

9-hydroxy-6-(4-hydroxyphenyl)-2,2-diphenyl-8H-1,3-dioxolo[4,5-g][1]benzopyran-8-one (1105056-24-3) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 14 h / 0 - 25 °C 2: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 3: potassium carbonate / N,N-dimethyl-formamide / 12 h / 0 - 25 °C / Inert atmosphere 4: potassium carbonate / N,N-dimethyl-formamide / 25 °C / Inert atmosphere 5: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr / Inert atmosphere View Scheme
Multi-step reaction with 5 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 2: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 3: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 4: potassium carbonate / N,N-dimethyl-formamide / 12 h / 25 °C / Inert atmosphere 5: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr View Scheme

9-hydroxy-2,2-diphenyl-6-[4-(phenylmethoxy)phenyl]-8H-1,3-dioxolo[4,5-g][1]benzopyran-8-one (1402607-40-2) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 12 h / 0 - 25 °C / Inert atmosphere 3: potassium carbonate / N,N-dimethyl-formamide / 25 °C / Inert atmosphere 4: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr / Inert atmosphere View Scheme
Multi-step reaction with 4 steps 1: acetic acid / water / 1.5 h / Inert atmosphere; Reflux 2: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 3: potassium carbonate / N,N-dimethyl-formamide / 12 h / 25 °C / Inert atmosphere 4: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr View Scheme

5,6,7-trihydroxy-2-[4-(phenylmethoxy)phenyl]-4H-1-benzopyran-4-one (1351585-69-7) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 0 - 25 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 25 °C / Inert atmosphere 3: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr / Inert atmosphere View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / N,N-dimethyl-formamide / 0 - 25 °C / Inert atmosphere 2: potassium carbonate / N,N-dimethyl-formamide / 12 h / 25 °C / Inert atmosphere 3: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr View Scheme

7-(benzyloxy)-2-(4-(benzyloxy)phenyl)-5,6-dihydroxy-4H-chromen-4-one (62252-32-8) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / N,N-dimethyl-formamide / 12 h / 25 °C / Inert atmosphere 2: hydrogen; palladium 10% on activated carbon / ethanol; tetrahydrofuran / 8 h / 760.05 Torr View Scheme

Iretol (487-71-8) → hispidulin (1447-88-7)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: boron trifluoride diethyl etherate / 20 °C / Cooling with ice; Inert atmosphere 2.1: potassium carbonate / acetone / 56 °C / Inert atmosphere 2.2: 0 - 20 °C / Inert atmosphere 3.1: sodium acetate / water; ethanol / 78 °C / Inert atmosphere 4.1: pyridine; iodine / 3 h / 90 °C 5.1: boron trichloride / dichloromethane / 1 h / -78 - 20 °C / Inert atmosphere View Scheme

2,4,6-trihydroxy-3-methoxyacetophenone (16297-01-1) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: potassium carbonate / acetone / 56 °C / Inert atmosphere 1.2: 0 - 20 °C / Inert atmosphere 2.1: sodium acetate / water; ethanol / 78 °C / Inert atmosphere 3.1: pyridine; iodine / 3 h / 90 °C 4.1: boron trichloride / dichloromethane / 1 h / -78 - 20 °C / Inert atmosphere View Scheme

(E)-1-(6-hydroxy-3-methoxy-2,4-bis-(methoxymethoxy)phenyl)-3-(4-benzyloxyphenyl)prop-2-en-1-one → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium acetate / water; ethanol / 78 °C / Inert atmosphere 2: pyridine; iodine / 3 h / 90 °C 3: boron trichloride / dichloromethane / 1 h / -78 - 20 °C / Inert atmosphere View Scheme

2,4,6-trihydroxybenzaldehyde (487-70-7) → hispidulin (1447-88-7)

Conditions	Yield
Multi-step reaction with 9 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 20 °C / Cooling with ice 2.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane; water / 20 °C 3.1: potassium carbonate / acetone / 56 °C / Inert atmosphere 4.1: hydrogenchloride / water; methanol / 20 °C 5.1: boron trifluoride diethyl etherate / 20 °C / Cooling with ice; Inert atmosphere 6.1: potassium carbonate / acetone / 56 °C / Inert atmosphere 6.2: 0 - 20 °C / Inert atmosphere 7.1: sodium acetate / water; ethanol / 78 °C / Inert atmosphere 8.1: pyridine; iodine / 3 h / 90 °C 9.1: boron trichloride / dichloromethane / 1 h / -78 - 20 °C / Inert atmosphere View Scheme
Multi-step reaction with 10 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / 0 °C / Inert atmosphere 1.2: 3 h / 0 - 20 °C / Inert atmosphere 2.1: silver trifluoroacetate; iodine / dichloromethane / 5 h / 0 - 20 °C 3.1: potassium carbonate / N,N-dimethyl-formamide / 3 h / 0 - 20 °C 4.1: bis-triphenylphosphine-palladium(II) chloride / toluene / 12 h / 100 °C 5.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 9 h / 0 - 20 °C 5.2: 1.5 h / 20 °C 6.1: potassium carbonate / acetone / 5 h / 56 °C 7.1: potassium hydroxide / water; ethanol / 24.5 h / 0 - 20 °C 8.1: hydrogenchloride / methanol; tetrahydrofuran / 8 h / 0 - 20 °C 9.1: iodine / dimethyl sulfoxide / 2 h / 120 °C 10.1: boron trichloride / dichloromethane / 1.33 h / -78 °C View Scheme
Multi-step reaction with 8 steps 1.1: N-ethyl-N,N-diisopropylamine / dichloromethane / 0.17 h / Cooling with ice; Inert atmosphere 1.2: 3 h / 20 °C / Inert atmosphere 2.1: silver trifluoroacetate; iodine / dichloromethane / 3 h / 0 - 20 °C 2.2: 3 h / 0 - 20 °C 3.1: bis-triphenylphosphine-palladium(II) chloride / toluene / 12 h / 100 °C 4.1: 3-chloro-benzenecarboperoxoic acid / dichloromethane / 8 h / 0 - 20 °C 5.1: potassium carbonate / acetone / 5 h / 56 °C 6.1: potassium hydroxide / ethanol; water / 24.5 h / 0 - 20 °C 6.2: 8 h / 0 - 20 °C 7.1: iodine / dimethyl sulfoxide / 2 h / 120 °C 8.1: boron trichloride / dichloromethane / 1.33 h / -78 °C View Scheme

hispidulin (1447-88-7) + methyl iodide (74-88-4) → salvigenin (6601-62-3) + pectolinarigenin (520-12-7)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 25℃; for 6h; Inert atmosphere;	A 38% B 49%

hispidulin (1447-88-7) → scutellarein (529-53-3)

Conditions	Yield
With pyridine hydrochloride for 3h;

hispidulin (1447-88-7) + acetic anhydride (108-24-7) → 5,7,4'-trihydroxy-6-methoxyflavone triacetate (1178-23-0)

Conditions	Yield
With pyridine

hispidulin (1447-88-7) + acetic anhydride (108-24-7) → luteolin tetraacetate (1061-93-4)

Conditions	Yield
With pyridine Acetylation;

Upstream product

• 17680-84-1 tectoridin 
• 1258506-19-2 5,6-dihydroxy-7-(methoxymethoxy)-2-(4-(methoxymethoxy)phenyl)-4H-chromen-4-one 
• 65490-09-7 2'-hydroxy-4',6'-bis(methoxymethoxy)acetophenone 
• 1132988-93-2 2-hydroxy-4,6-bis(methoxymethoxy)benzaldehyde 
• 529-53-3 scutellarein 
• 485-80-3 S-adenosyl-L-methionine 
• 212265-19-5 2,4,6-tris(O-methoxymethyl)benzaldehyde 
• 487-70-7 2,4,6-trihydroxybenzaldehyde 

Downstream Products

• 529-53-3 scutellarein 
• 1178-23-0 5,7,4'-trihydroxy-6-methoxyflavone triacetate 
• 1061-93-4 luteolin tetraacetate 
• 6601-62-3 salvigenin 
• 520-12-7 pectolinarigenin 

Relevant articles and documents

FLAVONOIDS OF Digitalis ciliata

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Enzymatic production of oroxylin A and hispidulin using a liverwort flavone 6-O-methyltransferase

Oroxylin A and hispidulin, compounds which are abundant in both Scutellaria and liverwort species, are important lead compounds for the treatment of ischemic cerebrovascular disease. Their enzymatic synthesis requires an O-methyltransferase able to interact with the related flavonoid's 6-OH group, but such an enzyme has yet to be identified in plants. Here, the gene encoding an O-methyltransferase (designated PaF6OMT) was isolated from the liverwort species Plagiochasma?appendiculatum. A test of alternative substrates revealed that its strongest preferences were baicalein and scutellarein, which were converted into, respectively, oroxylin A and hispidulin. Allowed a sufficient reaction time, the conversion rate of these two substrates was, respectively, 90% and 100%. PaF6OMT offers an enzymatic route to the synthesis of oroxylin A and hispidulin.

Semi-synthesis of a series natural flavonoids and flavonoid glycosides from scutellarin

Natural flavonoids and flavonoid glycosides exist in many plants and have been demonstrated to possess various clinically relevant properties, isolating large amounts of these compounds that have striking structural similarity from plant sources needs tedious isolation techniques. These processes limited their availability in structural diversity for structure?activity relationship (SAR) studies, and restrict large quantities for, as an example, their mechanistic evaluation of the in vivo activities. In this work, we developed a semi-synthetic strategy from scutellarin for the synthesis of a series of natural flavonoids and flavonoid glycosides. By taking this strategy, eight bioactive flavonoids with striking structural similarities were synthesized efficiently and practically. The sufficient amounts obtained products will greatly facilitate the SAR studies and mechanistic evaluation of the in vivo activities.

METHOD FOR PREPARING HISPIDULIN AND ITS DERIVATIVES

Provided is a method for preparing hispidulin or a derivative thereof. The method includes selective protection of trihydroxybenzaldehyde, followed by regioselective iodination, selective protection, Stille coupling, Baeyer-Villiger oxidation and basic hydrolysis to obtain a protected intermediate compound. Then, alkylation, Claisen-Schmidt condensation, cyclization and deprotection of the protected intermediate compound are performed to obtain hispidulin or the derivative thereof. The present disclosure provides an efficient method for total synthesis of hispidulin or the derivative thereof with concise reaction steps and high yield.