CN110746387B - Clerodane diterpene derivative, preparation method thereof and anti-inflammatory drug or inflammatory reaction inhibitor thereof - Google Patents
Clerodane diterpene derivative, preparation method thereof and anti-inflammatory drug or inflammatory reaction inhibitor thereof Download PDFInfo
- Publication number
- CN110746387B CN110746387B CN201911158677.7A CN201911158677A CN110746387B CN 110746387 B CN110746387 B CN 110746387B CN 201911158677 A CN201911158677 A CN 201911158677A CN 110746387 B CN110746387 B CN 110746387B
- Authority
- CN
- China
- Prior art keywords
- clerodane
- inflammatory
- diterpene derivative
- acetone
- silica gel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/58—One oxygen atom, e.g. butenolide
-
- 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]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
The invention discloses a clerodane diterpenoid derivative, a preparation method and an anti-inflammatory drug or an inflammatory reaction inhibitor thereof.
Description
Technical Field
The invention relates to the technical field of medicaments, in particular to a clerodane diterpenoid derivative, a preparation method and an anti-inflammatory medicament or an inflammatory reaction inhibitor thereof.
Background
Inflammation is a complex reaction of vascularized tissues to infection, exotoxin or cellular injury, involving the extravascular accumulation of plasma proteins and leukocytes, with symptoms often manifested as redness, swelling, fever, pain, etc. in the tissues. Inflammation is important for protecting the body from injury from endogenous or exogenous sources. However, abnormal or overactivated immune responses may cause damage to normal cells, tissues and organs. In addition to acute and chronic inflammation and autoimmune diseases, inflammation, a pathological condition, also induces and affects the development and progression of other diseases, such as cancer, alzheimer's disease, cardiovascular diseases, and the like.
There are many stimuli that induce inflammation, and when a body is infected by, for example, pathogenic microorganisms, pathogen-associated molecular patterns (PAMPs) are recognized, and the recognized signals are transmitted through Toll-like receptors (TLRs), CD14 receptors and other cytokine receptors, thereby triggering a series of defensive reactions, promoting the release of Cytokines (Cytokines), chemokines (Chemokines) and Growth Factors (Growth Factors) in the body, and allowing lymphocytes to migrate to the stimulated site, and finally triggering inflammation. Bacterial Lipopolysaccharide (LPS), a type of PAMPs, is a component of the cell wall of gram-negative bacteria that induces activation of multiple intracellular inflammatory signaling pathways, resulting in the release of a number of inflammatory mediators. Under the stimulation of the polypeptide, the expression levels of various proinflammatory cytokines such as tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and the like are obviously increased, and the polypeptide plays an important role in the inflammatory reaction process. Therefore, the inflammatory response of macrophages induced by LPS as a model for in vitro study of the mechanism of cellular inflammation has become a common way to study cellular inflammatory responses.
Anti-inflammatory drugs are the second largest class of drugs that are used in clinical quantities second to anti-infective drugs, and therefore, the development of new anti-inflammatory drugs is an urgent need and research focus.
Chinese has a long-standing Chinese herbal medicine research and application tradition, and a natural product is an important medicine molecule source. Beautyberry plants are used for treating various diseases such as inflammation, rheumatism, allergy, hemorrhage and the like in folk, but the research on the anti-inflammatory active ingredients of the beautyberry plants is not sufficient.
Hitherto, there have been no reports of the clerodane-type diterpene derivatives shown in the present application, no reports of pharmaceutical compositions containing the clerodane-type diterpene derivatives as an active ingredient, and no reports of applications of the clerodane-type diterpene derivatives and the pharmaceutical compositions thereof shown in the present application to the preparation of drugs for diseases caused by inflammation.
Disclosure of Invention
The invention aims to provide a clerodane diterpenoid derivative, a preparation method and an anti-inflammatory drug or an inflammatory reaction inhibitor thereof, so as to seek a substitute scheme of the existing anti-inflammatory drug.
In order to solve the technical problem, the invention adopts the following technical scheme:
a clerodane diterpene derivative has the following structural formula:
an anti-inflammatory drug or an inflammatory reaction inhibitor, a pharmaceutical composition containing a therapeutically effective amount of the aforementioned clerodane-type diterpene derivative, and a pharmaceutically acceptable carrier or excipient.
Further, for the treatment of inflammatory diseases, including but not limited to inflammation, sepsis, arthritis, and obesity, as well as diseases caused or mediated by inflammation.
A method for preparing clerodane diterpene derivatives comprises sequentially pretreating, extracting, purifying and separating stem and leaf of Callicarpa integrifolia to obtain clerodane diterpene derivatives.
Preferably, the pretreatment is drying and pulverizing whole callicarpa integrifolia stems and leaves.
Preferably, the extraction is carried out by extracting pulverized callicarpa fuliginosa stems and leaves with 70% acetone/water solution at room temperature.
Preferably, the product obtained by extraction is sequentially extracted by petroleum ether, ethyl acetate and n-butanol, and then the obtained extract is subjected to reduced pressure concentration and decoloration by MCI (micro porous silica gel) resin to obtain an extract.
Preferably, the separation is:
1) Dissolving the extract with chloroform, adsorbing on silica gel, evaporating at 20-25 deg.C until the solvent is evaporated, grinding, performing silica gel column chromatography, and gradient eluting with chloroform/methanol of 1;
2) Sectioning the part B obtained in the step 1) by adopting medium-pressure reverse-phase C-18 column chromatography, and carrying out gradient elution by using 10-100% methanol-water solution as an eluent to obtain B1-B8 fractions in sequence;
3) Passing the part B2 of the step 2) through a silica gel column, and taking petroleum ether-acetone as an eluent, specifically carrying out elution in 4 gradients, wherein the volume ratios of the 4 gradients of petroleum ether-acetone are respectively 10, 1 and 1;
4) Purifying the part B27 obtained in the step 3) by a silica gel column, and carrying out isocratic elution by using chloroform-acetone as an eluent with the volume ratio of 6) to obtain a B271-B276 fraction successively;
5) Separating the part B276 of the step 4) by using semi-preparative HPLC and acetonitrile-water with the volume ratio of 85 to 15 as an eluent to obtain the clerodane diterpene derivative.
Compared with the prior art, the invention has the beneficial effects that:
when the compound of the present invention is used as a medicament, it may be used as it is or in the form of a pharmaceutical composition. The pharmaceutical composition contains 0.1-99%, preferably 0.5-90% of the compound of the present invention, the balance being pharmaceutically acceptable, pharmaceutically acceptable carriers and/or excipients that are non-toxic and inert to humans and animals.
The pharmaceutically acceptable carrier or excipient is one or more of solid, semi-solid and liquid diluents, fillers and pharmaceutical adjuvants. The pharmaceutical composition of the present invention is used in the form of a dose per unit body weight. The medicine of the present invention may be orally taken and injected into intravenous injection and intramuscular injection.
Description of the drawings:
FIG. 1 shows the ELISA method for detecting the secretion of inflammatory factors IL-1 beta (A), IL-6 (B) and TNF alpha (C) in the cell culture supernatants of the treated group and the control group of the clerodane diterpene derivative I.
FIG. 2 is a structural diagram of X-single crystal diffraction of the clerodane diterpenoid derivative I of the invention
Detailed Description
In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is described in further detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and do not limit the invention.
The application discloses a clerodane diterpenoid derivative, which has a structural formula I as follows:
an anti-inflammatory drug or an inflammation reaction inhibitor, which comprises a pharmaceutical composition containing a therapeutically effective amount of the clerodane diterpene derivative and a pharmaceutically acceptable carrier or excipient, is used for treating inflammatory diseases and diseases caused or mediated by inflammation, wherein the inflammatory diseases comprise but are not limited to inflammation, septicemia, arthritis and obesity.
The preparation method of the clerodane diterpenoid derivative,
the method comprises the following steps: drying and pulverizing folium Callicarpae Formosanae;
extraction: extracting pulverized folium Callicarpae Formosanae stem and leaf with 70% acetone/water solution at room temperature;
and (3) purification: sequentially extracting the product obtained by extraction with petroleum ether, ethyl acetate and n-butyl alcohol, then carrying out reduced pressure concentration on the obtained extract liquor, and decoloring with MCI (methyl cellulose iodide) microporous resin to obtain an extract;
separation:
1) Dissolving the extract with chloroform, adsorbing on silica gel, evaporating at 20-25 deg.C until the solvent is evaporated, grinding, performing silica gel column chromatography, and gradient eluting with chloroform/methanol of 1;
2) Sectioning the part B obtained in the step 1) by adopting medium-pressure reverse-phase C-18 column chromatography, and carrying out gradient elution by using 10-100% methanol-water solution as an eluent to obtain B1-B8 fractions in sequence;
3) Passing the part B2 of the step 2) through a silica gel column, and taking petroleum ether-acetone as an eluent, specifically carrying out elution in 4 gradients, wherein the volume ratios of the 4 gradients of petroleum ether-acetone are respectively 10, 1 and 1;
4) Purifying the part B27 obtained in the step 3) by a silica gel column, and carrying out isocratic elution by using chloroform-acetone as an eluent with the volume ratio of 6) to obtain a B271-B276 fraction successively;
5) Separating the part B276 of the step 4) by using semi-preparative HPLC and acetonitrile-water with the volume ratio of 85 to 15 as an eluent to obtain the clerodane diterpene derivative.
Test example: inhibition of inflammation by clerodane diterpenoid derivatives I:
1. materials and methods
1.1 materials:
a clerodane-type diterpene derivative I; DMSO; RPMI 1640 medium; BI serum; penicillin streptomycin mixed solution mouse macrophage; mouse IL-1 beta ELISA kit; murine IL-6 ELISA kits; mouse TNF α ELISA kit.
1.2 solution preparation:
(1) RPMI 1640 complete medium preparation. Adding 10% serum and double antibody into the RPMI 1640 culture medium to prepare a complete RPMI 1640 culture solution;
(2) ELISA wash was formulated with 1XPBS with 0.05% Tween.
1.3 instruments
LabservK3 microplate reader; a cell incubator; clean bench.
1.4 Experimental procedures:
the clerodane-type diterpene derivative I was diluted to 50mM with DMSO, and macrophages were plated on 12-well cell culture plates. After the cells are attached to the wall, a DMSO control group and an Xci-17 drug group are set, the drugs or DMSO are added 2h in advance, 100ng/mL LPS is added for treatment for 0 h, 4 h and 8h respectively, nigericin is added into each hole for treatment for 30min in order to detect the secretion of IL-1 beta, and supernatant protein is collected for ELISA detection of various inflammatory factors. First, IL-1 beta, IL-6 and TNF alpha capture antibody solution is prepared by using coating buffer solution, added into an enzyme label plate and coated overnight at 4 ℃. Add 150. Mu.L ELISA wash to each well 5 times for 1min each time. Add 50. Mu.L of blocking solution to each well, and block for 1h at room temperature. Add 150. Mu.L ELISA wash to each well 5 times for 1min each time. Add 25. Mu.L of cell culture supernatant to each well, add the gradiently diluted protein standards to the remaining wells, incubate for 2h at room temperature. Add 150. Mu.L ELISA wash to each well 5 times for 1min each time. Add 25. Mu.L of detection antibody to each well and incubate for 1h at room temperature. Add 150. Mu.L ELISA wash to each well 5 times for 1min each time. mu.L of the corresponding secondary antibody solution was added to each well and incubated for 30min at room temperature in the dark. Add 150. Mu.L ELISA wash to each well 7 times for 2min each. Add 25. Mu.L of ELISA stop solution to each well. Finally, the ELISA plate is placed in an ELISA reader, and the value is read by laser with the wavelength of 450 nm.
2. As a result:
a standard curve is drawn according to the standard well data, and the secretion amount of the corresponding inflammatory factor in each sample is calculated by using the standard curve, and the specific result is shown in FIG. 1.
3. Conclusion
The experimental result shows that the clerodane diterpenoid derivative I can remarkably inhibit the secretion of inflammatory factors induced by LPS. The clodronane diterpenoid derivative I has obvious anti-inflammatory activity.
Example (b):
the preparation method of the clerodane diterpenoid derivative comprises the following steps:
1) Drying and pulverizing stem and leaf of folium Callicarpae Formosanae;
2) Extracting the stem and leaf parts of the callicarpa integrifolia crushed in the step 1) for 3 times at room temperature by using 70% acetone/water, combining acetone extracting solutions, filtering, and concentrating under reduced pressure;
3) Suspending the extracting solution obtained in the step 2) in an aqueous solution, sequentially extracting with petroleum ether, ethyl acetate and n-butanol, concentrating the ethyl acetate extraction part under reduced pressure, and decolorizing with MCI to obtain an extract;
4) Dissolving the extract obtained in the step 3) by using chloroform, adsorbing the extract on silica gel, putting the extract at room temperature until the solvent is volatilized, grinding the extract, performing silica gel column chromatography, and performing gradient elution by using chloroform/methanol of 1;
5) Sectioning the part B obtained in the step 4) by adopting medium-pressure reverse-phase C-18 column chromatography, and carrying out gradient elution by using 10-100% methanol-water solution as an eluent to obtain B1-B8 fractions in sequence;
6) Passing the part B2 of the step 5) through a silica gel column, and taking petroleum ether-acetone as an eluent, specifically carrying out elution in 4 gradients, wherein the volume ratios of the 4 gradients of petroleum ether-acetone are respectively 10, 1 and 1;
7) Purifying the part B27 obtained in the step 6) by a silica gel column, and carrying out isocratic elution by using chloroform-acetone as an eluent with the volume ratio of 6) to obtain a B271-B276 fraction successively;
8) Separating the part B276 of the step 7) by using semi-preparative HPLC and acetonitrile-water with the volume ratio of 85 to 15 as an eluent to obtain the clerodane diterpene derivative.
The semi-preparative HPLC used in this example was Agilent 1260 and a 9.4mm × 25cm Zorbax SB-C18 column; medium pressure liquid chromatography Lisui EZ purification III System was purchased from Shanghai Lisui Co., ltd; thin-layer chromatography silica gel and column chromatography silica gel of 100-200 meshes and 200-300 meshes are purchased from Qingdao Meigaoji Co., ltd; the reverse C18 silica gel was Lichroprep-18gel, 40-63 μm, available from Merck, darmstadt, germany, MCI-gel CHP-20P available from Mitsubishi Chemical corporation; sephadex LH-20 was purchased from Pharmacia. The structure of the above compound is as follows 1 H， 13 C NMR, IR, UV and mass spectral data were determined.
Structural data of clerodane diterpene derivative I:
the optical rotation was measured by SEPA-300 and Jascomodel 1020 polarimeters; infrared spectroscopy (IR) by KBr pellet method using a Tenor 27 type infrared spectrometer; the ultraviolet spectrum is measured by a UV-2401A type ultraviolet spectrometer; nuclear magnetic resonance spectrum is measured by Brucker AV-600 type, acetone is used as solvent, tetramethylsilane is used as internal standard; high resolution mass spectra were determined using an API Qstar Pulsar mass spectrometer.
The NMR data of the compounds are shown in tables 1 and 2; the number of the carbon atoms of the clerodane diterpenoid skeleton is shown as the following structural formula.
TABLE 1 preparation of the Clerodane-type diterpene derivatives (1-9) in the invention 1 H NMR spectral data Attribution (600 MHz, acetone) (delta: ppm, J: hz)
Table 2 this hairProcess for preparing diterpene derivatives of clerodane type in the mine 13 C NMR spectral data Attribution (600 MHz, acetone) (delta: ppm, J: hz)
Clerodane diterpene derivative I, needle crystal, [ alpha ]] 22 D -61.3(c 0.21,MeOH)；HRESIMS m/z 341.2086[M+Na] + Molecular formula C 20 H 30 O 3 (ii) a The molecular unsaturation was 6. 13 C-NMR and DEPT spectral data show 20 carbon signals, sp 2 5 hybridized carbons; combined infrared spectrum at 1747,1642,1073cm -1 There are clear absorption peaks at the equivalent, which can be assigned to 1 ester carbonyl and 2 double bonds. From the above, there should also be three different ring systems in the compound.
1 H– 1 Related signal H in H COSY spectrum 2 -1/H 2 -2/H 2 -3,H 3 -17/H-8,H 2 11/H-12, suggesting three ring system structural fragments. In HMBC spectrum, H 2 -1 and C-3; h 2 -2 with C-1 and C-3; h 3 -18 with C-3, C-4 and C-5; h 3 -19 and C-4 and C-6; h-10 with C-1 and C-19; h 2 -7 and C-5; h 3 -17 and C-7 and C-8; h 3 20 with C-8 and C-10, it is possible to deduce the A/B fused bicyclic framework fragment; then according to H 3 -20 and C-11; h 2 -11 and C-13; h-12 with C-9 and C-11; h-14 and C-15 and C-16, it is presumed that the compound is a five-membered lactone ring formed by connecting the C-15 and C-12 positions.
Also, as shown in FIG. 2, signals H-10 and H-8 are related by ROESY; h-8 and H-12; h 3 -19 and H 3 20, and considering the angle of the biosynthesis of the clerodane diterpene, the relative configuration of the compound can be presumed. The absolute spatial configuration of the compound is further diffracted according to a copper target X-single crystal [ Flack coefficient is-0.1 (2)]As a result of data analysis, the absolute configuration was determined to be 5R,8R,9S,10R,12S, and this compound was named Integrimine F.
Example 2:
the clerodane diterpene derivative I is prepared by the method of example 1, dissolved in a small amount of DMSO respectively, added with water for injection by a conventional method, finely filtered, encapsulated and sterilized to prepare injection.
Example 3:
the preparation method comprises the following steps of preparing the clerodane diterpene derivative I according to the method of the example 1, dissolving the clerodane diterpene derivative I in a small amount of DMSO respectively, dissolving the clerodane diterpene derivative I in sterile water for injection, stirring to dissolve the clerodane diterpene derivative I, filtering the obtained product by using a sterile suction filter funnel, performing sterile fine filtration, subpackaging the obtained product in ampoules, performing freeze drying at a low temperature, and performing sterile melt sealing to obtain the powder injection.
Example 4:
and (3) adding an excipient into the separated clerodane diterpenoid derivative I according to the weight ratio of the clerodane diterpenoid derivative I to the excipient of 9.
Example 5:
the method of example 1 is firstly used for preparing the clerodane diterpenoid derivative I, and excipients are respectively added according to the weight ratio of the clerodane diterpenoid derivative I to the excipients being 5.
Example 6:
the clerodane diterpene derivative I was prepared according to the method of example 1, and oral liquids were prepared according to the conventional oral liquid preparation method.
Example 7:
the clerodane diterpene derivative I is prepared according to the method of example 1, and the excipient is added according to the weight ratio of the clerodane diterpene derivative I to the excipient of 5.
Example 8:
the clerodane diterpene derivative I is prepared according to the method of example 1, and the excipient is added according to the weight ratio of the clerodane diterpene derivative I to the excipient of 3.
Although the invention has been described herein with reference to a number of illustrative embodiments thereof, it should be understood that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the spirit and scope of the principles of this disclosure. More specifically, various variations and modifications are possible in the component parts and/or arrangements of the subject combination arrangement within the scope of the disclosure, the drawings and the appended claims. In addition to variations and modifications in the component parts and/or arrangements, other uses will also be apparent to those skilled in the art.
Claims (6)
1. A clerodane diterpenoid derivative is characterized in that the structural formula is as follows:
2. an anti-inflammatory agent or an inflammatory reaction inhibitor, which comprises a therapeutically effective amount of the clerodane-type diterpene derivative according to claim 1 and a pharmaceutically acceptable carrier or excipient.
3. The anti-inflammatory agent or the inhibitor of inflammatory response according to claim 2, which is used for the treatment of inflammatory diseases and diseases caused or mediated by inflammation.
4. A process for producing the clerodane-type diterpene derivative according to claim 1, which comprises: comprises sequentially pretreating, extracting, purifying and separating callicarpa integrifolia stems and leaves to obtain the clerodane diterpene derivative;
sequentially extracting the extracted product with petroleum ether, ethyl acetate and n-butanol, concentrating the ethyl acetate extraction part under reduced pressure, and decolorizing with MCI small-pore resin to obtain extract;
1) Dissolving the extract with chloroform, adsorbing on silica gel, evaporating at 20-25 deg.C until the solvent is evaporated, grinding, performing silica gel column chromatography, and gradient eluting with chloroform/methanol of 1;
2) Partitioning the part B obtained in the step 1) by adopting medium-pressure reversed-phase C-18 column chromatography, and carrying out gradient elution by using 10-100% methanol-water solution as an eluent to obtain fractions B1-B8 successively;
3) Passing the part B2 of the step 2) through a silica gel column, and taking petroleum ether-acetone as an eluent, specifically carrying out elution in 4 gradients, wherein the volume ratios of the 4 gradients of petroleum ether-acetone are respectively 10, 1 and 1;
4) Purifying the part B27 obtained in the step 3) by a silica gel column, and carrying out isocratic elution by using chloroform-acetone as an eluent with the volume ratio of 6) to obtain a B271-B276 fraction successively;
5) Separating the part B276 of the step 4) by using semi-preparative HPLC and acetonitrile-water with the volume ratio of 85 to 15 as an eluent to obtain the clerodane diterpene derivative.
5. The method for producing the clerodane-type diterpene derivative according to claim 4, wherein the pretreatment comprises drying and pulverizing the stems and leaves of callicarpa fuliginosa.
6. The method for producing a clerodane-type diterpene derivative according to claim 4, wherein the extraction is carried out by extracting pulverized leaves and stems of Callicarpa integrifolia with a 70% acetone/water solution at room temperature.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911158677.7A CN110746387B (en) | 2019-11-22 | 2019-11-22 | Clerodane diterpene derivative, preparation method thereof and anti-inflammatory drug or inflammatory reaction inhibitor thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911158677.7A CN110746387B (en) | 2019-11-22 | 2019-11-22 | Clerodane diterpene derivative, preparation method thereof and anti-inflammatory drug or inflammatory reaction inhibitor thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN110746387A CN110746387A (en) | 2020-02-04 |
| CN110746387B true CN110746387B (en) | 2023-04-07 |
Family
ID=69284312
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201911158677.7A Active CN110746387B (en) | 2019-11-22 | 2019-11-22 | Clerodane diterpene derivative, preparation method thereof and anti-inflammatory drug or inflammatory reaction inhibitor thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN110746387B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113754533B (en) * | 2021-08-26 | 2023-12-01 | 海南师范大学 | Oxidized labdane diterpenoid compound, and separation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101550161A (en) * | 2008-04-03 | 2009-10-07 | 山东靶点药物研究有限公司 | Andrographolide derivative, salt, preparation method and application thereof |
| CN106074499A (en) * | 2016-06-02 | 2016-11-09 | 杭州更蓝生物科技有限公司 | The application in medicine of a kind of Crow alkane type diterpene-kind compound |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011057332A1 (en) * | 2009-11-10 | 2011-05-19 | University Of South Australia | Anti-inflammatory compounds |
-
2019
- 2019-11-22 CN CN201911158677.7A patent/CN110746387B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101550161A (en) * | 2008-04-03 | 2009-10-07 | 山东靶点药物研究有限公司 | Andrographolide derivative, salt, preparation method and application thereof |
| CN106074499A (en) * | 2016-06-02 | 2016-11-09 | 杭州更蓝生物科技有限公司 | The application in medicine of a kind of Crow alkane type diterpene-kind compound |
Non-Patent Citations (2)
| Title |
|---|
| Labdane diterpenes from Chloranthus serratus;Mi Zhang等;《Fitoterapia》;20130830;第91卷;第95-99页 * |
| 海南暗罗根克罗烷型二萜化学成分研究;李小宝等;《有机化学》;20170623;第37卷;第2763-2766页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN110746387A (en) | 2020-02-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109897077B (en) | Compound Oleraceamide E in purslane, and extraction separation method and application thereof | |
| CN114031579B (en) | Preparation and application of daphnane diterpenoid compounds in lilac daphne flower buds | |
| CN108129295B (en) | Abietane diterpene derivative and pharmaceutical composition and application thereof | |
| CN110746387B (en) | Clerodane diterpene derivative, preparation method thereof and anti-inflammatory drug or inflammatory reaction inhibitor thereof | |
| CN114213473A (en) | Three alkaloid compounds in purslane and extraction and separation method thereof | |
| CN111548327B (en) | Carbon-reduced kaurane diterpene, preparation method thereof and application thereof in preparation of antitumor drugs | |
| Engels et al. | A new diterpene and anti-inflammatory sesquiterpene lactones from Sigesbeckia orientalis | |
| CN108689969B (en) | Method for separating and purifying vanillin diterpenoid compounds in frankincense | |
| CN114213375B (en) | Sesquiterpene lactone compound and preparation method and application thereof | |
| CN111808153B (en) | Monoterpene glycoside compound and application thereof in preparation of anti-inflammatory drugs | |
| CN116120222A (en) | Antitumor and antiviral compound Talachalasin A-C and preparation method and application thereof | |
| Qiu et al. | Benzofuran ε-caprolactam glucosides, amides and phenylpropanoid derivatives with anti-inflammatory activity from Oxybaphus himalaicus | |
| CN111909228B (en) | Alkaloid compound and preparation method and application thereof | |
| CN111995645B (en) | Phenylpropanoid compound and preparation method and application thereof | |
| CN109503684B (en) | Iridoid glycoside compound and preparation method and application thereof | |
| CN110204589B (en) | Effective component of feather cockscomb seed, extraction method and application thereof in preparing neuroprotective medicament | |
| CN108478619B (en) | Convolvulus arvensis total resin glucoside extract, preparation method and medical application thereof | |
| CA3120117C (en) | Compounds for preventing and treating inflammation, preparation method and use thereof | |
| CN109734696A (en) | A kind of new diepoxy lignan compound and preparation method thereof | |
| CN115433152B (en) | Compound separated from golden silk plum fruit, preparation method and application | |
| CN116768912B (en) | Spiroindolone alkaloid compound in Isatis tinctoria as well as preparation method and application thereof | |
| CN114853713B (en) | Sesquiterpenoids in jellyfish herba Saussureae Involueratae, and extraction and separation method and application thereof | |
| CN114805465B (en) | Triterpene compound, preparation method and application thereof | |
| CN116333029B (en) | Tea seed saponin compound and application thereof | |
| CN116903578B (en) | Phenolic acid compound in Glechoma hederacea as well as extraction and separation method and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |