CN105503896A - New phloroglucin compounds, and preparation method and medical application thereof - Google Patents
New phloroglucin compounds, and preparation method and medical application thereof Download PDFInfo
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- CN105503896A CN105503896A CN201511019858.3A CN201511019858A CN105503896A CN 105503896 A CN105503896 A CN 105503896A CN 201511019858 A CN201511019858 A CN 201511019858A CN 105503896 A CN105503896 A CN 105503896A
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/10—Spiro-condensed systems
Abstract
The invention discloses new phloroglucin compounds, and a preparation method and medical application thereof. The phloroglucin compounds are reported for the first time, have novel structure, and can be extracted, separated and purified from dry mature seeds of tartary buckwheat. The in-vitro test proves that the compounds can directly inhibit proliferation of K562 cells, and the inhibiting capacity is enhanced as the concentration increases and the acting time is prolonged. Meanwhile, the new phloroglucin compounds can induce K562 cell apoptosis, and the apoptosis promoting effect is enhanced as the concentration and time increase. The compounds (I) can provide a potential means for treating chronic granulocytic leukemia, and can be used for developing drugs for treating chronic granulocytic leukemia.
Description
Technical field
The invention belongs to technical field of pharmaceuticals, be specifically related to from the dry mature seed of Radix Et Rhizoma Fagopyri Tatarici, be separated obtain a kind of and there is Phloroglucinol compounds for the treatment of chronic myelocytic leukemia effect and preparation method thereof.
Background technology
Polygonaceae (Polygonacea) Fagopyrum FagopyrumMill. plant has 15 kinds in the whole world, is distributed widely in Asia and Europe, and there is 1 mutation of 10 kinds in China, has 2 kinds to be cultivar.Common are buckwheat FagopyrumesculentumMoench, Radix Et Rhizoma Fagopyri Tatarici F.Tataricum (L.) Gaertn. and Wild Buckwheat Rhizome F.Dibotrys (D.Don) Hara, first two is mainly as food crop, the rhizome hyoscine of Wild Buckwheat Rhizome, has clearing heat and detoxicating, that the stasis of blood is dispelled in apocenosis effect.Radix Et Rhizoma Fagopyri Tatarici has another name called Radix Et Rhizoma Fagopyri Tatarici, tatar buckwheat, Wan Nianqiao, wild southern buckwheat, all has distribution in provinces and regions such as Southwestern China, Central-South, North China.Radix Et Rhizoma Fagopyri Tatarici has long history of being used as medicine.Important Arts for the People's Welfare: " head wind fears cold person, with noodle soup and powder for cake, more makes net for catching birds or fish perspire, though many decades is also healed "." figure is through book on Chinese herbal medicine ": " real stomach, beneficial strength ".Compendium of Material Medica: " sending down abnormally ascending wide intestines mill is stagnant, the swollen wind pain of the heat that disappears.Except gonorrhoea stasis, spleen is long-pending has loose bowels ".And record Radix Et Rhizoma Fagopyri Tatarici bitter, property is flat, cold, useful strength, continuous spirit, sharp knowledge, the wide intestines of sending down abnormally ascending, the effect of stomach invigorating." An Illustrated Book on Plants ": " performance disappears long-pending, and custom exhales clean intestines grass "." national herbal medicine compilation ": " regulating QI to relieve pain, invigorating spleen to remove dampness ".Radix Et Rhizoma Fagopyri Tatarici or the world today integrate one of nutrition, health care, medical natural health care, is called as the grain treasure of " food and medicament dual-purpose ".
Radix Et Rhizoma Fagopyri Tatarici, except the flavones ingredient do not had containing other cereals, also contains the materials such as steroid, phenols, activated protein, mineral element.From tartary buckwheat powder, seed, wheat bran and bud, isolated composition is mainly flavonoid and steroid material in recent years.
Modern pharmacological research shows, Radix Et Rhizoma Fagopyri Tatarici has hypoglycemic, anti-oxidant, antalgic and inflammation relieving, improves the multiple pharmacological effect such as microcirculation.To the rat by abdominal injection tetraoxypyrimidine hyperglycemia model, obviously blood sugar concentration can be reduced by gavage tartary buckwheat powder or Radix Et Rhizoma Fagopyri Tatarici capsule; Flavonoid substances in Radix Et Rhizoma Fagopyri Tatarici can reduce blood fat; The Flavonoid substances such as the rutin in Radix Et Rhizoma Fagopyri Tatarici, Quercetin can remove the free radical such as superoxide anion, hydroxy radical qiao; Chromocor compound in Radix Et Rhizoma Fagopyri Tatarici is mainly rutin, the resistibility of the capillary vessel that has vessel softening, improves microcirculation, maintains, reduce its permeability and fragility, promotion cell proliferation, prevents the effect such as aggegation of hemocyte.
Summary of the invention
The object of this invention is to provide and a kind ofly from the dry mature seed of Radix Et Rhizoma Fagopyri Tatarici, be separated obtain a kind of there is Phloroglucinol compounds for the treatment of chronic myelocytic leukemia 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 mature seed of Radix Et Rhizoma Fagopyri Tatarici is pulverized by (a), extract with 80 ~ 90% 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, 6 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 80:1,55:1,30:1,15:1 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 20:1,15:1 and 10:1; 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 75%, collect 8 ~ 10 column volume elutriants, elutriant concentrating under reduced pressure obtains pure compound (I).
Further, described macroporous resin is AB-8 type macroporous adsorbent resin.
Further, described alcohol heat reflux extracts the alcohol concn adopted is 85%.
A kind of 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 chronic myelocytic leukemia.
The application of described pharmaceutical composition in the medicine of preparation treatment chronic myelocytic leukemia.
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 mature seed (8kg) of Radix Et Rhizoma Fagopyri Tatarici is pulverized by (a), (25L × 3 time) are extracted with 85% 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 (355g) 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, 6 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 (136g); C in () step (b), 75% ethanol elution medicinal extract purification on normal-phase silica gel is separated, successively with volume ratio be 80:1 (8 column volumes), the methylene chloride-methanol gradient elution of 55:1 (8 column volumes), 30:1 (6 column volumes), 15:1 (8 column volumes) and 1:1 (5 column volumes) obtains 5 components; D component 4 (31g) is separated further by purification on normal-phase silica gel in () step (c), successively with volume ratio be 20:1 (8 column volumes), the methylene chloride-methanol gradient elution of 15:1 (10 column volumes) and 10:1 (6 column volumes) obtains 3 components; E in () step (d), component 2 (11g) reverse phase silica gel of octadecylsilane bonding is separated, with the methanol aqueous solution isocratic elution that concentration expressed in percentage by volume is 75%, collect 8-10 column volume elutriant, elutriant concentrating under reduced pressure obtains pure compound (I) (228mg).
Structural identification: yellow jelly; HR-ESIMS shows [M+Na]
+for m/z505.2918, can obtain molecular formula in conjunction with nuclear-magnetism feature is C
30h
42o
5, degree of unsaturation is 10.Hydrogen nuclear magnetic resonance modal data δ
h(ppm, DMSO-d
6, 400MHz): H-7 (2.47, m), H-7 (2.05, dd, J=13.7, 7.4), H-8 (1.84, m), H-10 (1.79, m), H-10 (1.41, m), H-11 (2.06, m), H-11 (1.73, m), H-12 (2.38, m), H-14 (2.84, d, J=14.3), H-14 (1.92, d, J=14.3), H-15 (1.35, s), H-16 (1.27, s), H-17 (2.89, m), H-17 (2.90, m), H-18 (5.13, t, J=7.5), H-20 (1.55, s), H-21 (1.68, s), H-22 (2.62, dd, J=13.1, 8.1), H-22 (2.41, dd, J=13.1, 8.2), H-23 (4.78, t, J=8.1), H-25 (1.46, s), H-26 (1.37, s), H-28 (3.72, m), H-29 (0.94, d, J=6.8), H-30 (1.16, d, J=6.8), carbon-13 nmr spectra data δ
c(ppm, DMSO-d
6, 100MHz): 197.1 (C, 1-C), 111.3 (C, 2-C), 197.2 (C, 3-C), 59.6 (C, 4-C), 208.5 (C, 5-C), 60.4 (C, 6-C), 26.9 (CH
2, 7-C), 42.8 (CH, 8-C), 78.3 (C, 9-C), 40.4 (CH
2, 10-C), 22.6 (CH
2, 11-C), 44.8 (CH, 12-C), 70.6 (C, 13-C), 38.7 (CH
2, 14-C), 27.8 (CH
3, 15-C), 23.6 (CH
3, 16-C), 33.5 (CH
2, 17-C), 118.3 (CH, 18-C), 135.6 (C, 19-C), 25.7 (CH
3, 20-C), 17.8 (CH
3, 21-C), 41.6 (CH
2, 22-C), 116.2 (CH, 23-C), 138.3 (C, 24-C), 25.5 (CH
3, 25-C), 17.5 (CH
3, 26-C), 209.1 (C, 27-C), 35.8 (CH, 28-C), 18.1 (CH
3, 29-C), 19.7 (CH
3, 30-C), carbon atom mark is see Fig. 1.
1hNMR composes display eight methyl signals (δ H0.94,1.16,1.27,1.35,1.37,1.46,1.55,1.68), and two olefinic methine protons (δ H4.78 and 5.13).
13cNMR composes display 30 carbon signals, comprises eight methyl, six methylene radical, five methynes (two olefinic methynes), and 11 quaternary carbons (three ketone carbonyls, three olefinic quaternary carbons, two contain oxygen quaternary carbon, and an olefinic is containing oxygen quaternary carbon).H in HMBC spectrum
2-7 and H
2-14 and C-3, C-4 and C-5, Me-15 and C-12, C-13 and C-14, Me-16 and C-8, C-9 and C-10, and H
2-17 and H
2-22 and the dependency of C-1, C-5 and C-6 show that this compound is Phloroglucinol compounds.In HMBC spectrum, H
2-17 and H
2-22 and C-1, C-5 and C-6, Me-20 and Me-21 and C-19 and C-18, and the dependency of Me-25 and Me-26 and C-24 and C-23 shows that C-6 position is connected with two 2-methyl-2-butene groups.According to two containing oxygen carbon signal [δ C70.6 (C-13) and 78.3 (C-9)], and nuclear magnetic data and degree of unsaturation, an existence oxo bridge between known C-9 and C-13.In HMBC spectrum, the dependency of Me-29 and Me-30 and C-27 and C-28 shows that this compound contains a sec.-propyl.In NOESY spectrum, the dependency of H-14 β and H-12 and H-7 β shows that B ring is chair conformation.In NOESY spectrum, the dependency of H-8 and Me-16 and H-12, Me-15 and H-12 and H-14 β shows H-8, Me-15 and Me-16 is beta comfiguration.In addition, H-18 and H-7 β, and the dependency of H-23 and H-14 β shows the upside of the sequence of C-5 and C-6 in A ring at spiral shell carbon C-4.Comprehensive hydrogen spectrum, carbon spectrum, HMBC spectrum and NOESY 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
K562 cell provided by Chinese Academy of Sciences's Shanghai biomass cells.Compound (I) is self-control, and HPLC normalization method purity is greater than 98%.RPMI-1640 dehydrated medium is purchased from Gibco company.Calf serum is purchased from Sijiqing Bioengineering Material Inst., Hangzhou City.Penicillin, Streptomycin sulphate are purchased from North China Pharmaceutical Factory.Glutamine, MTT, DMSO are purchased from AMRESCO.Annexinv-FITC cell apoptosis detection kit is purchased from Nanjing KaiJi Biology Science Development Co., Ltd.MOPS, Rnasin, agarose, smell second ingot, Huamei Bio-Engrg Co., of bromjophenol blue Huamei Bio-Engrg Co..
CO
2incubator (Thermo company of the U.S.), Bechtop (Suzhou Decontamination Equipment Plant), magnetic stirring apparatus (Shanghai Nanhui Telecommunication Apparatus Factory), inverted microscope (Japanese OLYMPUS company), horizontal type centrifuger (Anting Scientific Instrument Factory, Shanghai), electronic analytical balance (German Sartorius company), automatic microplate reader (German Humareader company), U-3010 type ultraviolet spectrophotometer (Japanese HITACHI company), flow cytometer (BECKMAN company of the U.S.), EppendorfCentrifuge5417R whizzer (German Eppendorf company).
Two, test method
1, the cultivation of K562 cell
By the culturing bottle of the cell strain newly bought surface 75% alcohol wipe 3 times.Cell suspension is sucked centrifuge tube, the centrifugal 10min of 1000rpm.Supernatant discarded, drips the RPMI-1640 perfect medium containing 10%NBS, and piping and druming is prepared into cell suspension gently.Be inoculated in culturing bottle, be placed in 37 DEG C, 5%CO
2cultivate in incubator, every day changes liquid and goes down to posterity.
2, experiment grouping
The RPMI-1640 of Normal group: 10%NBS; RPMI-1640+ final concentration 100mg/L compound (I) of experimental group: D1:10%NBS; I.e. RPMI-1640+ final concentration 200mg/L compound (I) of D2:10%NBS; I.e. RPMI-1640+ final concentration 400mg/L compound (I) of D3:10%NBS; I.e. RPMI-1640+ final concentration 800mg/L compound (I) of D4:10%NBS.
3, mtt assay detection compound (I) is on the impact of K562 cell proliferation
L () gets the good cell of growth conditions, cell is mixed with cell suspension, with 5 × 10 with the RPMI-1640 nutrient solution containing 10%NBS
3cells/well is inoculated in aseptic 96 well culture plates.(2) according to experiment grouping, often group adds the medicine 50 μ L of different concns, if acellular hole is blank group, often group establishes 8 multiple holes, and 96 well culture plates are put into CO
2cultivate in incubator; (3) 24,48 and 72h after take out 96 well culture plates, every hole adds 20 μ LMTT (5mg/mL), puts into CO
2hatch 4h in incubator, namely have hyacinthine crystallisate to generate, within the scope of certain cell count, the growing amount of crystallisate is directly proportional to cell count.(4) the SDS100 μ L that every hole adds acidifying puts into CO
2spend the night in incubator.(5) measure OD by microplate reader, return to zero with blank well during colorimetric.
4, AnnexinV-FITC/PI two dye Apoptosis by Flow Cytometry
(1) get the cell that growth conditions is good, with containing the RPMI-1640 nutrient solution of 10%NBS, cell is mixed with cell suspension, and to adjust cell concn be 5 × 10
5/ mL, is inoculated in aseptic 6 well culture plates, every hole 2mL cell.(2) add different concns medicine, 2mL/ hole according to experiment grouping, 6 well culture plates are put into CO
2cultivate in incubator.(3) collect each porocyte after 48h and 72h in centrifuge tube, the centrifugal 5min of 1000rpm, abandons supernatant.(4) with the PBS washed cell twice of 4 DEG C of precoolings, (1500rpm, centrifugal 5min), abandons supernatant, with 200 μ LBindingBuffer suspension cells, and moves in streaming pipe.(5), after often pipe adds 5 μ LAnnexinv-FITC mixing, 5 μ LPI are added, mixing.(6) room temperature, lucifuge reaction 10min, uses flow cytomery.
5, statistical procedures
Experimental group and control group all repeat 3 operations, and result is with (x ± s represents, P<0.05 is shown with significant difference.Employing one-way analysis of variance is compared between group.All data SPSS13.0 statistical softwares carry out statistical analysis.
Three, result and conclusion
1, mtt assay detection compound (I) is to the inhibited proliferation of K562 cell
After compound (I) effect K562 cell 24h, 48h, 72h, detect OD by microplate reader
490display: after effect 24h, D1 and D2 experimental group is to the not obvious (P>0.05 of cell K562 cyto-inhibition, P>0.05), D3 and D4 obviously can suppress 562 result (P<0.05, P<0.01), after effect 48h and 72h, the compound (I) of different concns all can suppress K562 cell proliferation, and strengthens with the effect of dosage and the increase antiproliferative effect of time.The results are shown in Table 1 (*: with contrast ratio P<0.05; *: with contrast ratio P<0.01).
2, Annexinv-FITC/PI two dye flow cytometry analysis result
It is apoptotic earliest events that phosphatide phthalein Serine (PhosphotidylSerine, PS) turns up.AnnexinV is a kind of Ca2
+dependency cardiolipin binding protein, can with PS high-affinity specific binding.Successively marked two transfect cells of FITC and PI (PropidiumIodide), by flow cytometer, viable cell, viable apoptotic cell (two-parameter scatter diagram right lower quadrant), non-viable apoptotic cell and non-viable non-apoptotic cell are distinguished.Result shows that compound (I) effect K562 cell 48h and 72h of different concns all can obviously induce K562 early apoptosis of cells, and this effect increases with the concentration of compound (I) and extended durations of action and obviously strengthening.The results are shown in Table 2 (*: with contrast ratio P<0.05; *: with contrast ratio P<0.01).
Conclusion, compound (I) directly can suppress the propagation of K562 cell, and rejection ability strengthens with the increase of concentration and the prolongation of action time.Meanwhile, compound (I) can induce K562 apoptosis, and the effect of this short apoptosis increases along with concentration and the increase of time.Result of study shows, and compound (I) may provide a kind of potential means for the treatment of chronic myelocytic leukemia.
MTT value (x ± s, N=8) after compound (I) the effect K562 cell of table 1 different concns
Early apoptosis rate (x ± s, N=3) after table 2 different concns compound (I) effect K562 cell
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
Prepared by 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 mature seed of Radix Et Rhizoma Fagopyri Tatarici is pulverized by (a), extract with 80 ~ 90% 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, 6 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 80:1,55:1,30:1,15:1 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 20:1,15:1 and 10:1; 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 75%, 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: described macroporous resin is AB-8 type macroporous adsorbent resin.
4. the preparation method of compound according to claim 2 (I), is characterized in that: it is 85% that described alcohol heat reflux extracts the alcohol concn adopted.
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 chronic myelocytic leukemia.
7. the application of pharmaceutical composition according to claim 5 in the medicine of preparation treatment chronic myelocytic leukemia.
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Cited By (4)
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CN105461732A (en) * | 2016-01-04 | 2016-04-06 | 范素琴 | Novel diterpenoid compound and preparation method and medical application thereof |
CN105481874A (en) * | 2015-12-22 | 2016-04-13 | 陈杰 | Novel diterpene compound for treating ovarian cancer |
CN105766964A (en) * | 2016-04-23 | 2016-07-20 | 何淑琼 | Agricultural herbicide and preparation method thereof |
CN105820208A (en) * | 2016-05-16 | 2016-08-03 | 苏州毕诺佳医药技术有限公司 | Novel withanolide compound and preparation method and medical application thereof |
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2015
- 2015-12-29 CN CN201511019858.3A patent/CN105503896A/en not_active Withdrawn
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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CN105481874A (en) * | 2015-12-22 | 2016-04-13 | 陈杰 | Novel diterpene compound for treating ovarian cancer |
CN105461732A (en) * | 2016-01-04 | 2016-04-06 | 范素琴 | Novel diterpenoid compound and preparation method and medical application thereof |
CN105766964A (en) * | 2016-04-23 | 2016-07-20 | 何淑琼 | Agricultural herbicide and preparation method thereof |
CN105820208A (en) * | 2016-05-16 | 2016-08-03 | 苏州毕诺佳医药技术有限公司 | Novel withanolide compound and preparation method and medical application thereof |
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