CN105348245A - Eriodictyol synthesis method - Google Patents

Eriodictyol synthesis method Download PDF

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Publication number
CN105348245A
CN105348245A CN201510868691.1A CN201510868691A CN105348245A CN 105348245 A CN105348245 A CN 105348245A CN 201510868691 A CN201510868691 A CN 201510868691A CN 105348245 A CN105348245 A CN 105348245A
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methoxy
ethyl acetate
eriodictyol
hydroxyl
methoxyl group
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郭文华
肖金霞
张瑜
肖红
王晓莹
赵景辉
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SHAANXI JIAHE PHYTOCHEM CO Ltd
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SHAANXI JIAHE PHYTOCHEM CO Ltd
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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
    • C07D311/32—2,3-Dihydro derivatives, e.g. flavanones

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  • Organic Chemistry (AREA)
  • Pyrane Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention provides an eriodictyol synthesis method. According to the eriodictyol synthesis method, isovanillin and 2,4,6-trihydroxyacetophenone are selected as starting materials, and eriodictyol is obtained through the following five steps: firstly, performing MOMCl protection on a hydroxyl of isovanillin; secondly, performing MOMCl protection on a hydroxyl of 2,4,6-trihydroxyacetophenone; thirdly, performing an aldol condensation reaction to generate chalcone; fourthly, performing Michael addition and cyclization; finally, carrying out MOM deprotection to obtain eriodictyol of which the total yield is 50-65%. As isovanillin and 2,4,6-trihydroxyacetophenone are selected as the starting materials, the eriodictyol synthesis method is high in yield and suitable for industrialized production.

Description

A kind of synthetic method of Eriodictyol
Technical field
The invention belongs to biological technical field, be specifically related to a kind of synthetic method of Eriodictyol.
Background technology
No. CAS, Eriodictyol is 552-58-9 molecular formula C 15h 12o 6, molecular weight 288.25, molecular structural formula:
It is the flavonoid compound be distributed widely in fruits and vegetables that Eriodictyol has another name called eriodictyol (eriodictyol), is mainly present in lemon and peanut.Flavonoid compound can play anti-oxidant activity as free radical aceeptor and chain terminator, and hydroxy position and hydroxylation degree and flavonoid compound resistance of oxidation have important relation, B ring have the flavones anti-oxidant activity of adjacent two phenolic hydroxyl groups the strongest.According to the chemical structure of eriodictyol, eriodictyol is flavones B ring with adjacent two phenolic hydroxyl groups, infers that eriodictyol is the very strong natural antioxidants of a kind of potential anti-oxidant activity.
The existing report of the research to eriodictyol biological activity and pharmacologically active both at home and abroad, eriodictyol has anti-inflammatory, analgesia, improves the effect of diabetes and diabetic complication.People's researchs such as Zhang Yifan show that eriodictyol has the ability of very strong removing DPPH free radical, but more weak to the Scavenging activity of hydroxy radical qiao.In addition, protein, lipid, DNA oxidative damage that eriodictyol can effectively protect AAPH to induce, this provide protection may be eriodictyol inhibits radical pair biomacromolecule attack by scavenging free radicals, shows that eriodictyol has good anti-oxidant activity.In research, eriodictyol can suppress the activity of liver cancer cell significantly, may be to make free-radical contents lower than physiological level by its antioxygenation, thus suppresses the activity of liver cancer cell.
Eriodictyol can be separated and obtain from plant, also directly can synthesize or obtain by Hesperidin is semi-synthetic, the eriodictyol of semi-synthetic preparation is through hydrolysis by Hesperidin, demethylation obtains, publication number be CN103145670A patent describes a kind of semi-synthetic novel process preparing luteolin, wherein relate to the preparation method of intermediate product eriodictyol, the method take Hesperidin as raw material, after the hydrolysis of acidic ethanol aqueous acid, add Aluminum chloride anhydrous demethylation and obtain eriodictyol, its shortcoming is that semi-synthetic eriodictyol easily introduces uncontrollable impurity, and produce in reaction process waste water be difficult to process.Publication number is the method that patent describes water chestnut skin extraction eriodictyol of CN1O4529983A, and it is raw material that technique have employed water chestnut, and raw material ratio is comparatively rare, and acetone extraction, the technology such as polyamide column separation, complex process, cost is higher.At present, the complete synthesis Technology document about eriodictyol is not found.
Summary of the invention
Problem to be solved by this invention is to provide the synthetic method that a kind of yield is high, be applicable to the Eriodictyol of suitability for industrialized production.
The technical scheme solved the problem: the synthetic method of the Eriodictyol provided, comprises the following steps:
Step 1: by Isovanillin, sodium methylate and acetone mix and blend, then adds methylcarbonate and continues to stir, add water, be extracted with ethyl acetate to obtain 3-methoxy methoxy base-4-methoxybenzaldehyde;
Step 2: by 2,4,6-trihydroxy-acetophenone, K 2cO 3with acetone mix and blend, then add MOMCl and continue to stir, add water, be extracted with ethyl acetate to obtain 2-hydroxyl-4-methoxy methoxy base-6-acetophenone;
Step 3: by the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone of the 3-methoxy methoxy base-4-methoxybenzaldehyde of step 1 gained, step 2 gained, KOH, dehydrated alcohol and water mix and blend, on the rocks, neutralize with hydrochloric acid, be extracted with ethyl acetate again, obtain 2-hydroxyl-4-methoxyl group-3,4,6-methoxy methoxy base cinnamophenone;
Step 4: by 2-hydroxyl-4-methoxyl group-3,4, the 6-methoxy methoxy base cinnamophenone of gained, sodium acetate, anhydrous, dehydrated alcohol and water back flow reaction, obtain 5,7,3-dimethoxy methoxyl group-4-melonia flavones;
Step 5: by 5,7,3-dimethoxy methoxyl group-4-melonia flavones of gained, dehydrated alcohol and hydrochloric acid reflux, obtain Eriodictyol.
Above-mentioned steps 1 is specifically: by Isovanillin, sodium methylate and acetone mix and blend, then adds methylcarbonate and continues to stir, add water, be extracted with ethyl acetate, merge organic phase, drying treatment, decompression evaporates ethyl acetate, obtains 3-methoxy methoxy base-4-methoxybenzaldehyde; The mass ratio of described Isovanillin, sodium methylate, acetone and methylcarbonate is 1:0.03-0.05:5-8:1-1.2.
Above-mentioned steps 2 is specifically: by 2,4,6-trihydroxy-acetophenone, K 2cO 3with acetone mix and blend, then add MOMCl and continue to stir, add water, be extracted with ethyl acetate, merge organic phase, drying treatment, decompression evaporates ethyl acetate, obtains 2-hydroxyl-4,6-dimethoxy methoxyacetophenone; Described 2,4,6-trihydroxy-acetophenones, K 2cO 3, to obtain mass ratio be 1:4.5-4.8:4-5:1.2-1.5 for acetone and MOMCl.
Above-mentioned steps 3 is specifically: by the 3-methoxy methoxy base-4-methoxybenzaldehyde of step 1 gained, the 2-hydroxyl-4 of step 2 gained, 6-dimethoxy methoxyacetophenone, KOH, dehydrated alcohol and water mix and blend, on the rocks, be neutralized to PH=6 ~ 7 with 3mol/L hydrochloric acid, be extracted with ethyl acetate again, merge organic phase, drying treatment, decompression evaporates ethyl acetate, residue ethyl alcohol recrystallization, obtain 2-hydroxyl-4-methoxyl group-3,4,6-methoxy methoxy base cinnamophenone; Described 3-methoxy methoxy base-4-methoxybenzaldehyde, 2-hydroxyl-4,6-dimethoxy methoxyacetophenone, KOH, dehydrated alcohol and quality are than being 1:1.2-1.3:0.5-0.6:4-5:0.5.
Above-mentioned steps 4 is specifically: by the 2-hydroxyl-4-methoxyl group-3 of gained, 4,6-methoxy methoxy base cinnamophenone, sodium acetate, anhydrous, dehydrated alcohol and water back flow reaction, be extracted with ethyl acetate, merge organic layer, drying treatment, low pressure is revolved except ethyl acetate obtains residue, 5,7,3-dimethoxy methoxyl group-4-melonia flavones is obtained with ethyl alcohol recrystallization; Described 2-hydroxyl-4-methoxyl group-3,4,6-methoxy methoxy base cinnamophenone, sodium acetate, anhydrous, dehydrated alcohol mass ratio are 1:0.001-0.005:1.5-3:0.5-0.8.
Above-mentioned steps 5 is specifically: by 5,7,3-dimethoxy methoxyl group-4-melonia flavones of gained, dehydrated alcohol and hydrochloric acid reflux, be cooled to room temperature, extraction into ethyl acetate, merge organic layer, drying treatment, decompression evaporates ethyl acetate, and resistates obtains Eriodictyol through ethyl alcohol recrystallization; The mass ratio of described 5,7,3-dimethoxy methoxyl group-4-melonia flavones, dehydrated alcohol and hydrochloric acid is 1:5-8:15-18.
Drying treatment in above-mentioned steps 1-5 adopts anhydrous MgSO4 dry.
Advantage of the present invention:
The present invention with Isovanillin and 2,4,6-trihydroxy-acetophenone for initiator, the high and applicable suitability for industrialized production of yield.
Embodiment
With Isovanillin and 2; 4; 6-trihydroxy-acetophenone is initiator, first by 2, and 4; the hydroxyl of 6-trihydroxy-acetophenone and the hydroxyl MOMCl of Isovanillin protect; there is aldol reaction again and generate cinnamophenone, then close ring by Michael addition, finally take off MOM protection; totally 5 steps are obtained by reacting eriodictyol, total recovery 50-65%.
Concrete technology flow process is as follows:
Embodiment 1
Step 1 adds Isovanillin 15.2g in 1000mL round-bottomed flask, sodium methylate 0.54g, and then acetone 100mL, stirring at room temperature 1h add methylcarbonate 18g, continues to stir 4h.Add water 100mL, with 300ml extraction into ethyl acetate three times, merges organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining greenish yellow solid is crude product 3-methoxy methoxy base-4-methoxybenzaldehyde, yield 86.4%.
Step 2 adds 2,4,6-trihydroxy-acetophenone 18.2g in 1000ml round-bottomed flask, K 2cO 382.8g, acetone 100mL, stirring at room temperature 1h, then add MOMCl22.8ml, continues to stir 4h, and add water 100mL, with ethyl acetate 300ml extraction, merges organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining yellow solid is 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product, yield 71.5%.
Step 3 adds the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 25.6g obtained in step 2 in 1000mL round-bottomed flask, with the 3-methoxy methoxy base obtained in step 1-4-methoxybenzaldehyde crude product 19.6g, KOH11.2g, dehydrated alcohol 100mL, water 10mL, stirring at room temperature 48h.In reaction solution, add trash ice 50g, then be neutralized to pH=6 ~ 7 with 3mol/LHCl, with ethyl acetate 300ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and residue ethyl alcohol recrystallization obtains yellow needle-like crystals. yield 62.3%.
Step 4 adds 2.-hydroxyl-4-methoxyl group-3,4, the 6-methoxy methoxy base cinnamophenone 43.4g sodium acetate, anhydrous 82mg that step 3 obtains in 1000mL round-bottomed flask, dehydrated alcohol 100mL, water 30mL, backflow 24h. ethyl acetate 300 extracts, merge organic layer, the dry 30min of anhydrous MgSO4, low pressure is revolved except ethyl acetate obtains residue, obtains light yellow crystal 5 with ethyl alcohol recrystallization, 7,3.-dimethoxy methoxyl group-4.-melonia flavones yield 32.3%.
Step 5 adds 5 in 1000mL round-bottomed flask, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 6g, dehydrated alcohol 500mL, 3mol/lHCl100mL, backflow 1h. is cooled to room temperature, with ethyl acetate 200ml extraction, merge organic layer, the dry 40min of anhydrous MgSO4, decompression evaporates ethyl acetate, and resistates obtains off-white color solid eriodictyol yield 92.7% through ethyl alcohol recrystallization.
Embodiment 2
Step 1 adds Isovanillin 30.4g in 1000mL round-bottomed flask, sodium methylate 1.08g acetone 200mL, and stirring at room temperature 1h, then adds methylcarbonate 36g, continues to stir 4h. and to add water 200mL, with 600ml extraction into ethyl acetate three times, merges organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining greenish yellow solid is crude product 3-methoxy methoxy base-4-methoxybenzaldehyde yield 87%.
Step 2 adds 2,4,6-trihydroxy-acetophenone 36.4g in 1000ml round-bottomed flask, K 2cO 3165g, acetone 100mL, stirring at room temperature 1h, then add MOMCl46ml, continues to stir 4h. and to add water 200mL, with ethyl acetate 500ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining yellow solid is 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 28g, yield 72%.
Step 3 adds the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 28g obtained in step 2 in 1000mL round-bottomed flask, with the 3-methoxy methoxy base obtained in step 1-4-methoxybenzaldehyde crude product 38g, KOH22g, dehydrated alcohol 200mL, water 20mL, stirring at room temperature 48h. add trash ice 100g in reaction solution, pH=6 ~ 7 are neutralized to again with 3mol/LHCl, with ethyl acetate 500ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and residue ethyl alcohol recrystallization obtains yellow needle-like crystals 40g. yield 61.3%.
Step 4 adds the 2.-hydroxyl-4-methoxyl group-3 that step 3 obtains in 1000mL round-bottomed flask, 4., and 6.-methoxy methoxy base cinnamophenone 40g sodium acetate, anhydrous 164mg,, dehydrated alcohol 200mL, water 60mL, backflow 24h. ethyl acetate 500 extracts, merge organic layer, the dry 30min of anhydrous MgSO4, low pressure is revolved except ethyl acetate obtains residue, light yellow crystal 5 is obtained with ethyl alcohol recrystallization, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 12.5g, yield 32.3%.
Step 5 adds 5 in 1000mL round-bottomed flask, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 12.5g, dehydrated alcohol 500mL, 3mol/lHCl100mL, backflow 1h. is cooled to room temperature, with ethyl acetate 300ml extraction, merge organic layer, the dry 40min of anhydrous MgSO4, decompression evaporates ethyl acetate, and resistates obtains off-white color solid eriodictyol 11.58g. yield 90% through ethyl alcohol recrystallization.
Embodiment 3
Step 1 adds Isovanillin 45g in 2000mL round-bottomed flask, sodium methylate 1.5g acetone 300mL, and stirring at room temperature 1h, then adds methylcarbonate 54g, continues to stir 4h. and to add water 300mL, with 900ml extraction into ethyl acetate three times, merges organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining greenish yellow solid is crude product 3-methoxy methoxy base-4-methoxybenzaldehyde 40g, yield 85%.
Step 2 adds 2,4,6-trihydroxy-acetophenone 54g in 2000ml round-bottomed flask, K 2cO 3250g, acetone 300mL, stirring at room temperature 1h, then add MOMCl70ml, continues to stir 4h. and to add water 300mL, with ethyl acetate 900ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining yellow solid is 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 38.34g, yield 69%.
Step 3 adds the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 38.34g obtained in step 2 in 2000mL round-bottomed flask, with the 3-methoxy methoxy base obtained in step 1-4-methoxybenzaldehyde crude product 40g, KOH33g, dehydrated alcohol 300mL, water 30mL, stirring at room temperature 48h. add trash ice 150g in reaction solution, pH=6 ~ 7 are neutralized to again with 3mol/LHCl, with ethyl acetate 900ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and residue ethyl alcohol recrystallization obtains yellow needle-like crystals 49.14g. yield 63%.
Step 4 adds the 2.-hydroxyl-4-methoxyl group-3 that step 3 obtains in 2000mL round-bottomed flask, 4., and 6.-methoxy methoxy base cinnamophenone 49.14g sodium acetate, anhydrous 240mg,, dehydrated alcohol 300mL, water 90mL, backflow 24h. ethyl acetate 900 extracts, merge organic layer, the dry 30min of anhydrous Na 2SO4, low pressure is revolved except ethyl acetate obtains residue, light yellow crystal 5 is obtained with ethyl alcohol recrystallization, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 15.1g, yield 30%.
Step 5 adds 5,7,3.-dimethoxy methoxyl group-4.-melonia flavones 15.1g in 2000mL round-bottomed flask, dehydrated alcohol 1000mL, 3mol/lHCl300mL, backflow 1h. is cooled to room temperature, divide three extractions with ethyl acetate 900ml, merge organic layer, anhydrous Na 2the dry 40min of SO4, decompression evaporates ethyl acetate, and resistates obtains off-white color solid eriodictyol 13.59g through ethyl alcohol recrystallization, yield 90%.
Embodiment 4
Step 1 adds Isovanillin 7.6g in 1000mL round-bottomed flask, sodium methylate 0.27g acetone 100mL, and stirring at room temperature 1h, then adds methylcarbonate 9g, continues to stir 4h. and to add water 100mL, with 300ml extraction into ethyl acetate three times, merges organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining greenish yellow solid is crude product 3-methoxy methoxy base-4-methoxybenzaldehyde 6.46g, yield 84.4%.
Step 2 adds 2,4,6-trihydroxy-acetophenone 9g in 1000ml round-bottomed flask, K 2cO 342g, acetone 100mL, stirring at room temperature 1h, then add MOMCl12ml, continues to stir 4h. and to add water 100mL, with ethyl acetate 300ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining yellow solid is 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 6.5g, yield 73%.
Step 3 adds the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 6.5g obtained in step 2 in 1000mL round-bottomed flask, with the 3-methoxy methoxy base obtained in step 1-4-methoxybenzaldehyde crude product 6.46g, KOH5.6g, dehydrated alcohol 100mL, water 10mL, stirring at room temperature 48h. add trash ice 50g in reaction solution, pH=6 ~ 7 are neutralized to again with 3mol/LHCl, with ethyl acetate 300ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and residue ethyl alcohol recrystallization obtains yellow needle-like crystals 8.06g, yield 63%.
Step 4 adds the 2.-hydroxyl-4-methoxyl group-3 that step 3 obtains in 1000mL round-bottomed flask, 4., and 6.-methoxy methoxy base cinnamophenone 8.06g sodium acetate, anhydrous 41mg,, dehydrated alcohol 100mL, water 30mL, backflow 24h. ethyl acetate 300 points of three extractions, merge organic layer, the dry 30min of anhydrous MgSO4, low pressure is revolved except ethyl acetate obtains residue, light yellow crystal 5 is obtained with ethyl alcohol recrystallization, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 2.5g, yield 32.3%.
Step 5 adds 5 in 1000mL round-bottomed flask, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 2.5g, dehydrated alcohol 200mL, 3mol/lHCl50mL, backflow 1h. is cooled to room temperature, with ethyl acetate 300ml extraction, merges organic layer, the dry 40min of anhydrous MgSO4, decompression evaporates ethyl acetate, and resistates obtains off-white color solid eriodictyol 2.15g through ethyl alcohol recrystallization, yield 90%.
Embodiment 5
Step 1 adds Isovanillin 12.16g in 1000mL round-bottomed flask, sodium methylate 0.432g acetone 150mL, and stirring at room temperature 1h, then adds methylcarbonate 27g, continues to stir 4h. and to add water 150mL, with 500ml extraction into ethyl acetate three times, merges organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining greenish yellow solid is crude product 3-methoxy methoxy base-4-methoxybenzaldehyde 10.58g, yield 85%.
Step 2 adds 2,4,6-trihydroxy-acetophenone 27.3g in 1000ml round-bottomed flask, K 2cO 3124.5g, acetone 150mL, stirring at room temperature 1h, then add MOMCl34.2ml, continues to stir 4h. and to add water 200mL, with ethyl acetate 500ml extraction, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and obtaining yellow solid is 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 19.93g, yield 73%.
Step 3 adds the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone crude product 19.93g obtained in step 2 in 1000mL round-bottomed flask, with the 3-methoxy methoxy base obtained in step 1-4-methoxybenzaldehyde crude product 10.58g, KOH16.8g, dehydrated alcohol 150mL, water 15mL, stirring at room temperature 48h. add trash ice 75g in reaction solution, pH=6 ~ 7 are neutralized to again with 3mol/LHCl, divide three extractions with ethyl acetate 500ml, merge organic layer, anhydrous Na 2sO 4dry 30min, decompression evaporates ethyl acetate, and residue ethyl alcohol recrystallization obtains yellow needle-like crystals 13.02g. yield 62.3%.
Step 4 adds the 2.-hydroxyl-4-methoxyl group-3 that step 3 obtains in 1000mL round-bottomed flask, 4., and 6.-methoxy methoxy base cinnamophenone 13.02g sodium acetate, anhydrous 6g,, dehydrated alcohol 150mL, water 50mL, backflow 24h. ethyl acetate 500 extracts, merge organic layer, the dry 30min of anhydrous MgSO4, low pressure is revolved except ethyl acetate obtains residue, light yellow crystal 5 is obtained with ethyl alcohol recrystallization, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 4g, yield 31.8%.
Step 5 adds 5 in 1000mL round-bottomed flask, 7,3.-dimethoxy methoxyl group-4.-melonia flavones 4g, dehydrated alcohol 300mL, 3mol/lHCl50mL, backflow 1h. is cooled to room temperature, with ethyl acetate 300ml extraction, merge organic layer, the dry 40min of anhydrous MgSO4, decompression evaporates ethyl acetate, and resistates obtains off-white color solid eriodictyol 3.68g yield 93% through ethyl alcohol recrystallization.

Claims (7)

1. a synthetic method for Eriodictyol, is characterized in that, comprises the following steps:
Step 1: by Isovanillin, sodium methylate and acetone mix and blend, then adds methylcarbonate and continues to stir, add water, be extracted with ethyl acetate to obtain 3-methoxy methoxy base-4-methoxybenzaldehyde;
Step 2: by 2,4,6-trihydroxy-acetophenone, K 2cO 3with acetone mix and blend, then add MOMCl and continue to stir, add water, be extracted with ethyl acetate to obtain 2-hydroxyl-4-methoxy methoxy base-6-acetophenone;
Step 3: by the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone of the 3-methoxy methoxy base-4-methoxybenzaldehyde of step 1 gained, step 2 gained; , KOH, dehydrated alcohol and water mix and blend, on the rocks, with hydrochloric acid neutralization, then be extracted with ethyl acetate, obtain 2-hydroxyl-4-methoxyl group-3,4,6-methoxy methoxy base cinnamophenone;
Step 4: by 2-hydroxyl-4-methoxyl group-3,4, the 6-methoxy methoxy base cinnamophenone of gained, sodium acetate, anhydrous, dehydrated alcohol and water back flow reaction, obtain 5,7,3-dimethoxy methoxyl group-4-melonia flavones;
Step 5: by 5,7,3-dimethoxy methoxyl group-4-melonia flavones of gained, dehydrated alcohol and hydrochloric acid reflux, obtain Eriodictyol.
2. the synthetic method of Eriodictyol according to claim 1, it is characterized in that, described step 1 is specifically: by Isovanillin, sodium methylate and acetone mix and blend, then add methylcarbonate to continue to stir, add water, be extracted with ethyl acetate, merge organic phase, drying treatment, decompression evaporates ethyl acetate, obtains 3-methoxy methoxy base-4-methoxybenzaldehyde; The mass ratio of described Isovanillin, sodium methylate, acetone and methylcarbonate is 1:0.03-0.05:5-8:1-1.2.
3. the synthetic method of Eriodictyol according to claim 1, is characterized in that, described step 2 specifically: by 2,4,6-trihydroxy-acetophenone, K 2cO 3with acetone mix and blend, then add MOMCl and continue to stir, add water, be extracted with ethyl acetate, merge organic phase, drying treatment, decompression evaporates ethyl acetate, obtains 2-hydroxyl-4-methoxy methoxy base-6-acetophenone; Described 2,4,6-trihydroxy-acetophenones, K 2cO 3, to obtain mass ratio be 1:4.5-4.8:4-5:1.2-1.5 for acetone and MOMCl.
4. the synthetic method of Eriodictyol according to claim 1, it is characterized in that, described step 3 is specifically: by the 2-hydroxyl-4-methoxy methoxy base-6-acetophenone of the 3-methoxy methoxy base-4-methoxybenzaldehyde of step 1 gained, step 2 gained, KOH, dehydrated alcohol and water mix and blend, on the rocks, PH=6 ~ 7 are neutralized to 3mol/L hydrochloric acid, be extracted with ethyl acetate again, merge organic phase, drying treatment, decompression evaporates ethyl acetate, residue ethyl alcohol recrystallization, obtains 2-hydroxyl-4-methoxyl group-3,4,6-methoxy methoxy base cinnamophenone; Described 3-methoxy methoxy base-4-methoxybenzaldehyde, 2-hydroxyl-4-methoxy methoxy base-6-acetophenone, KOH, dehydrated alcohol and quality are than being 1:1.2-1.3:0.5-0.6:4-5:0.5.
5. the synthetic method of Eriodictyol according to claim 1, it is characterized in that, described step 4 specifically: by the 2-hydroxyl-4-methoxyl group-3,4 of gained, 6-methoxy methoxy base cinnamophenone, sodium acetate, anhydrous, dehydrated alcohol and water back flow reaction, be extracted with ethyl acetate, merge organic layer, drying treatment, low pressure is revolved except ethyl acetate obtains residue, 5,7,3-dimethoxy methoxyl group-4-melonia flavones is obtained with ethyl alcohol recrystallization; Described 2-hydroxyl-4-methoxyl group-3,4,6-methoxy methoxy base cinnamophenone, sodium acetate, anhydrous, dehydrated alcohol mass ratio are 1:0.001-0.005:1.5-3:0.5-0.8.
6. the synthetic method of Eriodictyol according to claim 1, it is characterized in that, described step 5 is specifically: by 5,7,3-dimethoxy methoxyl group-4-melonia flavones of gained, dehydrated alcohol and hydrochloric acid reflux, be cooled to room temperature, extraction into ethyl acetate, merges organic layer, drying treatment, decompression evaporates ethyl acetate, and resistates obtains Eriodictyol through ethyl alcohol recrystallization; The mass ratio of described 5,7,3-dimethoxy methoxyl group-4-melonia flavones, dehydrated alcohol and hydrochloric acid is 1:5-8:15-18.
7. according to the synthetic method of the arbitrary described Eriodictyol of claim 2-6, it is characterized in that: the drying treatment in described step 1-5 adopts anhydrous MgSO4 dry.
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Cited By (3)

* Cited by examiner, † Cited by third party
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CN105886568A (en) * 2016-04-22 2016-08-24 浙江大学 Method for obtaining eriodictyol by biologically transforming naringenin
CN106619679A (en) * 2016-12-21 2017-05-10 郑州莉迪亚医药科技有限公司 Western medicine composition for treating wangbi and preparing method and application thereof

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