CN102399148A - Hypolipidemic compounds, preparation method thereof and purpose thereof - Google Patents
Hypolipidemic compounds, preparation method thereof and purpose thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of pharmaceutical chemistry, and relates to hypolipidemic compounds, a preparation method thereof and a purpose thereof. According to the novel compounds with hypolipidemic activity, a rubiaceae plant geophilaherbacea is adopted as a raw material, and novel 2,6-phenethanol dihydroxybenzoate is obtained by separation and identification through a solvent extraction and chromatography method. According to the invention, substituted aryl acid and substituted aryl alcohol are adopted as raw materials, and are subject to a reaction in an appropriate solvent with the effect of a catalyst under a certain temperature, such that 2,6-phenethanol dihydroxybenzoate and similar substances are produced. The compounds show substantial hypolipidemic effects in hypolipidemic models, and can be used for preparing novel hypolipidemic medicines. The extraction, separation, synthesis and preparation methods disclosed by the invention are advantaged in mild reaction condition, easy operation, and high yield.
Description
Affiliated field
The invention belongs to the pharmaceutical chemistry technical field, relate to one type of reducing blood-fat compound.
Background technology
World Health Organization's report, cardiovascular and cerebrovascular diseases is to cause human main causes of death.The hypertension that China causes because of hyperlipidemia every year, heart stalk, cerebral infarction, apoplexy, etc. rise with annual 12% speed; Only stroke patient annual nearly 3,500,000; Grownup's blood fat of 1/3 is generally higher.The death that the atherosclerosis that hyperlipidemia causes causes accounts for 75% of cardiovascular and cerebrovascular diseases mortality ratio, and finds per capita that growing up more than 30 years old of 80-90% the arteriosclerosis symptom is arranged, and is the stealthy killer of human health.In addition, discover that the peripheral arterial vascular disease also are a kind of class coronary heart disease relevant with dysbolism of blood fat.Reduce fat is prevention and the basic way of treating chronic diseases such as these cardiovascular and cerebrovascular diseases and obesity.The reducing blood-fat treatment is the focus that global the world of medicine pays close attention to always, transfers the sales volume of blood-lipoids medicine to reach 35,200,000,000 dollars in 2006; The same period, the medication of China's accent blood fat was 4,800,000,000 yuan.
The blood lipid-lowering medicine of present clinical use mainly contains: 1. cholic acid chelating agent class (Yang Shijie, Su Ruhao, Xiang Lan; Qiao Hailing. the present condition for application of hypolipidemic and progress. medical forum magazine 2006; 27,90-92. Wang Hai is brave, Wang Lin. the progress of blood lipid-lowering medicine. and foreign medical science pharmacy fascicle 2004; 31,160-166.); 2. suppress SUV synthetic or promote other non-key enzyme inhibitorss in medicine such as HMG-CoA reductase inhibitor (Statins), ACAT suppressor factor and the SUV biosynthetic process of cholesterol metabolic (Robinson JG.Simvastatin:present and future perspectives.Expert OpinionPharmacotherapy 2007,8,2159-2172. Yang Shi is outstanding; Reviving, you is good; Xiang Lan, Qiao Hailing. the present condition for application of hypolipidemic and progress. medical forum magazine 2006,27; 90-92. Wang Hai is brave; Wang Lin. the progress of blood lipid-lowering medicine. foreign medical science pharmacy fascicle 2004,31,160-166.); 3. high density lipoprotein increasing medicine (Yang Shijie, Su Ruhao, Xiang Lan; Qiao Hailing. the present condition for application of hypolipidemic and progress. medical forum magazine 2006; 27,90-92. Wang Hai is brave, Wang Lin. the progress of blood lipid-lowering medicine. and foreign medical science pharmacy fascicle 2004; 31; 160-166.Cannon CP.High-density lipoprotein cholesteroland residual cardiometabolic risk in metabolic syndrome.Clinical Cornerstone 2007,8, S14-S23.); 4. special type of triglyceride reducing class medicine such as shellfish, nicotinic acid class (Yang Shijie, Su Ruhao, Xiang Lan; Qiao Hailing. the present condition for application of hypolipidemic and progress. medical forum magazine 2006; 27,90-92. Wang Hai is brave, Wang Lin. the progress of blood lipid-lowering medicine. and foreign medical science pharmacy fascicle 2004; 31,160-166.); 5. drug combination (Yang Shijie, Su Ruhao, Xiang Lan, Qiao Hailing. the present condition for application of hypolipidemic and progress. medical forum magazine 2006,27,90-92.); 6. natural blood lipid-lowering medicine (Yang Shijie, Su Ruhao, Xiang Lan; Qiao Hailing. the present condition for application of hypolipidemic and progress. medical forum magazine 2006,27,90-92. Wang Hai is brave; Wang Lin. the progress of blood lipid-lowering medicine. foreign medical science pharmacy fascicle 2004,31,160-166.Bhutani KK; Birari R; Kapat K.Potential anti-obesity and lipid lowering natural products:A review.Natural ProductCommunications 2007,2,331-348.).These blood lipid-lowering medicines all exist shortcoming, deficiency and toxic side effect (RobinsonJG.Simvastatin:present and future perspectives.Expert Opinion Pharmacotherapy 2007,8,2159-2172. Yang Shi outstanding person; Reviving, you is good, Xiang Lan, Qiao Hailing. the present condition for application of hypolipidemic and progress. and medical forum magazine 2006; 27,90-92. Wang Hai is brave, Wang Lin. the progress of blood lipid-lowering medicine. and foreign medical science pharmacy fascicle 2004; 31; 160-166.Cannon CP.High-density lipoprotein cholesterol and residual cardiometabolic risk inmetabolic syndrome.Clinical Cornerstone 2007,8, S14-S23.Bhutani KK; Birari R; Kapat K.Potential anti-obesity and lipid lowering natural products:A review.Natural ProductCommunications 2007,2,331-348.); For example: widely used Statins major side effects is to cause metabolic disturbance, to the dual toxic action of liver and muscle.Serious adverse effects is a myopathy: rhabdomyolysis.Sarcolysis aggravation during drug combination (Phillips PS, Haas RH.Statin myopathy as a metabolic muscle disease.Expert RevCardiovasc Ther 2008,6 (7), 971-8.).Some hyperlipidemia patient is invalid to statin treatment; Press for novel blood lipid-lowering medicine (El Harchaoui K, Akdim F, Stroes ES; Trip MD; Kastelein JJ Current and futurepharmacologic options for the management of patients unable to achieve low-densitylipoprotein-cholesterol goals with statins.Am J Cardiovasc Drugs 2008,8 (4), 233-42.).The untoward reaction of fibrate has gastrointestinal reaction, serious liver, the kidney function damage of causing, and to increase myopathy dangerous with the Statins coupling.Medicine property rhabdomyolysis takes place after individual patient is taken medicine, and shows as myalgia, unable, jerk.The untoward reaction of nicotinic acid class medicine: nicotinic acid need be taken heavy dose of regulating blood fat effect that just has; Along with dosage strengthens; Spinoff increases thereupon; Mainly show as erythema, headache, weak etc., part patient gastritis, stomach ulcer and atrial arrhythmia, serum uric acid level also occur and untoward reaction such as increases.Gastrointestinal reactions such as that the untoward reaction of cholic acid chelating agent class comprises is nauseating, abdominal distension, constipation, diarrhoea, intestinal obstruction because gastrointestinal reaction is heavier, are not quite used at present clinically.Polyenoid class medicine is prone to be oxidized to atherogenic material, also has antiplatelet aggregative activity.
The present invention is on the hypolipidemic activity screening basis of a large amount of plant milk extracts; Under activity instructs; We separate from a kind of plant and have obtained activeconstituents wherein---and one type novel 2; 6-resorcylic acid phenylglycollic ester finds 2, and 6-resorcylic acid phenylglycollic ester has significant hypolipidemic activity; Based on the structure of this parent compound, the present invention has designed and synthesized a series of analogues, and screening active ingredients shows that can be applicable to reducing blood-fat treats.
Summary of the invention
The purpose of this invention is to provide one type of reducing blood-fat compound and preparation method thereof, and the purposes of this compounds aspect reducing blood-fat.
(research and development of natural products 2005,17 (3) 316-319) is gone up the plant milk extract that screening has hypolipidemic activity at LDL receptor-reporter gene screening system model of oneself own setting up for we.We find that the ethanol extraction of Herbaceous Geophila complete stool shows the intensive hypolipidemic activity.Herbaceous Geophila is a Rubiaceae Herbaceous Geophila platymiscium, and kind surplus this platymiscium has 40 is widely distributed in each torrid zone, subtropical zone; The west and south, south China are originated in, to the east of Taiwan in 3 kinds in China.
From the above-mentioned plant that screens hypolipidemic activity---madder wort Herbaceous Geophila (Geophila herbacea) is a raw material; We adopt solvent extraction to separate with chromatography method and have identified a kind of new 2; 6-resorcylic acid phenylglycollic ester compounds is shown in the following figure:
It is characterized by:
CF: colourless fine needle is brilliant
Mass spectrum: (ESI (-)): 257 (M-)
-.
Proton nmr spectra (600MHz, DMSO-d6, δ in ppm and TMS as internal standard): δ 9.95 (2H, s), 7.29～7.33 (4H; M), 7.23 (1H, m), 7.09 (1H, t; J=8.4Hz), 6.34 (2H, d, J=8.4Hz), 4.43 (2H; T, J=7.0Hz) and 2.99 (2H, t, J=7.0Hz).
Carbon-13 nmr spectra (150MHz, DMSO-d6, δ in ppm and TMS as internal standard): δ 168.3 (s), 157.9 (s), 138.5 (s); 132.9 (d), 129.4 (d), 128.8 (d), 126.8 (d); 107.6 (s), 107.2 (d), 65.7 (t), and 34.7 (t).
X-ray single crystal diffraction figure:
The present invention 2, and the extraction of 6-resorcylic acid phenylglycollic ester, separation, purifying can be achieved in the following manner:
Ethanol or methanol aqueous solution lixiviate madder wort Herbaceous Geophila (Geophila herbacea) meal with 70%-98% obtain vat liquor; Get total medicinal extract through concentrating vat liquor; Total medicinal extract with water-dispersion after with organic solvent extractions such as ETHYLE ACETATE or chloroform or ether or sherwood oil or benzene; Extraction liquid obtains extract through concentrating, and extract obtains above-claimed cpd through chromatographic separation.This compound is have hypolipidemic activity novel 2,6-resorcylic acid phenylglycollic ester, and white fine needle is brilliant, and its structure is through confirmations such as nucleus magnetic resonance, mass spectrum, X-single crystal diffractions.
The present invention's compound that extraction separation obtains from madder wort Herbaceous Geophila (Geophila herbacea) is newfound novel cpd with remarkable hypolipidemic activity.
The present invention is with this new compound 2, and 6-resorcylic acid phenylglycollic ester is a precursor structure, has designed and synthesized a series of analogues, can be applicable to the reducing blood-fat treatment, and said analogue general structure is following:
Wherein, R
1Be hydroxyl or methoxyl group, R
2Be hydroxyl or methoxyl group.
The preparation method
Above-mentioned 2, the preparation method of the analogue of 6-resorcylic acid phenylglycollic ester is following:
A, with 2; 6-mesitylenic acid and phenylethyl alcohol are raw material; With in methylene dichloride, chloroform, N, second cyanogen, THF, dioxane, the ETHYLE ACETATE any one or a few is solvent, under 0 ℃～reflux temperature condition, stirs 1～12 hour.
After b, reaction finish, total overall reaction liquid is filtered;
After the filtrating of c, filtration back gained concentrates, through silica gel column chromatography or directly concentrated, crystallization acquisition 2,6-mesitylenic acid phenylglycollic ester;
D, with 2 of gained, 6-mesitylenic acid phenylglycollic ester is dissolved in methylene dichloride or the chloroform, stirring at room adds 1～1.5 normal AlCl in batches
3, stirring at room, TLC detects, after reacting completely, in the slow impouring water of reaction solution, extracting and separating obtains organic layer, organic layer is concentrated into dried, through silica gel column chromatography or directly concentrate, crystallization gets 2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester;
E, the 2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester of gained is dissolved in methylene dichloride or the chloroform, stirring at room adds 2～3 normal AlCl3 in batches; Stirring at room, TLC detects, after reacting completely; In the slow impouring water of reaction solution, extracting and separating obtains organic layer, organic layer is concentrated into dried; Through silica gel column chromatography or directly concentrate, crystallization gets 2,6-resorcylic acid phenylglycollic ester.
The hypolipidemic activity of compound is achieved in the following manner among the present invention:
At first set up screening model; Promptly extract the normal liver tissue genomic dna, choose LDLR gene-1 66 to+35 these fragments, also in justice and antisense primer, add restriction enzyme site KpnI and BglII respectively according to its gene order design PCR primer; Carry out the PCR reaction; Enzyme is cut, and connects, and at last required dna fragmentation is cloned in the pGL3-Basic plasmid vector.
HepG2 cell (source ATCC) is contained the DMEM substratum of 10% calf serum, keeping cultivation under 37 ℃, 5%CO2 condition.Uses 0.25% trypsin digestion cell before the transfection, and with serum-free DMEM suspendible, add an amount of above-mentioned plasmid and transfection reagent carries out transfection by operation instructions, transfectional cell is inoculated in 96 orifice plates.
After accomplishing cell transfecting 24h, use fresh culture instead, add above-claimed cpd respectively,, as negative control, continue to cultivate behind the 24h as positive control with pravastatin (physiological saline solution) with the empty plasmid transfection according to following time-and-motion study uciferase activity.
Carrying out uciferase activity with reference to the detection kit operation instruction measures: inhale and abandon the supernatant in the culturing cell; Every hole adds the PBS washed cell twice; Add lysate 40 μ L, room temperature is placed 15min, makes the abundant cracking of cell; Add substrate and vibration, under the 562nm wavelength, measure relative flat light emission value; Uciferase activity detects with beta-galactosidase enzymes as confidential reference items; Carry out the mensuration of betagalactosidase activity according to operation instructions, both ratios promptly represent the plain enzymic activity value of relative fluorescence (relative luciferaseunit, RLU).
The active testing result is as shown in the table, and all test triplicate, average,
| RLU (relative fluorescence unit) | |
| The HepG2 cell | ?1137±172 |
| HepG2 transfection LDLR-Luc | ?11372±1092 |
| HepG2 transfection LDLR-Luc+ pravastatin (150 μ M=63.6 μ g/mL) | ?16364±1100 |
| HepG2 transfection LDLR-Luc+1 (100 μ g/mL) | ?20258±3040 |
| HepG2 transfection LDLR-Luc+2 (100 μ g/mL) | ?16328±2671 |
| HepG2 transfection LDLR-Luc+3 (100 μ g/mL) | ?18659±2938 |
The activity and the pravastatin of last all specimen of table are suitable.
The present invention has following advantage:
1, the present invention separate obtain 2,6-resorcylic acid phenylglycollic ester compounds has tangible hypolipidemic activity;
2, extraction of the present invention, extraction, separation processes are simple;
3, the present invention lays a good foundation for the development of novel blood lipid-lowering medicine.
Embodiment
Through specific embodiment the present invention is described further below, but embodiment does not limit protection scope of the present invention.
Embodiment 1:2, the extraction scheme of 6-resorcylic acid phenylglycollic ester
Herbaceous Geophila whole plant 5Kg (dry weight) pulverizes the back with 95% ethanol lixiviate (50L * 3), and concentrating under reduced pressure gets total medicinal extract 220g.Total medicinal extract is dissolved among the 2.0L warm water (about 50 ℃), and the cooling back is with ethyl acetate extraction (1.5L * 3), and concentrating under reduced pressure gets ETHYLE ACETATE part 80g.ETHYLE ACETATE part through the silica gel column chromatography gradient elution (CHCl3, CHCl3: CH3OH=50: 1,20: 1,10: 1,5: 1,2: 1, CH3OH) be divided into 10 parts (TLC detects, and same section combines); (sherwood oil: ETHYLE ACETATE=50: 1) separation obtains 4 small portions to Fr 2 through silica gel column chromatography; Wherein (sherwood oil: chloroform=3: 1) separation obtains the 70mg target compound to second small portion through silica gel column chromatography; Show that this compound is 2,6-resorcylic acid phenylglycollic ester through Wave Spectrum and X-single crystal diffraction.
Embodiment 2:2,6-dimethoxybenzoic acid phenylglycollic ester (2) synthetic
Take by weighing 200mg 2, the 6-dimethoxybenzoic acid is placed in the dry in advance round-bottomed flask of crossing, and adds the anhydrous CH2Cl2 of 10mL, stirs; Said apparatus is placed ice-water bath, and liquid temp to be mixed is reduced to 0 ℃, in this mixed solution, adds 250mg dicyclohexyl carbon imide, stirs to add 0.122mL phenylethyl alcohol, 6mg 4-N after 30 minutes; N-dimethyl--4-amido pyridine, stirring at room, TLC detects; After reacting completely, direct filtration, mother liquor concentrate residue; (sherwood oil: chloroform=2: 3) separation obtains 2,6-mesitylenic acid phenylglycollic ester, yield 90.6% to residue through silica gel column chromatography.Proton nmr spectra (600MHz, CDCl
3, δ in ppm and TMS as internal standard): δ 7.25～7.31 (5H, m), 7.22 (1H, m), 6.54 (2H; D, J=8.2Hz), 4.54 (2H, t, J=7.1Hz); 3.78 (6H, s) and 3.06 (2H, t, J=7.1Hz). carbon-13 nmr spectra (150MHz, CDCl
3, δ in ppm and TMS as internal standard): δ 166.5 (s), 157.4 (s), 138.0 (s), 131.1 (d), 129.0 (d), 128.4 (d), 126.4 (d), 113.3 (s), 104.0 (d), 65.7 (t), 56.0 (q), and 35.0 (t).
Synthesizing of embodiment 3:2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester (3)
With the foregoing description 2 obtain 2,6-mesitylenic acid phenylglycollic ester places in advance the dry round-bottomed flask of crossing, and adds the anhydrous CH of 10mL
2Cl
2, stir, add 1.2 normal AlCl in a small amount in batches
3, stirring at room, TLC detects; After reacting completely, in the slow impouring 20mL of reaction solution water, extracting and separating obtains organic layer; Organic layer is concentrated into dried 2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester, and the gained compound characterizes without physics and chemistry, directly does next step reaction.
Embodiment 4:2,6-resorcylic acid phenylglycollic ester (1) synthetic
2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester that the foregoing description 3 is obtained places the dry in advance round-bottomed flask of crossing, and adds the anhydrous CH of 10mL
2Cl
2, stir, add 2.2 normal AlCl in a small amount in batches
3, stirring at room, TLC detects, after reacting completely; In the slow impouring 20mL of reaction solution water, extracting and separating obtains organic layer, and organic layer is concentrated into small volume, and crystallization gets target compound---and 2; 6-resorcylic acid phenylglycollic ester, yield 92.1%, proton nmr spectra (600MHz, CDCl
3, δ in ppm and TMS as internal standard): δ 9.61 (2H, brs), 7.37 (2H, t; J=7.4Hz), 7.26～7.33 (4H, m), 6.44 (2H, d; J=8.2Hz), 4.73 (2H, t, J=6.7Hz); And 3.13 (2H, t, J=6.7Hz). carbon-13 nmr spectra (150MHz, CDCl
3, δ in ppm and TMS as internal standard): δ 169.7,160.9,136.6,136.5,129.0,128.6,127.3,108.2,100.0,66.9, and and 34.9.Mass spectrum: (ESI (-)): 257 (M-)
-Institute's synthetic compound physicochemical data is accredited as same compound with to separate the compound physicochemical data that obtains consistent.
Embodiment 5: the hypolipidemic activity test
(research and development of natural products 2005,17 (3) 316-319) upward screens the plant milk extract with hypolipidemic activity to LDL receptor-reporter gene screening system model of setting up at us.At first set up screening model; Promptly extract the normal liver tissue genomic dna, choose LDLR gene-1 66 to+35 these fragments, also in justice and antisense primer, add restriction enzyme site KpnI and BglII respectively according to its gene order design PCR primer; Carry out the PCR reaction; Enzyme is cut, and connects, and at last required dna fragmentation is cloned in the pGL3-Basic plasmid vector.
HepG2 cell (source ATCC) is contained the DMEM substratum of 10% calf serum, keeping cultivation under 37 ℃, 5%CO2 condition.Uses 0.25% trypsin digestion cell before the transfection, and with serum-free DMEM suspendible, add an amount of above-mentioned plasmid and transfection reagent carries out transfection by operation instructions, transfectional cell is inoculated in 96 orifice plates.
After accomplishing cell transfecting 24h, use fresh culture instead, add above-claimed cpd respectively,, as negative control, continue to cultivate behind the 24h as positive control with pravastatin (physiological saline solution) with the empty plasmid transfection according to following time-and-motion study uciferase activity.
Carrying out uciferase activity with reference to the detection kit operation instruction measures: inhale and abandon the supernatant in the culturing cell; Every hole adds the PBS washed cell twice; Add lysate 40 μ L, room temperature is placed 15min, makes the abundant cracking of cell; Add substrate and vibration, under the 562nm wavelength, measure relative flat light emission value; Uciferase activity detects with beta-galactosidase enzymes as confidential reference items; Carry out the mensuration of betagalactosidase activity according to operation instructions, both ratios promptly represent the plain enzymic activity value of relative fluorescence (relative luciferaseunit, RLU).
The active testing result is as shown in the table, and all test triplicate, averages, and the activity of all specimen and pravastatin is quite active as a result.
| RLU (relative fluorescence unit) | |
| The HepG2 cell | ?1137±172 |
| HepG2 transfection LDLR-Luc | ?11372±1092 |
| HepG2 transfection LDLR-Luc+ pravastatin (150 μ M=63.6 μ g/mL) | ?16364±1100 |
| HepG2 transfection LDLR-Luc+1 (100 μ g/mL) | ?20258±3040 |
| HepG2 transfection LDLR-Luc+2 (100 μ g/mL) | ?16328±2671 |
| HepG2 transfection LDLR-Luc+3 (100 μ g/mL) | ?18659±2938 |
Claims (9)
1. one type of reducing blood-fat compound has following chemical structural formula:
Wherein, R
1Be hydroxyl or methoxyl group, R
2Be hydroxyl or methoxyl group.
2. the described reducing blood-fat compound of claim 1 is characterized in that having following chemical structure:
3. the preparation method of the described reducing blood-fat compound of claim 1 is characterized in that: separation and Extraction or to be that raw material is synthetic with aryl acid and aryl alcohol make from madder wort Herbaceous Geophila Geophila herbacea.
4. the preparation method of the described reducing blood-fat compound of claim 3 is characterized in that: said from madder wort Herbaceous Geophila Geophila herbacea separation and Extraction may further comprise the steps:
A, with ethanol or the methanol aqueous solution lixiviate madder wort Herbaceous Geophila Geophila herbacea meal of 70%-98%, obtain total medicinal extract;
B, total medicinal extract with water-dispersion after, extract and obtain extract with organic solvent ETHYLE ACETATE or chloroform or ether or sherwood oil or benzene;
C, extract obtain target compound through the chromatographic separation purifying.
5. the preparation method of reducing blood-fat compound according to claim 4; It is characterized in that: described chromatographic separation is to adopt silica gel column chromatography; Mixed in 10: 1 by volume～2: 1 with sherwood oil or hexanaphthene or normal hexane or benzene or toluene and ETHYLE ACETATE or acetone or ether and to carry out wash-out, or adopt chloroform or methylene dichloride and methyl alcohol or ethanol or Virahol or propyl carbinol to mix in 100: 1 by volume～5: 1 to carry out wash-out and obtain.
6. the preparation method of reducing blood-fat compound according to claim 3 is characterized in that: said is that the synthetic title product of raw material comprises following step with aryl acid and aryl alcohol:
A, with 2; 6-mesitylenic acid and phenylethyl alcohol are raw material; With in methylene dichloride, chloroform, N, second cyanogen, THF, dioxane, the ETHYLE ACETATE any one or a few is solvent, under 0 ℃～reflux temperature condition, stirs 1～12 hour;
After b, reaction finish, total overall reaction liquid is filtered;
After the filtrating of c, filtration back gained concentrates, through silica gel column chromatography or directly concentrated, crystallization acquisition 2,6-mesitylenic acid phenylglycollic ester;
D, with 2 of gained, 6-mesitylenic acid phenylglycollic ester is dissolved in methylene dichloride or the chloroform, stirring at room adds 1～1.5 normal AlCl in batches
3, stirring at room, TLC detects, after reacting completely, in the slow impouring water of reaction solution, extracting and separating obtains organic layer, organic layer is concentrated into dried, through silica gel column chromatography or directly concentrate, crystallization gets 2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester;
E, the 2-hydroxyl-6-methoxybenzoic acid phenylglycollic ester of gained is dissolved in methylene dichloride or the chloroform, stirring at room adds 2～3 normal AlCl in batches
3, stirring at room, TLC detects, after reacting completely, in the slow impouring water of reaction solution, extracting and separating obtains organic layer, organic layer is concentrated into dried, through silica gel column chromatography or directly concentrate, crystallization gets 2,6-resorcylic acid phenylglycollic ester.
7. the preparation method of reducing blood-fat compound according to claim 6 is characterized in that: in the reaction system of step a, add dicyclohexyl carbon imide or 1-(3-dimethylamino-propyl)-3-ethyl carbodiimide and N, N-dimethyl-4-aminopyridine.
8. according to the preparation method of claim 6 or 7 described reducing blood-fat compounds; It is characterized in that: among step c, d, the e; Adopt silica gel column chromatography; Mixed in 10: 1 by volume～2: 1 with sherwood oil or hexanaphthene or normal hexane or benzene or toluene and ETHYLE ACETATE or acetone or ether and to carry out wash-out, or adopt chloroform or methylene dichloride and methyl alcohol or ethanol or Virahol or propyl carbinol to mix in 100: 1 by volume～5: 1 to carry out wash-out and obtain.
9. the described reducing blood-fat compound of claim 1 is in the purposes of preparation in the blood lipid-lowering medicine.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105037221A (en) * | 2015-06-18 | 2015-11-11 | 吉林大学珠海学院 | Compound with neuroprotective function and preparation method of compound |
| CN107164096A (en) * | 2017-05-27 | 2017-09-15 | 山东大学 | A kind of extraction purification of Geophila herbacea (L) O Kumtze volatile oil and detection method and its application |
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| CN107164096A (en) * | 2017-05-27 | 2017-09-15 | 山东大学 | A kind of extraction purification of Geophila herbacea (L) O Kumtze volatile oil and detection method and its application |
| CN107164096B (en) * | 2017-05-27 | 2021-03-02 | 山东大学 | Method for extracting, purifying and detecting volatile oil of aidi grass and application thereof |
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