529-53-3

Usage

Uses

Used in Pharmaceutical Applications:
SCUTELLAREIN is used as a pharmaceutical agent for its antioxidant activity, demonstrated in a total reactive antioxidant potential (TRAP) assay at a concentration of 1 μg/ml. It also exhibits enzyme inhibitory properties, as it inhibits sucrose hydrolysis by rat intestinal α-glucosidase and ATPase activity of the SARS coronavirus helicase nsP13 (IC50s = 12 and 0.86 μM, respectively).
Used in Anti-inflammatory Applications:
SCUTELLAREIN is used as an anti-inflammatory agent, as it decreases nitric oxide (NO) release and mRNA expression of inducible NO synthase (iNOS) and TNF-α induced by LPS in RAW 264.7 macrophages when used at a concentration of 50 μM.
Used in Anticancer Applications:
SCUTELLAREIN is used as an anticancer agent, as it has been shown to decrease tumor weight and volume in an HT-1080 human fibrosarcoma mouse xenograft model when administered at a concentration of 0.5 μg/g.
Used in Drug Delivery Systems:
Although not explicitly mentioned in the provided materials, SCUTELLAREIN's properties, such as its enzyme inhibitory and anti-inflammatory activities, suggest that it could potentially be used in drug delivery systems to enhance the delivery, bioavailability, and therapeutic outcomes of various treatments.

InChI:InChI=1/C15H10O6/c16-8-3-1-7(2-4-8)11-5-9(17)13-12(21-11)6-10(18)14(19)15(13)20/h1-6,16,18-20H

Synthetic route

5-hydroxy-4',6,7-trimethoxyflavone (19103-54-9) → scutellarein (529-53-3)

Conditions	Yield
With hydrogen bromide; acetic acid In water	97%

scutellarein 7-O-β-D-glucuronopyranoside methyl ester (119262-68-9) → scutellarein (529-53-3)

Conditions	Yield
With sulfuric acid In ethanol; water at 95℃; for 7h; Temperature; Time; Inert atmosphere;	96%
With hydrogenchloride In ethanol at 90℃; for 12h; Reagent/catalyst; Temperature; Inert atmosphere;	92.1%

5,6,7,4'-tetramethoxyflavone (1168-42-9) → scutellarein (529-53-3)

Conditions	Yield
With hydrogen bromide; acetic acid at 125℃; for 22h; Temperature; Inert atmosphere;	94%
With hydrogen bromide; acetic acid at 120℃; for 24h; Inert atmosphere;	90%
With hydrogen iodide

scutellarin (27740-01-8) → scutellarein (529-53-3)

Conditions	Yield
With sulfuric acid; water at 20℃; for 0.166667h; Concentration;	93%
With sulfuric acid In ethanol; water at 120℃; for 48h; Inert atmosphere;	85%
With sulfuric acid In water at 90℃; for 20h;	45%

4,5,6,7-tetra-O-acetylflavone (1180-46-7) → scutellarein (529-53-3)

Conditions	Yield
With methanol; sulfuric acid for 23h; Reagent/catalyst; Solvent; Temperature; Reflux;	92.3%

6-hydroxy-5,7-dimethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (6938-19-8) → scutellarein (529-53-3)

Conditions	Yield
With pyridine hydrochloride at 190 - 200℃; Cooling with ice; Inert atmosphere;	86%
With pyridine hydrochloride at 180℃; for 6h; Inert atmosphere;	2.6 g

5,6,7-trihydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one (6563-66-2) → scutellarein (529-53-3)

Conditions	Yield
With hydrogen bromide; acetic acid for 23h; Heating;	82%

7-hydroxy-5,8-dimethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (15044-65-2) → scutellarein (529-53-3)

Conditions	Yield
With hydrogen iodide

6-demethoxytangeretin (6601-66-7) → scutellarein (529-53-3)

Conditions	Yield
With hydrogen iodide; acetic anhydride

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

Conditions	Yield
With pyridine hydrochloride for 3h;

plantaginin (26046-94-6) → D-Glucose (2280-44-6) + scutellarein (529-53-3)

Conditions	Yield
With hydrogenchloride for 2h;
With hydrogenchloride In methanol for 3h; Heating;

isoscutellarein (41440-05-5) → scutellarein (529-53-3)

Conditions	Yield
With hydrogenchloride In methanol; water at 100℃; for 4h;

hydrogenchloride (7647-01-0) + isoscutellarein (41440-05-5) → scutellarein (529-53-3)

pectolinarigenin → scutellarein (529-53-3)

Conditions	Yield
With hydrogen iodide

scutellarin → scutellarein (529-53-3)

Conditions	Yield
With sulfuric acid

1-(4-methoxy-phenyl)-3-(2,3,4,6-tetramethoxy-phenyl)-propane-1,3-dione (859076-89-4) + hydrogen iodide (10034-85-2) → scutellarein (529-53-3)

1-(4-methoxy-phenyl)-3-(2,3,4,6-tetramethoxy-phenyl)-propane-1,3-dione (859076-89-4) + hydrogen iodide (10034-85-2) → scutellarein (529-53-3) + isoscutellarein (41440-05-5)

Conditions	Yield
at 135℃;

scutellarein 6,7-di-O-β-D-glucuronide → scutellarein (529-53-3)

Conditions	Yield
With 4b-glucuronidase at 37℃; for 2h; pH=5.2;

plantaginin (26046-94-6) → scutellarein (529-53-3)

Conditions	Yield
Acid hydrolysis;
With water Acidic conditions;

2,4,6-trihydroxyacetophenone (480-66-0) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: K2CO3 / acetone / 0.17 h / 20 °C 1.2: 45 percent / acetone / 24 h / Heating 2.1: ZnCl2; AcOH / 2 h / 140 - 150 °C 3.1: 84 mg / aq. NaOH; aq. H2O2 / 3 h / cooling 4.1: 82 percent / aq. HBr; acetic acid / 23 h / Heating View Scheme

5,7-dihydroxy-2-(4'-methoxyphenyl)-4H-1-benzopyran-4-one (480-44-4) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 3 steps 1: ZnCl2; AcOH / 2 h / 140 - 150 °C 2: 84 mg / aq. NaOH; aq. H2O2 / 3 h / cooling 3: 82 percent / aq. HBr; acetic acid / 23 h / Heating View Scheme

pectolinarigenin (101737-23-9) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: 84 mg / aq. NaOH; aq. H2O2 / 3 h / cooling 2: 82 percent / aq. HBr; acetic acid / 23 h / Heating View Scheme

4-methoxy-benzoyl chloride (100-07-2) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: K2CO3 / acetone / 0.17 h / 20 °C 1.2: 45 percent / acetone / 24 h / Heating 2.1: ZnCl2; AcOH / 2 h / 140 - 150 °C 3.1: 84 mg / aq. NaOH; aq. H2O2 / 3 h / cooling 4.1: 82 percent / aq. HBr; acetic acid / 23 h / Heating View Scheme
Multi-step reaction with 3 steps 1: sodium hydroxide / water / 5 h / 0 - 25 °C / pH 10 - 11 2: 12 h / 140 - 160 °C / 600.06 - 675.07 Torr 3: hydrogen bromide; L-valine / 32 h / 124 °C View Scheme

1-(2,4-dihydroxy-3,6-dimethoxy)phenylethanone (7499-99-2) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium-<4-methoxy benzoate> 2: aqueous hydriodic acid View Scheme

p-Methoxybenzoic anhydride (794-94-5) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium-<4-methoxy benzoate> 2: aqueous hydriodic acid View Scheme

1-(6-hydroxy-2,3,4-trimethoxy-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-dione (724459-08-9) → scutellarein (529-53-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: acetic acid; sodium acetate 2: acetic acid anhydride; aqueous hydriodic acid View Scheme

5,6,7-trihydroxy-2-[4-({5-O-[(2E)-3-(4-hydroxyphenyl)-1-oxo-2-propen-1-yl]-α-L-arabinofuranosyl}oxy)phenyl]-4H-1-benzopyran-4-one → p-Coumaric Acid (7400-08-0) + scutellarein (529-53-3)

Conditions	Yield
With hydrogenchloride; water for 0.666667h; Reflux;

scutellarein (529-53-3) + benzyl bromide (100-39-0) → 7-(benzyloxy)-2-(4-(benzyloxy)phenyl)-5,6-dihydroxy-4H-chromen-4-one (62252-32-8)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 12h; Inert atmosphere;	93%
With potassium carbonate In acetone for 6h; Solvent; Time; Temperature; Reflux;	53.8%

Upstream product

• 15044-65-2 7-hydroxy-5,8-dimethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one 
• 1168-42-9 5,6,7,4'-tetramethoxyflavone 
• 1447-88-7 hispidulin 
• 26046-94-6 plantaginin 
• 41440-05-5 isoscutellarein 
• 859076-89-4 1-(4-methoxy-phenyl)-3-(2,3,4,6-tetramethoxy-phenyl)-propane-1,3-dione 
• 10034-85-2 hydrogen iodide 
• 6563-66-2 5,6,7-trihydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one 
• 480-66-0 2,4,6-trihydroxyacetophenone 
• 480-44-4 5,7-dihydroxy-2-(4'-methoxyphenyl)-4H-1-benzopyran-4-one 
• 101737-23-9 pectolinarigenin 
• 724459-08-9 1-(6-hydroxy-2,3,4-trimethoxy-phenyl)-3-(4-methoxy-phenyl)-propane-1,3-dione 
• 520-36-5 5,7-dihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one 
• 1105056-24-3 9-hydroxy-6-(4-hydroxyphenyl)-2,2-diphenyl-8H-1,3-dioxolo[4,5-g][1]benzopyran-8-one 

Downstream Products

• 1180-46-7 4,5,6,7-tetra-O-acetylflavone 
• 19103-54-9 5-hydroxy-4',6,7-trimethoxyflavone 
• 21450-56-6 1,2,3,4-tetramethoxybenzene 
• 1019-52-9 4-hydroxy-3,5-dinitrobenzoic acid 
• 99-93-4 4-Hydroxyacetophenone 
• 99-96-7 4-hydroxy-benzoic acid 
• 108-73-6 3,5-dihydroxyphenol 
• 137231-90-4 (2R,3R)-10-Hydroxy-3-(4-hydroxy-3-methoxy-phenyl)-2-hydroxymethyl-7-(4-hydroxy-phenyl)-2,3-dihydro-1,4,8-trioxa-phenanthren-5-one 
• 137231-87-9 Scutellaprostin E 
• 60948-17-6 4',5-dihydroxy-6,7-methylenedioxyflavone 
• 6563-66-2 5,6,7-trihydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one 
• 520-12-7 pectolinarigenin 
• 27740-01-8 scutellarin 
• 137231-99-3 Acetic acid (2R,3R)-3-(4-acetoxy-3-methoxy-phenyl)-2-acetoxymethyl-7-(4-acetoxy-phenyl)-5-oxo-2,3-dihydro-5H-1,4,8-trioxa-phenanthren-10-yl ester 

Relevant academic research and scientific papers

Synthesis and protective effect of scutellarein on focal cerebral ischemia/reperfusion in rats

Scutellarein, the main metabolite of scutellarin in vivo, has relatively better solubility, bioavailability and bio-activity than scutellarin. However, compared with scutellarin, it is very difficult to obtain scutellarein from Nature. Therefore, the present study focused on establishing an efficient route for the synthesis of scutellarein by hydrolyzing scutellarin. Neurological deficit score and cerebral infarction volume with the administration of scutellarein were then used to compare its neuroprotective effects on focal cerebral ischemia/reperfusion in rats induced by middle cerebral artery occlusion (MCAO) with those of scutellarin. The results showed that scutellarein had better protective effect on focal cerebral ischemia/reperfusion than scutellarin, which laid the foundation for further research and development of scutellarein as a promising candidate for ischemic cerebro-vascular disease.

Synthesis and Bioactivity Characterization of Scutellarein Sulfonated Derivative

Scutellarin (1) has been widely used to treat acute cerebral infarction in clinic, but poor aqueous solubility decreases its bioavailability. Interestingly, scutellarin (1) could be metabolized into scutellarein (2) in vivo. In this study, a sulfonic group was introduced at position C-8 of scutellarein (2) to enhance the aqueous solubility of the obtained derivative (3). DPPH (1,1-diphenyl-2-picrylhydrazyl)-radical scavenging ability and antithrombic activity were also conducted to determine its bioactivity. The result showed that scutellarein derivate (3) could be a better agent for ischemic cerebrovascular disease treatment.

Organic synthesis method of scutellarein

The invention provides an organic synthesis method of scutellarein, wherein the organic synthesis method comprises the following steps: 1) by using p-methoxycinnamic acid as a raw material, synthesizing p-methoxycinnamoyl chloride under the catalytic action of an acyl chloride reagent and a catalyst; step 2) carrying out esterification reaction on p-methoxycinnamoyl chloride and 3,4,5-trimethoxyphenol under the action of Lewis acid, and then carrying out Fries rearrangement, so as to obtain 9-hydroxy-5,6,7,4'-tetramethoxychalcone; step 3) performing intramolecular cyclization on the 9-hydroxy-5,6,7,4'-tetramethoxychalcone under the action of an oxidizing agent to obtain 5,6,7,4'-tetramethoxyflavone; and step 4) demethylating the 5,6,7,4'-tetramethoxyflavone under the protection of N2 underthe action of a demethylating reagent to generate scutellarin. As the reaction operation is simple and safe, the post-treatment operation is easy, and the yield is high, the method has a wide industrial application prospect.

Benzoic acid nitrogen mustard fragment-containing compound and preparation method and use thereof

The invention relates to the field of natural medicine and medicine chemistry, and particularly relates to a compound containing benzoic acid nitrogen mustard fragment and a preparation process and use, in particular to a compound which introduces a benzoic acid nitrogen mustard fragment at a 4'-OH through a linking group after derivatization of the 6, 7-position of scutellarin, and a pharmaceutically acceptable salt thereof. The method also relates to the preparation process and antitumor activity of these compounds. The method of the benzoic acid nitrogen mustard fragment-containing compoundis shown in the general formula I, wherein m, n are as described in the claims and the specification. The formula is shown in the description.

Synthesis and biological evaluation of scutellarein alkyl derivatives as preventing neurodegenerative agents with improved lipid soluble properties

Background: Exogenous antioxidants are considered as a promising therapeutic approach to treat neurodegenerative diseases since they could prevent and/or minimize the neuronal damage by oxidation. Objective: Three series of lipophilic compounds structurally based on scutellarein (2), which is one metabolite of scutellarin (1) in vivo, have been designed and synthesized. Methods: Their antioxidant activity was evaluated by detecting the 2-thiobarbituric acid reactive substance (TBARS) produced in the ferrous salt/ascorbate-induced autoxidation of lipids, which were present in microsomal membranes of rat hepatocytes. The lipophilicity of these compounds indicated as partition coefficient between n-octanol and buffer was investigated by ultraviolet (UV) spectrophotometer. Results: This study indicated that compound 5e which had a benzyl group substituted at the C4'-OH position showed a potent antioxidant activity and good lipophilicity. Conclusion: 5e could be an effective candidate for preventing or reducing the oxidative status associated with the neurodegenerative processes.

Synthesis method of scutellarein

The invention provides a synthesis method of scutellarein, aiming at solving the problems in the prior art that the yield of chemically synthesized scutellarein is relatively low and a dangerous reagent is used in a synthesis process. The synthesis method comprises the following steps: step 1) taking ethyl acetoacetate and p-anisoyl chloride as raw materials and synthesizing ethyl 3-(4-methoxyphenyl)-3-oxopropanoateethyl p-anisoyl acetate; step 2) synthesizing 5,6,7,4'-tetramethoxy flavone through the ethyl 3-(4-methoxyphenyl)-3-oxopropanoateethyl p-anisoyl acetate and 3,4,5-trimethoyphenol; step 3) removing methyl from the 5,6,7,4'-tetramethoxy flavone to obtain a scutellarein crude product; step 4) purifying the scutellarein crude product to finally obtaining a high-content scutellareinrefined product.

Scaffold hopping strategy for the design, synthesis and biological activity evaluation of novel hexacyclic scutellarein derivatives with a 1,3-oxazine ring fused at A-ring

Background: Discovery of novel agents with anticoagulant and antioxidant activity is very important to treat cerebrovascular disease. Lead compound LR3d discovered in our laboratory exhibited stronger anticoagulant ability and good antioxidant activity, compared with scutellarein (2), which is the major in vivo active metabolite of the natural product scutellarin (1). Objective: Design and synthesis novel scutellarein derivatives with improved anticoagulant and antioxidant activity. Methods: By utilizing a scaffold hopping strategy on LR3d, we describe the design and synthesis of a series of novel hexacyclic scutellarein derivatives 4 with a 1,3-oxazine ring fused at positions 7 and 8 in A ring. The thrombin inhibitory activities of all these new compounds were studied by the analysis of thrombin time (TT), activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrinogen (FIB). The antioxidant abilities of these analogs were evaluated by using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) method through 1,1- diphenyl-2-picrylhydrazyl radical 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) assay. Results: Nine new hexacyclic scutellarein derivatives with a 1,3-oxazine ring fused at A-ring were synthesized, the results of the biological activity evaluation showed that compound 4e exhibited stronger anticoagulant and antioxidant ability compared to LR3d. Conclusion: 4e could be used for further development to treat ischemic cerebrovascular disease.

Scutellarin aglycone nitrogen mustard derivative and preparation method and application thereof

The invention belongs to the field of natural medicine and medicinal chemistry and relates to a scutellarin aglycone nitrogen mustard derivative and a preparation method and application thereof, in particular to a scutellarin aglycone nitrogen mustard derivative of which 4'-OH is combined with benzoic acid nitrogen mustard and a preparation method and antitumor activity thereof. The structure of the scutellarin aglycone nitrogen mustard derivative and pharmaceutically acceptable salt thereof is as shown in the general formula I, wherein R and n are as described in claims and the specification.The formula I is shown in the description.

Synthesis of scutellarein derivatives with antiproliferative activity and selectivity through the intrinsic pathway

To explore antitumor agents with potent efficacy and low toxicity, scutellarein derivatives with benzoic acid mustard (10a?c, 11a?c and 13a?c) were designed and synthesized. The antiproliferative activities of the target derivatives against A549, MCF-7 and Bel-7402 cancer cell lines were tested. Compound 10a showed the strongest potency with an IC50 value of 1.50 μM against MCF-7 cell line, and displayed low toxicity against human liver L-O2 normal cells (IC50 > 50 μM), showing specificity between normal and malignant cells. The mechanism studies revealed that 10a could induce apoptosis in MCF-7 cells, arrest MCF-7 cell cycle at the G1 phase and cause mitochondrial dysfunction in a concentration-dependant manner. Furthermore, the enhanced expression of the pro-apoptotic proteins caspase-9, caspase-3, Bax and cytochrome c, and the reduced expression of the anti-apoptotic protein Bcl-2 confirmed that 10a induced the intrinsic apoptosis pathway in MCF-7 cells. The potent antiproliferative activity and good selectivity guaranteed 10a a lead compound for the further development into anticancer therapeutics, especially for breast cancer.

A practical synthesis of the flavone, scutellarein

A practical and economical five-step synthesis of the flavone scutellarein has been achieved in 60% overall yield using the available and cheap 2,6-dimethoxy-1,4-benzoquinone as starting material. The reaction sequence involved reduction to the corresponding quinol, Friedel-Crafts acetylation, Claisen-Schmidt condensation with p-methoxybenzaldehyde, cyclisation and demethylation. The procedure is operationally simple and amenable to scale-up synthesis.