CN105418425A - Novel dibenzocyclooctadiene lignan compound and preparation method - Google Patents
Novel dibenzocyclooctadiene lignan compound and preparation method Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/52—Separation; Purification; Stabilisation; Use of additives by change in the physical state, e.g. crystallisation
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/56—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/48—Separation; Purification; Stabilisation; Use of additives
- C07C67/58—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/52—Esters of acyclic unsaturated carboxylic acids having the esterified carboxyl group bound to an acyclic carbon atom
- C07C69/533—Monocarboxylic acid esters having only one carbon-to-carbon double bond
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Abstract
The invention discloses a novel dibenzocyclooctadiene lignan compound and a preparation method thereof, and provides a structure of the compound, a pharmaceutical composition comprising the same, and a preparation method and applications of the pharmaceutical composition. The dibenzocyclooctadiene lignan compound is reported for the first time, has a novel structure, and is prepared by extracting dry eucommia bark and then separating and purifying the extract. The in-vitro experiment results show that the compound has a prominent inhibiting effect on the proliferation of human pancreatic cancer cell (MiaPaCa-2) under an anaerobic culture condition; as the concentration of the compound increases and action time goes on, the inhibiting effect becomes more prominent, namely, in a certain concentration range, the time-dosage dependence exists, and thus the compound can be used to develop drugs for treating pancreatic cancer.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to from the dry bark of the bark of eucommia, be separated obtain a kind of and there is biphenyl cyclooctene lignin compounds for the treatment of carcinoma of the pancreas effect and preparation method thereof.
Background technology
The bark of eucommia is the dry bark of the Eucommiaceae plant bark of eucommia (EucommiaulmoidesOliver), is Chinese famous and precious tonic herb.Shennong's Herbal is classified as top grade, call its " cure mainly waist and knee, bowl spares, beneficial vital essence, hard muscles and bones, wet except itching under the moon, dribbling urination.Clothes of a specified duration, make light of one's life by commiting suicide resistance to old ".Research in recent years shows, Folium Eucommiae and skin have similar chemical composition and pharmacological action, for skin hyoscine, can solve the problem that bark of eucommia medicine source plaque is weary.
Many scholars have carried out large quantity research to the chemical composition of the bark of eucommia.Find that the skin of the bark of eucommia, leaf, branch, fruit and the composition contained in spending are broadly divided into following a few class after deliberation.Lignanoids: comprise this main antihypertensive compositions of Pinoresinol diglucoside, cloves lipidol glucosulfone former times, olivil, Ji Niboxi Dick acid formicester, catechin etc., up to now, from the bark of eucommia, isolated Lignanoids compounds about 30 kinds, wherein much effective constituent has good activity at anti-tumor aspect.Phenylpropanoids: comprise coumaric acid, NSC 619661, chlorogenic acid and coniferyl etc.Iridoids: ulmoprenol, eucommioside, genipin, Geniposidic acid, Geniposide, aucubin, ajugoside, Harpagide butyric ester, thunder flutter appropriate glycosides, woodruff acid, asperuloside, 10-acetyl Scandoside and table ulmoprenol etc.Flavonoid: flavonoid compound is also one of principle active component of the bark of eucommia, the height of its content is the important indicator judging bark of eucommia crude drug and products thereof quality.Research finds that in the bark of eucommia, contained flavonoid compound is mainly kaempferol, Quercetin, astragalin, land brocade glycosides and rutin.
The bark of eucommia has invigorating the liver and kidney, strengthening the bones and muscles, rubbish in purged body, strengthen human body cell substance metabolism, prevent muscle skeleton aging, balanced human's blood pressure, decomposer inner cholesterol, reduce body fat, recover blood vessel elasticity, diuresis heat-clearing, broad-spectrum antimicrobial, stimulating central nervous system, improves white blood cell count, strengthens the remarkable efficacy such as body immunity.
Summary of the invention
The object of this invention is to provide and a kind ofly from the dry bark of the bark of eucommia, be separated obtain a kind of there is biphenyl cyclooctene lignin compounds for the treatment of carcinoma of the pancreas effect and preparation method thereof.
Above-mentioned purpose of the present invention is achieved by technical scheme below:
There is the compound (I) of following structural formula,
The preparation method of described compound (I), comprise following operation steps: the dry bark of the bark of eucommia is pulverized by (a), extract with 75 ~ 85% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste, use sherwood oil, ethyl acetate and water saturated n-butanol extraction successively, obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract respectively; Acetic acid ethyl ester extract macroporous resin removal of impurities in (b) step (a), first use 10% ethanol elution, 8 column volumes, then use 75% ethanol elution, 10 column volumes, collect 75% ethanol eluate, concentrating under reduced pressure obtains 75% ethanol elution thing medicinal extract; C in () step (b), 75% ethanol elution medicinal extract purification on normal-phase silica gel is separated, obtain 5 components successively with the methylene chloride-methanol gradient elution that volume ratio is 85:1,45:1,25:1,12:1 and 1:1; D in () step (c), component 4 is separated further by purification on normal-phase silica gel, obtain 3 components successively with the methylene chloride-methanol gradient elution that volume ratio is 20:1,12:1 and 5:1; E in () step (d), component 2 reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collect 8 ~ 10 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I).
Further, in step (a), extract with 80% alcohol heat reflux, united extraction liquid.
Further, described macroporous resin is AB-8 type macroporous adsorbent resin.
Pharmaceutical composition, the described compound (I) wherein containing treatment significant quantity and pharmaceutically acceptable carrier.
The application of described compound (I) in the medicine of preparation treatment carcinoma of the pancreas.
The application of described pharmaceutical composition in the medicine of preparation treatment carcinoma of the pancreas.
When the compounds of this invention is used as medicine, directly can uses, or use with the form of pharmaceutical composition.
This pharmaceutical composition contains the compounds of this invention (I) for the treatment of significant quantity, and all the other are acceptable on pharmacology, nontoxic to humans and animals and pharmaceutically acceptable carrier of inertia and/or vehicle.
Described pharmaceutically acceptable carrier or vehicle are that one or more are selected from solid, semisolid and liquid diluent, filler and pharmaceutical preparation assistant agent.Pharmaceutical composition of the present invention is used with the form of per weight dose.Medicine of the present invention is applied to by form that is oral or injection the patient needing treatment.For time oral, tablet, slow releasing tablet, controlled release tablet, capsule, dripping pill, micropill, suspensoid, emulsion, powder or granule, oral liquid etc. can be made into; During for injecting, can be made into water-based or oily solution, aseptic powder injection, liposome or the emulsion etc. of sterilizing.
Accompanying drawing explanation
Fig. 1 is compound (I) structural formula;
Fig. 2 is that the theoretical ECD value of compound (I) compares with experiment ECD value.
Embodiment
Further illustrate essentiality content of the present invention below in conjunction with embodiment, but do not limit scope with this.Although be explained in detail the present invention with reference to preferred embodiment, those of ordinary skill in the art should be appreciated that and can modify to technical scheme of the present invention or equivalent replacement, and does not depart from essence and the scope of technical solution of the present invention.
Embodiment 1: compound (I) is separated preparation and structural identification
Reagent source: ethanol, sherwood oil, ethyl acetate, propyl carbinol, methylene dichloride are analytical pure, purchased from Shanghai Ling Feng chemical reagent company limited, methyl alcohol, analytical pure, purchased from Jiangsu Han Bang chemical reagent company limited.
Preparation method: the dry bark (10kg) of (a) bark of eucommia is pulverized, (25L × 3 time) are extracted with 80% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste (3L), use sherwood oil (3L × 3 time), ethyl acetate (3L × 3 time) and water saturated propyl carbinol (3L × 3 time) to extract successively, obtain petroleum ether extract, acetic acid ethyl ester extract (398g) and n-butyl alcohol extract respectively; Acetic acid ethyl ester extract AB-8 type macroporous resin removal of impurities in (b) step (a), first use 10% ethanol elution, 8 column volumes, use 75% ethanol elution, 10 column volumes again, collect 75% ethanol eluate, concentrating under reduced pressure obtains 75% ethanol elution thing medicinal extract (163g); C in () step (b), 75% ethanol elution medicinal extract 200-300 order purification on normal-phase silica gel is separated, successively with volume ratio be 85:1 (8 column volumes), the methylene chloride-methanol gradient elution of 45:1 (8 column volumes), 25:1 (8 column volumes), 12:1 (10 column volumes) and 1:1 (5 column volumes) obtains 5 components; D component 4 (49g) 200-300 order purification on normal-phase silica gel is separated further in () step (c), successively with volume ratio be 20:1 (8 column volumes), the methylene chloride-methanol gradient elution of 12:1 (10 column volumes) and 5:1 (5 column volumes) obtains 3 components; E in () step (d), component 2 (30g) the reverse phase silica gel ODS-C18 of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collect 8 ~ 10 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I) (143mg).
Structural identification: white amorphous powder; HR-ESIMS shows [M+Na]
+for m/z505.2226, can obtain molecular formula in conjunction with nuclear-magnetism feature is C
28h
34o
7, degree of unsaturation is 12.Hydrogen nuclear magnetic resonance modal data δ
h(ppm, DMSO-d
6, 500MHz): H-4 (6.71, s), H-6 (3.24, d, J=13.5), H-6 (3.47, d, J=13.5), H-8 (2.68, m), H-9 (2.26, dd, J=13.5, 7.7), H-9 (2.59, d, J=13.5), H-11 (6.42, s), H-17 (0.78, d, J=7.2), H-18 (4.90, s), H-18 (5.06, s), H-3 ' (5.83, m), H-4 ' (1.68, dq, J=6.2, 1.0), H-5 ' (1.68, s), 2-OMe (3.78, s), 3-OMe (3.86, s), 12-OMe (3.76, s), 13-OMe (3.75, s), 14-OMe (3.47, s), carbon-13 nmr spectra data δ
c(ppm, DMSO-d
6, 125MHz): 142.3 (C, 1-C), 139.4 (C, 2-C), 151.5 (C, 3-C), 112.3 (CH, 4-C), 131.6 (C, 5-C), 42.8 (CH
2, 6-C), 151.6 (C, 7-C), 39.5 (CH, 8-C), 33.6 (CH
2, 9-C), 134.4 (C, 10-C), 110.2 (CH, 11-C), 151.7 (C, 12-C), 139.8 (C, 13-C), 150.7 (C, 14-C), 121.3 (C, 15-C), 124.1 (C, 16-C), 16.0 (CH
3, 17-C), 109.2 (CH
2, 18-C), 165.4 (C, 1 '-C), 127.3 (C, 2 '-C), 136.7 (CH, 3 '-C), 15.1 (CH
3, 4 '-C), 19.8 (CH
3, 5 '-C), 60.4 (CH
3, 2-OMe), 55.8 (CH
3, 3-OMe), 55.6 (CH
3, 12-OMe), 60.3 (CH
3, 13-OMe), 60.2 (CH
3, 14-OMe), carbon atom mark is see Fig. 1.Infrared spectra shows that this compound contains carbonyl (1737cm
-1) and phenyl ring (1642 and 1494cm
-1) group.
1h and
13cNMR composes a display bimodal methyl signals (δ H0.78, d, J=7.2Hz, Me-17), two benzyl methylene radical (δ H3.24, d, J=13.5Hz, H-6 and 3.47, d, J=13.5Hz, H-6; δ H2.26, dd, J=13.5,7.7Hz, H-9 and 2.59, d, J=13.5Hz, H-9), two fragrant simple substance subsignal (δ H6.42, H-11 and 6.71, H-4), an outer methylene signals (δ H4.90 of ring, s, H-18 and 5.06, s, H-18) five methoxyl groups (δ H3.47,3.75,3.76,, and angeloyl groups [δ H1.68 (dq, a J=6.2 3.78 and 3.86), 1.0Hz, H-4 '), 1.68 (s, H-5 '), 5.83 (m, H-3 '); δ C15.1 (C-4 '), 19.8 (C-5 '), 127.3 (C-2 '), 136.7 (C-3 '), 165.4 (C-1 ')].In being composed by HMBC, H-4 (δ H6.71) is positioned at C-1 position to the long-range relevant known angeloyl groups of C-1 (δ C142.3).In HMBC spectrum, methoxyl group signal (δ H3.78,3.86,3.76,3.75 and 3.47) C-2 is shown with the dependency between corresponding carbon signal (δ C139.4,151.5,151.7,139.8 and 150.7), C-3, C-12, C-13 and C-14 position is connected with a methoxyl group respectively.The outer methylene signals (δ H4.90, s, H-18 and 5.06, s, H-18) of ring, and carbon signal (δ C109.2, C-18; δ C151.6, C-7) show to there is double bond between C-7 and C-18.In ROESY spectrum, the dependency of H-11 and H-9 β and Me-17 shows that Me-17 is beta comfiguration.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and ROESY spectrum, and document is about correlation type nuclear magnetic data, can substantially determine this compound as shown in Figure 1, steric configuration is determined further by ECD test, theoretical value and experimental value basically identical (Fig. 2).
Embodiment 2: compound (I) pharmacological action is tested
One, material and instrument
Human pancreas cancer MiaPaCa-2 cell is so kind as to give by institute of oncology of Tumour Hospital Attached To Tianjin Medical Univ..Compound (I) is made by oneself, and HPLC normalization method purity is greater than 98%.FBS, trypsinase-EDTA Digestive system are purchased from Hyclone company of the U.S..PBS powder is purchased from Tianjin Run Tai development in science and technology company limited.DMEM low sugar nutrient solution is purchased from Gibco company of the U.S..MTT is purchased from Sigam company of the U.S..DMSO is purchased from Beijing Chemical Plant.Benzylpenicillin sodium for injection is purchased from HARBIN PHARMACEUTICAL GROUP CO., LTD. General Pharm. Factory.Streptomycin sulphate for injection is purchased from Dalian Merro Pharmaceutical Co., Ltd..
Bechtop, cell culture incubator (Thermo company of the U.S.), 4 DEG C of refrigerators,-20 DEG C of refrigerators (Qingdao company of Haier),-80 DEG C of refrigerators (FormaScientific), electric drying oven with forced convection (Tianjin laboratory apparatus factory), opticmicroscope (Japanese Olympus company), inverted phase contrast microscope (German leica company), hypervelocity refrigerated centrifuge (HIT), microplate reader (Shanghai Kehua Bio-engineering Co., Ltd), E-Centrifuge (Wealtec), micro sample adding appliance (German Eppendorf), electronic thermostatic water-bath (Yuyao City east electric instrument factory), high-pressure sterilizing pot (Shandong Medical Devices Co., Ltd. of Xinhua), electronic balance (Shanghai balance equipment factory).
Two, test method
1, cell cultures:
(1) normal oxygen is cultivated: human pancreas cancer MiaPaCa-2 cell is put into 5%CO
2, 37 DEG C, the CO of saturated humidity
2adherent culture in incubator, changes nutrient solution in good time, cell attachment growth merge to 80% ~ 90% time go down to posterity.
(2) anoxic is cultivated: human pancreas cancer MiaPaCa-2 cell is placed on 5%CO
2, 94%N
2, 1%O
2, 37 DEG C, cultivate in the anoxic cell of saturated humidity.Anoxic cell is set up: hypoxia device is adjustable culture vessel, has an air inlet port and a production well.During experiment, anoxic cultured cells is put into adjustable culture vessel, be filled with low-oxygen gas mixture body (5%CO by air inlet port
2+ 95%N
2+ 1%O
2), record little indoor oxygen concentration and maintain after 1% airtight, move in cell culture incubator, 37 DEG C of cultivations.Every 24h qi of chong channel ascending adversely and ventilation once rearmounted 37 DEG C of incubators continuation cultivation again, collects each group of cell, respectively for MTT experiment after 24h, 48h, 72h.
2, the detection of cell proliferation
(1) collect logarithmic phase MiaPaCa-2 cell, be prepared into single cell suspension and count, adjustment concentration is with every hole 5 × l0
3individual cell is inoculated in 96 porocyte culture plates, and every hole cumulative volume 100 μ L (the aseptic PBS of marginal pore same volume fills), in 5%CO
2, 37 DEG C, the CO of saturated humidity
2cultivate in incubator, after cell formation individual layer, abandon supernatant give different concns compound (I) process.
(2) blank group (not adding the equal-volume nutrient solution of drug treating) and compound (I) medicine 20 μm of ol/L, 40 μm of ol/L, 80 μm of ol/L are divided), often group establishes 6 parallel holes, experiment in triplicate, inserts 37 DEG C, 5%CO
2, 94%N
2, 1%O
2anoxic cell in cultivate 24h, 48h, 72h respectively.
(3) after rinsing 96 porocyte culture plate 2 times gently with PBS, every hole adds l0 μ LMTT (5mg/mL), centrifugally after continuing to cultivate 4h abandons supernatant, and every hole adds the DMSO of 15 μ L, puts 15min that shaking table vibrates, crystallisate is fully dissolved.
(4) enzyme-linked immunosorbent assay instrument measures the absorbance (A value) in each hole in 570nm place, calculates cell proliferation inhibition rate.
(5) inhibiting rate (%)=(blank group average A-value-medicine group average A-value)/blank group average A-value × 100%.
(6) take concentration as transverse axis, inhibiting rate (%) is longitudinal axis drafting inhibiting rate histogram.
3, statistical method
Adopt SPSS17.0 to carry out data processing, measurement data measurement data meets normal distribution, with mean scholar standard deviation
represent, comparing between mean and adopt one-way analysis of variance or t inspection, is that difference has statistical significance with P<0.05.
Three, result and conclusion
MTT result shows: when (1) compound (I) intervenes human pancreas cancer MiaPaCa-2 cell same equal time (24h, 48h, 72h), along with the increase of compound (I) concentration (in experimental concentration scope), OD value corresponding to it is less, when showing that compound (I) is identical to human pancreas cancer MiaPaCa-2 cell intervention time under anoxic conditions, along with the increase of drug level, cell survival rate reduces.The results are shown in Table 1 (note:
ap<0.01VS control group;
bp<0.01VS20 μm of ol/L group;
cp<0.01VS40 μm of ol/L group).
(2) after (20 μm of ol/L, 40 μm of ol/L, 80 μm of ol/L) compound (I) of different concns intervenes human pancreas cancer MiaPaCa-2 cell 48h, under different concns effect, cell proliferation inhibition rate is respectively (20.13 ± 0.80) %, (34.83 ± 0.66) %, (45.68 ± 1.45) %, inhibiting rate increases in rising trend with drug level, and group difference has statistical significance (P<0.05).After compound (I) intervention carcinoma of the pancreas MiaPaCa-2 cell 24h, 48h, 72h of 80 μm of ol/L, MiaPaCa-2 inhibitory rate of cell growth is respectively (38.78 ± 0.92) %, (45.68 ± 1.45) %, (55.95 ± 2.20) %, increase in time-dependent manner, group difference has statistical significance (P<0.05).The results are shown in Table 2 (note:
ap<0.01VS control group;
bp<0.01VS20 μm of ol/L group;
cp<0.01VS40 μm of ol/L group).
Conclusion, compound (I) has obvious inhibited proliferation to human pancreas cancer MiaPaCa-2 cell under anoxic culture condition, along with increase and the prolongation of action time of compound (I) concentration, restraining effect is more obvious, i.e. lifetime within the scope of finite concentration---dose-dependently.This may become another new approaches for the treatment of of pancreatic cancer.
Table 1 compound (I) on the impact of human pancreas cancer MiaPaCa-2 Growth of Cells (n=6,
)
Table 2 compound (I) on the impact of human pancreas cancer MiaPaCa-2 inhibitory rate of cell growth (n=6,
)
Embodiment 3
The preparation of tablet: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, vehicle is added, pelletizing press sheet than the ratio for 1:9 in itself and excipient weight.
Embodiment 4
The preparation of oral liquid: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, oral liquid method for making makes oral liquid routinely.
Embodiment 5
The preparation of capsule or granule: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, add vehicle in itself and excipient weight than the ratio for 1:9, make capsule or granule.
Embodiment 6
The preparation of injection liquid: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, inject with water routinely, essence filter, injection liquid is made in embedding sterilizing.
Embodiment 7
The preparation of aseptic powder injection: by embodiment 1 method first obtained compound (I), and the salt utilizing organic acid to make as tartrate or citric acid or formic acid or oxalic acid etc., mineral acid example hydrochloric acid or sulfuric acid or phosphoric acid, be dissolved in sterile water for injection, stirring makes molten, filter with aseptic suction funnel, aseptic essence filter again, be sub-packed in ampoule, after frozen drying, aseptic sealing by fusing obtains powder injection.
The effect of above-described embodiment is essentiality content of the present invention is described, but does not limit protection scope of the present invention with this.Those of ordinary skill in the art should be appreciated that and can modify to technical scheme of the present invention or equivalent replacement, and does not depart from essence and the protection domain of technical solution of the present invention.
Claims (7)
1. there is the compound (I) of following structural formula,
2. the preparation method of compound according to claim 1 (I), it is characterized in that comprising following operation steps: the dry bark of the bark of eucommia is pulverized by (a), extract with 75 ~ 85% alcohol heat reflux, united extraction liquid, be concentrated into without alcohol taste, use sherwood oil, ethyl acetate and water saturated n-butanol extraction successively, obtain petroleum ether extract, acetic acid ethyl ester extract and n-butyl alcohol extract respectively; Acetic acid ethyl ester extract macroporous resin removal of impurities in (b) step (a), first use 10% ethanol elution, 8 column volumes, then use 75% ethanol elution, 10 column volumes, collect 75% ethanol eluate, concentrating under reduced pressure obtains 75% ethanol elution thing medicinal extract; C in () step (b), 75% ethanol elution medicinal extract purification on normal-phase silica gel is separated, obtain 5 components successively with the methylene chloride-methanol gradient elution that volume ratio is 85:1,45:1,25:1,12:1 and 1:1; D in () step (c), component 4 is separated further by purification on normal-phase silica gel, obtain 3 components successively with the methylene chloride-methanol gradient elution that volume ratio is 20:1,12:1 and 5:1; E in () step (d), component 2 reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 70%, collect 8 ~ 10 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I).
3. the preparation method of compound according to claim 2 (I), is characterized in that: in step (a), extracts, united extraction liquid with 80% alcohol heat reflux.
4. the preparation method of compound according to claim 2 (I), is characterized in that: described macroporous resin is AB-8 type macroporous adsorbent resin.
5. a pharmaceutical composition, is characterized in that: the compound according to claim 1 (I) wherein containing treatment significant quantity and pharmaceutically acceptable carrier.
6. the application of compound according to claim 1 (I) in the medicine of preparation treatment carcinoma of the pancreas.
7. the application of pharmaceutical composition according to claim 5 in the medicine of preparation treatment carcinoma of the pancreas.
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Cited By (1)
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|---|---|---|---|---|
| CN106008549A (en) * | 2016-06-03 | 2016-10-12 | 朱正直 | Limonin compounds and preparation method thereof |
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|---|---|---|---|---|
| CN106008549A (en) * | 2016-06-03 | 2016-10-12 | 朱正直 | Limonin compounds and preparation method thereof |
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Application publication date: 20160323 |