CN111620809A - Aristolochia lactam compound and preparation method and application thereof - Google Patents
Aristolochia lactam compound and preparation method and application thereof Download PDFInfo
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- CN111620809A CN111620809A CN202010604897.4A CN202010604897A CN111620809A CN 111620809 A CN111620809 A CN 111620809A CN 202010604897 A CN202010604897 A CN 202010604897A CN 111620809 A CN111620809 A CN 111620809A
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- aristololactam
- aristolactam
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- -1 Aristolochia lactam compound Chemical class 0.000 title claims abstract description 20
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- 241000726094 Aristolochia Species 0.000 title abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 19
- 210000002437 synoviocyte Anatomy 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 15
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 11
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 8
- 230000035755 proliferation Effects 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- AADCWJFQHQIXSD-UHFFFAOYSA-N Aristololactam Natural products COC1=C(OC)C=C2C3=C(OC)C(OC)=CC(C(=O)N4C)=C3C4=CC2=C1 AADCWJFQHQIXSD-UHFFFAOYSA-N 0.000 claims description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- 239000000284 extract Substances 0.000 claims description 11
- 239000012046 mixed solvent Substances 0.000 claims description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- 241001189830 Fissistigma Species 0.000 claims description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000003480 eluent Substances 0.000 claims description 9
- 241000776601 Fissistigma oldhamii Species 0.000 claims description 8
- MXOKGWUJNGEKBH-UHFFFAOYSA-N aristololactam Chemical class COC1=CC=CC(C2=C34)=C1C=C3NC(=O)C4=CC1=C2OCO1 MXOKGWUJNGEKBH-UHFFFAOYSA-N 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 239000002808 molecular sieve Substances 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 claims description 6
- 238000004809 thin layer chromatography Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 238000004587 chromatography analysis Methods 0.000 claims description 5
- 238000004440 column chromatography Methods 0.000 claims description 5
- KPVDACWQNCRKTG-UHFFFAOYSA-N Aristololactam II Natural products C=1C(C(=O)N2)=C3C2=CC2=CC=CC=C2C3=C2OCOC2=1 KPVDACWQNCRKTG-UHFFFAOYSA-N 0.000 claims description 4
- 229930187117 aristolactam Natural products 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 238000007865 diluting Methods 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000007791 liquid phase Substances 0.000 claims description 3
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical group CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000741 silica gel Substances 0.000 claims description 3
- 229910002027 silica gel Inorganic materials 0.000 claims description 3
- 239000000725 suspension Substances 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 2
- 238000002791 soaking Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 3
- 230000000694 effects Effects 0.000 abstract description 14
- 230000003356 anti-rheumatic effect Effects 0.000 abstract description 4
- 102000003855 L-lactate dehydrogenase Human genes 0.000 description 10
- 108700023483 L-lactate dehydrogenases Proteins 0.000 description 10
- 229940079593 drug Drugs 0.000 description 10
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 7
- 210000004027 cell Anatomy 0.000 description 6
- 229960000485 methotrexate Drugs 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- 230000003833 cell viability Effects 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- 241000196324 Embryophyta Species 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000011534 incubation Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000006143 cell culture medium Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000012258 culturing Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 241001081440 Annonaceae Species 0.000 description 1
- 235000009025 Carya illinoensis Nutrition 0.000 description 1
- 241001453450 Carya illinoinensis Species 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 239000012228 culture supernatant Substances 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 1
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Rheumatology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an aristolochia lactam compound, which has the following structural formula,
the invention also discloses a preparation method of the compound and application of the compound in preparing a medicament for resisting rheumatoid arthritis. The invention discovers the activity of the compound in inhibiting the proliferation of rheumatoid arthritis synovial cells for the first time, and the compound can be used for preparing the anti-rheumatoid arthritis medicament.
Description
Technical Field
The invention relates to the technical field of phytochemistry, and particularly relates to an aristolochia lactam compound and a preparation method and application thereof.
Background
Fissistigma Oldhamii (Fissistigma titentangense Tsiang et al T.Li) is a plant of Fissistigma Oldhamii of Annonaceae. The plant can be used as medicine, and its stem and leaf can be used for treating fracture and edema, and its whole plant can be used for treating rheumatalgia, deadlimb, etc. The fissistigma angustifolia contains a large amount of compounds, and a new-structure compound with obvious drug effect needs to be extracted urgently, so that the medicinal value of the fissistigma angustifolia is fully exerted.
Disclosure of Invention
The invention aims to provide an aristolochia lactam compound with a new structure, which is extracted and separated from fissistigma angustifolia. And provides a preparation method of the aristololactam compound. The invention finally aims to solve the technical problem of providing the application of the aristololactam compound.
In order to solve the technical problems, the technical scheme adopted by the invention is as follows:
an aristololactam compound, which has the following structural formula:
the preparation method of the preferable aristololactam compound comprises the following steps:
(1) preparation of Fissistigma Oldhamii extract
Cold soaking or hot extracting dry stems of fissistigma angustifolia with 30-95% v/v ethanol solution to obtain an extracting solution, and concentrating under reduced pressure to obtain a paste, namely the fissistigma angustifolia extract;
(2) separating and purifying
Diluting the Fissistigma Oldhamii extract with water to obtain suspension, sequentially extracting with petroleum ether and ethyl acetate, concentrating the ethyl acetate extractive solution under reduced pressure to obtain extract, and separating by column chromatography, thin layer chromatography, and molecular sieve chromatography to obtain the target compound.
Further, in the step (1) and the step (2), the concentration under reduced pressure is carried out at a temperature of 30 to 70 ℃ and a pressure of-0.06 to-0.15 MPa, preferably at a temperature of 40 to 55 ℃, preferably at a pressure of-0.09 to-0.1 MPa, more preferably at a temperature of 45 ℃ and preferably at a pressure of-0.095 MPa.
Further, in the step (1), the volume concentration of the ethanol solution is 70-80%.
Further, in the step (2), the column chromatography conditions are as follows: and (3) loading the mixture to a 200-300-mesh silica gel column, wherein an ethyl acetate-petroleum ether mixed solvent with 10% of ethyl acetate volume percentage is used as an eluent.
Further, in the step (2), the thin layer chromatography conditions are as follows: a methanol-chloroform mixed solvent with 5 percent of methanol volume percentage is taken as a developing solvent.
Further, in the step (2), the molecular sieve chromatography conditions are as follows: the molecular sieve is Sephadex LH-20, and chloroform-methanol mixed solvent with 50% chloroform volume percentage is used as eluent.
Further, in the step (2), the eluent of the high-performance liquid phase is acetonitrile and water with a volume ratio of 60: 40.
The application of the aristololactam compound in preparing the anti-rheumatoid arthritis medicine is also within the protection scope of the invention.
The application of the aristololactam compound in preparing the medicament for inhibiting the proliferation of the synovial cells of the rheumatoid arthritis is also within the protection scope of the invention. Wherein, the synoviocytes are primary rat synoviocytes.
Compared with the prior art, the invention has the beneficial effects that: the aristoloctam A with a new structure extracted and separated from fissistigma zerumbet1Moreover, the invention discovers the activity of the compound in inhibiting the proliferation of rheumatoid arthritis synovial cells for the first time, and the compound can be used for preparing the anti-rheumatoid arthritis medicament.
Drawings
FIG. 1 shows Aristoloctam A, example 1 of the present invention1(1) Hydrogen spectrum of (c);
FIG. 2 shows Aristoloctam A according to example 1 of the present invention1(1) Carbon spectrum of (a).
Detailed Description
In order to better understand the technical content of the invention, specific examples are provided below to further illustrate the invention.
The experimental methods used in the examples of the present invention are all conventional methods unless otherwise specified.
The materials, reagents and the like used in the examples of the present invention can be obtained commercially without specific description.
Example 1: preparation of aristololactam compound.
(1) Extracting 10Kg dry stem of Fissistigma Oldhamii with 75% v/v ethanol solution for 3 times and 7 days to obtain extractive solution, concentrating under reduced pressure to obtain paste, and concentrating at 45 deg.C under-0.095 MPa to obtain 1000g Fissistigma Oldhamii extract.
(2) Diluting the extract with distilled water (3L) to obtain suspension, sequentially extracting with petroleum ether (3L × 3 times) and ethyl acetate (3L × 3 times), concentrating the ethyl acetate extract to obtain extract (about 256g), performing silica gel column chromatography with petroleum ether-ethyl acetate mixed solvent (100: 0-0: 100, V/V) and ethyl acetate-methanol (100: 0-0: 100, V/V) in increasing polarity, and collecting the fraction at 400mL each time. Similar fractions were pooled and split into 9 fractions, Fr.1-9, by TLC detection.
(3) Fr.2 is eluted by using a 200-300-mesh silica gel column, an ethyl acetate-petroleum ether mixed solvent with 10% of ethyl acetate volume percentage is used as an eluent, thin-layer chromatography is carried out by using a methanol-chloroform mixed solvent with 5% of methanol volume percentage as a developing agent, and fractions are combined according to the chromatography effect to obtain 3 components Fr.2-1, Fr.2-2 and Fr.2-3.
(4) Fr.2-2 uses chloroform-methanol mixed solvent with 50% chloroform volume percentage as eluent to carry out molecular sieve Sephadex LH-20 column chromatography to remove pigment to obtain a component Fr.2-2-1, Fr.2-2-1 is analyzed and prepared by high performance liquid phase, the eluent is acetonitrile and water with the volume ratio of 60:40 to obtain a new aristoloctalactam, and the new aristoloctam A is named as aristoloctam A1. The hydrogen spectrum and carbon spectrum are shown in figure 1-2.
Aristolactam A1: as a pale yellow powder. High resolution mass spectrum display of [ M + H ]]+280.0736, indicating that the molecular formula of the compound is C17H13NO4。1H NMR(400MHz,Acetone)9.73,8.75,8.74,7.85,7.83,7.70,7.26,7.25,7.24,7.23,7.10,4.13,3.99。13C NMR (101MHz, Acetone)168.10,157.56,151.89,148.95,129.87,129.33,127.52,123.59,122.64,116.44,113.42,109.29,103.86,59.60, 54.79. According to1H，13CNMR shows that the compound has a framework of aristololactam, and the connection mode of three groups can be determined by the association of 3-OMe and 3-carbon, the association of 6-OMe and 6-carbon, H-8 and C-6/9 and the association of H-2 and C-1/3 in HMBC spectrum. Thus far, the structure of the compound confirmation is shown in the following figure and is named Aristoloctam A1。
Aristolactam A1The results of structural identification of (a) are as follows:
example 2
This example differs from example 1 in that, in step (1), the ethanol solution has a volume concentration of 30%; in the step (1) and the step (2), the concentration temperature is about 35 ℃, and the pressure is-0.15 MPa. The product structure obtained was the same as in example 1.
Example 3
This example differs from example 1 in that, in step (1), the ethanol solution has a volume concentration of 95%; in the step (1) and the step (2), the concentration temperature is about 65 ℃, and the pressure is-0.06 MPa. The product structure obtained was the same as in example 1.
Test example: pharmacological Activity test
Experimental Material
Cell: synoviocytes (primary rat synoviocytes).
Cell culture solution: primary rat synovial cell culture medium.
Reagent: thiazole blue (3- (4, 5-dimethylthiozol-2-yl) -2, 5-diphenyltetrazolium bromide, MTT, Sigma). Lactate Dehydrogenase (LDH) kit (available from pecan). Methotrexate (MTX, Shanghai Xinyi pharmaceutical Co., Ltd.). 1.4 Instrument: 96-well cell culture plates; an infinite 200Pro multifunctional microplate reader.
Experimental methods
MTT method for determining inhibitory effect of drug on synovial cells
Synovial cells were inoculated into 96-well plates (1 × 10) at log phase4Individual cells/well) set as blank group (no drug administration), methotrexate group (1. mu.g/mL methotrexate administration), administration group (10, 50, 100. mu.g/mL drug administration-Aristoctam A prepared in example 11) And the culture was incubated overnight before the experiment. After 48 hours of incubation in which cells were administered with different concentrations of drugs, 10. mu.L of MTT at a concentration of 5mg/mL was added to each well, and after further incubation for 4 hours, the culture supernatant was carefully discarded, 100. mu.L of DMSO was added to each well to dissolve formazan crystals, and after complete dissolution, the optical density (OD value) was measured at 570nm with a microplate reader after shaking 5min at room temperature. Cell viability was calculated from the OD values.
LDH Activity assay to determine the Effect of drugs on synovial cell viability
Synovial cells were inoculated into 96-well plates (1 × 10) at log phase4Individual cells/well) set as blank group (no drug administration), methotrexate group (1. mu.g/mL methotrexate administration), administration group (10, 50, 100. mu.g/mL drug administration-Aristoctam A prepared in example 11) And culturing and incubating overnight, taking cell supernatant after the culture of each group of cells is finished, and detecting the LDH activity by using an LDH detection kit. The activity of LDH was calculated according to the following formula.
Statistical method
Experimental data were analyzed using SPSS 22.0 statistical software. Results are given as mean. + -. standard deviation
Show that differences between groups were analyzed by one-way ANOVA. With P<0.05 was considered statistically different. IC of the sample tested50Values were obtained by analyzing experimental data with SPSS 22.0 statistical software.
Results of the experiment
(1) MTT method for determining inhibitory effect of drug on synovial cells
After culturing for 48h by using drugs with different concentrations, the MTT method detects the cell proliferation effect. Detecting IC of a sample50The values are as follows:
compound aristoctam A1IC of50IC of positive control (methotrexate) with a value of 3.2. mu.M50The value was 1.2. mu.M. The results show that the compound Aristoctam A1Has good inhibitory effect on synovial cells.
(2) LDH Activity assay to determine the Effect of drugs on synovial cell viability
After 48h of incubation with different concentrations of drug, cell viability was measured by the LDH activity assay. The results show that LDH activity in cell culture media is not greatly biased after treatment with different concentrations of drug.
The above results show that Aristolochia lactam compound Aristoloctam A1Has good inhibitory effect on synovial cells and has little influence on LDH activity in cell culture solution. Experiments show that the aristololactam compound has good effect of resisting rheumatoid arthritis and can be used for preparing the anti-rheumatoid arthritis medicament.
Claims (10)
1. An aristololactam compound, which is characterized by the following structural formula:
2. the process for producing aristolactam compound according to claim 1, comprising the steps of:
(1) preparation of Fissistigma Oldhamii extract
Cold soaking or hot extracting dry stems of fissistigma angustifolia with 30-95% v/v ethanol solution to obtain an extracting solution, and concentrating under reduced pressure to obtain a paste, namely the fissistigma angustifolia extract;
(2) separating and purifying
Diluting the Fissistigma Oldhamii extract with water to obtain suspension, sequentially extracting with petroleum ether and ethyl acetate, concentrating the ethyl acetate extractive solution under reduced pressure to obtain extract, and separating by column chromatography, thin layer chromatography, and molecular sieve chromatography to obtain the target compound.
3. The method for producing aristolactam compounds according to claim 2, wherein the concentration under reduced pressure in step (1) and step (2) is performed at 30 to 70 ℃ and at a pressure of-0.06 to-0.15 MPa.
4. The method for preparing aristololactam compounds according to claim 2, wherein in step (1), the volume concentration of the ethanol solution is 70-80%; in the step (1) and the step (2), the concentration is carried out under reduced pressure, the temperature is 40-55 ℃, and the pressure is-0.09 to-0.1 MPa.
5. The method for preparing aristololactam compound according to claim 2, wherein in step (2), the column chromatography conditions are as follows: and (3) loading the mixture to a 200-300-mesh silica gel column, wherein an ethyl acetate-petroleum ether mixed solvent with 10% of ethyl acetate volume percentage is used as an eluent.
6. The method for producing aristolactam compounds according to claim 2, wherein in step (2), said thin layer chromatography conditions are: a methanol-chloroform mixed solvent with 5 percent of methanol volume percentage is taken as a developing solvent.
7. The method for producing aristolactam compounds according to claim 2, wherein in step (2), the molecular sieve chromatography conditions are: the molecular sieve is Sephadex LH-20, and chloroform-methanol mixed solvent with 50% chloroform volume percentage is used as eluent.
8. The method for preparing aristolactam compound according to claim 2, wherein in step (2), the eluent with high performance liquid phase is acetonitrile and water with volume ratio of 60: 40.
9. Use of the aristololactam compound of claim 1 in the preparation of a medicament for treating rheumatoid arthritis.
10. Use of the aristololactam compound of claim 1 in the preparation of a medicament for inhibiting the proliferation of synovial cells in rheumatoid arthritis.
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| CN103288790A (en) * | 2013-06-28 | 2013-09-11 | 天津医科大学 | Preparation method and application of triterpenoid with effect of resisting rheumatoid arthritis |
| CN105641005A (en) * | 2015-11-11 | 2016-06-08 | 海南师范大学 | Fissistigma tungfangense extract, preparation method and applications thereof |
| CN107118218A (en) * | 2017-05-25 | 2017-09-01 | 海南大学 | The preparation method and its usage of aristolo-lactam class noval chemical compound |
| CN109232384A (en) * | 2018-09-05 | 2019-01-18 | 海南师范大学 | Aristolo-lactam class compound and its preparation method and application |
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