CN105085267A - Synthetic method for salvianolic acid A - Google Patents
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Abstract
The invention provides a synthetic method for salvianolic acid A. The synthetic method is characterized by comprising a step of subjecting a salvianolic acid A synthetic precursor (10) to demethylation so as to prepare salvianolic acid A. A synthetic route is described in the specification. The prepared salvianolic acid A has a purity of 90 to 94%; and the purity of the prepared salvianolic acid A can be increased to 97% after preparative HPLC purification.
Description
Technical field
The present invention relates to medicinal chemistry art, in particular to the synthetic method of salvianolic acid A.
Background technology
Salviamiltiorrhizabung is the dried roots of Labiatae (Labiatae) Salvia (Salvia) the plant red sage root (SalviamiltiorrhizaBunge).Bitter, cold nature, the red sage root is one of the most frequently used medicinal material, be used for the treatment of the cardiovascular and cerebrovascular diseases such as stenocardia, hypertension, coronary heart disease and apoplexy, having invigorating blood circulation addiction, nourishing blood to tranquillize the mind, cool blood row's carbuncle and effect of toxin expelling myogenic, is the conventional flavour of a drug of invigorating blood circulation of Chinese medicine addiction.Clinical study also confirms, the red sage root contains number of chemical composition and has biological activity widely, and its traditional pharmacology is to expand blood vessel, promoting blood circulation and removing blood stasis, and it is main for improving microcirculation.Modern pharmacological research shows, the red sage root still has antitumor, antisepsis and anti-inflammation, antiandrogen, suppresses hyperplasia of sebacous glands, anti-liver cirrhosis, anti-fibrosis, promotes the multiple pharmacologically active such as tissue repair and regeneration.The chemical composition of the red sage root mainly can be divided into water soluble component and fat-soluble component, and wherein water-soluble components is mainly Salvianic acidA and salvianolic acid A, B, C, D, E etc., and red sage root water soluble ingredient has phenolic acid structure more.(Jiang Wende since domestic scholars obtains resisting myocardial ischemia composition Salvianic acidA first from Salvia miltiorrhiza Bge water extract, Salvianic acidA and another two kinds of water-soluble Components in Salvia miltiorrhizas resist myocardial ischemia and research to coronary artery effect, Shanghai first medical college journal, 1982, 9 (1): 13), within 1984, report again isolated another aqueous soluble active constituent-salvianolic acid A (LiLN from the red sage root first, TanR, ChenWM.SalvianolicacidA, anewdepsidefromrootsofSalviamiltiorrhiza [J] .PlantaMed, 1984, 50 (3): 227).Prove through pharmacological research for many years, salvianolic acid A has unique curative effect in treatment coronary heart diseases and angina pectoris.And have widely pharmacologically active (Yang Qin, Zhao Chaowei. red sage root pharmacological research present situation. Chinese medicine company, 2003,12 (10): 78), for clinical development new drug provides theoretical foundation.
It is reported salvianolic acid be most important activeconstituents in red sage root water soluble ingredient (Du Guanhua. Determination of water-soluble active constituents of radix--salvianolic acid progress, preclinical medicine and clinical, 2000,20 (5): 10-14).The highest with content of danshinolic acid B in Radix Salviae Miltiorrhizae total phenolic acids, therefore, the emphasis of people's exploitation concentrates on salvianolic acid B, and content is lower, active stronger salvianolic acid A (salvianolicacidA) is ignored because cannot carry out suitability for industrialized production by people.By consulting literatures, we can learn that the content of salvianolic acid A in the red sage root is about 5/10000ths, therefore, even if extracted by a series of method, can only obtain trace danshen root salvianolic acid A, be applied to clinical in, can not be accepted by patient because its price is too high; But danshen root salvianolic acid A has good pharmacologically active (Song Yan equality, salvianolic acid A and salvianolic acid B improve myocardial ischemia in rats effect and compare [J]. Chinese Chinese materia medica information magazine, 2007,14 (9): 36), can be applied in medicine, protective foods, therefore, a lot of medical personal wishes salvianolic acid A to carry out suitability for industrialized production, is developed as patent medicine preparation.
Because salvianolic acid A has anti-oxidant, ischemic myocardial protection, antithrombotic, neuroprotective, anti-hepatic fibrosis and prevent and treat the pharmacologically active such as diabetes and complication significantly, it is for many years the focus of researcher research always.Preparation method now for salvianolic acid A mainly extracts from crude drug.Wang Jinhui etc. disclose salviamiltiorrhizabung efficient part and sustained release preparation thereof and medicinal use and preparation method at CN1352985A, its active component of red sage root Radix Salviae Miltiorrhizae total phenolic acids content more than 90%, and salvianolic acid A content is more than 10%.Wang Jinhui etc. disclose preparation method and the medicinal use of SLA-A and composition thereof in salviamiltiorrhizabung at CN1397276A, and it has clear curative effect, and side effect is little, the feature of easy administration.Active component of red sage root A (SLA-A) its content is more than or equal to 90%.Zhu Changfu etc. disclose a kind of extracting method of salvianolic acid A at CN1830947A, by red rooted salvia water or ethanol-extracted, after extracting concentrated solution, adopt high-temperature high-voltage reaction, cross purification by column chromatography salvianolic acid A, again through adjust pH, with organic solvent extraction, concentrate drying, obtain salvianolic acid A, in extract, salvianolic acid A content can reach more than 80%, and can realize scale operation.Qu Haibin etc. disclose a kind of process for purification of salvianolic acid A at CN101353306A, adopt organic solvent extractionprocess extraction Salvia miltiorrhiza Bge water extract to obtain salvianolic acid A crude extract, extract decon with sour water, organic phase obtains high-purity danshinolic acid A through concentrating, after drying.The inventive method purifying rate of recovery reaches more than 95%, and the purity of salvianolic acid A reaches more than 90%.Sun Longru etc. provide medicinal material of a kind of salvianolic acid A high-content and its production and use in CN102793745A, with the red sage root or also make other vegetable drugs containing salvianolic acid B that the red sage root uses in different areas for raw material is by high temperature, high pressure, super-humid conditions process, the salvianolic acid B contained by medicinal material is hydrolyzed in plant tissue cell, sloughs a phenylpropyl alcohol acidic group and carboxyl, changes into salvianolic acid A.
The processing method of danshen root salvianolic acid A extraction purification is disclosed in existing document and patent, although can salvianolic acid A be obtained, but its emphasis is all placed on being separated how by danshen root salvianolic acid A and impurity, its extraction yield is very low, cannot realize in suitability for industrialized production, also cannot obtain the salvianolic acid A of " patent medicine " level, this is one difficulty of pendulum in face of a lot of researcher.
To extract from the red sage root material obtained be the mixture of water soluble component due to direct, purity is low, various interaction between component causes character unstable, oxidizable, and the content of salvianolic acid A is lower in the red sage root, in addition red sage root resource-constrained, extraction purification difficulty, these have impact on the quality of clinical application and the further exploitation of natural drug and sustainable utilization.So artificial complete synthesis salvianolic acid A and derivative thereof have certain learning value and practical significance.
Summary of the invention
In order to solve in prior art the problem being difficult to obtain salvianolic acid A from natural product, the invention provides a kind of method of synthesizing salvianolic acid A.
First the present invention has synthesized Segment A
then from rosmarinic acid, after methylating, hydrolysis obtains fragment B smoothly
segment A and B, through condensation, obtain the salvianolic acid A (intermediate 9) of seven methyl, and adopt trimethylammonium stannic hydroxide removing METH, purifying obtains intermediate 10, utilizes boron tribromide demethylation finally to obtain salvianolic acid A.Synthetic route is as follows:
Specifically, the invention provides a kind of synthetic method of salvianolic acid A, it is characterized in that, synthesize precursor (10) by salvianolic acid A and prepare salvianolic acid A through demethylating reaction, synthetic route is as follows:
In above-mentioned synthetic method, the detailed process of described demethylating reaction is: be dissolved in methylene dichloride by described salvianolic acid A synthesis precursor, at room temperature slowly add halid solution, stirring at room temperature is to having reacted, after aftertreatment, obtain salvianolic acid A by silicagel column and gel column purifying.
In above-mentioned synthetic method, wherein said halogenide is lithium iodide, lithium chloride, aluminum chloride, alchlor, hydride hydrogen, boron trifluoride, boron trichloride, boron tribromide, triiodide boron, trimethyl silicane iodine, dimethyl boron bromide, silicon tetrachloride, cerous compounds or diiodinating magnesium.
In above-mentioned synthetic method, wherein said halid solution is the solution of halogenide in methylene dichloride, trichloromethane, water, acetonitrile, ethanol or 1,2-ethylene dichloride.
In above-mentioned synthetic method, wherein, synthesize described salvianolic acid A by compound (A) and compound (B) and synthesize precursor (10), wherein compound (A) and compound (B) have following structural formula respectively:
In above-mentioned synthetic method, wherein by compound (A) and compound (B) synthesize described salvianolic acid A synthesize precursor (10) synthetic route as follows:
In above-mentioned synthetic method; wherein; the detailed process being prepared compound (9) by compound (A) and compound (B) is: compound (A), compound (B) and condensing agent are dissolved in dry chloroform under nitrogen protection; be stirred to reaction at ambient temperature to complete; through aftertreatment; cross silica column purification, vacuum-drying obtains compound (9).
In above-mentioned synthetic method, wherein, described condensing agent is DMAP/DCC, HOBt/EDCI or EDC/DMAP.
In above-mentioned synthetic method, wherein, by compound (9) prepare salvianolic acid A synthesize precursor (10) detailed process be: compound (9) and tin compound are added 1, in 2-ethylene dichloride, reflux 24 hours, be cooled to room temperature, dilute with the mixed solution of dilute hydrochloric acid and ethyl acetate, separatory, aqueous phase is extracted with ethyl acetate, and merges organic phase, with anhydrous magnesium sulfate drying, concentrated, silica column purification obtains salvianolic acid A synthesis precursor.
In above-mentioned synthetic method, wherein, described tin compound is trialkyl tin hydroxides, dialkyl group two stannic hydroxide or alkyl three stannic hydroxide.
The present invention devises the comparatively reasonably synthetic route of salvianolic acid A and prepares, and for providing a necessary basis and reference at the artificial complete synthesis salvianolic acid A of the further further investigation in this field, and provides production line for suitability for industrialized production.The purity of the salvianolic acid A that the present invention obtains is 90 ~ 94%, and this sample of 90 ~ 94% purity after preparation HPLC purifying can bring up to 97%.
Embodiment
Below by specific embodiment, the invention will be further described.
Following non-limiting example can make the present invention of those of ordinary skill in the art's comprehend, but does not limit the present invention in any way.
The synthesis of embodiment 1 compound 2
2, the 3-dimethoxy benzaldehydes (1) of 34.0g (0.21mol) are dissolved in the methyl alcohol of 120ml, do not stop to stir.The sodium borohydride taking 4.7g (0.124mol) adds in reaction solution in batches carefully.Then, at room temperature stir 1h, TLC analyzes, and reacts completely.Stopped reaction, revolves steaming and is removed by solvent methanol.Residue methylene dichloride dissolves, washing, saturated common salt water washing, anhydrous magnesium sulfate drying.Filter, except desolventizing, obtain light grey thick liquid, be settled into solid, the 34.0g that weighs (yield 99%).For subsequent use.
The synthesis of embodiment 2 compound 3
Taking 16.8g (0.1mol) 2,3-dimethoxy-benzyl alcohol (2) is dissolved in the methylene dichloride of 450ml, make it dissolve completely, and ice bath is cooled to 0 DEG C.The bromine of 17.6g (5.64ml) to be dissolved in the methylene dichloride of 50ml and to be placed in constant pressure funnel.The process dripped keeps temperature all the time lower than 5 DEG C, dropwises, start to remove ice bath, rise to room temperature after about 0.5h.The reaction of TLC monitoring at any time.After about 2h, react complete, at once the 1M sodium hydrogen carbonate solution of 100ml is added in solution, extraction, washing, saturated common salt water washing, anhydrous magnesium sulfate drying.Revolve and steam except desolventizing, obtain clear yellow viscous thing, recrystallization in methyl alcohol, obtains yellow crystals, filtration drying.Obtain 22g yellow solid, productive rate 71%.Mp74℃,1H-NMR(400MHz,CDCl3):3.88(3H,s),3.99(3H,s),4.73(2H,s),6.80(1H,d,J＝8.8Hz),7.29(1H,d,J＝8.8Hz)。
The synthesis of embodiment 3 compound 4
22g compound 3 is dissolved in the toluene of 500ml, and adds the triphenylphosphine of 18.6g, vigorous stirring.And start to be warming up to backflow, approximately stir after 10 minutes, solution starts to become muddy, creates white solid.After backflow 4h, be cooled to room temperature, have a large amount of white precipitates to generate, filter, vacuum-drying.Obtain the white solid of 38.5g, productive rate 95%.Mp169℃。1H-NMR(400MHz,CDCl3):3.75(s,3H),3.79(s,3H),5.16(d,2H,J＝14Hz),6.75(d,1H,J＝8.8Hz),7.05(d,1H,J＝8.8Hz),7.58-7.82(m,15H)。
The synthesis of embodiment 4 compound 5
The methanol solution of 18.6ml (5.4M) sodium methylate is placed in the methyl alcohol of 100ml drying, vigorous stirring.Be dissolved in by 57.2g compound 4 in the methyl alcohol of 200ml drying, dropping is entered simultaneously, stirs 0.5h.The Veratraldehyde of 16.6g is also dissolved in the methyl alcohol of 200ml drying and drips, after dropwising, and temperature rising reflux 5h.TLC analyzes.Except desolventizing, recrystallization in methyl alcohol, filters, dry, obtains 30.0g faint yellow solid.Mp80℃1H-NMR(400MHz,CDCl3):3.80(s,3H),3.89(s,3H),3.93(s,3H),3.98(s,3H),6.71(d,1H,J＝8.8Hz),6.90(d,1H,J＝8.8Hz),7.07(d,1H,J＝16.4Hz),7.09-7.13(m,2H),7.33(d,1H,J＝8.8Hz),7.39(d,1H,J＝16.4Hz)。
The synthesis of embodiment 5 compound 6
Under nitrogen protection, the compound 5 of 18.9g is dissolved in the THF of 200ml drying, and is cooled to-78 DEG C.N-Butyl Lithium (2.5M) solution of 40ml is slowly dripped in reaction solution, keeps reacting liquid temperature not higher than-70 DEG C, stir half an hour again after dripping, rise to-20 DEG C subsequently.The THF of DMF and the 100ml drying of 38.6ml drying mixing is added in reaction solution, then reacts half an hour.The 1MHCl aqueous solution of 200ml is added wherein, then stirs for some time.With the extraction into ethyl acetate of 3*200ml, merge organic phase, anhydrous sodium sulfate drying, revolve and steam the most of solvent of removing, leave standstill cooling, produce and precipitate in a large number, filtration drying.Concentrate filtrate after column purification (PE:ET=2:1), obtain 11.8g faint yellow solid altogether, productive rate is 72.1% again.1H-NMR(400MHz,CDCl3):3.84(s,3H),3.94(s,3H),3.97(s,3H),3.98(s,3H),6.77(d,1H,J＝16.4Hz),6.91(d,1H,J＝8.8Hz),6.98(d,1H,J＝8.8Hz),7.11-7.13(m,2H),7.43(d,1H,J＝16.4Hz),7.76(d,1H,J＝8.8Hz),10.13(s,1H)。
The synthesis of embodiment 6 Segment A
The compound 6 of 9.84g, the propanedioic acid of 9.36g and 30ml piperidines are all dissolved in 500ml pyridine, stirring reaction 5h under 100 DEG C of conditions.TLC analyzes, and now stop heating, be cooled to room temperature, most of pyridine removes by underpressure distillation.Add the hydrochloric acid of a large amount of 1M to pH=1.Extraction into ethyl acetate three times (3*200ml), merge organic phase, saturated common salt water washing, anhydrous magnesium sulfate drying, except desolventizing, obtains 8.0g yellow solid, productive rate 72%.Mp200℃；
1H-NMR(400MHz,CDCl
3):3.82(s,3H),3.93(s,3H),3.95(s,3H),3.97(s,3H),6.32(d,1H,J＝15.6Hz),6.70(d,1H,J＝16.4Hz),6.89(d,1H,J＝8.4Hz),6.91(d,1H,J＝8.4Hz),7.09(d,1H,J＝8.4Hz),7.11(s,1H),7.20(d,1H,J＝16.4Hz),7.43(d,1H,J＝8.4Hz),8.13(d,1H,J＝16.4Hz)。
The synthesis of embodiment 7 compound 8
The rosmarinic acid crude extract of 50g about 20%, after 500mL water dissolution, with 200mL extraction into ethyl acetate three times, 7.9 grams of crude products are obtained after concentrated, 700mL butanone is added in the round-bottomed bottle that above-mentioned 7.9g crude product is housed, add and add 30g Anhydrous potassium carbonate again, slowly drip 22mL methyl-sulfate, heat 85 DEG C of reactions 22 hours.TLC follows the tracks of, and raw material primitive reaction is complete.Cooling, suction filtration, after filtrate is concentrated, obtains 16.7g crude product.For subsequent use.Take a morsel to be separated and obtain oily matter, nuclear-magnetism confirms as pentamethyl-rosmarinic acid.
1H-NMR(400MHz,CDCl
3):3.11(m,2H),3.68(s,3H),3.79(s,3H),3.80(s,3H),3.84(s,6H),5.31,(m,1H),6.29(d,1H,J＝15.9Hz),6.75(m,3H),6.80(d,2H,J＝8.3Hz),6.91(s,1H),7.03(d,1H,J＝8.4Hz),7.60(d,1H,J＝15.9Hz)。
The synthesis of embodiment 8 fragment B
Get the thick product 18.0g of above-claimed cpd 8, add methyl alcohol 200mL and dissolve, then slowly add powdered sodium methoxide in batches, stirring at room temperature 2 hours, TLC analyzes, and primitive reaction is complete.Add saturated aqueous ammonium chloride 50mL, with 200mL extraction into ethyl acetate three times, dry concentrated after silica gel column chromatography be separated, obtain oily matter 4.8g, yield 48%.
1H-NMR(400MHz,CDCl
3):2.81(bs,1H),2.92(m,1H),3.01(m,1H),3.76(s,3H),3.83(s,3H),3.84(s,3H),4.41,(m,1H),6.74(m,3H)。
The synthesis of embodiment 9 compound 9
Under the condition of nitrogen protection, the EDC of the Salvianic acidA (compd B) of the compd A of 11.3g, 6.7g, DMAP and 23.3g of 18.4g is dissolved in the chloroform of 150ml drying, stirs 6 days at ambient temperature.TLC detects (PE:Et=2:1), and after completion of the reaction, add water raw material methyl protection Salvianic acidA extraction, saturated common salt water washing, anhydrous magnesium sulfate drying.Removed by chloroform after filtration, cross silica column purification (PE:Et=5:1 ~ 1:1), vacuum-drying obtains 13.0g yellow, viscous object, productive rate 75%.
1HNMR(400MHz,CDCl
3):8.01(1H,d),7.30(1H,d),7.12(1H,d),7.04(1H,s),7.02(1H,s),6.80(2H,m),6.64(4H,m),6.27(1H,d),5.29(1H,m),3.87(3H,s),3.82(6H,s),3.75(6H,s),3.74(3H,s),3.66(3H,s),3.06(2H,m)。
The synthesis of embodiment 10 compound 10
10g (17.3mmol) compound 9 and 15g (83mmol) trimethylammonium stannic hydroxide are added in reaction flask, add 1,2-ethylene dichloride (500mL), reflux 24 hours, be cooled to room temperature, dilute with the mixed solution of 1N dilute hydrochloric acid and ethyl acetate, separatory, aqueous phase is extracted with ethyl acetate 100mL*2.Merge organic phase, with anhydrous magnesium sulfate drying, concentrated.Silica gel column chromatography is separated, and obtains compound 106.5g, yield 67%.Nuclear-magnetism shows obvious carboxylic acid H, and product confirms.1HNMR(400MHz,DMSO-d6):12.5(bs,1H),7.88(1H,d,J＝16.0Hz),7.60(1H,d),7.24(1H,d),7.19(1H,d,J＝16.4Hz),7.09(2H,m),6.95(1H,d),6.82(1H,d),6.71(2H,m),6.56(1H,d,J＝16.4Hz),6.43(1H,d,J＝16.0Hz),5.51(1H,m),3.87(3H,s),3.81(3H,s),3.78(3H,s),3.71(3H,s),3.69(3H,s),3.66(3H,s),2.93-3.06(2H,m)。
The synthesis of embodiment 11 salvianolic acid A (SAA)
Be dissolved in 100mL methylene dichloride by 2.0g (3.5mmol) compound 10, then room temperature slowly adds the dichloromethane solution of boron tribromide, and stirring at room temperature four hours, reaction product pours NaHCO into
3in saturated solution, tune pH, to neutral, is extracted with ethyl acetate, dry concentrated, and the content obtaining brown thick liquid 0.7g, HPLC analysis salvianolic acid A is 25%.Use column chromatography, final acquisition 102mg faint yellow solid (yield 5.9%, HPLC purity is 94%).
1HNMR(MeOD,400MHz,δ,ppm)：2.96(1H,dd,J＝14.3,8.5Hz),3.07(1H,dd,J＝14.3,4.1Hz),5.18(1H,dd,J＝8.4,4.1Hz),6.29(1H,d,J＝15.8Hz),6.55(1H,dd,J＝8.04,1.60Hz),6.63(1H,d,J＝16.Hz),6.67(1H,d,J＝8.56Hz),6.74(1H,d,J＝2.0Hz),6.77(1H,d,J＝8.0Hz)6.78(1H,d,J＝8.0Hz),6.89(1H,dd,J＝8.16,1.56Hz),7.08(1H,d,J＝2.0Hz),7.12(1H,d,J＝8.32Hz),7.15(1H,d,J＝16.00Hz),8.06(1H,d,J＝15.80Hz)。Described collection of illustrative plates consistent with bibliographical information (Liu Shengsheng etc., herbal medicine, 2011,42,247-250).
Although illustrate and describe embodiments of the invention, for the ordinary skill in the art, be appreciated that and can carry out multiple change, amendment, replacement and modification to these embodiments without departing from the principles and spirit of the present invention, scope of the present invention is by claims and equivalents thereof.
Claims (10)
1. a synthetic method for salvianolic acid A, is characterized in that, synthesize precursor (10) by salvianolic acid A and prepare salvianolic acid A through demethylating reaction, synthetic route is as follows:
2. synthetic method according to claim 1, the detailed process of described demethylating reaction is: be dissolved in methylene dichloride by described salvianolic acid A synthesis precursor, at room temperature slowly add halid solution, stirring at room temperature is to having reacted, after aftertreatment, obtain salvianolic acid A by silicagel column and gel column purifying.
3. synthetic method according to claim 2, wherein said halogenide is lithium iodide, lithium chloride, aluminum chloride, alchlor, hydride hydrogen, boron trifluoride, boron trichloride, boron tribromide, triiodide boron, trimethyl silicane iodine, dimethyl boron bromide, silicon tetrachloride, cerous compounds or diiodinating magnesium.
4. synthetic method according to claim 3, wherein said halid solution is the solution of halogenide in methylene dichloride, trichloromethane, water, acetonitrile, ethanol or 1,2-ethylene dichloride.
5. the synthetic method according to any one of claim 1-4, wherein, synthesize described salvianolic acid A by compound (A) and compound (B) and synthesize precursor (10), wherein compound (A) and compound (B) have following structural formula respectively:
6. synthetic method according to claim 5, wherein by compound (A) and compound (B) synthesize described salvianolic acid A synthesize precursor (10) synthetic route as follows:
7. synthetic method according to claim 6; wherein; the detailed process being prepared compound (9) by compound (A) and compound (B) is: compound (A), compound (B) and condensing agent are dissolved in dry chloroform under nitrogen protection; be stirred to reaction at ambient temperature to complete; through aftertreatment; cross silica column purification, vacuum-drying obtains compound (9).
8. synthetic method according to claim 7, wherein, described condensing agent is DMAP/DCC, HOBt/EDCI or EDC/DMAP.
9. synthetic method according to claim 6, wherein, the detailed process being prepared salvianolic acid A synthesis precursor (10) by compound (9) is: compound (9) and tin compound are added 1, in 2-ethylene dichloride, reflux 24 hours, be cooled to room temperature, dilute with the mixed solution of dilute hydrochloric acid and ethyl acetate, separatory, aqueous phase is extracted with ethyl acetate, and merges organic phase, with anhydrous magnesium sulfate drying, concentrated, silica column purification obtains salvianolic acid A synthesis precursor.
10. synthetic method according to claim 9, wherein, described tin compound is trialkyl tin hydroxides, dialkyl group two stannic hydroxide or alkyl three stannic hydroxide.
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| CN106317118B (en) * | 2016-08-22 | 2018-06-26 | 河南省法恩莱特新能源科技有限公司 | A kind of synthetic method of six (4- hydroxyl-oxethyls) ring, three phosphonitrile |
| CN107266304A (en) * | 2017-03-24 | 2017-10-20 | 王晓季 | Natural products Salvianolic Acid F novel synthesis |
| CN107417532A (en) * | 2017-04-27 | 2017-12-01 | 合肥工业大学 | A kind of resveratrol acrylic acid phenolic ester analog derivative and its production and use |
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