CN1544427A - Luteolin semi-synthesis method - Google Patents
Luteolin semi-synthesis method Download PDFInfo
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- CN1544427A CN1544427A CNA2003101077125A CN200310107712A CN1544427A CN 1544427 A CN1544427 A CN 1544427A CN A2003101077125 A CNA2003101077125 A CN A2003101077125A CN 200310107712 A CN200310107712 A CN 200310107712A CN 1544427 A CN1544427 A CN 1544427A
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Abstract
The invention discloses a process for synthesizing cyanidenon by using a natural extract as base stock which comprises the step of, (1) synthesizing Diosmin, (2) synthesizing Eriodictyol, (3) synthesizing cyanidenon. The advantages of the invention are, cheap and fully available raw material, simple operation, stable reaction conditions, and readiness of isolation and purification.
Description
Technical field: the present invention relates to a kind of is the semisynthesis of the luteolin of basic raw material with the natural extract.
Background technology: luteolin (blue or green blue aglycon, digicitrine, luteolin,) be to produce isolated identical effective constituent in the Herba Ajugae (Ajuga decumbensThunb.) from Herba Dracocephali Integrifolii (Dracocephatum integrifolium Bge.) and Anhui, extraction yield extremely low (being about 2/10000ths), its structure be 3 ', 4 ', 5, the 7-kaempferol.It is reported that it is expected to be developed as the medicine of treatment chronic bronchitis.The clinical study of a hundreds of bronochitics participation shows that this product is efficient to surpass 90%, and the direct release person reaches 63.8%; To the chronic bronchitis shape, can both effectively alleviate as cough, expectoration, asthma etc., and do not see the toxic report of liver, heart or kidney.Luteolin also has multiple biological activity and pharmacological action: 1. strong and stable town's phlegm effect; 2. phlegm-dispelling functions; 3. antiasthmatic effect; 4. bacteriostatic action; 5. anti-infectious function in the stronger body; 6. antagonism histamine and vagusstoff are to the excitation of tracheae silver flesh; 7. has anti-oxidation characteristics etc.In recent years, studies show that of clinical pharmacology, luteolin is existing outstanding curative effect aspect anti-inflammatory, antibiotic, treatment cardiovascular disorder, and becomes the reference substance of chromocor compound composition detection in all kinds of patent medicine gradually.Countries such as the U.S. are widely used in the natural health-care products aspect with it, and demand just constantly increases.Because it is in the outstanding curative effect of anti-virus aspect and being extensive use of of aspects such as food fresh keeping, luteolin has broad application prospects.Because its low levels in natural medicinal plant, low extraction yield is difficult to satisfy the growing market requirement, so study the emphasis that the semisynthesis of effective, practical luteolin is correlative study.At present, the total synthesis method of bibliographical information mainly contains two: 1.1980 years, the total synthesis method of employing Hierhammer such as Lu Yuhua report was raw material with the Phloroglucinol; get 2 by the Hoesch legal system; 4, the 6-trihydroxy-acetophenone is with methyl protection 4; generate corresponding cinnamophenone with the isovanillin condensation behind the 6-dihydroxyl; 6 days consuming time, and yield is low, has synthesized luteolin through 5 steps such as tin anhydride oxidation, hydroiodic acid HI demethylation again; yield is 3～4% only, makes it lose the possibility of suitability for industrialized production.2.2003 year; it is that raw material improves above-mentioned total synthesis method that Ge Xia etc. also adopt Phloroglucinol; that is: will get 2 with the Hoesch legal system; 4; the 6-trihydroxy-acetophenone use instead chloromethyl methyl ether protect 2-hydroxyl-4; 6-dimethoxy methoxyacetophenone; make 2 '-hydroxyl-3 through the potassium hydroxide-ethanol system; 4; 4; 6-tetramethyl oxygen methoxyl group cinnamophenone, again through tin anhydride oxidation, dilute hydrochloric acid deprotection and in three thallium trinitrate (TTN)s-methanol system oxidation transposition, deprotection again condensation get luteolin, yield is 22%.The technology that above-mentioned total synthesis method prepares luteolin is extremely complicated, and production cost is higher.Reaction is starting raw material with basic chemical raw materials, and per step intermediate is difficult to purifying, cause the yield of the finished product low, and biological activity is lower, and toxicity is big.Only limit to the laboratory theoretical research stage, be unfavorable for the popularization and the application of large-scale commercial production and product.
Summary of the invention: the object of the present invention is to provide a kind of is the semisynthesis of the new luteolin of raw material with natural Hesperidin, it comprises that a. synthesizes diosmin, b. synthetic diosmetin, c. synthetic three steps of luteolin, concrete operation method is: a. diosmin synthetic: Hesperidin is added in pyridine or the dimethyl sulfoxide (DMSO) organic solvent, the sulfuric acid that adds catalyzer iodine and/or catalytic amount more respectively carries out dehydrogenation, reflux and stir, the consumption W/V=1 of Hesperidin and organic solvent wherein: (4～8), Hesperidin is 1 with the consumption mol ratio of iodine: (0.6～2), under 50～120 ℃ of conditions, reacted 5～16 hours, after the cooling, the filtration precipitate also washes with water, thick product, be that 5～10% NaOH solution fully dissolves with concentration then, add again and the isopyknic methyl alcohol of NaOH, with concentration is that 5～10% HCl transfers pH to 3～5, separate out the near-white solid, suction filtration is washed to neutrality, drying promptly gets diosmin; B. diosmetin is synthetic: diosmin is dissolved in methyl alcohol, ethanol or the ethylene glycol organic solvent, add hydrochloric acid or sulfuric acid more respectively and carry out the desugar glycosides, diosmin wherein: organic solvent: mineral acid (W/V/V)=1: (16～32): (0.4～2), temperature of reaction are between 50～120 ℃, reflux 1～5 hour, get yellow settled solution, in the impouring frozen water, place and separate out yellow solid, suction filtration goes out thick product then, with methyl alcohol, ethanol or Virahol organic solvent recrystallization, promptly get diosmetin; C. luteolin is synthetic: add the new haloid acid that steams in diosmetin, under the cooling conditions, drip organic solvent diacetyl oxide or glacial acetic acid and advance demethylation, wherein diosmetin: haloid acid: organic solvent (W/V/V)=1: (15～40): (4～20); Reflux, temperature of reaction are between 70～120 ℃, stir 5～12 hours, and cooling is placed and separated out yellow product; Leaching the back is that 5～20% sodium bisulfite or sodium sulfite solution wash with concentration, washes with water to neutrality again, and cryodrying gets the luteolin crude product; With gained crude product methyl alcohol, ethanol or Virahol organic solvent recrystallization, crystalline product is luteolin then.The present invention is that the natural extract-Hesperidin with biologically active is a starting raw material, gained intermediate diosmin, diosmetin etc. are the natural product of biologically active in its each step building-up process, so adopt this semisynthesis can produce above-mentioned three kinds of products simultaneously; Compare with total synthesis method, the product that this method makes all has higher biological activity and higher yield and purity, and production cost is low; Take off hydroformylation step and adopt iodine/pyridine, iodine/dimethyl sulfoxide (DMSO)/systems such as sulfuric acid, the reaction conditions gentleness, product purity and yield are all higher; The solvent system raw material that adopts in the desugar glycosides process is easy to get and easy control of reaction conditions, product do not decompose and productive rate higher; Adopted the more cheap Hydrogen bromide of price/diacetyl oxide system in the demethylation process, the demethylation effect is better, the conversion rate of products height.Because solvent system can repeatedly recycle, synthetic cost is reduced greatly; Whole synthesis technique raw material cheaply is easy to get, and is simple to operate, stable reaction conditions, and control easily, product is easy to separation and purification, and total yield of products can reach 40～47%, and purity reaches 95%.Production cost is lower, and environmental pollution is little.
Embodiment one: the working method of the synthetic luteolin of present embodiment comprises three steps: (I) synthetic, (III) luteolin of synthetic, (II) diosmetin of diosmin is synthetic.
(I). synthetic diosmin: Hesperidin is added in pyridine or the dimethyl sulfoxide (DMSO) organic solvent, add catalyzer iodine more respectively, the sulfuric acid that also need add catalytic amount again in dimethyl sulfoxide (DMSO) carries out dehydrogenation, reflux and stir, the consumption W/V=1 of Hesperidin and organic solvent wherein: (4～8), Hesperidin is 1 with the consumption mol ratio of iodine: (0.6～2), under 50～120 ℃ of conditions, reacted 5～16 hours, after the cooling, the filtration precipitate also washes with water, thick product, be that 5～10% NaOH solution fully dissolves with concentration then, add again and the isopyknic methyl alcohol of NaOH, with concentration is that 5～10% HCl transfers pH to about 3～5, separate out the near-white solid, suction filtration is washed to neutrality, dry, promptly get diosmin, product purity 97%, yield 90～94%.
(II). synthetic diosmetin: step (I) gained diosmin is dissolved in methyl alcohol, ethanol or the ethylene glycol organic solvent, add hydrochloric acid or sulfuric acid more respectively and carry out the desugar glycosides, diosmin wherein: organic solvent: mineral acid (W/V/V)=1: (1 6～32): (0.4～2), temperature of reaction is between 50～120 ℃, refluxed 1～5 hour, get yellow settled solution, in the impouring frozen water, yellow solid is separated out in placement, suction filtration goes out thick product then, with methyl alcohol, ethanol or Virahol organic solvent recrystallization, promptly gets diosmetin, product purity 98%, yield 70～72%.
(III). synthetic luteolin: in (II) step gained diosmetin, add the new haloid acid that steams, haloid acid is Hydrogen bromide or hydroiodic acid HI, under the cooling conditions, drip organic solvent diacetyl oxide or glacial acetic acid and carry out demethylation, wherein diosmetin: haloid acid: organic solvent (W/V/V)=1: (15～40): (4～20); Reflux, temperature of reaction are between 70～120 ℃, stir 5～12 hours, and cooling is placed and separated out yellow product; Leaching the back is that 5～20% sodium bisulfite or sodium sulfite solution wash with concentration, washes with water to neutrality again, and cryodrying gets the luteolin crude product;
Hydrogen bromide/diacetyl oxide, hydroiodic acid HI/diacetyl oxide mother liquor can be recycled, and to add an amount of, a certain proportion of above-mentioned solvent system more again about 10～30% at every turn, can recycle conversion rate of products height, nearly 100% 3～6 times.
With gained crude product methyl alcohol, ethanol or Virahol organic solvent recrystallization, get light yellow crystalline product and be luteolin then, purity 95%, yield is 65～70%.
Principle of the present invention is as follows:
(1) luteolin chemical name: 3 ', 4 ', 5, the 7-kaempferol
Chemical structural formula:
(2) synthetic method
This method comprises following three steps:
1. dehydrogenation
3. demethylation
Whole synthesis technique comprises following three steps:
The first step is a dehydrogenation reaction, is raw material with the bioactive Hesperidin that has that extracts from orange peel, adopts iodine/pyridine, iodine/dimethyl sulfoxide (DMSO)/system dehydrogenations such as sulfuric acid to make diosmin, 50～120 ℃ of temperature of reaction, and the reaction times was at 5～16 hours.Feed stock conversion reaches 100%, product purity 97%, yield 90～94%.
Second step prepared diosmetin for the reaction of hydrolysis desugar glycosides by diosmin, and the main hydrolyzation system that adopts is: methyl alcohol/hydrochloric acid, ethylene glycol/sulfuric acid, ethylene glycol/hydrochloric acid, ethanol/sulfuric acid, methyl alcohol/sulfuric acid etc.Temperature of reaction is between 50～120 ℃, and the reaction times is 1～5 hour.Product purity 98%, yield are 70～72%.
The 3rd step was demethylating reaction, prepared luteolin by diosmetin: adopt demethylation reagent systems such as Hydrogen bromide, Hydrogen bromide/diacetyl oxide, hydroiodic acid HI/diacetyl oxide, temperature of reaction is between 70～120 ℃, and the reaction times is 5～12 hours.Product purity 95%, yield 65～70%.
Embodiment two: the operating process of present embodiment is:
(I). diosmin synthetic: take into account in the 1L there-necked flask of reflux condensing tube and add Hesperidin 75g, pyridine 450ml to agitator, temperature are housed, be heated to moltenly entirely, add iodine 32g again, be heated to 90～95 ℃, reflux and stir 11h, cooling with water-bath.Separate out a large amount of solids, filter, the filter cake massive laundering gets the thick product of near-white.Thick product is dissolved in 5%NaOH solution, filter clear liquor, to wherein adding isopyknic methyl alcohol, transfer pH to about 3～5 with 5%HCl, separate out the near-white solid, suction filtration is washed to neutrality.Dry product 70.2g, purity 97%, the yield 94% of getting.
(II) diosmetin is synthetic: take into account in the 500ml there-necked flask of reflux condensing tube and add step (I) gained diosmin 10g to agitator, temperature are housed, successively add methyl alcohol 200ml and dense H again
2SO
410ml in 80～90 ℃ of reflux 3h, in the yellow settled solution impouring of the gained frozen water, separates out yellow solid.Suction filtration is used ethyl alcohol recrystallization, gets yellow fine acicular crystal 3 .56g, product purity 98%, yield 72%.
(III) luteolin is synthetic: to agitator is housed, temperature is taken into account in the 500ml there-necked flask of reflux condensing tube, adds diosmetin 6g, adds the new HBr150ml of steaming, under the water-bath cooling, slowly drips diacetyl oxide 40ml.Be heated to 90～120 ℃ of stirring 9～11h that reflux.Cooling, placement is spent the night, and separates out yellow solid.Leach the back with the washing of about 10% sodium sulfite solution, wash with water to neutrality again, cryodrying gets thick product 5.3g, with must light yellow needle crystal product 4.0g after the recrystallizing methanol, and purity 95%, yield is 70%.
Embodiment three: the operating process of present embodiment is:
(I). diosmin synthetic: take into account in the 1L there-necked flask of reflux condensing tube and add Hesperidin 75g, dimethyl sulfoxide (DMSO) 350ml to agitator, temperature are housed, be heated to moltenly entirely, add the sulfuric acid of iodine 15g and catalytic amount again, be heated to 70～90 ℃ with water-bath, reflux and stir 10～12h, cooling.Separate out a large amount of solids, filter, the filter cake massive laundering gets the thick product of near-white.It is 10% NaOH solution that thick product is dissolved in concentration, filter clear liquor, to wherein adding and the isopyknic methyl alcohol of NaOH, be 10% HCl accent pH to 3～4 with concentration, separate out the near-white solid, suction filtration is washed to neutrality.Dry product 67.1g, purity 97%, the yield 90% of getting.
(II) diosmetin is synthetic: take into account in the 500ml there-necked flask of reflux condensing tube and add step (I) gained diosmin 10g to agitator, temperature are housed, successively add ethanol 200ml and dense HCl10ml again, in 70～80 ℃ of reflux 3h, in the yellow settled solution impouring of the gained frozen water, separate out yellow solid.Suction filtration is used ethyl alcohol recrystallization, gets yellow fine acicular crystal 3 .35g, product purity 98%, yield 70%.
(III) luteolin is synthetic: to agitator is housed, temperature is taken into account in the 500ml there-necked flask of reflux condensing tube, adds diosmetin 6g, adds the new Hydrogen bromide 150ml that steams, and under the water-bath cooling, slowly drips glacial acetic acid 40ml.Be heated to 90～120 ℃ of stirring 8～10h that reflux.Cooling, placement is spent the night, and separates out yellow solid.Leaching the back is the washing of 15～20% sodium sulfite solution with concentration, washes with water to neutrality again, and cryodrying gets thick product, with must being luteolin by light yellow needle crystal product 3.72g behind the ethyl alcohol recrystallization, and purity 95%, yield is 65%.
Embodiment four: the operating process of present embodiment is:
(I). diosmin synthetic: take into account in the 1L there-necked flask of reflux condensing tube and add Hesperidin 75g, dimethyl sulfoxide (DMSO) 340ml to agitator, temperature are housed, be heated to moltenly entirely, add the sulfuric acid of iodine 10g and catalytic amount again, be heated to 100～120 ℃, reflux and stir 12～16h, cooling.Separate out a large amount of solids, filter, the filter cake massive laundering gets the thick product of near-white.It is 10% NaOH solution that thick product is dissolved in concentration, filter clear liquor, to wherein adding and the isopyknic methyl alcohol of NaOH, be 10% HCl accent pH to 4～5 with concentration, separate out the near-white solid, suction filtration is washed to neutrality.Dry product 67.1g, purity 97%, the yield 90% of getting.
(II) diosmetin is synthetic: take into account in the 500ml there-necked flask of reflux condensing tube and add step (I) gained diosmin 10g to agitator, temperature are housed, successively add ethylene glycol 200ml and dense H again
2SO
410ml in 100～120 ℃ of reflux 2～4h, in the yellow settled solution impouring of the gained frozen water, separates out yellow solid.Suction filtration is used ethyl alcohol recrystallization, gets yellow fine acicular crystal 3 .35g, product purity 98%, yield 70%.
(III) luteolin is synthetic: to agitator is housed, temperature is taken into account in the 500ml there-necked flask of reflux condensing tube, adds diosmetin 6g, adds the new hydroiodic acid HI 150ml that steams, and under the water-bath cooling, slowly drips glacial acetic acid 40ml.Be heated to 80～90 ℃ of stirring 8～9h that reflux.Cooling, placement is spent the night, and separates out yellow solid.Leaching the back is the washing of 10% sodium sulfite solution with concentration, washes with water to neutrality again, and cryodrying gets thick product, with must being luteolin by light yellow needle crystal product 3.72g after the recrystallizing methanol, and purity 95%, yield is 65%.
Embodiment five: the operating process of present embodiment is:
(I). diosmin synthetic: take into account in the 1L there-necked flask of reflux condensing tube and add Hesperidin 75g, pyridine 400ml to agitator, temperature are housed, be heated to moltenly entirely, add iodine 30g again, be heated to 90～98 ℃, reflux and stir 10h, cooling with water-bath.Separate out a large amount of solids, filter, the filter cake massive laundering gets the thick product of near-white.Thick product is dissolved in 10%NaOH solution, filter clear liquor, to wherein adding isopyknic methyl alcohol, transfer pH to about 4～5 with 7%HCl, separate out the near-white solid, suction filtration is washed to neutrality.Dry product 70.1g, purity 97%, the yield 93% of getting.
(II) diosmetin is synthetic: take into account in the 500ml there-necked flask of reflux condensing tube and add step (I) gained diosmin 10g to agitator, temperature are housed, successively add ethylene glycol 200ml and dense HCl10ml again, in 110～120 ℃ of reflux 2～5h, in the yellow settled solution impouring of the gained frozen water, separate out yellow solid.Suction filtration is used ethyl alcohol recrystallization, gets yellow fine acicular crystal 3 .35g, product purity 98%, yield 70%.
(III) luteolin is synthetic: to agitator is housed, temperature is taken into account in the 500ml there-necked flask of reflux condensing tube, adds diosmetin 6g, adds the new hydroiodic acid HI 140ml that steams, and under the water-bath cooling, slowly drips diacetyl oxide 36ml.Be heated to 110 ℃ of stirring 5～7h that reflux.Cooling, placement is spent the night, and separates out yellow solid.Leaching the back is the washing of 15% sodium sulfite solution with concentration, washes with water to neutrality again, and cryodrying gets thick product, with must being luteolin by light yellow needle crystal product 4.0g after the recrystallizing methanol, and purity 95%, yield is 70%.
Embodiment six: the operating process of present embodiment is:
(I). diosmin synthetic: take into account in the 1L there-necked flask of reflux condensing tube and add Hesperidin 75g, pyridine 400ml to agitator, temperature are housed, be heated to moltenly entirely, add iodine 30g again, be heated to 90～98 ℃, reflux and stir 10h, cooling with water-bath.Separate out a large amount of solids, filter, the filter cake massive laundering gets the thick product of near-white.Thick product is dissolved in 10%NaOH solution, filter clear liquor, to wherein adding isopyknic methyl alcohol, transfer pH to about 4～5 with 7%HCl, separate out the near-white solid, suction filtration is washed to neutrality.Dry product 70.1g, purity 97%, the yield 93% of getting.
(II) diosmetin is synthetic: take into account in the 500ml there-necked flask of reflux condensing tube and add step (I) gained diosmin 10g to agitator, temperature are housed, successively add methyl alcohol 200ml and dense HCl10ml again, in 50～70 ℃ of reflux 2～3h, in the yellow settled solution impouring of the gained frozen water, separate out yellow solid.Suction filtration is used ethyl alcohol recrystallization, gets yellow fine acicular crystal 3 .35g, product purity 98%, yield 70%.
(III) luteolin is synthetic: to agitator is housed, temperature is taken into account in the 500ml there-necked flask of reflux condensing tube, adds diosmetin 6g, adds the new Hydrogen bromide 150ml that steams, and under the water-bath cooling, slowly drips glacial acetic acid 40ml.Be heated to 90～120 ℃ of stirring 8～10h that reflux.Cooling, placement is spent the night, and separates out yellow solid.Leaching the back is the washing of 15～20% sodium sulfite solution with concentration, washes with water to neutrality again, and cryodrying gets thick product, with must being luteolin by light yellow needle crystal product 3.72g behind the ethyl alcohol recrystallization, and purity 95%, yield is 65%.
Embodiment seven: the operating process of present embodiment is:
(I). diosmin synthetic: take into account in the 1L there-necked flask of reflux condensing tube and add Hesperidin 75g, pyridine 450ml to agitator, temperature are housed, be heated to moltenly entirely, add iodine 32g again, be heated to 90～95 ℃, reflux and stir 11h, cooling with water-bath.Separate out a large amount of solids, filter, the filter cake massive laundering gets the thick product of near-white.Thick product is dissolved in 5%NaOH solution, filter clear liquor, to wherein adding isopyknic methyl alcohol, transfer pH to about 3～5 with 5%HCl, separate out the near-white solid, suction filtration is washed to neutrality.Dry product 70.2g, purity 97%, the yield 94% of getting.
(II) diosmetin is synthetic: take into account in the 500ml there-necked flask of reflux condensing tube and add step (I) gained diosmin 10g to agitator, temperature are housed, successively add ethanol 200ml and dense H again
2SO
410ml in 70～80 ℃ of reflux 2～4h, in the yellow settled solution impouring of the gained frozen water, separates out yellow solid.Suction filtration is used ethyl alcohol recrystallization, gets yellow fine acicular crystal 3 .35g, product purity 98%, yield 70%.
(III) luteolin is synthetic: to agitator is housed, temperature is taken into account in the 500ml there-necked flask of reflux condensing tube, adds diosmetin 6g, adds the new HBr150ml of steaming, under the water-bath cooling, slowly drips diacetyl oxide 40ml.Be heated to 90～120 ℃ of stirring 9～11h that reflux.Cooling, placement is spent the night, and separates out yellow solid.Leach the back with the washing of about 10% sodium sulfite solution, wash with water to neutrality again, cryodrying gets thick product 5.3g, with must light yellow needle crystal product 4.0g after the recrystallizing methanol, and purity 95%, yield is 70%.
Claims (5)
1, a kind of semisynthesis of luteolin, it is characterized in that it comprises that a. synthesizes diosmin, b. synthetic diosmetin, c. synthetic three steps of luteolin, concrete operation method is: a. diosmin synthetic: Hesperidin is added in pyridine or the dimethyl sulfoxide (DMSO) organic solvent, the sulfuric acid that adds catalyzer iodine and/or catalytic amount more respectively carries out dehydrogenation and carries out dehydrogenation, reflux and stir, the consumption W/V=1 of Hesperidin and organic solvent wherein: (4～8), Hesperidin is 1 with the consumption mol ratio of iodine: (0.6～2), under 50～120 ℃ of conditions, reacted 5～16 hours, after the cooling, the filtration precipitate also washes with water, thick product, be that 5～10% NaOH solution fully dissolves with concentration then, add again and the isopyknic methyl alcohol of NaOH, with concentration is that 5～10% HCl transfers pH to 3～5, separate out the near-white solid, suction filtration is washed to neutrality, drying promptly gets diosmin; B. diosmetin is synthetic: diosmin is dissolved in methyl alcohol, ethanol or the ethylene glycol organic solvent, add hydrochloric acid or sulfuric acid more respectively and carry out the desugar glycosides, diosmin wherein: organic solvent: mineral acid (W/V/V)=1: (16～32): (0.4～2), temperature of reaction are between 50～120 ℃, reflux 1～5 hour, get yellow settled solution, in the impouring frozen water, place and separate out yellow solid, suction filtration goes out thick product then, with methyl alcohol, ethanol or Virahol organic solvent recrystallization, promptly get diosmetin; C. luteolin is synthetic: add the new haloid acid that steams in diosmetin, under the cooling conditions, drip organic solvent diacetyl oxide or glacial acetic acid and carry out demethylation, wherein diosmetin: haloid acid: organic solvent (W/V/V)=1: (15～40): (4～20); Reflux, temperature of reaction are between 70～120 ℃, stir 5～12 hours, and cooling is placed and separated out yellow product; Leaching the back is that 5～20% sodium bisulfite or sodium sulfite solution wash with concentration, washes with water to neutrality again, and cryodrying gets the luteolin crude product; With gained crude product methyl alcohol, ethanol or Virahol organic solvent recrystallization, crystalline product is luteolin then.
2, the semisynthesis of luteolin according to claim 1 is characterized in that described haloid acid is Hydrogen bromide or hydroiodic acid HI.
3, the semisynthesis of luteolin according to claim 1, the dehydrogenation systems when it is characterized in that preparing diosmin are that pyridine adds the iodine system, and perhaps dimethyl sulfoxide (DMSO) adds iodine and adds sulfuric acid system.
4, the semisynthesis of luteolin according to claim 1, desugar glycosides system when it is characterized in that preparing diosmetin adopts methyl alcohol to add sulfuric acid system, and perhaps methyl alcohol adds hydrochloric acid system, and perhaps ethylene glycol adds sulfuric acid system, perhaps ethylene glycol adds hydrochloric acid system, and perhaps ethanol adds sulfuric acid system.
5, the semisynthesis of luteolin according to claim 1 is characterized in that preparing in the demethylation system of luteolin, and Hydrogen bromide adds diacetyl oxide system and hydroiodic acid HI and adds the diacetyl oxide system and can be recycled; Adding the novel solvent that accounts for system volume 10～30% after using again gets final product.
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