CN104788406A - Dictamnus phenolic acid B as well as preparation method and application thereof - Google Patents
Dictamnus phenolic acid B as well as preparation method and application thereof Download PDFInfo
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- CN104788406A CN104788406A CN201510169899.4A CN201510169899A CN104788406A CN 104788406 A CN104788406 A CN 104788406A CN 201510169899 A CN201510169899 A CN 201510169899A CN 104788406 A CN104788406 A CN 104788406A
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- phenolic acid
- shaggy
- fruited dittany
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- ZRNATXVEWWOSSH-UHFFFAOYSA-N COc1cc(C(O)=O)ccc1Oc1cc(C(OCC(COC2=O)(C2O)O)=O)cc(OC)c1O Chemical compound COc1cc(C(O)=O)ccc1Oc1cc(C(OCC(COC2=O)(C2O)O)=O)cc(OC)c1O ZRNATXVEWWOSSH-UHFFFAOYSA-N 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
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Abstract
The invention discloses dictamnus phenolic acid B as well as a preparation method and application thereof, relates to a compound as well as a preparation method and application thereof, and provides a novel substance which can be used for eliminating free radicals and has the antitumor activity in vitro as well as a preparation method and application of the novel substance. The chemical name of the dictamnus phenolic acid B is as follows: 3-(4-Carboxy-2-methoxy-phenoxy)-4-hydroxy-5-methoxy-benzoic acid 3,4-dihydroxy-5-oxo-tetrahydro-furan-3-ylmethyl ester. The preparation method of the dictamnus phenolic acid B comprises the following steps: (1) crushing dictamnus dasycapus for extraction with ethanol; (2) recovering an extract for dispersion, and utilizing petroleum ether, chloroform and ethyl acetate for extraction; (3) conducting a preparative high performance liquid chromatography on an ethyl acetate extraction layer to obtain the dictamnus phenolic acid B. The dictamnus phenolic acid B is applied to preparation of drugs for eliminating the free radicals and suppressing tumors.
Description
Technical field
The present invention relates to the purposes of a kind of compound and preparation method thereof and this compound.
Background technology
Free radical, chemically also referred to as " radical ", refers to that the molecule of compound is under the ambient conditionss such as photo-thermal, covalent linkage generation homolysis and the atom with unpaired electron formed or group.During the uneven cracking of covalent linkage, two interatomic share electron pairs are transferred on one of them atom completely, and consequently define positively charged and electronegative ion, this fracture mode is referred to as the heterolytic fission of key.
Free radical, the hazardous compound produced in body oxidizing reaction, has strong oxidizing property, can damage tissue and the cell of body, and then cause chronic disease and aging effect.
Numerous medical research and clinical trial prove: human body cell electronics is the source of ten thousand diseases by plunder, free radical is a kind of material (unsaturated electron species) lacking electronics, electronics is fought for everywhere after entering human body, if seize the electronics of cell protein molecule, make protein connect side chain generation alkylation, formed distortion molecule and carcinogenic.This distortion molecule lacks electronics due to oneself, removes the electronics capturing neighboring molecule again, make again neighboring molecule also occur distortion and carcinogenic.Like this, vicious cycle will form the protein molecular of a large amount of distortion.Transgenation, forms a large amount of cancer cells, finally occurs cancer.And when free radical or distortion molecule have grabbed the electronics of gene, people directly will obtain cancer.Therefore, suppress or eliminate that radical pair delays senility, preventing disease all has positive effect.
Tumour (tumour) refers to that body is under the effect of the various tumorigenesis factor, the true tumor (neogrowth) that local organization hyperplasia is formed, because this true tumor is many in occupancy block-like protrusions, also claim vegetation (neoplasm).World's cancer report is estimated, within 2012, Cancer in China number of the infected is 306.5 ten thousand, accounts for 1/5th of whole world morbidity; Number of cancer deaths is 220.5 ten thousand, accounts for global number of cancer deaths's 1/4th.Therefore, can the material of inhibition tumor cell have great importance to saving the life of countless patient.
Summary of the invention
Shaggy-fruited dittany phenolic acid B of the present invention and preparation method thereof and the purposes of shaggy-fruited dittany phenolic acid B provide a kind ofly can eliminate free radical and novel substance with anti tumor activity in vitro and its preparation method and application.
The molecular formula of shaggy-fruited dittany phenolic acid B is C
21h
20o
12, molecular weight is 464.0953, and molecular structural formula is:
Above-mentioned shaggy-fruited dittany phenolic acid B is prepared according to the following steps:
One, Root-bark of Densefruit Pittany is pulverized, be placed in extractor concentration that Soxhlet dynamic extraction concentrates unit be 95% ethanol extract;
Two, ethanol extraction carry out concentrated after disperse with isopyknic water, then use sherwood oil, chloroform and extraction into ethyl acetate successively;
Three, acetic acid ethyl ester extract carries out silica gel column chromatography, be the methylene dichloride of 100:0 ~ 0:100 by volume ratio: methyl alcohol is wash-out successively, get methylene dichloride: methyl alcohol is that the eluate of 100:3 carries out secondary loading silica gel column chromatography, be the methylene dichloride of 100:0 ~ 0:100 by volume ratio: acetone is wash-out successively, get methylene dichloride: acetone is the eluate loading hydroxypropyl dextran gel column chromatography of 100:20, be the chloroform of 1:1 by volume ratio: methyl alcohol carries out wash-out, cut is collected with the speed of per minute 30, the stage casing elutriant of wash-out 2 h before harvest light color is prepared high performance liquid chromatography, collecting elution time is the absorption peak occurred for the 47th minute, namely shaggy-fruited dittany phenolic acid B is obtained,
Wherein, step 3 preparative high-performance liquid chromatographic take volume ratio as the methyl alcohol of 60:40: water is moving phase, and flow velocity is 3ml/ minute.
Above-mentioned shaggy-fruited dittany phenolic acid B is as the application preparing scavenging free radicals and antitumor drug.
Root-bark of Densefruit Pittany (Dictamnus dasycapus), another name: Cortex Dictamni, stereotyped writing ox, Root-bark of Seguin Argyreia, the fresh grass of sheep, the root skin of Rutaceae per nnial herb shaggy-fruited dittany and Dictamnus angustifolius is conventional Chinese medicinal materials and medication among the people.Spring, Qiu Erji excavate root, and removing silt and tertia, strip root skin, and section is dry; Raw use; There is heat-clearing and damp-drying drug, the effect of removing toxic substances of dispeling the wind; Extremely conventional in treating for skin disease, cure mainly: wind-heat wets the rubella caused by poison; Eczema; Mange; Jaundice; Damp-heat arthralgia.
Shaggy-fruited dittany phenolic acid B of the present invention extracts from Root-bark of Densefruit Pittany, chemistry 3-(4-Carboxy-2-methoxy-phenoxy)-4-hydroxy-5-methoxy-benzoic acid 3,4-dihydroxy-5-oxo-tetrahydro-furan-3-ylmethyl ester by name.
Shaggy-fruited dittany phenolic acid B is white powder, knows for acid through bromine cresols chlorine colour developing inspection; There is blackening at ultraviolet 254nm place, there is fluorescence at ultraviolet 365nm place; Use 10%H
2sO
4spot after solution colour developing is brown.Specific rotatory power is [α]
20 d+ 0.021 (c=0.2, MeOH); The hydroxyl group absorption peak of infrared spectra display shaggy-fruited dittany phenolic acid B is (3415cm
-1), carbonyl absorption peak is (1787,1708cm
-1), the absorption peak of aromatic ring is (1593.4cm
-1).In UV spectrum, shaggy-fruited dittany phenolic acid B has two maximum absorption bands at 262nm and 210nm.HR-FAB-MS provides molecular ion peak: [M]
+be 464.0953, prompting molecular formula is C
21h
20o
12.
The purity of the shaggy-fruited dittany phenolic acid B that the inventive method obtains is high, reaches more than 98.5%.
Shaggy-fruited dittany phenolic acid B of the present invention has stronger Free-radical scavenging activity, is 0.087 to the IC50 of DPPH free radical; And there is anti tumor activity in vitro, to HepG2 liver cancer cell and NCI-H460 lung carcinoma cell, there is strong rejection capability.Shaggy-fruited dittany phenolic acid B of the present invention can be made scavenging free radicals and the antitumor drugs such as injection, freeze-dried powder, infusion solution or oral preparations (comprising tablet, granule, soft capsule, hard capsule, oral liquid and sustained-release preparation).
Embodiment
Technical solution of the present invention is not limited to following cited embodiment, also comprises the arbitrary combination between each embodiment.
Embodiment one: the molecular formula of present embodiment shaggy-fruited dittany phenolic acid B is C
21h
20o
12, molecular weight is 464.0953, and molecular structural formula is:
Present embodiment shaggy-fruited dittany phenolic acid B is fat-soluble compound, has carboxyl to be slightly soluble in water.
Embodiment two: present embodiment shaggy-fruited dittany phenolic acid B is prepared according to the following steps:
One, Root-bark of Densefruit Pittany is pulverized, be placed in extractor concentration that Soxhlet dynamic extraction concentrates unit be 95% ethanol extract;
Two, ethanol extraction carry out concentrated after disperse with isopyknic water, then use sherwood oil, chloroform and extraction into ethyl acetate successively;
Three, acetic acid ethyl ester extract carries out silica gel column chromatography, be the methylene dichloride of 100:0 ~ 0:100 by volume ratio: methyl alcohol is wash-out successively, get methylene dichloride: methyl alcohol is that the eluate of 100:3 carries out secondary silica gel column chromatography, be the methylene dichloride of 100:0 ~ 0:100 by volume ratio: acetone is wash-out successively, get methylene dichloride: acetone is the eluate loading hydroxypropyl dextran gel column chromatography of 100:20, be the chloroform of 1:1 by volume ratio: methyl alcohol carries out wash-out, cut is collected with the speed of per minute 30, the stage casing elutriant of wash-out 2 h before harvest light color is prepared high performance liquid chromatography, collecting elution time is the absorption peak occurred for the 47th minute, namely shaggy-fruited dittany phenolic acid B is obtained,
Wherein, step 3 preparative high-performance liquid chromatographic take volume ratio as the methyl alcohol of 60:40: water is moving phase, and flow velocity is 3ml/ minute.
Present embodiment adopts Shimadzu LC-8A preparative high performance liquid chromatography, and detector is SPD-10AT type UV-detector.The filler of chromatographic column is C-18 reverse phase silica gel.
Present embodiment 50kg Root-bark of Densefruit Pittany is pulverized, is extracted, and final acquisition shaggy-fruited dittany phenolic acid B is 10.3mg, and purity reaches 98.7%, and the nuclear magnetic resonance data of shaggy-fruited dittany phenolic acid B is as shown in table 1.
Table 1
| Position | δH(α/βJ in Hz) | δC | Position | δH(α/βJ in Hz) | δC |
| 1 | 166.9 | 14 | 165.0 | ||
| 2 | 125.5 | 15 | 4.27,2H,m | 65.6 | |
| 3 | 7.59,1H,d,1.8 | 113.2 | 16 | 75.5 | |
| 4 | 148.9 | 17 | 4.48,1H,d,6.9 | 70.3 | |
| 5 | 150.1 | 18 | 175.2 | ||
| 6 | 6.65,1H,d,8.4 | 115.6 | 19α | 4.11,1H,d,9.6 | 72.1 |
| 7 | 7.48.1H,dd,8.4.1.8 | 122.8 | 19β | 4.31,1H,m, | |
| 8 | 142.2 | 21 | 3.88,3H,s | 55.8 | |
| 9 | 143.5 | 22 | 3.90,3H,s | 56.3 | |
| 10 | 148.9 | C1-OH | 12.9,1H,s | ||
| 11 | 7.45,1H,d,1.8 | 109.5 | C9-OH | 9.99,1H,s | |
| 12 | 119.6 | C16-OH | 5.61,1H,s | ||
| 13 | 7.32,1H,d,1.8 | 115.6 | C17-OH | 6.03,1H,d,7.2 |
Embodiment three: the difference of present embodiment and embodiment two is: it is that normal pressure extracts that step one Soxhlet dynamic extraction concentrates unit pressure setting ,-0.8MPa negative pressure concentrates, and Extracting temperature sets 90 DEG C.Other step and parameter identical with embodiment two.
Embodiment four: the difference of present embodiment and embodiment two is: in step 3, high performance liquid chromatography take volume ratio as the acetonitrile of 19:100: water is moving phase, collecting elution time is the absorption peak occurred for the 49th minute.Other step and parameter identical with embodiment two.
Present embodiment 50kg Root-bark of Densefruit Pittany is pulverized, is extracted, and final acquisition shaggy-fruited dittany phenolic acid B is 10.3mg, and purity reaches 98.6%, and the nuclear magnetic resonance data of shaggy-fruited dittany phenolic acid B is identical with table 1.
Embodiment 1
Shaggy-fruited dittany phenolic acid B prepared by embodiment two and four is formulated as 5mmolL respectively
-1the aqueous solution, then to carry out gradient dilution be 2.5mmolL
-1, 1.25mmolL
-1, 0.625mmolL
-1, 0.3125mmolL
-1, 0.16mmolL
-1, 0.08mmolL
-1, 0.04mmolL
-1; In diluent, add DPPH solution respectively, the feature purple of DPPH solution shoals, and has maximum absorption at 517nm place, and the IC50 that can record shaggy-fruited dittany phenolic acid B removing DPPH free radical prepared by embodiment two and four according to the change of absorbancy is 0.087.
Embodiment 2
Experimental technique: adopt platform to expect blue row's dye method, add 1.2 × 10 in 96 orifice plates
5people's tumour suspension cell HepG2 and NCI-H460 of concentration, add the shaggy-fruited dittany phenolic acid B of different concns, act on after 72 hours and expect blue living cell counting number with platform, shaggy-fruited dittany phenolic acid B extracorporeal anti-tumor cell minimal effective concentration (as shown in table 2) detected, prove that shaggy-fruited dittany phenolic acid B has stronger anti-tumor activity, there is the activity of inhibition tumor cell.
Table 2 shaggy-fruited dittany phenolic acid B extracorporeal anti-tumor cell minimal effective concentration
| HepG2 liver cancer cell | NCI-H460 lung carcinoma cell | |
| Shaggy-fruited dittany phenolic acid B | 15μg/ml | 18μg/ml |
Claims (5)
1. shaggy-fruited dittany phenolic acid B, is characterized in that the molecular formula of shaggy-fruited dittany phenolic acid B is C
21h
20o
12, molecular weight is 464.0953, and molecular structural formula is:
2. the preparation method of shaggy-fruited dittany phenolic acid B described in claim 1, is characterized in that shaggy-fruited dittany phenolic acid B is prepared according to the following steps:
One, Root-bark of Densefruit Pittany is pulverized, be placed in extractor concentration that Soxhlet dynamic extraction concentrates unit be 95% ethanol extract;
Two, ethanol extraction carry out concentrated after disperse with isopyknic water, then use sherwood oil, chloroform and extraction into ethyl acetate successively;
Three, acetic acid ethyl ester extract carries out silica gel column chromatography, be the methylene dichloride of 100:0 ~ 0:100 by volume ratio: methyl alcohol is wash-out successively, get methylene dichloride: methyl alcohol is that the eluate of 100:3 carries out secondary silica gel column chromatography, be the methylene dichloride of 100:0 ~ 0:100 by volume ratio: acetone is wash-out successively, get methylene dichloride: acetone is the eluate loading hydroxypropyl dextran gel column chromatography of 100:20, be the chloroform of 1:1 by volume ratio: methyl alcohol carries out wash-out, cut is collected with the speed of per minute 30, the stage casing elutriant collecting light color is prepared high performance liquid chromatography, collecting elution time is the absorption peak occurred for the 47th minute, namely shaggy-fruited dittany phenolic acid B is obtained,
Wherein, step 3 preparative high-performance liquid chromatographic take volume ratio as the methyl alcohol of 60:40: water is moving phase, and flow velocity is 3ml/ minute.
3. the preparation method of shaggy-fruited dittany phenolic acid B according to claim 2, it is characterized in that step one Soxhlet dynamic extraction concentrates unit pressure setting is that normal pressure extracts, and-0.8MPa negative pressure concentrates, and Extracting temperature sets 90 DEG C.
4. the preparation method of shaggy-fruited dittany phenolic acid B according to claim 2, is characterized in that in step 3, preparative high-performance liquid chromatographic take volume ratio as the acetonitrile of 19:100: water is moving phase, and collecting elution time is the absorption peak occurred for the 49th minute.
5. the purposes use of shaggy-fruited dittany phenolic acid B, is characterized in that shaggy-fruited dittany phenolic acid B is as the application preparing scavenging free radicals and antitumor drug.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115636855A (en) * | 2022-11-08 | 2023-01-24 | 齐齐哈尔医学院 | Dictamnus dasycarpus glycoside R and preparation method and application thereof |
| CN115745829A (en) * | 2022-11-08 | 2023-03-07 | 齐齐哈尔医学院 | Dictamnus dasycarpus acyl alkali A and preparation method and application thereof |
| CN116621891A (en) * | 2023-05-25 | 2023-08-22 | 齐齐哈尔医学院 | Dictamni-containing phenolic glycoside C and preparation method and application thereof |
| CN116693485A (en) * | 2023-06-07 | 2023-09-05 | 齐齐哈尔医学院 | Dittany ester C and preparation method and application thereof |
| CN116715707A (en) * | 2023-06-07 | 2023-09-08 | 齐齐哈尔医学院 | Dictamni-containing phenolic glycoside D and preparation method and application thereof |
-
2015
- 2015-04-10 CN CN201510169899.4A patent/CN104788406B/en not_active Expired - Fee Related
Non-Patent Citations (1)
| Title |
|---|
| I.F.COTTRELL，ET AL.: "Acyloxylactonisations mediated by lead tetracarboxylates", 《TETRAHEDRON》 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN115636855A (en) * | 2022-11-08 | 2023-01-24 | 齐齐哈尔医学院 | Dictamnus dasycarpus glycoside R and preparation method and application thereof |
| CN115745829A (en) * | 2022-11-08 | 2023-03-07 | 齐齐哈尔医学院 | Dictamnus dasycarpus acyl alkali A and preparation method and application thereof |
| CN115745829B (en) * | 2022-11-08 | 2023-06-09 | 齐齐哈尔医学院 | Dictamni-acyl base A and preparation method and application thereof |
| CN116621891A (en) * | 2023-05-25 | 2023-08-22 | 齐齐哈尔医学院 | Dictamni-containing phenolic glycoside C and preparation method and application thereof |
| CN116621891B (en) * | 2023-05-25 | 2023-10-31 | 齐齐哈尔医学院 | Dictamni-containing phenolic glycoside C and preparation method and application thereof |
| CN116693485A (en) * | 2023-06-07 | 2023-09-05 | 齐齐哈尔医学院 | Dittany ester C and preparation method and application thereof |
| CN116715707A (en) * | 2023-06-07 | 2023-09-08 | 齐齐哈尔医学院 | Dictamni-containing phenolic glycoside D and preparation method and application thereof |
| CN116693485B (en) * | 2023-06-07 | 2023-11-21 | 齐齐哈尔医学院 | Dittany ester C and preparation method and application thereof |
| CN116715707B (en) * | 2023-06-07 | 2024-02-02 | 齐齐哈尔医学院 | Dictamni-containing phenolic glycoside D and preparation method and application thereof |
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