CN113735918B - Labdane diterpene glycoside compound and preparation method thereof - Google Patents
Labdane diterpene glycoside compound and preparation method thereof Download PDFInfo
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- CN113735918B CN113735918B CN202111118458.3A CN202111118458A CN113735918B CN 113735918 B CN113735918 B CN 113735918B CN 202111118458 A CN202111118458 A CN 202111118458A CN 113735918 B CN113735918 B CN 113735918B
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- glycoside
- water
- ethyl acetate
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- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/18—Acyclic radicals, substituted by carbocyclic rings
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C07H1/00—Processes for the preparation of sugar derivatives
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Abstract
The invention discloses a labdane diterpene glycoside compound and a preparation method thereof, the compound is obtained by separating a water-decocted extract from stems of Rubus chingii Hu of Rubus, called raspberry glycoside B, the raspberry glycoside B is detected by various means such as superconducting nuclear magnetic resonance spectrum, mass spectrum and the like, and the molecular formula is determined to be C26H44O8The molecular weight is 484, the chemical structural formula is formula (I), the raspberry glycoside B is subjected to in vitro activity screening, and the result shows that the compound has obvious inhibition effect on human bladder cancer cells and human colon cancer cells, can be used as an anti-tumor drug,
Description
Technical Field
The invention relates to the technical field of medicines, and in particular relates to a novel labdane diterpenoid glycoside compound raspberry glycoside B separated and purified from stems of Rubus chingii Hance and a preparation method thereof. The compound has obvious inhibiting effect on tumor cell strains, can be used as a lead compound for developing new anti-tumor medicaments, and can also be used for developing medicaments for treating various clinically common multiple cancers.
Background
Rubi fructus is dried immature fruit of Rubus chingii Hu of Rubus of Rosaceae, has effects of invigorating kidney, stopping nocturnal emission, reducing urination, nourishing liver and improving eyesight, and can be used for treating spermatorrhea, enuresis, pollakisuria, sexual impotence, premature ejaculation, dim eyesight, etc. At present, the raspberry is collected in the first part of the pharmacopoeia of the people's republic of China, 2020 edition.
Modern researches show that the raspberry mainly contains terpenoids, flavonoid components and phenolic acid components. At present, the compounds that have been isolated from raspberry are mainly: triterpenes, diterpenes, flavonoids, etc.
Diterpenes are a class of compounds consisting of 4 isoprene units and containing 20 carbon atoms. The main skeleton of diterpenes is up to 20. Among them, the enantiomers of the skeleton such as kaurane, gibberellin, substituane and aconitane are common. Many oxygenated derivatives of diterpenes have a variety of biological activities. Such as paclitaxel, andrographolide, tanshinone, bilobalide, stevioside, etc. Diterpenes have anti-tumor, antioxidant, anti-inflammatory, immunosuppressive, etc. effects.
The prior art "Three new labdane-type di-terpen glycosides from the from of Rubus chingii and the cytoxic activities against five human cells lines" journal homepage: www.elsevier.com/locate discloses the following Three compounds,
Ent-labdane-type diterpene glucosides from leaves of Rubus chingii [J]. Phytochemistry1984, 23(3): 615-621 discloses the following four compounds
The compounds are said to have anti-tumor effects.
In the process of researching the components of the stems of the Chinese raspberry, the inventor unexpectedly obtains a novel labdane diterpenoid glycoside compound which is not reported in the existing literature. The compound is deeply researched, has more obvious anti-tumor effect than the prior art, reduces side effect and can be applied to the preparation of medicaments for treating cancers or tumors.
Disclosure of Invention
The invention aims to provide a novel labdane diterpenoid glycoside compound raspberry glycoside B extracted from Rubus chingii.
Another object of the present invention is to provide a process for preparing the above-mentioned labdane-type diterpene glycoside compound, raspberry glycoside B.
The invention also aims to provide application of the labdane diterpenoid glycoside compound raspberry glycoside B in preparation of cancer and/or antitumor drugs.
The technical scheme is as follows: the inventor of the invention further researches on the basis of the prior art, finds that the anticancer active ingredients of the Rubus chingii Hance of Chongren county of Chongzhou city, Jiangxi province are mainly the compounds in the invention, and no document reports that the Rubus chingii glycoside B is used for treating cancers and/or tumors at present through data review.
Therefore, the invention provides a compound, wherein the compound is raspberry glycoside B, and the structural formula of the compound is shown as the formula (I):
the invention further provides a pharmaceutically acceptable salt of the compound, wherein the pharmaceutically acceptable salt is selected from salts of the labdane diterpenoid glycoside compound raspberry glycoside B with inorganic acid and organic acid, or salts with alkali metal and alkaline earth metal.
The inventor firstly extracts and separates a new labdane diterpenoid glycoside compound named raspberry glycoside B, 13 from the raspberry stems collected from Chongren county of Chongzhou city, Fuxi provinceE-enantiomer-labdane-8 (16), 14-diene-3 beta, 15, 18-trihydroxy-18-oxo-beta-D-glucoside, formula C26H44O8The molecular weight is 484, and the chemical structural formula is shown as a formula (I).
The preparation steps of the labdane diterpenoid glycoside compound raspberry glycoside B are as follows in sequence:
(1) extracting solution of the stems of the Chinese raspberry: 5.5kg of the rubus chingii corm stems are decocted for 2 times by adding water, 55L of water is added for each time, the decoction is decocted for 2 hours each time, and the 2 decoction liquids are combined to obtain rubus chingii corm stem extracting solution;
(2) concentrating the extract of the stems of the Chinese raspberry: concentrating the extract of the seed and stem of Rubus chingii Hemsl under reduced pressure to obtain 3L concentrate;
(3) and (3) extraction: taking 3L of the concentrated solution of the seed stems of the Chinese-east raspberry, adding 60L of purified water for dissolving, firstly extracting with dichloromethane for three times, 60L each time, retaining a water phase, extracting the water phase with ethyl acetate for three times, and combining organic phases to obtain an ethyl acetate extract;
(4) concentrating the extract: concentrating the ethyl acetate extractive solution under reduced pressure to obtain 42.1g ethyl acetate concentrated solution;
(5) and (3) column chromatography separation: dissolving the ethyl acetate concentrated solution with 500ml of methanol, mixing the ethyl acetate concentrated solution with 1:1.5 silica gel, filling the sample into a silica gel chromatographic column by a dry method, wherein the inner diameter of the silica gel chromatographic column is 5cm, the column height is 120cm, the particle size of silica gel filled in the column is 100-200 meshes, and the volume ratio of dichloromethane-methanol = 12: 1,10: 1,9: 1,8: 1,6: 1,5: 1,4: eluting with 4L of eluent at a ratio of 1, collecting 56 parts of eluate fractions, each 500mL, concentrating under reduced pressure to dryness, detecting with thin layer chromatography, combining 25-32 th parts of dried eluate fractions (7.5 g), and purifying with reversed-phase ODS column chromatography, methanol-water = 10: 100 → 100: performing gradient elution for 0, eluting 2L of eluent in each proportion, collecting 100% methanol-eluted fraction, separating the fraction by Sephadex LH-20 column chromatography, eluting with methanol, detecting by TLC to obtain rubusoside B as main spot, and drying to obtain crude product 503mg of rubusoside B;
(6) purification of monomeric compound: the crude product of the raspberry glycoside B is purified by reversed phase high performance preparative liquid chromatography, the chromatographic conditions are as follows: a chromatographic column: c18 5 µm,250mm × 20 mm; detection wavelength: 210 nm; eluting with acetonitrile-water =24:76 as eluent; the flow rate is 10 mL/min; collecting 130min eluate, and drying the eluate to obtain 8.7mg of raspberry glycoside B.
The raspberry glycoside B is detected by high performance liquid chromatography, and the chromatographic conditions are as follows: c18 ，250 mm × 4.6 mm，5 μm; mobile phase: methanol-water =24: 78; detection wavelength: 210 nm; column temperature: 30 ℃; sample introduction amount: 10 mu l, and the purity of the raspberry glycoside B is more than or equal to 99 percent through the calculation of an area normalization method.
The invention further provides application of the labdane diterpenoid glycoside compound raspberry glycoside B or pharmaceutically acceptable salts thereof in preparing antitumor drugs. The tumor is selected from: gastric cancer, liver cancer, colon cancer or bladder cancer.
The invention also comprises a pharmaceutical composition containing the labdane diterpenoid glycoside compound raspberry glycoside B or pharmaceutically acceptable salts thereof. The pharmaceutical composition further comprises a pharmaceutically acceptable carrier. The pharmaceutical composition is in a form of a formulation suitable for pharmaceutical use, the pharmaceutical formulation being selected from: tablet, capsule, granule, pill, powder, unguent, suspension, injection, suppository, drop, dripping pill, oral liquid or patch.
The labdane diterpenoid glycoside compound raspberry glycoside B is detected by various means such as superconducting nuclear magnetic resonance spectrum, mass spectrum and the like, the chemical structure and the physicochemical properties of the raspberry glycoside B are determined, and the raspberry glycoside B is white powder and is easy to dissolve in organic reagents such as acetone, propylene glycol, pyridine, methanol and the like. UV (CH)3OH) λ max 210 nm。
The experiment proves that the raspberry glycoside B is 1 multiplied by 10-8 mol/L ~ 1×10-5Has obvious inhibiting effect on human gastric cancer cells and human colon cancer cells at mol/L, and IC50Are respectively 6.8μM and 3.6μM。
Drawings
FIG. 1 is a high resolution mass spectrum illustrating the molecular weight of raspberry glycoside B;
FIG. 2 shows nuclear magnetic resonance1H NMR spectrum, which shows hydrogen (-C = C-H, -CH) in raspberry glycoside B structure2OH，-CH-O-，-OCH3Etc.);
FIG. 3 shows nuclear magnetic resonance13C NMR spectrum of raspberry glycoside B structure, which shows carbon (-C = C-, -C = O, -CH)2-O-，-CH-O-，-OCH3Etc.);
FIG. 4 is a nuclear magnetic resonance HSQC spectrum illustrating the assignment of carbon and hydrogen in the raspberry glycoside B structure;
FIG. 5 is a nuclear magnetic resonance HMBC spectrogram, which illustrates the positions of methoxyl, aromatic hydrogen, carbonyl and the like in the raspberry glycoside B structure.
Detailed Description
The invention is further illustrated by the following examples. The following examples must be interpreted to illustrate the invention without limiting it. Simple modifications of the invention in accordance with its spirit fall within the scope of the claimed invention.
Shimadzu LC-2030C 3D Plus type liquid chromatograph (Shimadzu, Japan); shimadzu model 20-AD preparative high performance liquid chromatography (Shimadzu corporation, Japan); buchi medium pressure liquid preparative chromatography (gummy, switzerland); sartorius model BP211D electronic balance (satolis group, germany); an Autopol IV-T/V polarimeter (DKSH, USA); varian UNITY INOVA 600 superconducting nuclear magnetic resonance apparatus (Varian Corp., USA); waters ACQUITY UPLC/Xevo G2Q TOF high resolution mass spectrometer (Waters corporation, USA); an electric heating constant temperature water bath (Shanghai leap into medical instrument factory); EYELA SB-1000 rotary evaporator, model EYELA A-1000S circulating water vacuum pump (EYELA, Japan). Sephadex LH-20 (Amersham Biosciences, Sweden); c18The reverse phase filler is a Japanese YMC product; preparing chromatographic column YMC (10 μm, 250X 20 mm); column chromatography silica gel and thin layer chromatography silica gel are produced by Qingdao ocean factory; the water is Milli-Q first-grade water; the reagents used for chromatography are chromatographic grade reagents; all other reagents used were analytical grade.
Example 1: the extraction and separation method of the labdane diterpenoid glycoside compound raspberry glycoside B in the Rubus chingii Hance comprises the following steps:
the cotyledon of Rubus chingii is collected from Chongren county of Fuzhou city of Jiangxi province, and is identified as Rubus chingii of Rubus by Hakken-Securio of drug detection research institute of Jiangxi provinceRubus chingiiHu stem, specimen was kept in the specimen room of the institute for drug testing, Jiangxi province.
The preparation steps of the raspberry glycoside B are as follows in sequence:
(1) extracting solution of the stems of the Chinese raspberry: 5.5kg of the rubus chingii corm stems are decocted for 2 times by adding water, 55L of water is added for each time, the decoction is decocted for 2 hours each time, and the 2 decoction liquids are combined to obtain rubus chingii corm stem extracting solution;
(2) concentrating the extract of the stems of the Chinese raspberry: concentrating the extract of the seed and stem of Rubus chingii Hemsl under reduced pressure to obtain 3L concentrate;
(3) and (3) extraction: taking 3L of the concentrated solution of the seed stems of the Chinese-east raspberry, adding 60L of purified water for dissolving, firstly extracting with dichloromethane for three times, 60L each time, retaining a water phase, extracting the water phase with ethyl acetate for three times, and combining organic phases to obtain an ethyl acetate extract;
(4) concentrating the extract: concentrating the ethyl acetate extractive solution under reduced pressure to obtain 42.1g ethyl acetate concentrated solution;
(5) and (3) column chromatography separation: dissolving the ethyl acetate concentrated solution with 500ml of methanol, mixing the ethyl acetate concentrated solution with 1:1.5 silica gel, filling the sample into a silica gel chromatographic column by a dry method, wherein the inner diameter of the silica gel chromatographic column is 5cm, the column height is 120cm, the particle size of silica gel filled in the column is 100-200 meshes, and the volume ratio of dichloromethane-methanol = 12: 1,10: 1,9: 1,8: 1,6: 1,5: 1,4: eluting with 4L of eluent at a ratio of 1, collecting 56 parts of eluate fractions, each 500mL, concentrating under reduced pressure to dryness, detecting with thin layer chromatography, combining 25-32 th parts of dried eluate fractions (7.5 g), and purifying with reversed-phase ODS column chromatography, methanol-water = 10: 100 → 100: performing gradient elution for 0, eluting 2L of eluent in each proportion, collecting 100% methanol-eluted fraction, separating the fraction by Sephadex LH-20 column chromatography, eluting with methanol, detecting by TLC to obtain rubusoside B as main spot, and drying to obtain crude product 503mg of rubusoside B;
(6) purification of monomeric compound: the crude product of the raspberry glycoside B is purified by reversed phase high performance preparative liquid chromatography, the chromatographic conditions are as follows: a chromatographic column: c18 5 µm,250mm × 20 mm; detection wavelength: 210 nm; eluting with acetonitrile-water =24:76 as eluent; the flow rate is 10 mL/min; collecting 130min eluate, and drying the eluate to obtain 8.7mg of raspberry glycoside B.
The raspberry glycoside B is detected by high performance liquid chromatography, and the chromatographic conditions are as follows: c18 (250 mm × 4.6 mm，5 μm); mobile phase: methanol-water (24: 78); detection wavelength: 210 nm; column temperature: 30 ℃; sample introduction amount: 10 mu l, and the purity of the raspberry glycoside B is more than or equal to 99 percent through the calculation of an area normalization method.
Example 2: identification of structure of labdane diterpene glycoside compound raspberry glycoside B
The physical and chemical properties of raspberry glycoside B are as follows: white amorphous powder, easily soluble in organic reagent such as acetone, pyridine, methanol, etc., and UV (CH)3OH) λmax210 nm. The ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry gives the peak of the quasi-molecular ionm/z507.2933 [M + Na]+，(calcd for C26H44O8Na, 507.2933), combined1H-NMR and13C-NMR spectrum to determine its molecular formula as C26H44O8。1H and13the C NMR data are shown in Table 1, and the signal attribution of all carbon atoms and hydrogen atoms and the chemical structure of the compound are determined by measuring two-dimensional H-C correlation spectrum (HSQC), H-C remote correlation spectrum (HMBC) and the like. The chemical structural formula is as follows:
note: INOVA 600 MHz;δthe chemical shift is in the unit ppm,1H-NMR and13C-NMR measurement of the solvent to be C5D5N; the attribution of the nuclear magnetic resonance signals is completed on the basis of HSQC and HMBC two-dimensional spectrums.
The compound with the closest structure to the compound of the invention is shown to be goshonoside F2, the structure is compared as follows:
example 3, preparation of goshonoside F2:
(1) extracting solution of the stems of the Chinese raspberry: 5.5kg of the rubus chingii corm stems are decocted for 2 times by adding water, 55L of water is added for each time, the decoction is decocted for 2 hours each time, and the 2 decoction liquids are combined to obtain rubus chingii corm stem extracting solution;
(2) concentrating the extract of the stems of the Chinese raspberry: concentrating the extract of the seed and stem of Rubus chingii Hemsl under reduced pressure to obtain 3L concentrate;
(3) and (3) extraction: taking 3L of the concentrated solution of the seed stems of the Chinese-east raspberry, adding 60L of purified water for dissolving, firstly extracting with dichloromethane for three times, 60L each time, retaining a water phase, extracting the water phase with ethyl acetate for three times, and combining organic phases to obtain an ethyl acetate extract;
(4) concentrating the extract: concentrating the ethyl acetate extractive solution under reduced pressure to obtain 42.1g ethyl acetate concentrated solution;
(5) and (3) column chromatography separation: dissolving the ethyl acetate concentrated solution with 500ml of methanol, mixing the ethyl acetate concentrated solution with 1:1.5 silica gel, filling the sample into a silica gel chromatographic column by a dry method, wherein the inner diameter of the silica gel chromatographic column is 5cm, the column height is 120cm, the particle size of silica gel filled in the column is 100-200 meshes, and the volume ratio of dichloromethane-methanol = 12: 1,10: 1,9: 1,8: 1,6: 1,5: 1,4: eluting with 4L of eluent at a ratio of 1, collecting 56 parts of eluate fractions, each 500mL, concentrating under reduced pressure to dryness, detecting with thin layer chromatography, combining 25-32 th parts of dried eluate fractions (7.5 g), and purifying with reversed-phase ODS column chromatography, methanol-water = 10: 100 → 100: performing gradient elution for 0, eluting 2L of eluent in each proportion, collecting 100% methanol-eluted fraction, separating the fraction by Sephadex LH-20 column chromatography, eluting with methanol, detecting by TLC to obtain rubusoside B as main spot, and drying to obtain crude product 503mg of rubusoside B;
(6) purification of monomeric compound: subjecting crude raspberry glycoside B (503mg) to reverse phase high performance preparative liquid chromatography (column: C)18 5 µm,250mm × 20mm, detection wavelength: 210 nm) and acetonitrile-water (24:76, v/v, 10 mL/min) is used as an eluent, raspberry glycoside B (8.7 mg) of the invention is prepared at 130min through a preparation liquid phase, goshonoside F1 is prepared at 150 min through the preparation liquid phase, goshonoside F1(30.4mg) is obtained after drying, goshonoside F2 is prepared at 180 min through the preparation liquid phase, and goshonoside F2(45.7mg) is obtained after drying.
The raspberry glycoside B, the goshonoside F1 and the goshonoside F2 are detected by high performance liquid chromatography, and the chromatographic conditions are as follows: c18 (250 mm × 4.6 mm，5 μm); mobile phase: methanol-water (24: 78); detection wavelength: 210 nm; column temperature: 30 ℃; sample introduction amount: 10 mu l, calculated by an area normalization method, raspberry glycoside B, goshonoside F1, goshonoside F2 is more than or equal to 99 percent.
Example 4: in vitro antitumor Activity test of labdane diterpene glycoside Compound Raspberry glycoside B
Drugs for experiments: negative control: saline, positive control: goshonoside F2, test agent: the invention relates to a raspberry glucoside B, which comprises raspberry glucoside B,
the test principle is as follows: MTT method: the yellow thiazole blue MTT (3- (4, 5-Aimethylthiazolidiz-2-yl) -2, 5-Aiphenyltetrazolium bromide) can be reduced into insoluble blue-purple formazan (Formanzan) by the dehydrogenase related to NAAP (nicotinamide adenine dinucleotide phosphate, coenzyme II) existing in mitochondria of living cells, the enzyme disappears in dead cells, and the MTT is not reduced. After the formazan is dissolved by AMSO (dimethyl sulfoxide), the optical density (OA) can be detected at 570nm by an enzyme-labeling instrument, and the optical density value is in direct proportion to the number of living cells.
The cell lines used were: HT-1376 (human bladder cancer cells) and HCT-8 (human colon cancer cells).
The test method comprises the following steps:MTT method: taking cells in logarithmic growth phase, digesting, fully blowing and beating into single cell suspension, counting, diluting into 1 × 104 cell/mL, inoculated in 96-well culture plates, 100μL/well. The sample to be tested is designed into 4 concentration levels, the positive control is designed into 1 concentration level, and then 100 is added into the experimental holeμL medium of samples of different concentration levels, each concentration level paralleling 3 wells. The control group was added with an equal volume of solvent. Placing 96-well culture plate at 37 deg.C and 5% CO2After culturing in a saturated humidity incubator for 96 hours, the culture medium was discarded, a freshly prepared serum-free medium containing 0.20 mg/mL MTT was added to each well, and after further culturing at 37 ℃ for 4 hours, the mixture was centrifuged to remove the supernatant. 150 per wellμThe Formazan precipitate was dissolved by L AMSO and placed on a micro-shaker to be shaken for 5 minutes to be fully dissolved. Measuring the rate at 570nm on BIORAA 550 model enzyme standard instrument, plotting to obtain a measurement curve, and reading the Inhibition Concentration (IC) of the drug on the curve50) The value is obtained.
The calculation method comprises the following steps: tumor cell growth inhibition (%) = (1-assay well measurement/control well measurement) × 100%.
The results of the experiments are shown in the following table.
To summarize: raspberry glycoside B has inhibitory effect on human bladder cancer cells and human colon cancer cells, and can be used for developing medicine for treating cancer or tumor.
Claims (8)
1. A compound is raspberry glycoside B, and the structural formula of the compound is shown as the formula (I):
2. the pharmaceutically acceptable salt of the compound of claim 1, wherein the pharmaceutically acceptable salt is a salt of the compound of formula (I) with an alkali metal or an alkaline earth metal.
3. A process for the preparation of a compound according to claim 1, characterized by the following steps in sequence:
(1) extracting solution of the stems of the Chinese raspberry: 5.5kg of the rubus chingii corm stems are decocted for 2 times by adding water, 55L of water is added for each time, the decoction is decocted for 2 hours each time, and the 2 decoction liquids are combined to obtain rubus chingii corm stem extracting solution;
(2) concentrating the extract of the stems of the Chinese raspberry: concentrating the extract of the seed and stem of Rubus chingii Hemsl under reduced pressure to obtain 3L concentrate;
(3) and (3) extraction: taking 3L of the concentrated solution of the seed stems of the Chinese-east raspberry, adding 60L of purified water for dissolving, firstly extracting with dichloromethane for three times, 60L each time, retaining a water phase, extracting the water phase with ethyl acetate for three times, and combining organic phases to obtain an ethyl acetate extract;
(4) concentrating the extract: concentrating the ethyl acetate extractive solution under reduced pressure to obtain 42.1g ethyl acetate concentrated solution;
(5) and (3) column chromatography separation: dissolving the ethyl acetate concentrated solution with 500ml of methanol, mixing the ethyl acetate concentrated solution with 1:1.5 silica gel, filling the sample into a silica gel chromatographic column by a dry method, wherein the inner diameter of the silica gel chromatographic column is 5cm, the column height is 120cm, the particle size of silica gel filled in the column is 100-200 meshes, and the volume ratio of dichloromethane-methanol is 12: 1,10: 1,9: 1,8: 1,6: 1,5: 1,4: eluting with 4L of eluent 1, collecting 56 parts of eluate, collecting 500mL of eluate, concentrating under reduced pressure to dryness, detecting with thin layer chromatography, combining 25-32 th dried eluate fractions 7.5g, and purifying with reversed-phase ODS column chromatography, methanol-water-10: 100 → 100: performing gradient elution for 0, eluting 2L of eluent in each proportion, collecting 100% methanol-eluted fraction, separating the fraction by Sephadex LH-20 column chromatography, eluting with methanol, detecting by TLC to obtain rubusoside B as main spot, and drying to obtain crude product 503mg of rubusoside B;
(6) purification of monomeric compound: the crude product of the raspberry glycoside B is purified by reversed phase high performance preparative liquid chromatography, the chromatographic conditions are as follows: a chromatographic column: c185 μm,250mm × 20 mm; detection wavelength: 210 nm; eluting with acetonitrile-water (24: 76) as eluent; the flow rate is 10 mL/min; collecting the eluate for 130minDrying to obtain raspberry glycoside B8.7 mg.
4. The use of a compound as claimed in claim 1 for the preparation of an antineoplastic medicament.
5. The use according to claim 4, wherein the tumor is selected from the group consisting of: gastric cancer, liver cancer, colon cancer or bladder cancer.
6. A pharmaceutical composition comprising a compound of claim 1 or a pharmaceutically acceptable salt of claim 2.
7. The pharmaceutical composition of claim 6, further comprising a pharmaceutically acceptable carrier.
8. The pharmaceutical composition of claim 7, wherein the pharmaceutical composition is selected from the group consisting of: tablet, capsule, granule, pill, powder, unguent, suspension, injection, suppository, drop, dripping pill, oral liquid or patch.
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| CN103316024A (en) * | 2013-06-18 | 2013-09-25 | 中国人民解放军第二军医大学 | Application of labdane diterpene glycoside compounds in rubus chingii Hu as medicine |
| CN104861010A (en) * | 2014-11-27 | 2015-08-26 | 江西省食品药品检验所 | New labdane diterpene glycoside compound, preparation method therefor and applications |
| CN105085449A (en) * | 2014-05-13 | 2015-11-25 | 上海中医药大学 | Labdane type diterpene derivatives and preparation method and application thereof |
| CN106606506A (en) * | 2015-10-21 | 2017-05-03 | 复旦大学 | Use of enantio-labdane-type diterpene compounds in preparation of anti-complement drugs |
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| CN103316024A (en) * | 2013-06-18 | 2013-09-25 | 中国人民解放军第二军医大学 | Application of labdane diterpene glycoside compounds in rubus chingii Hu as medicine |
| CN105085449A (en) * | 2014-05-13 | 2015-11-25 | 上海中医药大学 | Labdane type diterpene derivatives and preparation method and application thereof |
| CN104861010A (en) * | 2014-11-27 | 2015-08-26 | 江西省食品药品检验所 | New labdane diterpene glycoside compound, preparation method therefor and applications |
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