CN111484471A - Preparation method of hispidulin - Google Patents

Preparation method of hispidulin Download PDF

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CN111484471A
CN111484471A CN201910083880.6A CN201910083880A CN111484471A CN 111484471 A CN111484471 A CN 111484471A CN 201910083880 A CN201910083880 A CN 201910083880A CN 111484471 A CN111484471 A CN 111484471A
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scutellarin
acid
hispidulin
reaction
mixture
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颜世强
李英霞
王玉杰
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Fudan University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/28—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only
    • C07D311/30—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3 with aromatic rings attached in position 2 only not hydrogenated in the hetero ring, e.g. flavones
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/22—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4
    • C07D311/26—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 4 with aromatic rings attached in position 2 or 3
    • C07D311/40—Separation, e.g. from natural material; Purification

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  • Organic Chemistry (AREA)
  • Steroid Compounds (AREA)

Abstract

The invention relates to the field of chemical synthesis, relates to a novel preparation method of hispidulin, and particularly relates to a method for preparing and synthesizing hispidulin by using scutellarin as a raw material. The method takes scutellarin as a raw material, and can efficiently semi-synthesize the hispidulin through three reactions of carboxyl esterification, selective methylation and glycosyl hydrolysis. The method has the advantages of few reaction steps, only 3 steps, high reaction yield, cheap and easily-obtained reaction reagents and low production cost; the reaction condition is mild, no harsh reaction condition exists, the operation is easy, and the method is suitable for industrial production.

Description

Preparation method of hispidulin
Technical Field
The invention relates to the field of chemical synthesis, relates to a novel preparation method of hispidulin, and particularly relates to a method for preparing and synthesizing hispidulin by using scutellarin as a raw material.
Background
The data discloses that the hispidulin, also known as hispidulin, is a flavonoid active ingredient extracted from saussurea involucrate. In recent years, domestic and foreign research shows that the hispidulin has the functions of resisting bacteria, inflammation, oxidation, thrombus, epilepsy, osteoporosis, mutagenesis, neuroprotection and the like. Has obvious inhibition effect on the proliferation of human pancreatic cancer, gastric cancer, ovarian cancer, glioma and other cell strains.
Studies have shown that hispidulin has a wide range of biological activities, and the compounds show increasing interest to pharmacologists and medicinal chemists in this field; the existing preparation and synthesis methods of the hispidulin mainly comprise three methods, namely semi-synthesis, total synthesis and enzymatic synthesis.
Semisynthetic literature on the hispidulin is reported from the same topic group that researchers in four documents from 2013-2015 all report semisynthetic preparation of the hispidulin by using scutellarin as a starting material, wherein the semisynthetic preparation of the hispidulin by using the scutellarin as the starting material is unfortunately proved by using semisynthetic data of the hispidulin obtained by using the scutellarin as the starting material, wherein the semisynthetic data of the breviscapine obtained by using the scutellarin as the starting material are respectively represented by using 7 steps of 10.7% total yield (Shen M.Z.Z.T. L et.Org.Chem.2013, 10,733), 7.1% total yield of the reactions of the steps (L in H.et. J.J.Mol.Sci.2015, 16,7587) and 8.2% of the total yield of the semisynthetic data of the semisynthetic material obtained by using the semisynthetic data of the hispidulin obtained by using the semisynthetic data of the semisynthetic material obtained by using the semisynthetic data of the semisynthetic.
As a method for synthesizing high plantaginine, it is reported that Kavvadias and its co-workers in 2004 complete chemical synthesis of high plantaginine with 2,4, 6-trihydroxyacetophenone as a starting material in a total yield of 1.1% by 9-step reaction, (Kavvadias D.et al Br.J.Pharmacol.2004,142, 811-820.) Chao et al in 2015 complete chemical synthesis of high plantaginine with 2,4, 6-trihydroxybenzaldehyde as a starting material in 11-step reaction, but the total yield is only 1.6%, (ChaoS.W.et al.J.nat.prod.2015,78, 1969. Chen 1976.) in order to increase the reaction yield to prepare an amount sufficient for bioactivity study, then the synthesis route of Chen et al is optimized and improved, and similarly 2,4, 6-trihydroxybenzaldehyde is prepared as a starting material, and finally, 26.9% total yield of this compound is obtained by 8-step reaction, and the total yield of this compound is obtained by extraction of high nuclear magnetic spectrum, which is consistent with the data obtained in the above-mentioned publication No. 7, and 7.
The university of Shandong, college of medicine, reports that the enzymatic synthesis of the hispidulin can efficiently prepare the hispidulin by selectively methylating 6-phenolic hydroxyl of scutellarein by using the liverwort flavones 6-O-methyltransferase (Zhang Y.Y.et al.FEBS L ets, 2016,590,2619-2628), and the nuclear magnetic spectrum data of the hispidulin prepared by the enzymatic synthesis is consistent with the nuclear magnetic spectrum data of the hispidulin extracted and separated from the original literature, but the practice shows that the liverwort flavones 6-O-methyltransferase used in the preparation method are obtained by using a gene recombination mode, and have the defects of longer period, smaller enzyme purification amount, unsuitability for large-scale industrialization and the like.
Based on the current state of the art, the inventors of the present application intend to provide a novel method for preparing hispidulin.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, provides a novel preparation method of hispidulin, and particularly relates to a method for preparing and synthesizing hispidulin by using scutellarin as a raw material.
The invention semi-synthesizes and prepares the hispidulin by taking the scutellarin as the starting material, has short synthesis steps, low cost, high yield and high product purity, and is suitable for industrial production.
In order to achieve the purpose, the invention adopts the following technical scheme:
the preparation method comprises the following steps:
Figure BDA0001961136830000021
the invention provides a synthesis method of hispidulin, which specifically comprises the following steps:
using scutellarin as a starting material, and carrying out methyl esterification on carboxyl under the condition of an acidic catalyst to obtain scutellarin methyl ester (compound 2);
b, carrying out nucleophilic substitution reaction on the generated scutellarin methyl ester (compound 2) and methyl iodide in the presence of an acid binding agent to generate 6-OMe scutellarin methyl ester (compound 3);
c, carrying out hydrolysis reaction on the generated compound 3 under the action of an acid catalyst to obtain a target compound 4.
The reaction solvent used in the step a is methanol.
The acidic catalyst adopted in the step a is one of thionyl chloride, perchloric acid, concentrated sulfuric acid, concentrated nitric acid, trifluoroacetic acid and concentrated hydrochloric acid or a mixture thereof, and is preferably thionyl chloride or concentrated sulfuric acid.
The concentration of scutellarin in the methanol solution in the step a is preferably 10-100 mg m L-1More preferably 20 to 30mg m L-1。
The acid-binding agent adopted in the step b is inorganic base such as: one or a mixture of potassium carbonate, cesium carbonate, sodium hydride, potassium bicarbonate and sodium bicarbonate; organic bases such as: one or a mixture of N, N-diisopropylethylamine, triethylamine, ethylenediamine and DBU, and preferably inorganic base potassium carbonate.
The organic solvent adopted in the step b is one or a mixture of N, N-dimethylformamide, N-dimethylacetamide, acetone, acetonitrile, tetrahydrofuran, chloroform and ethyl acetate, and preferably N, N-dimethylformamide or N, N-dimethylacetamide.
The molar ratio of scutellarin methyl ester to methyl iodide in the step b is preferably 1: 1-1: 2, and more preferably 1: 1.2.
The acidic catalyst used in the step c of the reaction is one of concentrated sulfuric acid, concentrated hydrochloric acid, concentrated nitric acid and trifluoroacetic acid or a mixture thereof, and concentrated sulfuric acid is preferred.
The reaction solvent used in the step c is one or a mixture of ethanol, methanol, isopropanol, acetonitrile and water, preferably 90% ethanol.
The reaction temperature in the step c is preferably 60 to 150 ℃, and more preferably 100 to 120 ℃.
The nuclear magnetic spectrum data of the hispidulin prepared by the method is consistent with the nuclear magnetic spectrum data of the hispidulin extracted and separated from the original literature.
Compared with the prior art, the invention has the following advantages:
the reaction steps are few, only 3 steps are needed, and the method is the shortest synthetic route for preparing the hispidulin so far; the reaction yield is high and is obviously higher than that reported in the prior literature; the reaction reagent is cheap and easy to obtain, and the production cost is low; the reaction condition is mild, no harsh reaction condition exists, and the method is suitable for industrial production.
The invention will be better understood from the following examples. However, one skilled in the art will readily appreciate that the specific material ratios, process conditions, and results thereof described in the examples are illustrative only and should not be taken as limiting the invention.
Detailed Description
Example 1: synthesis of scutellarin methyl ester 2
A500 m L round-bottomed flask was charged with 200m L anhydrous methanol, and SOCl was slowly added dropwise under ice bath2(7.25m L, 100mmol), removing ice bath after dropwise addition, stirring at room temperature for 1h, adding scutellarin 1(4.62g,10mmol), stirring at room temperature for 9h, and collecting the solution, and collecting the filtrate, wherein the filtrate is T L C (V)Ethyl acetate:VIsopropanol (I-propanol):VWater (W)The reaction is complete in 4:2: 1); directly filtering to obtain scutellarin methyl ester 2(4.67g, 98%);1H-NMR(400MHz,DMSO-d6)12.85(s,1H,5-OH),10.39(s,1H,4’-OH),7.93(d,J＝9.0Hz,2H,H-2’,H-6’),7.00(s,1H,H-8),6.94(d,J＝9.0Hz,2H,H-3’,H-5’),6.81(s,1H,H-3),5.28(d,J＝7.0Hz,1H,H-1”),4.20(d,J＝6.0Hz,1H,H-2”),3.70-3.90(3H,m,other sugarprotons),3.68(3H,s,-OCH3)；13C-NMR(125MHz,DMSO-d6):182.8,169.7,164.5,161.6,151.3,149.4,147.3,130.8,128.9,121.7,116.4,106.3,102.9,100.2,93.9,75.7,75.4,73.1,71.8,52.4(-OCH3)。
example 2: synthesis of scutellarin methyl ester 2
Scutellarin 1(4.62g,10mmol) is suspended in 300m L anhydrous methanol in a 500m L round bottom flask, concentrated sulfuric acid (0.03m L) is slowly added dropwise at room temperature, after the dropwise addition is finished, the mixture is heated and refluxed for 3h, and T L C (V L C)Ethyl acetate:VIsopropanol (I-propanol):VWater (W)4:2:1) reaction was complete. Naturally cooling to room temperature, and concentrating under reduced pressure to obtain scutellarin methyl ester 2(4.72g, 98%).1H-NMR(400MHz,DMSO-d6)12.85(s,1H,5-OH),10.39(s,1H,4’-OH),7.93(d,J＝9.0Hz,2H,H-2’,H-6’),7.00(s,1H,H-8),6.94(d,J＝9.0Hz,2H,H-3’,H-5’),6.81(s,1H,H-3),5.28(d,J＝7.0Hz,1H,H-1”),4.20(d,J＝6.0Hz,1H,H-2”),3.70-3.90(3H,m,other sugar protons),3.68(3H,s,-OCH3)；13C-NMR(125MHz,DMSO-d6):182.8,169.7,164.5,161.6,151.3,149.4,147.3,130.8,128.9,121.7,116.4,106.3,102.9,100.2,93.9,75.7,75.4,73.1,71.8,52.4(-OCH3)。
Example 3: synthesis of scutellarin methyl ester 2
Scutellarin 1(4.62g,10mmol) is suspended in 200m L anhydrous methanol in a 500m L round bottom flask, 70% perchloric acid (0.03m L) is slowly added dropwise at room temperature, after the dropwise addition is finished, the mixture is heated and refluxed for 3h, and T L C (V)Ethyl acetate:VIsopropanol (I-propanol):VWater (W)After the reaction was completed at 4:2:1), the reaction mixture was naturally cooled to room temperature and concentrated under reduced pressure to obtain scutellarin methyl ester 2(4.72g, 98%).1H-NMR(400MHz,DMSO-d6)12.85(s,1H,5-OH),10.39(s,1H,4’-OH),7.93(d,J＝9.0Hz,2H,H-2’,H-6’),7.00(s,1H,H-8),6.94(d,J＝9.0Hz,2H,H-3’,H-5’),6.81(s,1H,H-3),5.28(d,J＝7.0Hz,1H,H-1”),4.20(d,J＝6.0Hz,1H,H-2”),3.70-3.90(3H,m,other sugar protons),3.68(3H,s,-OCH3)；13C-NMR(125MHz,DMSO-d6):182.8,169.7,164.5,161.6,151.3,149.4,147.3,130.8,128.9,121.7,116.4,106.3,102.9,100.2,93.9,75.7,75.4,73.1,71.8,52.4(-OCH3)。
Example 4: synthesis of 6-OMe scutellarin methyl ester 3
In a 250m L round-bottomed flask, Compound 2(3.81g,8.0mmol) was dissolved in 50m L N, N-dimethylformamide and anhydrous K was added with stirring at room temperature2CO3(1.66g,12.0mmol), MeI (0.60m L, 9.6mmol) dropwise under nitrogen, stirring overnight at 40 ℃ and T L C (V)Methylene dichloride:VMethanolNo. 20:1) the starting material disappeared, the reaction was poured into 50m L ice water, extracted with ethyl acetate (25m L× 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatographed to give compound 3(1.53g, 39%);1H-NMR(400MHz,DMSO-d6)12.98(s,1H,5-OH),10.42(s,1H,4’-OH),7.95(d,J＝7.8Hz,2H,H-2’,H-6’),7.07(s,1H,H-8),6.95(d,J＝8.1Hz,2H,H-3’,H-5’),6.86(s,1H,H-3),5.62(d,J＝3.9Hz,1H),5.52(d,J＝5.3Hz,1H,H-1”),5.36(d,J＝4.9Hz,2H),4.20(d,J＝9.1Hz,1H),3.76(s,3H,-OCH3),3.66(s,3H,-OCH3)；13C-NMR(125MHz,DMSO-d6):182.33,169.22,164.38,161.38,155.94,152.68,152.13,132.53,128.59,121.11,116.02,105.92,102.77,99.39,93.91,75.67,75.30,72.81,71.34,60.33,52.03。
example 5: synthesis of 6-OMe scutellarin methyl ester 3
In a 250m L round-bottomed flask, Compound 2(3.81g,8.0mmol) was dissolved in 50m L N, N-dimethylacetamide and anhydrous K was added with stirring at room temperature2CO3(1.66g,12.0mmol), MeI (0.75m L, 12.0mmol) was added dropwise under nitrogen, and after stirring overnight at 40 ℃ T L C (V)Methylene dichloride:VMethanolNo. 20:1) the starting material disappeared, the reaction was poured into 50m L ice water, extracted with ethyl acetate (25m L× 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatographed to give compound 3(1.26g, 32%);1H-NMR(400MHz,DMSO-d6)12.98(s,1H,5-OH),10.42(s,1H,4’-OH),7.95(d,J＝7.8Hz,2H,H-2’,H-6’),7.07(s,1H,H-8),6.95(d,J＝8.1Hz,2H,H-3’,H-5’),6.86(s,1H,H-3),5.62(d,J＝3.9Hz,1H),5.52(d,J＝5.3Hz,1H,H-1”),5.36(d,J＝4.9Hz,2H),4.20(d,J＝9.1Hz,1H),3.76(s,3H,-OCH3),3.66(s,3H,-OCH3)；13C-NMR(125MHz,DMSO-d6):182.33,169.22,164.38,161.38,155.94,152.68,152.13,132.53,128.59,121.11,116.02,105.92,102.77,99.39,93.91,75.67,75.30,72.81,71.34,60.33,52.03。
example 6: synthesis of 6-OMe scutellarin methyl ester 3
Compound 2(3.81g,8.0mmol) was dissolved in 50m L N, N-dimethylformamide in a 250m L round bottom flask, anhydrous DIPEA (1.98m L, 12.0mmol) was added under stirring at room temperature, MeI (0.60m L, 9.6mmol) was added dropwise under nitrogen protection, and after stirring overnight at 40 ℃, T L C (V)Methylene dichloride:VMethanolNo. 20:1) the starting material disappeared, the reaction was poured into 50m L ice water, extracted with ethyl acetate (25m L× 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatographed to give compound 3(1.14g, 29%);1H-NMR(400MHz,DMSO-d6)12.98(s,1H,5-OH),10.42(s,1H,4’-OH),7.95(d,J＝7.8Hz,2H,H-2’,H-6’),7.07(s,1H,H-8),6.95(d,J＝8.1Hz,2H,H-3’,H-5’),6.86(s,1H,H-3),5.62(d,J＝3.9Hz,1H),5.52(d,J＝5.3Hz,1H,H-1”),5.36(d,J＝4.9Hz,2H),4.20(d,J＝9.1Hz,1H),3.76(s,3H,-OCH3),3.66(s,3H,-OCH3)；13C-NMR(125MHz,DMSO-d6):182.33,169.22,164.38,161.38,155.94,152.68,152.13,132.53,128.59,121.11,116.02,105.92,102.77,99.39,93.91,75.67,75.30,72.81,71.34,60.33,52.03。
example 7: synthesis of hispidulin 4
In a 250m L round-bottomed flask, Compound 3(4.19g,8.55mmol) was suspended in a mixed solvent of 135m L ethanol and 18.8m L water, concentrated sulfuric acid 18.8m L was added dropwise under stirring at room temperature, and after completion of the addition, T L C (V) was refluxed at 100 ℃ overnightMethylene dichloride:VMethanolNo. 20:1) the starting material disappeared, cooled naturally to room temperature, washed with water, extracted with ethyl acetate (100m L× 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatographed to give hispidulin (2.33g, 91%);1H-NMR(400MHz,DMSO-d6)13.05(s,1H),10.72(s,1H),10.37(s,1H),7.92(d,J＝8.5Hz,2H),6.92(d,J＝8.5Hz,2H),6.77(s,1H),6.59(s,1H),3.74(s,3H)；13C-NMR(125MHz,DMSO-d6):182.18,163.86,161.20,157.28,152.81,152.43,131.38,128.51,121.25,116.00,104.12,102.41,94.28,60.00。
example 8: synthesis of hispidulin 4
In a 250m L round-bottomed flask, suspend Compound 3(4.19g,8.55mmol) in a mixed solvent of 135m L isopropanol and 18.8m L water, add dropwise concentrated sulfuric acid 18.8m L under stirring at room temperature, reflux overnight at 120 ℃ after the addition, T L C (V)Methylene dichloride:VMethanolNo. 20:1) the material disappeared, cooled naturally to room temperature, washed with water, extracted with ethyl acetate (100m L× 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatographed to give hispidulin (2.30g, 90%);1H-NMR(400MHz,DMSO-d6)13.05(s,1H),10.72(s,1H),10.37(s,1H),7.92(d,J＝8.5Hz,2H),6.92(d,J＝8.5Hz,2H),6.77(s,1H),6.59(s,1H),3.74(s,3H)；13C-NMR(125MHz,DMSO-d6):182.18,163.86,161.20,157.28,152.81,152.43,131.38,128.51,121.25,116.00,104.12,102.41,94.28,60.00。
example 9: synthesis of hispidulin 4
In a 250m L round-bottomed flask, suspend Compound 3(4.19g,8.55mmol) in a mixed solvent of 135m L ethanol and 18.8m L water, add dropwise concentrated hydrochloric acid 18.8m L under stirring at room temperature, reflux overnight at 100 ℃ after the addition, T L C (V)Methylene dichloride:VMethanolNo. 20:1) the material disappeared, cooled naturally to room temperature, washed with water, extracted with ethyl acetate (100m L× 3), washed with saturated brine, dried over anhydrous sodium sulfate, concentrated, and column chromatographed to give hispidulin (1.82g, 71%);1H-NMR(400MHz,DMSO-d6)13.05(s,1H),10.72(s,1H),10.37(s,1H),7.92(d,J＝8.5Hz,2H),6.92(d,J＝8.5Hz,2H),6.77(s,1H),6.59(s,1H),3.74(s,3H)；13C-NMR(125MHz,DMSO-d6):182.18,163.86,161.20,157.28,152.81,152.43,131.38,128.51,121.25,116.00,104.12,102.41,94.28,60.00。

Claims (8)

1. a preparation method of hispidulin is characterized by comprising the following steps:
using scutellarin as a starting material, and carrying out methyl esterification on carboxyl under the action of an acidic catalyst to obtain scutellarin methyl ester;
b, carrying out nucleophilic substitution reaction on the generated scutellarin methyl ester and methyl iodide in the presence of an acid-binding agent to generate 6-OMe scutellarin methyl ester;
c, carrying out glycosidic bond hydrolysis reaction on the generated 6-OMe scutellarin methyl ester under the action of an acid catalyst to prepare the hispidulin.
2. The preparation method according to claim 1, wherein the reaction solvent used in step a is methanol, and the concentration of scutellarin in the methanol solution is 10-100 mg m L-1Preferably 20 to 30mg m L-1。
3. The method according to claim 1, wherein the acidic catalyst in step a is one of thionyl chloride, perchloric acid, concentrated sulfuric acid, concentrated nitric acid, concentrated hydrochloric acid, trifluoroacetic acid or a mixture thereof, preferably thionyl chloride or concentrated sulfuric acid.
4. The preparation method according to claim 1, wherein the acid-binding agent used in step b is an inorganic base selected from the group consisting of: one or a mixture of potassium carbonate, cesium carbonate, sodium hydride, potassium bicarbonate and sodium bicarbonate; an organic base selected from: one or a mixture of N, N-diisopropylethylamine, triethylamine, ethylenediamine and DBU, and preferably inorganic base potassium carbonate.
5. The method according to claim 1, wherein the organic solvent used in step b is one or a mixture of N, N-dimethylformamide, N-dimethylacetamide, acetone, acetonitrile, tetrahydrofuran, chloroform and ethyl acetate, preferably N, N-dimethylformamide or N, N-dimethylacetamide.
6. The preparation method according to claim 1, wherein the molar ratio of the methyl scutellarin to the methyl iodide in the step b is 1: 1-1: 2, preferably 1: 1.2.
7. The method according to claim 1, wherein the acidic catalyst used in step c is one of concentrated sulfuric acid, concentrated hydrochloric acid, concentrated nitric acid, trifluoroacetic acid or a mixture thereof, preferably concentrated sulfuric acid.
8. The preparation method according to claim 1, wherein the reaction solvent used in step c is one or a mixture of ethanol, methanol, isopropanol, acetonitrile, water, preferably 90% ethanol; the reaction temperature is 60-150 ℃, and preferably 100-120 ℃.
CN201910083880.6A 2019-01-29 2019-01-29 Preparation method of hispidulin Pending CN111484471A (en)

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Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104311518A (en) * 2014-11-18 2015-01-28 南京中医药大学 Preparation method for 6-methoxyscutellarin

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104311518A (en) * 2014-11-18 2015-01-28 南京中医药大学 Preparation method for 6-methoxyscutellarin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
颜世强 等: "灯盏花乙素半合成柳穿鱼叶苷研究", 《有机化学》 *

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