CN101519342A - Novel method for synthesizing Resveratrol by means of organic zinc halide reagent - Google Patents
Novel method for synthesizing Resveratrol by means of organic zinc halide reagent Download PDFInfo
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- CN101519342A CN101519342A CN200910021800A CN200910021800A CN101519342A CN 101519342 A CN101519342 A CN 101519342A CN 200910021800 A CN200910021800 A CN 200910021800A CN 200910021800 A CN200910021800 A CN 200910021800A CN 101519342 A CN101519342 A CN 101519342A
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Abstract
The invention discloses a novel method for synthesizing Resveratrol by means of organic zinc halide reagent. The method comprises the following steps: firstly, carrying out reaction between 4-substituent benzyl bromide and activated zinc powder for 0.5 to 1 hour at normal temperature to prepare 4-substituent zinc benzyl bromide; secondly, carrying out reaction between 4-substituent zinc benzyl bromide and 3,5-disubstituent benzaldehyde for 7 to 8 hours, at a temperature between 30 DEG C below zero and normal temperature, in the presence of Lewis acid and catalysts, and hydrolyzing the reaction product by a saturated ammonium chloride solution to obtain Resveratrol derivative after extraction, drying and separation; and finally, hydrolyzing the Resveratrol derivative to obtain the object product. The novel method adopts most commonly used chemical materials and auxiliary agents, so raw materials are easily obtained and the cost is low; moreover, the method has the advantages of simple synthesis steps, short process route, high total yield and single synthesis product; meanwhile, the method does not cause pollution in the whole synthesis process and is environment-friendly.
Description
Technical field
The invention belongs to chemosynthesis technical field, relate to a kind of synthetic method for preparing trans-resveratrol, relate in particular to a kind of novel method of synthesizing Resveratrol by means of organic zinc halide reagent.
Background technology
Trans-resveratrol has multiple pharmacologically active; as antibiotic, anti-oxidant, preventing heart disease, anticancer, anti-platelet aggregation, protection liver, estrogen effect, radioprotective, immunomodulatory, anti-AIDS activity etc., also can repair the cell DNA damage due to the atypical pneumonia prescription.Trans-resveratrol can suppress the activity of plurality of enzymes or cytokine, as suppressing leukotriene B
4Generate and rise antiphlogistic effects, the inhibition PGH
2Synthetic enzyme, go back oxygenase I, protein kinase, tyrosine oxidase, ribonucleotide reductase, tumour necrosis factor etc. and play antitumor action.Particularly importantly trans-resveratrol has no infringement to normal human body cell, and good pharmacologically active is arranged, and probably is developed to a kind of curative effect height, the little new drug of side effect.
Obtain trans-resveratrol at present and mainly contain three kinds of approach: (1) is the plant extract method.This method influence ecological environment, cost height, throughput are little etc.; (2) be biological fermentation process or transgenosis method.The required enzyme that this method production cycle is long, process is complicated and be difficult for making; (3) be chemical synthesis.Chemical synthesis is concluded the three kinds of methods that mainly contain, i.e. Witting reaction, Heck reaction and Perkin reaction.The simple gentleness of Witting reaction conditions, raw material are easy to get, but route is long, consumption is big, cost is high, pollution is big, and the product of its generation is the cis-trans diolefine, and product is complicated; The Heck reaction scheme is short, and the product configuration is single, but raw material must be difficult to obtain through polystep reaction; The Perkin reaction scheme is long, and cost is higher.
Summary of the invention
The object of the present invention is to provide a kind of raw material to be simple and easy to, reaction scheme is short, the reaction product single novel method of utilizing synthesizing Resveratrol by means of organic zinc halide reagent.
The present invention utilizes the novel method of synthesizing Resveratrol by means of organic zinc halide reagent, comprises following processing step:
(1) preparation of Verakanol derivative: with the tetrahydrofuran (THF) is solvent, 4-substituting group cylite and activated zinc powder is reacted at normal temperatures be prepared into 4-substituting group cylite zinc in 0.5～1 hour; Make 4-substituting group cylite zinc and 3 again, the disubstituted phenyl aldehyde of 5-under the effect of Lewis acid, catalyzer, in-30 ℃～normal-temperature reaction 7～8 hours, reaction product saturated ammonium chloride solution hydrolysis, extraction, dry, separate promptly.Its building-up reactions formula is as follows:
Wherein, substituting group P is an ethanoyl.
The mol ratio of described activated zinc powder and 4-substituting group cylite is 1:0.5～1:0.35; Described 4-substituting group cylite, 3, the mol ratio of the disubstituted phenyl aldehyde of 5-, Lewis acid, catalyzer is (1:2.25:1.25:0.02)～(1:3.5:1.5:0.05).
The Lewis acid that the present invention adopts is trimethylchlorosilane, titanium tetrachloride, iron trichloride or aluminum chloride; Catalyzer is acetylacetonate nickel, triphenyl phosphorus Palladous chloride, triphenyl phosphorus nickelous chloride or triphenyl phosphorus cobalt chloride.
(2) preparation of target compound trans-resveratrol
Verakanol derivative is dissolved in the tetrahydrofuran (THF), add anhydrous methanol, add sodium methylate again, stirring reaction solvent evaporated after 4～5 hours under nitrogen protection, regulate pH value to 1～4 with dilute hydrochloric acid, with using anhydrous magnesium sulfate drying behind the ethyl acetate extraction, solvent evaporated gets faint yellow solid again, and the mixture recrystallization with the first alcohol and water obtains target compound again; The add-on of sodium methylate is 3.0～3.3 times of Verakanol derivative molar weight; The add-on of described anhydrous methanol is 2～3 times of Verakanol derivative molar weight; The volume ratio of methyl alcohol and water is 1:1～1:1.2 in the mixture of first alcohol and water.Its reaction formula is as follows:
The trans-resveratrol of the present invention's preparation detects by infrared spectrogram, hydrogen nuclear magnetic resonance wave spectrogram, nuclear magnetic resonance of carbon wave spectrogram, and its characterization data conforms to bibliographical information, shows that the target compound trans-resveratrol synthesizes successfully.
The present invention compared with prior art has the following advantages and beneficial effect:
1, the inventive method synthetic trans-resveratrol, product is single, and the product purity height can reach 98%;
2, the present invention adopts the most frequently used chemical feedstocks and auxiliary agent, and raw material is easy to get or easily purchases, and cost is lower, for good condition is created in the commercial scale production and the commercialization of product;
3, synthesis step of the present invention is simple, operational path short, and the relative prior art of overall yield is compared higher (productive rate of prior art is generally 30～41%, and productive rate of the present invention can reach 48%);
4, the advantages of nontoxic raw materials of the present invention's employing, production process is pollution-free, and is environmentally friendly.
Embodiment
The present invention is described further below by specific embodiment.
(1) Verakanol derivative---(E)-3, the preparation of 5-diacetoxy-4 '-acetoxy diphenyl ethylene
At the bottom of three necks of constant pressure funnel 100ml are housed, in the flask, add the 0.17g zinc powder, use nitrogen protection, add 5 trimethylchlorosilane activation, make solvent, stirred at normal temperatures 5 minutes with the 1ml tetrahydrofuran (THF).The zinc powder activation finishes.The mixed solution of 0.63g 4-acetoxyl group cylite and 5ml tetrahydrofuran (THF) is slowly splashed under the ice bath cooling, drip off the back and continue to stir at normal temperatures 40 minutes, make 4-acetoxyl group cylite zinc.
Other gets flask at the bottom of three necks that constant pressure funnel 100ml is housed, and adds 0.1g triphenyl phosphorus Palladous chloride (Pd (PPh
3)
2Cl
2), make solvent with the 2ml tetrahydrofuran (THF), the above-mentioned 4-acetoxyl group cylite zinc that makes is slowly splashed into, dripping off the back continues to stir 10 minutes, bathe cooling with cryosel, add 0.40g 3,5-diacetoxy phenyl aldehyde, 0.6ml trimethylchlorosilane, 5ml tetrahydrofuran (THF) mixed solution.Drip off the back and continue to stir 8 hours, get blackish green liquid, add the hydrolysis of 5ml saturated ammonium chloride solution, add the 5ml ether simultaneously, stirred 15 minutes.With 5ml * 3 extracted with diethyl ether, merge organic phase, use anhydrous magnesium sulfate drying.With the chromatography silica gel post separate to purify (sherwood oil: ethyl acetate=8:1), the white plates crystal be Verakanol derivative---(E)-3,5-diacetoxy-4 '-acetoxy diphenyl ethylene, fusing point, 116～118 ℃, productive rate, 67%.
Its reaction formula is as follows:
(2) trans-resveratrol---(E)-3, the preparation of 5-dihydroxyl-4 '-hydroxy stibene
With 0.8g (E)-3; 5-diacetoxy-4 '-acetoxy diphenyl ethylene is dissolved in the two mouthfuls of flasks of 50ml of packing in the 10ml tetrahydrofuran (THF); add the 10ml anhydrous methanol; after add the 0.4g sodium methylate in batches; under nitrogen protection, stirred 4～5 hours; back solvent evaporated adds an amount of water; splashing into dilute hydrochloric acid at turbid, to make pH value be 3, uses ethyl acetate extraction again, the organic solvent anhydrous magnesium sulfate drying; the faint yellow solid of evaporate to dryness; with mixed solution (volume ratio of first alcohol and water the is 1:1) recrystallization of first alcohol and water, get target product (E)-3,5-dihydroxyl-4 '-hydroxy stibene 0.35g; fusing point: 255～257 ℃, productive rate 76%.Its reaction formula is as follows:
(E)-3 of present embodiment preparation, the spectral data of 5-dihydroxyl-4 '-hydroxy stibene characterizes as follows:
1HNMR(400MHz，CDCl
3)：δ(Hz)：9.55(s，1H，4’-OH)，9.21(s，2H，3，5-OH)，7.38(dd，2H，J＝8.4，2’，6’-H)，6.95(d，1H，Jtrans＝16.2，H-β)6.80(d，1H，Jtrans＝16.2，H-α)，6.74(dd，2H，J＝8.1，H-3’and?H-5’)，6.39(d，2H，H-2，6)，6.12(t，1H，J＝2.1，4-H)。
13CNM(400MHz，DMSO)：δ＝158.5，157.2，139.2，128.0，127.8，125.6，115.5，104.3，01.7
IR (KBr): v (cm
-1)=3230.76 (broad peak), 1585.86 (s), 1508.33 (s), 1381.03 (s), 1325.27 (s), 1263.37 (d), 1148.64 (s), 962.54 (s), 829.39 (s).
Claims (4)
1, a kind of novel method of synthesizing Resveratrol by means of organic zinc halide reagent comprises following processing step:
(1) preparation of Verakanol derivative: be to be solvent with the tetrahydrofuran (THF), 4-substituting group cylite and activated zinc powder are reacted at normal temperatures be prepared into 4-substituting group cylite zinc in 0.5～1 hour; Make 4-substituting group cylite zinc and 3 again, the disubstituted phenyl aldehyde of 5-under the effect of Lewis acid, catalyzer, in-30 ℃～normal-temperature reaction 7～8 hours, reaction product saturated ammonium chloride solution hydrolysis, extraction, dry, separate the derivative of trans-resveratrol; The mol ratio of described zinc powder and 4-substituting group cylite is 1:0.5～1:0.35; Described 4-substituting group cylite, 3, the mol ratio of the disubstituted phenyl aldehyde of 5-, Lewis acid, catalyzer is (1:2.25:1.25:0.02)～(1:3.5:1.5; 0.05).
(2) preparation of trans-resveratrol: Verakanol derivative is dissolved in the tetrahydrofuran (THF), add anhydrous methanol, add sodium methylate again, stirring reaction solvent evaporated after 4～5 hours under nitrogen protection, regulate pH value to 1～4 with dilute hydrochloric acid, with using anhydrous magnesium sulfate drying behind the ethyl acetate extraction, solvent evaporated gets faint yellow solid again, and the mixture recrystallization with the first alcohol and water obtains target compound again; The add-on of sodium methylate is 3.0～3.3 times of Verakanol derivative molar weight; The add-on of described anhydrous methanol is 2～3 times of Verakanol derivative molar weight; The volume ratio of methyl alcohol and water is 1:1～1:1.2 in the mixture of first alcohol and water.
2, as the novel method of claim 1 synthesizing Resveratrol by means of organic zinc halide reagent, it is characterized in that: described substituting group is an ethanoyl.
3, as the novel method of claim 1 synthesizing Resveratrol by means of organic zinc halide reagent, it is characterized in that: described Lewis acid is trimethylchlorosilane, titanium tetrachloride, iron trichloride or aluminum chloride.
4, as the novel method of claim 1 synthesizing Resveratrol by means of organic zinc halide reagent, it is characterized in that: described catalyzer is acetylacetonate nickel, triphenyl phosphorus Palladous chloride, triphenyl phosphorus nickelous chloride, triphenyl phosphorus cobalt chloride.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101693642B (en) * | 2009-10-17 | 2013-01-23 | 西北师范大学 | Method for synthesizing 1,2-diphenylethylene compounds |
| CN109970517A (en) * | 2019-04-28 | 2019-07-05 | 杭州瑞树生化有限公司 | A kind of preparation method of resveratrol compounds |
-
2009
- 2009-03-17 CN CN200910021800A patent/CN101519342A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101693642B (en) * | 2009-10-17 | 2013-01-23 | 西北师范大学 | Method for synthesizing 1,2-diphenylethylene compounds |
| CN109970517A (en) * | 2019-04-28 | 2019-07-05 | 杭州瑞树生化有限公司 | A kind of preparation method of resveratrol compounds |
| CN109970517B (en) * | 2019-04-28 | 2021-09-17 | 杭州师范大学 | Preparation method of resveratrol compound |
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