CN103030647B - Method for synthesizing glabridin - Google Patents
Method for synthesizing glabridin Download PDFInfo
- Publication number
- CN103030647B CN103030647B CN201310015218.XA CN201310015218A CN103030647B CN 103030647 B CN103030647 B CN 103030647B CN 201310015218 A CN201310015218 A CN 201310015218A CN 103030647 B CN103030647 B CN 103030647B
- Authority
- CN
- China
- Prior art keywords
- glabridin
- dimethoxy
- hydroxyl
- reaction
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a method for synthesizing glabridin. The method comprises the following steps: using acetophenone protected by phenol hydroxy as a raw material, carrying out a Willgerodt-Kindler reaction to obtain aryl phenylacetic acid, and carrying out a Friedel-Crafts reaction to obtain an isoflavones compound; causing the isoflavones compound to carry out Pd/C catalytic hydrogenation to obtain a isoflavanone compound; and causing the isoflavanone compound to carrying out a crclizationreaction, a conyl reduction reaction and a removing phenolic hydroxyl group protection group reaction to obtain the glabridin. The operation and the serparation of the steps of the method are simple, the yield is higher, the used reagents are common reagents, are cheap and are easily obtained, the path is shorter, and the tptal yield is not lower than 20 percent.
Description
Technical field
The present invention relates to a kind of synthetic method of glabridin, belong to fine chemical technology field.
Background technology
Glabridin is topmost isoflavones components in glycyrrhiza glabra, is only present in the cork layer and rotten root of glycyrrhiza glabra root, in glycyrrhiza glabra isoflavones, accounts for 11%.Stable in properties under glabridin normal temperature, have whitening, antibacterial, anti-oxidant, anticancer, spasmolytic, anti-inflammatory, anti-quick, protect the liver, remove the effects such as free radical, and have certain reducing blood-fat and hypotensive effect, in the control of arteriosclerosis and cardiovascular disorder, also demonstrate good medicinal DEVELOPMENT PROSPECT.
The chemical synthesis of the glabridin of report has two lines at present.In patent JP2006008604A, with 2,4-, bis-mesyloxy toluylic acids, be that raw material makes glabridin, synthetic route is as follows:
The method is through 6 steps, total recovery 25.8%, and separated but the reaction of every step has all related to column chromatography, cost is higher, and has used highly toxic ethylene dichloride equal solvent, to environment, brings very large pollution, is difficult to carry out suitability for industrialized production.
2007, the people such as Keepyung Nahm reported an other synthetic route (Bull.Korean Chem.Soc., 2007,28,481), and the 2,4-dihydroxyacetophenone of take makes glabridin as raw material, and synthetic route is as follows:
This route makes glabridin through ten steps reactions, yield 6.2%, and wherein committed step compound 1 and 2 condensation reaction need to be carried out at-78 ℃, are not suitable for scale operation.
Summary of the invention
Object of the present invention is intended to overcome technical deficiency and synthetic method that a kind of glabridin is provided, and the methyl phenyl ketone of take through phenolic hydroxyl group protection is raw material, through six-step process, makes glabridin.
The technical scheme that the present invention takes is:
A synthetic method for glabridin, comprises that step is as follows:
(1) there is Willgerodt-Kindler with sulphur powder, morpholine and react in the methyl phenyl ketone 2,4-dialkoxy being replaced, reaction, by sodium hydroxide alkaline hydrolysis, adjust pH, filtration, makes the toluylic acid that 2,4-dialkoxy replaces under reflux condition;
(2) there is Friedel-Crafts reaction in the toluylic acid and the Resorcinol that 2,4-dialkoxy are replaced, product is without separation under the effect of boron trifluoride diethyl etherate, adds DMF after being cooled to room temperature, then under 50～55 ℃ of conditions, splashes into MeSO
2the mixed solution of Cl and DMF, reacts 5-6h at 70～80 ℃ after dripping off again, recrystallization after solvent evaporated, obtain compound 7-hydroxyl-2 ', 4 '-dialkoxy isoflavones (being compound 3);
(3) by 7-hydroxyl-2 ', 4 '-dialkoxy isoflavones add Pd/C catalyzer through Pd/C catalytic hydrogenation make 7-hydroxyl-2 ', 4 '-dialkoxy isoflavan (being compound 4);
(4) by 7-hydroxyl-2 ', 4 '-dialkoxy isoflavan and 3-methyl-2-alkene butyraldehyde carry out annulation, separating-purifying must be with the isoflavones (being compound 5) of dihydropyrane ring;
(5) isoflavones with dihydropyrane ring (being compound 5) is added to reductive agent and reaction medium reflux is carried out carbonyl reduction, obtain alkoxyl group glabridin (being compound 6);
(6) alkoxyl group glabridin (compound 6) is added to deprotecting regent ice-water bath stirs or heating reflux reaction is sloughed phenolic hydroxyl group and protected to obtain glabridin.
In above-mentioned synthetic method, in step (1) 2, the molar ratio range of the methyl phenyl ketone that 4-dialkoxy replaces and sulphur powder, morpholine, sodium hydroxide is 1:(2～2.5): (2～2.5): (0.8～1.2).The time of Willgerodt-Kindler reaction is 7-9h.Described alkaline hydrolysis is the sodium hydroxide solution backflow alkaline hydrolysis 7-9h that adds concentration 10～20wt% under room temperature.Described adjust pH is for to adjust pH=1～2 with concentrated hydrochloric acid.The methyl phenyl ketone that 2,4-dialkoxy replaces preferably 2,4-dimethoxy-acetophenone.
In step (2) 2, toluylic acid, Resorcinol, MeSO that 4-dialkoxy replaces
2the molar ratio range of Cl is 1:(0.9～1): (3～5), 6～8 times of the toluylic acid quality that boron trifluoride diethyl etherate consumption is 2,4-dialkoxy replaces.Under room temperature, adding DMF consumption is 0.3～0.8 times of boron trifluoride diethyl etherate quality.MeSO
2the mixed solution of Cl and DMF is by MeSO
2cl mixes with DMF mass ratio 1:1.Described Friedel-Crafts reaction is 80～95 ℃ of reaction 2-3h.Wherein boron trifluoride diethyl etherate is both as solvent, again as lewis acid catalyst.Recrystallization solvent is selected alcohols, ester class, halohydrocarbon, as ethyl acetate, isopropyl acetate, ethanol, methyl alcohol, Virahol, propyl carbinol, methylene dichloride, trichloromethane; First-selected alcohols, as ethanol.
The described Pd/C catalytic hydrogenation of step (3) be take acetic acid as solvent, catalytic hydrogenation 10-12h under 1atm pressure, reflux conditions.Pd/C and 7-hydroxyl-2 ', the molar ratio range of 4 '-dialkoxy isoflavones is 0.1～0.4:1.Acetic acid consumption be 7-hydroxyl-2 ', 40～80 times of 4 '-dialkoxy isoflavones quality.
7-hydroxyl-2 described in step (4) ', the molar ratio range of 4 '-dialkoxy isoflavan and 3-methyl-2-alkene butyraldehyde is 1:(1.1～1.5).Annulation is that to take pyridine or picoline be solvent, under reflux conditions, reacts 12-14h, solvent load be 7-hydroxyl-2 ', 20～50 times of 4 '-dialkoxy isoflavan quality; Or make solvent with toluene, under phenylo boric acid and acetic acid catalysis, back flow reaction 6-8h, toluene consumption be 7-hydroxyl-2 ', 30～60 times of 4 '-dialkoxy isoflavan quality, 7-hydroxyl-2 ', 4 '-dialkoxy isoflavan, phenylo boric acid molar ratio range are 1:1.2～1.6, acetic acid is 1:20～30 with volume of toluene than scope.
Reductive agent described in step (5) is NaBH
4/ AlCl
3, LiAlH
4, LiAlH
4/ AlCl
3time, reaction medium is selected from tetrahydrofuran (THF), ether.Compound 5 is 1:5～15 with reductive agent molar ratio range, and reaction medium consumption is 20～50 times of compound 5 quality, the reflux temperature that temperature of reaction is reaction medium, and TLC monitoring reaction course, reacts completely for 3～6 hours.
When the reductive agent described in step (5) is Zn (Hg), compound 5 is 1:10～15 with reductive agent molar ratio range, and reaction medium is 35-37% concentrated hydrochloric acid, back flow reaction 20～30 hours, TLC monitoring reaction course.
Reductive agent described in step (5) is NH
2nH
2during/NaOH, compound 5 is 1:5～15 with reductive agent molar ratio range, and reaction medium is glycol ether, and 190～210 ℃ are reacted 6～9 hours, TLC monitoring reaction course.
Compound 6 described in step (6), deprotecting regent molar ratio range are 1:8～15, the preferred boron tribromide of deprotecting regent, Hydrogen bromide, trimethyl silicane iodine, hydroiodic acid HI.
Concrete synthetic route of the present invention is as follows, and in statement below, specific synthetic product is according to the numbering in structural formula, with Arabic numerals, represents.Me represents methyl.
Wherein, R=Me.
The methyl phenyl ketone that the present invention be take through phenolic hydroxyl group protection is raw material, and six-step process makes glabridin, and yield is higher, wherein 7-hydroxyl-2 ', the preparation of 4 '-dialkoxy isoflavones adopts one kettle way, simply efficient.
Each step operation of the inventive method is separated simple, and productive rate is higher, and agents useful for same is common agents, cheap and easy to get, and route is shorter, and total recovery is not less than 20%.
Embodiment
Below by embodiment in detail the present invention is described in detail, but the scope of the invention is not limited to following embodiment.
Embodiment 1
(1) synthetic 2,4-dimethoxyphenylacetic acid (compound 2)
By compound 2,4-dimethoxy-acetophenone (0.1mol), sulphur powder (0.2mol), morpholine (0.2mol) are placed in reaction flask stirring heating backflow 7h, be cooled to room temperature, add 200mL methylene dichloride to dissolve, with 6N salt acid elution (100mL * 2), collect organic phase underpressure distillation except desolventizing, obtain brown oil.Add 20wt% sodium hydroxide solution stirring and refluxing 7h, be cooled to room temperature, with concentrated hydrochloric acid, adjust pH=1～2, filter and collect gained solid, obtain compound 2, yield 85%.
(2) synthetic 7-hydroxyl-2 ', 4 '-dimethoxy isoflavones (compound 3)
Compound 2(0.1mol) and Resorcinol (0.1mol) mix, under fresh boron trifluoride diethyl etherate (60mL) katalysis, 85 ℃ of reaction 3h, generate coupled product.After cool to room temperature, add dry DMF (50mL), drip the dimethyl formamide solution (about 90g) of methylsulfonyl chloride (0.4mol) at 55 ℃, after finishing in 70 ℃ of reaction 6h.Underpressure distillation is except desolventizing, and residue ethyl alcohol recrystallization, obtains compound 3, yield 63%.
(3) synthetic 7-hydroxyl-2 ', 4 '-dimethoxy isoflavan (compound 4)
Compound 3(0.05mol), 10%Pd/C(0.005mol) be mixed in acetic acid (100mL) and pass into hydrogen, be heated to reflux, under 1atm, reduce 10h, filtration, pressure reducing and steaming acetic acid, obtain brown crude product, crude product obtains whitening compound 4 through toluene recrystallization, yield 62%.
(4) synthetic compound 5
Compound 4(0.02mol), 3-methyl-2-alkene butyraldehyde (0.024mol) is mixed in anhydrous pyridine (100mL), back flow reaction 12h, be chilled to room temperature, after 6N salt acid elution, extraction into ethyl acetate, anhydrous sodium sulfate drying, Zheng desolventizes, obtain brown oil, after being dissolved in n-hexane, freezing crystallization 12h, obtains light yellow solid, i.e. compound 5, yield 74%.
(5) synthetic compound 6
Under 0 ℃, nitrogen protection, to compound 5 (0.01mol), add tetrahydrofuran (THF) 200mL; be filled with stirring and dissolving; add lithium aluminium hydride (10eq) in batches; after the 3h that refluxes; be cooled to room temperature; add ethyl acetate cancellation reaction, concentrated solvent is by separated compound 6, the yield 76% of obtaining of column chromatography.
(6) synthetic glabridin
Under nitrogen protection, to compound 6 (0.01mol), add methylene dichloride 200mL, be filled with stirring and dissolving, drip the BBr that contains 0.1mol
3dichloromethane solution 50mL, ice-water bath stirs 2h.After the completion of the reaction, the reaction liquid into the ice water, extracting with dichloromethane, drying with anhydrous sodium sulfate, the solvent to obtain a crude product after removal, the toluene / cyclohexane was pale yellow solid, i.e., glabridin, yield of 87%
1H?NMR(DMSO,600MHz):δ9.39(s,1H),9.11(s,1H),6.86(d,1H,J=7.8Hz),6.83(d,1H,J=8.4Hz),6.54(d,1H,J=9.6Hz),6.33(s,1H),6.29(d,1H,J=8.4Hz),6.19(d,1H,J=8.4Hz),5.64(d,1H,J=10.2Hz),4.23(d,1H,J=10.2Hz),3.93(t,1H,J=10.2Hz),3.29(t,1H,J=10.2Hz),2.89(dd?appeared?t,1H,J=11.4Hz),2.69(dd,1H,J=16.2and4.2Hz),1.76(s,6H);
13C?NMR(DMSO,125MHz):δ157.31,156.28,151.65,149.67,129.76,129.62,127.99,117.85,116.86,115.17,109.99,108.53,106.70,102.92,75.65,70.17,31.31,30.41,27.77,27.66;ESI-MS:m/z(%)=347(100)[M+Na
+].
Embodiment 2
Synthesizing with embodiment 1 of compound 2,3,4,6 and glabridin, different is the preparation of compound 5.
Compound 5 was prepared: compound 4 (0.02mol), 3- methyl -2- allyl aldehyde (0.024mol) mixed with anhydrous pyridine (80mL), reflux reaction for 10h, cooling to room temperature, the 6N hydrochloric acid washing, ethyl acetate extraction, drying with anhydrous sodium sulfate, after solvent removal, the brown oily substance, soluble Yu Zheng hexane after freezing crystallization 12h, pale yellow solid, i.e., compounds 5, 77% yield.
Embodiment 3
Synthesizing with embodiment 1 of compound 2,3,4,6 and glabridin, different is the preparation of compound 5.
Compound 5 was prepared under the protection of nitrogen compounds:, 4 (0.01mol), 3- -2- (0.012mol) methyl allyl aldehyde, benzene boric acid (0.012mol), acetic acid 50mL mixed with 250mL in toluene, water return 7h, decompression, in addition to the solvent, the residue by silica gel column chromatography to yield compounds 5, 71%.
Embodiment 4
Synthesizing with embodiment 1 of compound 2,3,4,5 and glabridin, different is the preparation of compound 6.
The preparation of compound 6: add sodium borohydride (10eq), aluminum chloride (5eq) in 100mL tetrahydrofuran (THF), stir under room temperature, slowly drip compound 5(1eq) tetrahydrofuran solution, after the 5h that refluxes, add dilute hydrochloric acid cancellation reaction.Concentrated remove tetrahydrofuran (THF) and by dichloromethane extraction, anhydrous sodium sulfate drying, column chromatography separation, obtain compound 6, yield 61%.
Embodiment 5
Synthesizing with embodiment 1 of compound 2,3,4,5 and glabridin, different is the preparation of compound 6.
The preparation of compound 6: add concentrated hydrochloric acid in freshly prepd zinc amalgam, by compound 5(1eq) be suspended in reaction solution, backflow 24h, in reaction process, every 6h adds 10mL concentrated hydrochloric acid.Reaction finishes, by dichloromethane extraction, anhydrous sodium sulfate drying, column chromatography separation, to obtain compound 6, yield 76%.
Embodiment 6
Compound 2,3,4,5,6 is synthetic with embodiment 1, and different is the preparation of last glabridin.
Synthetic glabridin
Compound 5 (0.01mol) is joined in 40% Hydrogen bromide, be filled with stirring, reflux 12h.After the completion of the reaction, the reaction liquid into the ice water, extracting with dichloromethane, drying with anhydrous sodium sulfate, the solvent residue after removal, by silica gel column chromatography to pale yellow solid, i.e., glabridin, yield of 77%.
Claims (9)
1. a synthetic method for glabridin, is characterized in that, comprises that step is as follows:
(1) 2,4-dimethoxy-acetophenone under reflux condition, Willgerodt-Kindler is occurred to sulphur powder, morpholine and react, reaction, by sodium hydroxide alkaline hydrolysis, adjust pH, filtration, makes 2,4-dimethoxyphenylacetic acid;
(2) 2,4-dimethoxyphenylacetic acid and Resorcinol, under the effect of boron trifluoride diethyl etherate, Friedel-Crafts reaction is occurred to, product is without separation, adds DMF after being cooled to room temperature, then under 50～55 ℃ of conditions, splashes into MeSO
2the mixed solution of Cl and DMF, reacts 5-6h at 70～80 ℃ after dripping off again, recrystallization after solvent evaporated, obtain compound 7-hydroxyl-2 ', 4 '-dimethoxy isoflavones;
(3) by 7-hydroxyl-2 ', 4 '-dimethoxy isoflavones add Pd/C catalyzer through Pd/C catalytic hydrogenation make 7-hydroxyl-2 ', 4 '-dimethoxy isoflavan;
(4) by 7-hydroxyl-2 ', 4 '-dimethoxy isoflavan and 3-methyl-2-alkene butyraldehyde carry out annulation, separating-purifying must be with the isoflavones of dihydropyrane ring;
(5) isoflavones with dihydropyrane ring is added to reductive agent and reaction medium reflux is carried out carbonyl reduction, obtain dimethoxy glabridin;
(6) dimethoxy glabridin is added to deprotecting regent ice-water bath stirs or heating reflux reaction is sloughed phenolic hydroxyl group and protected to obtain glabridin.
2. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, in step (1) 2, the molar ratio range of 4-dimethoxy-acetophenone and sulphur powder, morpholine, sodium hydroxide is 1:2～2.5:2～2.5:0.8～1.2.
3. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, in step (2) 2, and 4-dimethoxyphenylacetic acid, Resorcinol, MeSO
2the molar ratio range of Cl is 1:0.9～1:3～5, and boron trifluoride diethyl etherate consumption is 6～8 times of 2,4-dimethoxyphenylacetic acid quality, and under room temperature, adding DMF consumption is 0.3～0.8 times of boron trifluoride diethyl etherate quality, MeSO
2the mixed solution of Cl and DMF is by MeSO
2cl mixes with DMF mass ratio 1:1.
4. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, the described Friedel-Crafts reaction of step (2) is 80～95 ℃ of reaction 2-3h.
5. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, the described Pd/C catalytic hydrogenation of step (3) be take acetic acid as solvent, catalytic hydrogenation 10-12h under 1atm pressure, reflux conditions; Pd/C and 7-hydroxyl-2 ', the molar ratio range of 4 '-dimethoxy isoflavones is 0.1～0.4:1, acetic acid consumption be 7-hydroxyl-2 ', 40～80 times of 4 '-dimethoxy isoflavones quality.
6. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, described 7-hydroxyl-2 of step (4) ' and, the molar ratio range of 4 '-dimethoxy isoflavan and 3-methyl-2-alkene butyraldehyde is 1:1.1～1.5.
7. the synthetic method of a kind of glabridin according to claim 1, it is characterized in that, the described annulation of step (4) is that to take pyridine or picoline be solvent, under reflux conditions, react 12-14h, solvent load be 7-hydroxyl-2 ', 20～50 times of 4 '-dimethoxy isoflavan quality; Or make solvent with toluene, under phenylo boric acid and acetic acid catalysis, back flow reaction 6-8h, toluene consumption be 7-hydroxyl-2 ', 30～60 times of 4 '-dimethoxy isoflavan quality, 7-hydroxyl-2 ', 4 '-dimethoxy isoflavan, phenylo boric acid molar ratio range are 1:1.2～1.6, acetic acid is 1:20～30 with volume of toluene than scope.
8. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, the reductive agent described in step (5) is selected from NaBH
4/ AlCl
3, LiAlH
4, LiAlH
4/ AlCl
3, Zn (Hg), NH
2nH
2/ NaOH.
9. the synthetic method of a kind of glabridin according to claim 1, is characterized in that, in step (6), deprotecting regent selects boron tribromide, Hydrogen bromide, trimethyl silicane iodine or hydroiodic acid HI.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310015218.XA CN103030647B (en) | 2013-01-16 | 2013-01-16 | Method for synthesizing glabridin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310015218.XA CN103030647B (en) | 2013-01-16 | 2013-01-16 | Method for synthesizing glabridin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103030647A CN103030647A (en) | 2013-04-10 |
| CN103030647B true CN103030647B (en) | 2014-10-29 |
Family
ID=48018087
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310015218.XA Active CN103030647B (en) | 2013-01-16 | 2013-01-16 | Method for synthesizing glabridin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103030647B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105859736B (en) * | 2016-05-06 | 2017-10-10 | 亿利耐雀生物科技有限公司 | Glabridin Schiff analog derivative and its preparation and application |
| PL3524609T3 (en) * | 2016-10-04 | 2021-12-27 | Glaceum, Inc. | Process for the preparation of 3-phenyl-2,3,4,8,9,10-hexahydropyrano[2,3-f]chromene derivatives, optical isomers thereof, and intermediates of the process |
| CN108440553B (en) * | 2018-03-16 | 2020-08-04 | 烟台六谛医药科技有限公司 | Method for asymmetrically synthesizing optical-purity glabridin by ruthenium compound catalysis |
| TWI804600B (en) * | 2018-04-03 | 2023-06-11 | 南韓商格雷森伍股份有限公司 | METHOD FOR SYNTHESIZING 3-PHENYL-2,8-DIHYDROPYRANO[2,3-ƒ]CHROMENE DERIVATIVES |
| CN108704088A (en) * | 2018-08-13 | 2018-10-26 | 彭水县绿忆环保科技有限公司 | A kind of complex anti-tumor traditional Chinese medicine preparation and preparation method thereof |
| CN108704087A (en) * | 2018-08-13 | 2018-10-26 | 彭水县绿忆环保科技有限公司 | Chinese herbal medicine for preventing |
| CN109232603B (en) * | 2018-10-29 | 2020-12-22 | 陕西师范大学 | Method for synthesizing glabridin |
| KR20210014521A (en) * | 2019-07-30 | 2021-02-09 | 주식회사 글라세움 | Synthesizing Method Of 2-((6-(hydroxymethyl)chromene-5-yl)oxy)-1-phenylethanone Derivative |
| CN110551137B (en) * | 2019-09-29 | 2022-06-10 | 浙江惠松制药有限公司 | Method for extracting and purifying glabridin and application of glabridin in cosmetics |
| CN111362961B (en) * | 2020-04-29 | 2021-12-10 | 玉林师范学院 | Method for asymmetrically synthesizing optical purity glabridin |
| CN113651832B (en) * | 2021-09-03 | 2022-08-16 | 河北工业大学 | Method for synthesizing optically pure glabridin |
| CN114315851B (en) * | 2022-01-03 | 2023-10-24 | 安徽大学绿色产业创新研究院 | Synthesis method of glabridin drug intermediate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1871228A (en) * | 2003-10-20 | 2006-11-29 | Bicbio株式会社 | A manufacturing process of isoflavan or isoflavene derivatives |
| CN101007001A (en) * | 1996-08-30 | 2007-08-01 | 诺沃根研究有限公司 | Therapeutic methods and compositions involving isoflavones |
| CN102161648A (en) * | 2011-02-18 | 2011-08-24 | 中国药科大学 | Preparation method and applications of isoflavone type compounds with selective estrogen receptor modulating activity |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2006008604A (en) * | 2004-06-25 | 2006-01-12 | Kuraray Co Ltd | Method for producing isoflavan derivative |
| JP2006008606A (en) * | 2004-06-25 | 2006-01-12 | Kuraray Co Ltd | Method for optical resolution of isoflavan derivative |
-
2013
- 2013-01-16 CN CN201310015218.XA patent/CN103030647B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101007001A (en) * | 1996-08-30 | 2007-08-01 | 诺沃根研究有限公司 | Therapeutic methods and compositions involving isoflavones |
| CN1871228A (en) * | 2003-10-20 | 2006-11-29 | Bicbio株式会社 | A manufacturing process of isoflavan or isoflavene derivatives |
| CN102161648A (en) * | 2011-02-18 | 2011-08-24 | 中国药科大学 | Preparation method and applications of isoflavone type compounds with selective estrogen receptor modulating activity |
Non-Patent Citations (6)
| Title |
|---|
| Absolute Configurations of (±)-Glabridin Enantiomers;Mihyang Kim,等;《Bull. Korean Chem. Soc.》;20091231;第30卷(第2期);第415-418页 * |
| Facile and Efficient Synthesis of (±)-Glabridin;Sang-Ku Yoo,等;《Bull. Korean Chem. Soc.》;20071231;第28卷(第3期);第481-484页 * |
| JP特开2006-8604A 2006.01.12 |
| JP特开2006-8606A 2006.01.12 |
| Mihyang Kim,等.Absolute Configurations of (±)-Glabridin Enantiomers.《Bull. Korean Chem. Soc.》.2009,第30卷(第2期),第415-418页. |
| Sang-Ku Yoo,等.Facile and Efficient Synthesis of (±)-Glabridin.《Bull. Korean Chem. Soc.》.2007,第28卷(第3期),第481-484页. |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103030647A (en) | 2013-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103030647B (en) | Method for synthesizing glabridin | |
| Sawyer et al. | Physical properties and synthetic utility of. alpha.-alkoxyorganolithium species as studied through ligand selectivity in tin-lithium exchange | |
| CN102653533B (en) | Total synthesis method of mangostin | |
| GB2174991A (en) | Cyclodextrin complexes with dibenzo (bd)pyran derivatives and their preparation and pharmaceutical formulation | |
| CN109761943B (en) | Synthesis method of C-3 alkyl substituted coumarin derivative | |
| CN101195575B (en) | process for producing (E)-3-dimethoxy-4'-acetoxy diphenyl ethylene | |
| CN102766088B (en) | Novel process for synchronizing 4,4'-dibromo-2,2'-bipyridyl | |
| CN102875340B (en) | Sarpogrelate intermediate and preparation method thereof | |
| CN101007754A (en) | Homotriptycene analog compound and its preparing process | |
| CN101891595A (en) | Method for preparing hydroxytyrosol | |
| CN108558625B (en) | Synthesis method of boron trifluoride catalyzed benzophenone compound | |
| CN101437784B (en) | 4-(4-alkylcyclohexyl)benzaldehyde | |
| CN108238875B (en) | Synthesis method of bromoisobutenyl methyl ether and application of bromoisobutenyl methyl ether in preparation of C14 aldehyde | |
| CN105001107A (en) | Synthetic method for methyl caulophine | |
| CN101747169A (en) | Method for synthesizing light-sensitive material 2,3,4,4'-Tetrahydroxybenzophenone | |
| CN101591248A (en) | A kind of synthetic method of methyl benzoate | |
| CN103342630A (en) | Method for synthesizing diaryl ether compounds | |
| CN102875396B (en) | Preparation method of sarpogrelate hydrochloride | |
| CN102557910A (en) | Deprotection method for phenolic hydroxyl group | |
| CN102627563B (en) | Phthalic acid compound, its preparation method and application | |
| CN103384655A (en) | Intermediates for the preparation of beta-santalol | |
| CN109665948A (en) | A method of ortho vanillin is prepared by raw material of catechol | |
| CN102249832A (en) | Novel synthesis method of alpha-hydroxyl arone compound | |
| CN100537577C (en) | Preparation process of 6'-nitroindolyline benzspriothiane | |
| CN104529726A (en) | Preparation method of hydroxyacetophenone |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20221229 Address after: 250306 Room 3115, No. 135, Ward Avenue, Ping'an Street, Changqing District, Jinan City, Shandong Province Patentee after: Shandong Jiqing Technology Service Co.,Ltd. Address before: 250014 No. 19, ASTRI Road, Lixia District, Shandong, Ji'nan Patentee before: SHANDONG ANALYSIS AND TEST CENTER |
|
| TR01 | Transfer of patent right |