491-67-8

Basic information

• Product Name: Baicalein
• Synonyms: BAICALEIN(SH)NOW RG GRADE;Baicalein, monohydrate, 5,6,7-Trihydroxy-2-phenyl-4H-chromen-4-one monohydrate;Baicelein;Noroxylin;5,6,7-trihydroxy-2-phenyl-4H-chroMen-4-one;Baicalein 98%;5,6,7-trihydroxy-2-phenyl-4-chromenone hydrate;5,6,7-trihydroxy-2-phenyl-chromen-4-one hydrate
• CAS NO: 491-67-8
• Molecular Formula: C₁₅H₁₀O₅
• Molecular Weight: 270.24
• Product Categories: Aromatics;Heterocycles;API;chemical reagent;pharmaceutical intermediate;phytochemical;reference standards from Chinese medicinal herbs (TCM).;standardized herbal extract;natural product;Tri-substituted Flavones;The group of Scutellaria;Inhibitors
• Mol File: 491-67-8.mol
• Article Data: 34

Chemical Properties

• Melting Point: 256-271 °C(lit.)
• Boiling Point: 373.35°C (rough estimate)
• Flash Point: 225.257 °C
• Appearance: Yellow crystalline solid
• Density: 1.3280 (rough estimate)
• Vapor Pressure: 8.55E-18mmHg at 25°C
• Refractive Index: 1.5000 (estimate)
• Storage Temp.: 2-8°C
• Solubility: DMSO (Slightly), Methanol (Slightly)
• PKA: 6.31±0.40(Predicted)
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 1 week.
• Merck: 14,942
• BRN: 272683
• CAS DataBase Reference: Baicalein(CAS DataBase Reference)
• NIST Chemistry Reference: Baicalein(491-67-8)
• EPA Substance Registry System: Baicalein(491-67-8)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-36
• WGK Germany: 3
• RTECS: DJ3100898
• Hazardous Substances Data: 491-67-8(Hazardous Substances Data)

Usage

Description

Baicalein (491-67-8) is an inhibitor of protein tyrosine kinase in leukemia (CEM) cells. Induces cell cycle arrest and apoptosis.1?Originally reported as a selective inhibitor of 12-lipoxygenase, baicalein has since been shown to inhibit both 12-LO and 15-LO (IC50=0.64 μM for 12-LO and 1.6 μM for 15-LO).2 Baicalein displays anti-inflammatory activity and inhibits adjuvant-induced arthritis. Also inhibits prolyl oligopeptidase (IC50=36 μM).3

Chemical Properties

Yellow Crystalline Solid

Uses

Different sources of media describe the Uses of 491-67-8 differently. You can refer to the following data:
1. Baicalein is a flavonoid originally isolated from the roots of Scutellaria baicalensis Georgi. Several different functions of baicalein have been reported. Platelet 12-lipoxygenase is inhibited by baicalein with an ID50 value of 0.12 μM, with minimal inhibition of platelet cyclooxygenase-1 (IC50 = 0.83 mM). Baicalein inhibits lipid peroxidation, as assessed by production of TBARS, with an IC50 value of 5 μM. In addition to these effects, baicalein may play a role in apoptosis, as the compound inhibits cell growth of three human hepatocellular carcinoma cell lines with IC50 values ranging from 17-70 μg/ml.
2. antiviral (HIV)
3. An inhibitor of 12-lipoxygenase, leukotriene biosynthesis and release of lysosomal enzymes. It also inhibits cellular Ca2+ uptake and mobilization and adjuvant-induced arthritis. Baicalein is the fl avonoid component of Nepalese and Sino-Japanese crude drugs.
4. inhibitor of lipoxidase and leukotriene biosynthesis
5. An inhibitor of Ca2+ uptake, 5-LO, and 12-LO

Definition

ChEBI: A trihydroxyflavone with the hydroxy groups at positions C-5, -6 and -7.

General Description

Baicalein, a flavonoid, is a xanthine oxidase inhibitor. Anti-inflammatory effects of baicalein in peripheral human leukocytes has been studied.

Biological Activity

Inhibitor of 5- and platelet 12-lipoxygenases (IC 50 values are 9.5 and 0.12 mM respectively). Also inhibits Raf-mediated MEK-1 phosphorylation in C6 rat glioma cells and induces G1 and G2 cell cycle arrest by decreasing cdk1, cdk2, cyclin D2 and cyclin A expression. Anti-inflammatory in vivo .

Biochem/physiol Actions

The flavonoid component of Nepalese and Sino-Japanese crude drugs. Baicalein, a major flavone of Scutellariae baicalensis, inhibits the 12-lipoxygenase (12-LOX) pathway of arachidonic acid metabolism, which inhibits cancer cell proliferation and induces apoptosis.

References

1) Lee?et al. (2005),?Baicalein induced cell cycle arrest and apoptosis in human lung squamous carcinoma CH27 cells; Anticancer Res.,?25?959 2) Deschamps?et al. (2006),?Baicalein is a potent in vitro inhibitor against both reticulocyte 15-human and platelet 12-human lipoxygenases; Bioorg. Med. Chem.,?14?4295 3) Tarrago?et al. (2008),?Baicalin, a prodrug able to reach the CNS, is a prolyl oligopeptidase inhibitor; Bioorg. Med. Chem.,?16?7516

InChI:InChI=1/C15H10O5.H2O/c16-9-6-11(8-4-2-1-3-5-8)20-12-7-10(17)14(18)15(19)13(9)12;/h1-7,17-19H;1H2

Synthetic route

baicalin (21967-41-9) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With sulfuric acid; water at 20℃; for 0.166667h;	93%
With sulfuric acid In water at 90℃; for 0.0833333h;	71.9%
With sulfuric acid at 90℃; for 0.166667h;	29.3%

Baicalin methyl ester (82475-03-4) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With sulfuric acid In ethanol; water at 95℃; for 8.5h; Inert atmosphere;	97%
With hydrogenchloride In ethanol at 85℃; for 12h; Temperature; Reagent/catalyst; Inert atmosphere;	91.8%

5,7-dimethoxy-6-hydroxyflavone (119892-40-9) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogen bromide at 120 - 130℃; Reagent/catalyst; Temperature; Reflux;	91%
With hydrogen bromide at 120℃; Reagent/catalyst; Temperature; Inert atmosphere;	88%
Multi-step reaction with 2 steps 1: potassium carbonate; acetone 2: aqueous hydriodic acid; acetic acid anhydride / 140 °C View Scheme

5,6,7-trimethoxyflavone (973-67-1) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogen bromide; acetic acid at 130℃;	92%
With hydrogen bromide; acetic acid for 18h; Heating;	89%
With pyridine hydrochloride at 190℃; for 6.5h; Inert atmosphere;	85%

5,6-dihydroxy-7-methoxyflavone (29550-13-8) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With water; hydrogen bromide; acetic acid for 18h; Reflux;	85%
With water; hydrogen bromide; Aliquat 336 at 105℃; for 8h; Catalytic behavior;	80%
With hydrogen iodide; acetic anhydride

4-oxo-2-phenyl-4H-1-benzopyran-5,6,7-triyl triacetate (67047-05-6) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Stage #1: 4-oxo-2-phenyl-4H-1-benzopyran-5,6,7-triyl triacetate With sodium hydroxide In water; acetone at 0℃; for 1h; Stage #2: With hydrogenchloride In water; acetone pH=6 - 7;	66.7%

oroxylin A (480-11-5) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With water; hydrogen bromide; Aliquat 336 at 105℃; for 7h; Catalytic behavior;	84%
With hydrogen bromide; acetic acid for 12h; Heating;	81%

2',4',5',6'-tetrahydroxyflavone (671791-94-9) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogenchloride; lithium hydroxide; sulfuric acid In tetrahydrofuran; acetic acid

C15H12O6 → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With sulfuric acid; acetic acid for 1h; Reflux;

baicalein 6-O-β-D-glucopyranoside (28279-72-3) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogenchloride In methanol at 90℃; for 0.5h;

baicalein 7-O-β-(6''-O-malonylglycoside) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogenchloride In methanol at 90℃; for 0.5h;

cinnamoyl chloride (102-92-1) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: 90 percent / BF3-Et2O / 0.25 h / Heating 2: 87 percent / I2; DMSO / 2 h / Heating 3: 89 percent / HBr; glacial AcOH / 18 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 90 percent / BF3-Et2O / 0.25 h / Heating 2: 87 percent / I2; DMSO / 2 h / Heating 3: 88 percent / HBr; glacial AcOH / 2 h / Heating 4: 81 percent / HBr; glacial AcOH / 12 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 90 percent / BF3-Et2O / 0.25 h / Heating 2: 91 percent / HBr; glacial AcOH / 2 h / Heating 3: 46 percent / I2; DMSO / Heating 4: 81 percent / HBr; glacial AcOH / 12 h / Heating View Scheme
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate / toluene 2: iodine / dimethyl sulfoxide 3: hydrogen bromide; acetic acid / 130 °C View Scheme
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate / dichloromethane / 0.17 h / Reflux 2: iodine / dimethyl sulfoxide / 3 h / Reflux 3: hydrogen bromide; acetic acid / 48 h View Scheme

6,7-dihydroxy-5-methoxyflavone (150036-33-2) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogenchloride

3,4,5-trimethoxyphenol (642-71-7) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: BF3-Et2O / 0.25 h 2: KOH / ethanol 3: 87 percent / I2; DMSO / 2 h / Heating 4: 89 percent / HBr; glacial AcOH / 18 h / Heating View Scheme
Multi-step reaction with 5 steps 1: BF3-Et2O / 0.25 h 2: KOH / ethanol 3: 87 percent / I2; DMSO / 2 h / Heating 4: 88 percent / HBr; glacial AcOH / 2 h / Heating 5: 81 percent / HBr; glacial AcOH / 12 h / Heating View Scheme
Multi-step reaction with 5 steps 1: BF3-Et2O / 0.25 h 2: KOH / ethanol 3: 91 percent / HBr; glacial AcOH / 2 h / Heating 4: 46 percent / I2; DMSO / Heating 5: 81 percent / HBr; glacial AcOH / 12 h / Heating View Scheme

7-hydroxy-5-methoxy-4-oxo-2-phenyl-4H-chromene-6-carbaldehyde (412027-80-6) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: aq. NaOH solution; aqueous hydrogen peroxide 2: aqueous hydrochloric acid View Scheme

6-hydroxy-2,3,4-trimethoxyacetophenone (22248-14-2) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: KOH / ethanol 2: 87 percent / I2; DMSO / 2 h / Heating 3: 89 percent / HBr; glacial AcOH / 18 h / Heating View Scheme
Multi-step reaction with 4 steps 1: KOH / ethanol 2: 87 percent / I2; DMSO / 2 h / Heating 3: 88 percent / HBr; glacial AcOH / 2 h / Heating 4: 81 percent / HBr; glacial AcOH / 12 h / Heating View Scheme
Multi-step reaction with 4 steps 1: KOH / ethanol 2: 91 percent / HBr; glacial AcOH / 2 h / Heating 3: 46 percent / I2; DMSO / Heating 4: 81 percent / HBr; glacial AcOH / 12 h / Heating View Scheme

3,6-dihydroxy-2,4-dimethoxyacetophenone (6962-57-8) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium benzoate / 180 °C / Unter vermindertem Druck und anschliessend Erwaermen mit wss.-aethanol. Kalilauge 2: potassium carbonate; acetone 3: aqueous hydriodic acid; acetic acid anhydride / 140 °C View Scheme
Multi-step reaction with 3 steps 1: hydrogenchloride; sodium hydroxide / water / 48 h / 20 °C / Inert atmosphere 2: iodine; sodium hydrogensulfite / dimethylsulfoxide-d6 / 48 h / 120 °C / Cooling with ice 3: hydrogen bromide / 120 °C / Inert atmosphere View Scheme

6′-hydroxy-2′,3′,4′-trimethoxychalcone (70185-52-3, 74064-14-5) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: iodine / dimethyl sulfoxide 2: hydrogen bromide; acetic acid / 130 °C View Scheme
Multi-step reaction with 2 steps 1: iodine / dimethyl sulfoxide / 3 h / Reflux 2: hydrogen bromide; acetic acid / 48 h View Scheme

Cinnamic acid (621-82-9) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: thionyl chloride / benzene / Reflux 2: boron trifluoride diethyl etherate / toluene 3: iodine / dimethyl sulfoxide 4: hydrogen bromide; acetic acid / 130 °C View Scheme
Multi-step reaction with 4 steps 1: oxalyl dichloride; N,N-dimethyl-formamide / dichloromethane / 2 h / 20 °C / Cooling with ice 2: boron trifluoride diethyl etherate / dichloromethane / 0.17 h / Reflux 3: iodine / dimethyl sulfoxide / 3 h / Reflux 4: hydrogen bromide; acetic acid / 48 h View Scheme

(E)-3-phenylacrylic acid (140-10-3) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane / 2 h / 20 °C / Cooling with ice 2: boron trifluoride diethyl etherate / 0.17 h / Reflux 3: iodine / dimethyl sulfoxide / 3 h / Reflux 4: hydrogen bromide; acetic acid / 48 h / Reflux View Scheme
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate; acetic anhydride / 1,2-dichloro-ethane; methanol / 8 h / 90 °C / Reflux 2: iodine / dimethyl sulfoxide / 6 h / 180 °C 3: hydrogen bromide / 120 - 130 °C / Reflux View Scheme

phenol (108-95-2) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: acetic acid; sulfuric acid; sodium bromide; dihydrogen peroxide / 20 - 45 °C 2.1: copper(l) chloride / methanol; N,N-dimethyl-formamide / 100 - 110 °C 3.1: boron trifluoride diethyl etherate / chloroform / 36 h / 20 - 60 °C 3.2: 120 °C / Reflux 4.1: iodine / dimethyl sulfoxide / 6 h / 180 °C 5.1: hydrogen bromide / 120 - 130 °C / Reflux View Scheme
Multi-step reaction with 5 steps 1: acetic acid; sulfuric acid; sodium bromide; dihydrogen peroxide / 20 - 45 °C 2: copper(l) chloride / methanol; N,N-dimethyl-formamide / 100 - 110 °C 3: boron trifluoride diethyl etherate; acetic anhydride / 1,2-dichloro-ethane; methanol / 8 h / 90 °C / Reflux 4: iodine / dimethyl sulfoxide / 6 h / 180 °C 5: hydrogen bromide / 120 - 130 °C / Reflux View Scheme
Multi-step reaction with 6 steps 1: acetic acid; sulfuric acid; sodium bromide; dihydrogen peroxide / 20 - 45 °C 2: copper(l) chloride / methanol; N,N-dimethyl-formamide / 100 - 110 °C 3: boron trifluoride diethyl etherate / chloroform / 10 h / 20 - 60 °C 4: boron trifluoride diethyl etherate; acetic anhydride / chloroform / 36 h / 60 °C / Reflux 5: iodine / dimethyl sulfoxide / 6 h / 180 °C 6: hydrogen bromide / 120 - 130 °C / Reflux View Scheme

2,4,6-tribromophenol (118-79-6) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: copper(l) chloride / methanol; N,N-dimethyl-formamide / 100 - 110 °C 2.1: boron trifluoride diethyl etherate / chloroform / 36 h / 20 - 60 °C 2.2: 120 °C / Reflux 3.1: iodine / dimethyl sulfoxide / 6 h / 180 °C 4.1: hydrogen bromide / 120 - 130 °C / Reflux View Scheme
Multi-step reaction with 4 steps 1: copper(l) chloride / methanol; N,N-dimethyl-formamide / 100 - 110 °C 2: boron trifluoride diethyl etherate; acetic anhydride / 1,2-dichloro-ethane; methanol / 8 h / 90 °C / Reflux 3: iodine / dimethyl sulfoxide / 6 h / 180 °C 4: hydrogen bromide / 120 - 130 °C / Reflux View Scheme
Multi-step reaction with 5 steps 1: copper(l) chloride / methanol; N,N-dimethyl-formamide / 100 - 110 °C 2: boron trifluoride diethyl etherate / chloroform / 10 h / 20 - 60 °C 3: boron trifluoride diethyl etherate; acetic anhydride / chloroform / 36 h / 60 °C / Reflux 4: iodine / dimethyl sulfoxide / 6 h / 180 °C 5: hydrogen bromide / 120 - 130 °C / Reflux View Scheme

2,4,6-trimethoxyphenol (20491-92-3) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: boron trifluoride diethyl etherate / chloroform / 36 h / 20 - 60 °C 1.2: 120 °C / Reflux 2.1: iodine / dimethyl sulfoxide / 6 h / 180 °C 3.1: hydrogen bromide / 120 - 130 °C / Reflux View Scheme
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate; acetic anhydride / 1,2-dichloro-ethane; methanol / 8 h / 90 °C / Reflux 2: iodine / dimethyl sulfoxide / 6 h / 180 °C 3: hydrogen bromide / 120 - 130 °C / Reflux View Scheme
Multi-step reaction with 4 steps 1: boron trifluoride diethyl etherate / chloroform / 10 h / 20 - 60 °C 2: boron trifluoride diethyl etherate; acetic anhydride / chloroform / 36 h / 60 °C / Reflux 3: iodine / dimethyl sulfoxide / 6 h / 180 °C 4: hydrogen bromide / 120 - 130 °C / Reflux View Scheme

wogonin (632-85-9) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogen iodide; acetic anhydride at 150℃;

7-hydroxy-5,8-dimethoxyflavone (3316-54-9) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
With hydrogen iodide; acetic anhydride at 150℃;

Cinnamoyl chloride (102-92-1) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate / 0.17 h / Reflux 2: iodine / dimethyl sulfoxide / 3 h / Reflux 3: hydrogen bromide; acetic acid / 48 h / Reflux View Scheme

5-hydroxy-2,4,6-trimethoxyacetophenone (103777-45-3) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1: boron trifluoride diethyl etherate; acetic anhydride / chloroform / 36 h / 60 °C / Reflux 2: iodine / dimethyl sulfoxide / 6 h / 180 °C 3: hydrogen bromide / 120 - 130 °C / Reflux View Scheme

benzaldehyde (100-52-7) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: boron trifluoride diethyl etherate / chloroform / 36 h / 20 - 60 °C 1.2: 120 °C / Reflux 2.1: iodine / dimethyl sulfoxide / 6 h / 180 °C 3.1: hydrogen bromide / 120 - 130 °C / Reflux View Scheme

2,6-dimethoxy-p-quinone (530-55-2) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 5 steps 1: sodium dithionite / water / 3 h / 20 °C 2: boron trifluoride diethyl etherate / chloroform / 10 h / 20 - 90 °C 3: hydrogenchloride; sodium hydroxide / water / 48 h / 20 °C / Inert atmosphere 4: iodine; sodium hydrogensulfite / dimethylsulfoxide-d6 / 48 h / 120 °C / Cooling with ice 5: hydrogen bromide / 120 °C / Inert atmosphere View Scheme

2,6-dimethoxy-1,4-hydroquinone (15233-65-5) → 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8)

Conditions	Yield
Multi-step reaction with 4 steps 1: boron trifluoride diethyl etherate / chloroform / 10 h / 20 - 90 °C 2: hydrogenchloride; sodium hydroxide / water / 48 h / 20 °C / Inert atmosphere 3: iodine; sodium hydrogensulfite / dimethylsulfoxide-d6 / 48 h / 120 °C / Cooling with ice 4: hydrogen bromide / 120 °C / Inert atmosphere View Scheme

benzaldehyde dimethyl acetal (1125-88-8) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → C22H14O5

Conditions	Yield
With hydrogenchloride In tetrahydrofuran; water for 2h;	100%

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + methyl iodide (74-88-4) → 5,6,7-trimethoxyflavone (973-67-1)

Conditions	Yield
With pyridine; potassium carbonate; potassium iodide In acetone at 60℃; for 8h; Reflux;	95%
With potassium carbonate In acetone for 8h; Heating;	82%
With potassium carbonate; acetone

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + acetic anhydride (108-24-7) → 4-oxo-2-phenyl-4H-1-benzopyran-5,6,7-triyl triacetate (67047-05-6)

Conditions	Yield
With pyridine at 70℃; for 6h;	94%
With sodium acetate at 80℃; for 2h;	92%
With sodium acetate at 75℃;	91.1%

morpholine (110-91-8) + formaldehyd (50-00-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 8-morpholinemethylene baicalein (852333-36-9)

Conditions	Yield
In methanol at 55℃;	93.5%
In methanol; water at 20℃; for 2h; Mannich reaction;	69%

pyrrolidine (123-75-1) + formaldehyd (50-00-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 5,6,7-trihydroxy-2-phenyl-8-(pyrrolidin-1-ylmethyl)-4H-chromen-4-one (1060171-73-4)

Conditions	Yield
In methanol at 45℃;	92.5%
In methanol; water at 20℃; for 2h; Mannich reaction;	71%
In methanol; water at 70℃; for 8h; Mannich Aminomethylation;

formaldehyd (50-00-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + di-n-propylamine (142-84-7) → 8-dipropylaminemethylene baicalein

Conditions	Yield
In methanol at 45℃;	92.5%

methoxypolyethylene glycol carboxylic acid + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → conjugate of methoxy-polyethylene glycol and baicalein

Conditions	Yield
With dmap; benzotriazol-1-ol; dicyclohexyl-carbodiimide In dichloromethane at 20℃;	92%

Dichlorodiphenylmethane (2051-90-3) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + diazomethyl-trimethyl-silane (18107-18-1) → 6,7-(diphenylmethylenedioxy)-5-methoxyflavone

Conditions	Yield
Stage #1: Dichlorodiphenylmethane; 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one at 170℃; for 1h; Stage #2: diazomethyl-trimethyl-silane In tetrahydrofuran; methanol; hexane at 20℃; for 24h;	90%

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + (R,R)-1,2-diphenylethylenediamine (35132-20-8) → (2R,3R)-5-hydroxy-2,3,8-triphenyl-3,4-dihydro-1H-pyrano[3,2-f]quinoxalin-10(2H)-one

Conditions	Yield
In ethanol at 20℃; for 168h;	90%

1-methyl-piperazine (109-01-3) + formaldehyd (50-00-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 5,6,7-trihydroxy-8-((4-methylpiperazin-1-yl)methyl)-2-phenyl-4H-chromen-4-one (1060171-92-7)

Conditions	Yield
In methanol at 50℃;	89.5%
In methanol; water at 20℃; for 2h; Mannich reaction;	72.2%
In methanol at 55℃; for 4h;

amyl iodide (628-17-1) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 5-hydroxy-6,7-(dipentyloxy)flavone

Conditions	Yield
With potassium carbonate In acetone for 24h; Heating;	87%
With potassium carbonate In acetone for 24h; Heating / reflux;	87%

formaldehyd (50-00-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → bis(5,6,7-trihydroxyflavon-8-yl)methane

Conditions	Yield
In ethanol; water at 90℃; for 8h; Condensation;	85%

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + β-D-galactopyranosyl-(1->4)-α-D-glucopyranosyl fluoride (7584-85-2, 7792-96-3, 30048-41-0, 66701-54-0, 71328-30-8, 103531-01-7, 149342-82-5) → 6-O-β-lactosyl-baicalein

Conditions	Yield
With Tris buffer at 37℃; pH=7.0;	84%
With Tris-HCl buffer at 25℃; pH=7.8; Enzyme kinetics;

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + acetic anhydride (108-24-7) → 5-hydroxy-4-oxo-2-phenyl-4H-1-benzopyran-6,7-diyl diacetate (731817-58-6)

Conditions	Yield
With pyridine; sodium acetate at 120℃; for 8h;	84%
With pyridine; dmap for 24h;

1-chloro-2,4-dinitro-6-trifluoromethylbenzene (392-95-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 7-(2,4-dinitro-6-(trifluoromethyl)phenoxy)-5,6-dihydroxy-2-phenyl-4H-chromen-4-one

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 20℃;	83%

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → C15H6(2)H4O5

Conditions	Yield
Stage #1: 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one With [D]-sodium hydroxide; platinum on activated charcoal; water-d2 at 130℃; for 12h; Inert atmosphere; Stage #2: With formic acid at 130℃; for 12h; Temperature; Inert atmosphere;	83%

5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + L-proline (147-85-3) → baicalein L-proline cocrystals (1:1)

Conditions	Yield
In ethanol; ethyl acetate at 20 - 50℃;	82.6%

1-Iodooctane (629-27-6) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 5-hydroxy-6,7-(dioctyloxy)flavone

Conditions	Yield
With potassium carbonate In acetone for 30h; Heating;	82%
With potassium carbonate In acetone for 30h; Heating / reflux;	82%

1-bromo-hexane (111-25-1) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 6,7-(dihexyloxy)-5-hydroxyflavone

Conditions	Yield
With potassium carbonate In acetone for 24h; Heating;	82%
With potassium carbonate In acetone for 24h; Heating / reflux;	82%

Dichlorodiphenylmethane (2051-90-3) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 9-hydroxy-2,2,6-triphenyl-[1,3]dioxolo[4,5-g]chromen-8-one

Conditions	Yield
at 170℃; for 1h;	81%

caffeic acid (331-39-5) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → C23H18O7 (1266114-33-3)

Conditions	Yield
With cerium(III) chloride heptahydrate; sodium iodide In ethanol; acetonitrile for 0.2h; Reflux;	80%

formaldehyd (50-00-0) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) + dimethyl amine (124-40-3) → 8-((dimethylamino)methyl)-5,6,7-trihydroxy-2-phenyl-4H-chromen-4-one (516484-10-9)

Conditions	Yield
In methanol; water at 20℃; for 2h; Mannich reaction;	79%
In methanol at 20℃; for 1.5h; Mannich Aminomethylation;	10.5%

4-chloro-3,5-dinitrobenzotrifluoride (393-75-9) + 5,6,7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one (491-67-8) → 6,7-bis(2,6-dinitro-4-(trifluoromethyl)phenoxy)-5-hydroxy-2-phenyl-4H-chromen-4-one

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 20℃;	78%

Upstream product

• 29550-13-8 5,6-dihydroxy-7-methoxyflavone 
• 35990-03-5 Baicalein-6-O-β-D-glucopyranosiduronsaeure 
• 6959-90-6 1-(6-hydroxy-2,3,4-trimethoxy-phenyl)-3-phenyl-propane-1,3-dione 
• 67047-05-6 4-oxo-2-phenyl-4H-1-benzopyran-5,6,7-triyl triacetate 
• 63635-39-2 2,3,4,6-tetrahydroxyacetophenone 
• 530-55-2 2,6-dimethoxy-p-quinone 
• 15233-65-5 2,6-dimethoxy-1,4-hydroquinone 
• 150036-33-2 6,7-dihydroxy-5-methoxyflavone 
• 491-78-1 5-Hydroxyflavone 
• 480-40-0 5,7-dihydroxy-2-phenyl-chromen-4-one 
• 82475-03-4 Baicalin methyl ester 
• 20491-92-3 2,4,6-trimethoxyphenol 
• 118-79-6 2,4,6-tribromophenol 
• 108-95-2 phenol 

Downstream Products

• 35683-17-1 dihydrobaicalein 
• 126380-10-7 3-phenyl-1-(2,3,4,6-tetrahydroxyphenyl)-1-propanone 
• 137527-39-0 6-acetoxy-5,7-dimethoxy-2-phenyl-chromen-4-one 
• 67047-06-7 7-(benzyloxy)-4-oxo-2-phenyl-4H-1-benzopyran-5,6-diyl diacetate 
• 119120-32-0 6,7-methylenedioxy-5-methoxyflavone 
• 1060171-73-4 5,6,7-trihydroxy-2-phenyl-8-(pyrrolidin-1-ylmethyl)-4H-chromen-4-one 
• 852333-36-9 5,6,7-trihydroxy-8-(morpholinomethyl)-2-phenyl-4H-chromen-4-one 
• 852333-34-7 5,6,7-trihydroxy-2-phenyl-8-(thiomorpholinomethyl)-4H-chromen-4-one 
• 1060171-92-7 5,6,7-trihydroxy-8-((4-methylpiperazin-1-yl)methyl)-2-phenyl-4H-chromen-4-one 

Relevant articles and documents

Enzyme-polysaccharide interaction and its influence on enzyme activity and stability

An attempt was made to probe and elucidate the influence of three kinds of polysaccharides including the negatively charged sodium carboxymethyl cellulose (CMC), the uncharged methyl cellulose (MC) and the positively charged sodium carboxymethyl chitosan (CMCS), on the catalytic activity and stability of the model enzyme, β-d-glucuronidase (GUS). DSC analysis showed that the denaturing temperature of GUS was increased by 7 °C in the presence of CMC, but decreased in the presence of MC or CMCS by 5 and 3 °C, respectively. This variation was in good accordance with changes in the enzyme's catalytic activity. Circular dichroism was employed to characterize the conformational changes of GUS before and after the addition of the polysaccharide. It suggested that charged polysaccharides, CMC and CMCS, were favorable for improving the pH stability and the storage stability of GUS, whereas uncharged MC did not show such a stabilizing effect. At an elevated temperature up to 70 °C, GUS in CMC solution remained 78% activity and displayed the highest thermal stability among the three enzyme-polysaccharide pairs. The electrostatic interaction between enzyme and polysaccharides was closely relevant to the enzyme conformation, activity and stability.

ADDITIONAL FLAVONOIDS FROM ELICITOR-TREATED CELL CULTURES OF CEPHALOCEREUS SENILIS

Five major flavonoids induced by chitin in Cephalocereus senilis cell suspension cultures have been reported previously.We describe here five minor induced flavonoids including two new and three known ones.The two new compounds are (2S)-5,6,7-trihydroxyflavanone 7-glycoside and baicalein 7-(6''-malonylglucoside).

Biotransformation of Chrysin to Baicalein: Selective C6-Hydroxylation of 5,7-Dihydroxyflavone Using Whole Yeast Cells Stably Expressing Human CYP1A1 Enzyme

Naturally occurring polyphenolic compounds are of medicinal importance because of their unique antioxidant, anticancer, and chemopreventive properties. Baicalein, a naturally occurring polyhydroxy flavonoid possessing a diverse range of pharmacological activities, has been used in traditional medicines for treatment of various ailments. Apart from its isolation from natural sources, its synthesis has been reported via multistep chemical approaches. Here, we report a preparative-scale biotransformation, using whole yeast cells stably expressing human cytochrome P450 1A1 (CYP1A1) enzyme that allows regioselective C6-hydroxylation of 5,7-dihydroxyflavone (chrysin) to form 5,6,7-trihydroxyflavone (baicalein). Molecular modeling reveals why chrysin undergoes such specific hydroxylation mediated by CYP1A1. More than 92% reaction completion was obtained using a shake-flask based process that mimics fed-batch fermentation. Such highly efficient selective hydroxylation, using recombinant yeast cells, has not been reported earlier. Similar CYP-expressing yeast cell based systems are likely to have wider applications in the syntheses of medicinally important polyphenolic compounds.

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Flavonoid derivative as well as preparation method and identification method thereof

The invention discloses a flavonoid derivative, which has structure formulas shown as a general formula (I) and a general formula (II) as in the description, wherein R1 is alkyl or cyclo alkane; R2 isalkyl or cyclo alkane; R1, R2 and nitrogen atoms form cycloaliphatic ring or heterocycle; R3 is alkyl or aryl or aralkyl; the value of n is 1 to 10. The invention also discloses a preparation methodand an identification method of the flavonoid derivative.

Synthesis of oroxylin A starting from naturally abundant baicalin

– A new approach to oroxylin A, a monomethylated trihydroxyflavone, is described. The starting material was baicalin, a representative naturally abundant flavonoid glucuronide. First, conditions for the cleavage of the glycosidic bond were established, using a mixture of water and conc. sulfuric acid (5:2) at 121 °C for 40 min. The hydrolysis was performed in a high-pressure steam sterilizer so that the temperature and reaction time were precisely controlled. Subsequent acetylation of the crude material furnished baicalein 6,7-diacetate on a preparative scale and in a reproducible manner. Next, the C-7 position was protected site-selectively with a methoxymethyl (MOM) group, taking advantage of an unexpected sequential migration of the two acetyl groups among the C-5, C-6, and C-7 positions under basic conditions. The removal of the two remaining acetyl groups followed by site-selective methylation of the C-6 position furnished 5-hydroxy-6-methoxy-7-methoxymethoxyflavone (oroxylin A C-7 MOM ether). Finally, by the deprotection of the MOM ether, oroxylin A was obtained in 6 total steps and 62% overall yield from baicalin.