CN1793137A - Process for semi-synthesizing of apiolin - Google Patents

Process for semi-synthesizing of apiolin Download PDF

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CN1793137A
CN1793137A CN 200510097010 CN200510097010A CN1793137A CN 1793137 A CN1793137 A CN 1793137A CN 200510097010 CN200510097010 CN 200510097010 CN 200510097010 A CN200510097010 A CN 200510097010A CN 1793137 A CN1793137 A CN 1793137A
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apigenin
alcohol
synthetic method
naringenin
aqueous systems
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CN100371335C (en
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闫卫东
曹丹
邵云东
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Zhejiang Skyherb Biotechnology Inc
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Zhejiang University ZJU
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Abstract

The invention discloses a semi compounding method for apium celery element that uses natural extract as basic raw material. It uses pomelo peel element as raw material, 1, 4-dioxy cyclohexane as reaction solvent, taking oxidative dehydrogenation reaction with iodine to form raw apium celery element. Taking multi-steps recrystallizing, the refined apium celery element would be gained. The invention is easy to operate, stable reacting condition, easy to control. The yield would be 60-70% and the purity could be over 97%. And it is low cost, no harmful to the environment.

Description

The semisynthesis of apigenin
Technical field
The present invention relates to a kind of is the semisynthesis of the apigenin of basic raw material with the natural extract.
Background technology
Apigenin (apigenin) belongs to chromocor compound, at samphire celery (Apium graveolensvar.dulce) leaf; Selaginaceae Selaginella tamariscina (Selaginella tamariscina) herb; Content in Cupressaceae Chinese juniper (Sabinachinensis) leaf is abundanter.
Apigenin is present in the various plants with the form of plant yellow pigment, and pure product outward appearance is a yellow powder, and nothing is smelt tasteless.It is natural antioxidants.Chemistry is called 5,7, and 4 '-trihydroxyflavone, molecular formula and molecular weight are C 15H 10O 5With 270.25,347.5 ℃ of fusing points, water-soluble hardly, be slightly soluble in hot alcohol, be dissolved in rare KOH solution.
Its structure is as follows:
Figure A20051009701000031
Bibliographical information, celery have the effect of protection action of the heart and treatment Parkinson's disease, can step-down and influence nervus centralis.Apigenin is antiviral in addition, inhibitory enzyme activity, and Green Tea Extract absorbs action of ultraviolet ray.Industrial to the preparation of apigenin generally is to realize by the extraction of plant or other modes are extracted.The extraction agent of plant extract is generally methyl alcohol and ethanol, such as utilizing methyl alcohol leaching Glossy Privet Fruit apigenin and other flavonoids effective constituents (Xiong Yuhui, the research of flavone component in the Glossy Privet Fruit, Hubei Normal University's journal, 1999,6 (21), 59-62), perhaps utilize the tip of a leaf (Redaelli, C.Extractive process for preparing apigenin, 1982 of 30% aqueous ethanolic solution continuous extraction Bulgaria camomile, USP4,313,880), obtain very pure apigenin.Because the content of apigenin in the middle of natural phant is low, low extraction yield, high energy consumption, expensive, be difficult to satisfy the growing market requirement.1981, employing alkaline buffer solutions such as H.HARTNER add the iodine system, with naringenin as reactant, with corresponding buffered soln as solvent, with iodine as the oxydehydrogenation agent, reacted 12 hours, the productive rate of the apigenin that obtains is about 50%, and by product is (Voigtlaender a lot, H.W.The conversion of flavanones to flavones, proceeding of the Bioflavonoid Symposium, Munich, 1981).As seen this method has also lost the value of suitability for industrialized production, and technology and complexity thereof, and production cost is higher.Also have report to be dissolved in the central reaction of pyridine with naringenin and iodine at present, the apigenin yield is better, and purity is also higher, but the pyridine price is higher, increase production cost, and it is to the disagreeableness smell of human body, is unfavorable for industrial carrying out.
Summary of the invention
The purpose of this invention is to provide a kind of is raw material with the natural plant extracts, and cost is low, is suitable for the semisynthesis of the apigenin of suitability for industrialized production.
The semisynthesis of apigenin is characterized in that under alkaline environment, with naringenin as raw material, at solvent 1, in the 4-dioxy hexanaphthene, under 50～130 ℃ of temperature and Iod R, oxydehydrogenation generates the apigenin crude product, and crude product dissolves with alkaline solution, adds alcohol, regulate pH value 4～7, separate out crystal, suction filtration, with methyl-sulphoxide/aqueous systems or dimethyl formamide/aqueous systems or alcohol/aqueous systems recrystallization, leave standstill, filter, obtain the purified apigenin; Perhaps reflux and purify, obtain refining apigenin with acetone.
Among the present invention, said alkaline environment is that mass percent concentration is 0.05%～1% potassium hydroxide or sodium hydroxide.The consumption of iodine is 0.5～1.5 times of naringenin mole number.Naringenin and solvent 1, the consumption of 4-dioxy hexanaphthene is 1: 3～1: 20 by the mass/volume ratio.Preferable reaction temperature is 70～115 ℃.Said alcohol can be to contain the monohydroxy-alcohol that carbon number is C1～C6, dibasic alcohol or trivalent alcohol.Said ketone can be to contain monoketone or the diketone that carbon number is C1～C6.
The present invention is that the natural extract with biologically active is that the starting raw material reaction obtains apigenin.Obtain the reacting phase ratio of apigenin with the plant extract method with pyridine as solvent, this method cost is low, and the reaction conditions gentleness is environmentally friendly, and product purity and yield are all higher; The solvent system that adopts in the acid hydrolysis process, raw material are easy to get and low price, easy control of reaction conditions, and safety, pollution-free, the productive rate height.From entire synthesis process, most of solvent can reclaim, and utilizes again, and 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.The apigenin purity that makes can reach more than 97%.
Inventive principle is as follows:
Method: the naringenin oxidation obtains apigenin
Embodiment
Further specify the present invention below in conjunction with embodiment.
Embodiment 1 is with the 40g naringenin, and 0.5g sodium hydroxide and 30.48g iodine are dissolved in 400ml 1, and in the 4-dioxy hexanaphthene, 6 hours (120 ℃) reflux.Concentration of reaction solution adds 700ml water to 100ml, leaves standstill suction filtration.The thick product apigenin that obtains fully dissolves with 600ml 5%NaOH solution, adds methyl alcohol again, and adjusting the pH value with hydrochloric acid is 6, separates out a large amount of crystal, suction filtration.With the 150ml acetone above gained apigenin of reflux purifying, filtration drying, obtain 24g purity and be 98.2% apigenin, yield 60%.
Embodiment 2:
With the 40g naringenin, 0.7g potassium hydroxide and 38.10g iodine are dissolved in 500ml 1, and in the 4-dioxy hexanaphthene, 100 ℃ of waters bath with thermostatic control were reacted 8 hours.Concentration of reaction solution adds 700ml water to 120ml, leaves standstill suction filtration.The thick product apigenin that obtains fully dissolves with 10%KOH solution 500ml, adds 800ml glycerine again, adjusts the pH value with hydrochloric acid and is about 5, separates out a large amount of crystal, suction filtration.Be washed to neutrality, drying.With the dissolving of 150ml dimethyl formamide, add water, precipitation.Obtain 28g purity after the drying and be 98.5% apigenin, yield 65.4%.
Embodiment 3:
With the 40g naringenin, 0.5g potassium hydroxide and 38.10g iodine are dissolved in 300ml 1, in the 4-dioxy hexanaphthene, and 50 ℃ of waters bath with thermostatic control.Concentration of reaction solution adds 600ml water to 100ml, leaves standstill suction filtration.The thick product apigenin that obtains fully dissolves with 3%NaOH solution 800ml, adds 800ml ethanol again, and adjusting the pH value with hydrochloric acid is 6, separates out a large amount of crystal, suction filtration.Be washed to neutrality, drying.With the dissolving of 150ml methyl-sulphoxide, filter, add water, precipitation.Get the 20g apigenin, its purity is 97.8%, yield 50%.
Embodiment 4:
With the 40Kg naringenin, 500g sodium hydroxide and 38.1Kg iodine are dissolved in 450L 1, in the middle of the 4-dioxy hexanaphthene, reflux and stir 8 hours, and concentration of reaction solution adds 800L water to 100L, leaves standstill filtration.Obtain to such an extent that apigenin fully dissolves with 5%NaOH solution 500L, add 800L ethanol again, adjust pH=6, separate out a large amount of crystal, suction filtration with hydrochloric acid.Repeat recrystallization method among the embodiment 1 with NaOH, obtain 35Kg apigenin crude product.With 100L 1,4-dioxy hexanaphthene fully dissolves, and adds 1000L water, filtering-depositing.Obtain apigenin after drying, obtain the about 28Kg of apigenin, purity is 97.5%, yield 70%.

Claims (7)

1. the semisynthesis of apigenin is characterized in that under alkaline environment, with naringenin as raw material, at solvent 1, in the 4-dioxy hexanaphthene, under 50～130 ℃ of temperature and Iod R, oxydehydrogenation generates the apigenin crude product, and crude product dissolves with alkaline solution, adds alcohol, regulate pH value 4～7, separate out crystal, suction filtration, with methyl-sulphoxide/aqueous systems or dimethyl formamide/aqueous systems or alcohol/aqueous systems recrystallization, leave standstill, filter, obtain the purified apigenin; Perhaps reflux and purify, obtain refining apigenin with acetone.
2. apigenin synthetic method according to claim 1 is characterized in that said alkali is that mass percent concentration is 0.05%～1% potassium hydroxide or sodium hydroxide.
3. apigenin synthetic method according to claim 1, the consumption that it is characterized in that iodine are 0.5～1.5 times of naringenin mole number.
4. apigenin synthetic method according to claim 1 is characterized in that naringenin and solvent 1, and the consumption of 4-dioxy hexanaphthene is 1: 3～1: 20 by the mass/volume ratio.
5. apigenin synthetic method according to claim 1 is characterized in that temperature of reaction is 70～115 ℃.
6. apigenin synthetic method according to claim 1 is characterized in that said alcohol is to contain the monohydroxy-alcohol that carbon number is C1～C6, dibasic alcohol or trivalent alcohol.
7. apigenin synthetic method according to claim 1 is characterized in that said ketone is to contain monoketone or the diketone that carbon number is C1～C6.
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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102367245A (en) * 2011-11-30 2012-03-07 中国药科大学 Apigenin amorphous compound and preparation method thereof
CN103772336A (en) * 2014-02-23 2014-05-07 闻永举 Semi-synthesis method of phenolic hydroxyl flavonoid compounds and iodine recycling method
CN113557234A (en) * 2020-06-19 2021-10-26 邦泰生物工程(深圳)有限公司 Semi-synthesis method of apigenin

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP3215787B2 (en) * 1995-11-08 2001-10-09 日本たばこ産業株式会社 Tobacco flavor enhancer
CN1544427A (en) * 2003-11-20 2004-11-10 黑龙江大学 Luteolin semi-synthesis method
CN1640872A (en) * 2004-01-14 2005-07-20 南京莱尔生物化工有限公司 Novel semi-synthetic versulin preparing process
CN1687054A (en) * 2005-03-23 2005-10-26 浙江大学 Method for preparing compound of luteolin

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102367245A (en) * 2011-11-30 2012-03-07 中国药科大学 Apigenin amorphous compound and preparation method thereof
CN103772336A (en) * 2014-02-23 2014-05-07 闻永举 Semi-synthesis method of phenolic hydroxyl flavonoid compounds and iodine recycling method
CN103772336B (en) * 2014-02-23 2016-08-31 闻永举 Phenolic hydroxyl group flavone compound semisynthesis and iodine recovery method
CN113557234A (en) * 2020-06-19 2021-10-26 邦泰生物工程(深圳)有限公司 Semi-synthesis method of apigenin
WO2021253361A1 (en) * 2020-06-19 2021-12-23 邦泰生物工程(深圳)有限公司 Semi-synthesis method for apigenin
CN113557234B (en) * 2020-06-19 2023-12-01 邦泰生物工程(深圳)有限公司 Semi-synthesis method of apigenin

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