CN115160336B - Oxygen-containing five-membered ring derivative of euphorbia lathyris alkane diterpene, preparation method and application thereof - Google Patents
Oxygen-containing five-membered ring derivative of euphorbia lathyris alkane diterpene, preparation method and application thereof Download PDFInfo
- Publication number
- CN115160336B CN115160336B CN202210859063.7A CN202210859063A CN115160336B CN 115160336 B CN115160336 B CN 115160336B CN 202210859063 A CN202210859063 A CN 202210859063A CN 115160336 B CN115160336 B CN 115160336B
- Authority
- CN
- China
- Prior art keywords
- membered ring
- euphorbia
- beta
- methyl
- oxygen
- 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
Classifications
-
- C—CHEMISTRY; METALLURGY
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/72—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 spiro-condensed with carbocyclic rings
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides an oxygen-containing five-membered ring derivative of a follower alkane type diterpene, a preparation method thereof and application thereof in preparing antitumor drugs. The oxygen-containing five-membered ring derivative of the euphorbia lathyris diterpene is any one of 1 beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1,1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1 and 1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L3. Compared with the Euphorbia pekinensis L1 (EFL 1) and the Euphorbia pekinensis L1 (EFL 3), the oxygen-containing five-membered ring derivative of the euphorbia pekinensis provided by the invention has remarkable anti-tumor activity, can be used for preparing anti-tumor drugs, and is an anti-tumor active compound with development value.
Description
Technical Field
The invention belongs to the field of pharmaceutical chemistry, relates to oxygen-containing five-membered ring derivatives of euphorbia pekinensis L1 and euphorbia pekinensis L3, and in particular relates to an oxygen-containing five-membered ring derivative of euphorbia pekinensis diterpene, a preparation method of the oxygen-containing five-membered ring derivative and application of the oxygen-containing five-membered ring derivative in preparation of antitumor drugs.
Background
The prior art discloses that euphorbia factor L1 (EFL 1) and euphorbia factor L3 (EFL 3) belong to euphorbia lathyris diterpenoid compounds, are rich in content, have obvious anti-tumor multi-drug resistance (MDR), but have no tumor cytotoxic activity. The research of structure-activity relationship shows that the difference of substituent groups on the parent nucleus can obviously change the MDR activity of the compound.
Studies have disclosed that euphorbia lathyris diterpene compounds were first isolated from euphorbia lathyris Euphorbia lathyris L (Tetrahedron Letters,1971, 18:1325-1328). Subsequently, a plurality of euphorbia-lathyris diterpenoid derivatives were also isolated from other plants, such as 5 euphorbia-lathyris diterpenoid ester derivatives with tumor cell apoptosis inducing and antitumor multi-drug resistance activities isolated from euphorbiaceae plant Euphorbia lagascae (Planta medical, 2005,72:162-168). At present, the structural modification of the syntenic alkane diterpenoid compound mainly comprises the aspects of hydrolysis of side chain ester bonds, acylation of side chain hydroxyl groups and the like, wherein some antitumor MDR active derivatives (Bioorganic) with good activity are also obtained&Medicinal Chemistry,2014, 22:6392-6400). But with backbone functional groups such as C-14 carbonyl, C 12/13 Double bond and C 6/17 The effect of double bonds or epoxy on their activity is not yet clear.
Disclosure of Invention
Borane (BH) 3 ) Reducible carbonyl groups and double bonds, diisobutylaluminum hydride (Dibal) readily reduces carbonyl groups in the α, β -unsaturated ketone structure. The invention utilizes BH 3 And Dibal respectively reduces double bonds and carbonyl groups at C-14 positions of the EFL1 and the EFL3 to obtain oxygen-containing five-membered ring derivatives of follow-up alkane diterpenes, and the anti-tumor activity of the oxygen-containing five-membered ring derivatives is researched.
The specific technical scheme of the invention is as follows:
the invention provides an oxygen-containing five-membered ring derivative of euphorbia lathyris diterpene, which is characterized in that the oxygen-containing five-membered ring derivative of euphorbia lathyris diterpene is any one of 1 'beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1, 1' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1 and 1 'beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L3, wherein the structural formulas of 1' beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1,1 'beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1 and 1' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) eup factor L3 are respectively shown as the following formulas 1-3:
the invention also provides a preparation method of the oxygen-containing five-membered ring derivative of the euphorbia lathyris diterpene, which is characterized in that the synthetic route is shown as a and b:
the preparation method of the oxygen-containing five-membered ring derivative of the follow-up alkane diterpene provided by the invention can also have the technical characteristics that the specific process of the synthetic route a is as follows: dissolving EFL1 in anhydrous tetrahydrofuran, dropwise adding BH at-20deg.C 3 Then slowly heating to room temperature in an ice-water bath, stirring and reacting for 4 hours, adding water to quench the reaction after the reaction is completed, adding dichloromethane to extract, washing an organic layer by saturated saline water, removing water by anhydrous magnesium sulfate, filtering, concentrating the filtrate under reduced pressure, and separating by a silica gel chromatographic column and semi-preparative HPLC to obtain 1 beta-methyl-14, 15- (1, 3-dioxygen five-membered ring) -13-ene euphorbia factor L1 and 1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxygen five-membered ring) euphorbia factor L1.
The preparation method of the oxygen-containing five-membered ring derivative of the follow-up alkane diterpene provided by the invention can also have the technical characteristics that the specific process of the synthetic route b is as follows: dissolving EFL3 in anhydrous THF, dropwise adding Dibal at-78 ℃, stirring under the protection of nitrogen at-78 ℃ for 2h, adding ethyl acetate for quenching reaction, gradually heating to room temperature, stirring for 1h, adding saturated ammonium chloride solution, dropwise adding a small amount of 1M diluted hydrochloric acid, adding ethyl acetate for extraction, washing with saturated saline water, dehydrating with anhydrous magnesium sulfate, filtering, concentrating the filtrate under reduced pressure, and separating by a silica gel chromatographic column and semi-preparative HPLC to obtain 1' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxygen five-membered ring) euphorbia factor L3.
The invention also provides application of the oxygen-containing five-membered ring derivative of the euphorbia lathyris diterpenoid in preparing antitumor drugs.
Effects and effects of the invention
Because the oxygen-containing five-membered ring derivative of the follower alkane diterpene provided by the invention utilizes BH 3 EFL1 and Dibal are subjected to chemical modification on EFL3 to obtain 1 beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1,1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1 and 1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L3.
Therefore, compared with the euphorbia factor L1 (EFL 1) and the euphorbia factor L1 (EFL 3), the oxygen-containing five-membered ring derivative of the euphorbia lathyris diterpene provided by the invention has remarkable antitumor activity, can be used for preparing antitumor drugs, and is an antitumor active compound with development value.
Drawings
FIG. 1 is a structural formula of an oxygen-containing five-membered ring derivative of a follower-alkane-type diterpene of an embodiment of the present invention.
Detailed Description
The following examples illustrate the specific steps of the present invention, but are not limited thereto.
The terms used in the present invention generally have meanings commonly understood by those of ordinary skill in the art unless otherwise indicated.
In the following examples, various processes and methods, which are not described in detail, are conventional methods well known in the art.
The reagents used in the examples below are commercially available in general, and the experimental procedures and conditions not noted are referred to in the art as conventional procedures and conditions.
Specific embodiments of the present invention will be described below with reference to examples and drawings.
Example 1 ]
This example provides 2 oxygen-containing five-membered ring derivatives of follower alkane diterpenes, 1 "beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1 and 1" beta-methyl-14α -hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1, the structural formulas are shown in the following formulas 1 and 2, respectively:
the embodiment also provides a preparation method of the oxygen-containing five-membered ring derivative of the euphorbia lathyris diterpene, and the synthetic route is shown in the following figure a:
the specific process is as follows:
EFL1 (100 mg,0.181 mmol) was dissolved in anhydrous THF and BH was added dropwise at-20 ℃ 3 (0.54mL,0.54mmol,1M in THF,3.0equiv) then slowly warmed to room temperature in an ice-water bath, stirred for 4h, quenched with water after completion of the reaction, extracted with dichloromethane, the organic layer washed with saturated brine, dehydrated with anhydrous magnesium sulfate, filtered, and the filtrate concentrated under reduced pressure and separated by silica gel chromatography (petroleum ether-ethyl acetate, 20-5:1) and semi-preparative HPLC to give 1 "beta-methyl-14, 15- (1, 3-dioxofive-membered ring) -13-eneeuphorbia factor L1 (20 mg, yield 21%) and 1" beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxofive-membered ring) euphorbia factor L1 (35 mg, yield 35%),
wherein, semi-preparative HPLC chromatography conditions were as follows:
chromatographic column: ODS-A (10.0X105 mm,5 μm, YMC); the flow rate is 2.5mL/min; column temperature: 25 ℃; DAD detection wavelength: 230nm and 280nm; mobile phase: the acetonitrile-water system was eluted isocratically.
1: mobile phase: 97% acetonitrile; retention time: 18min;
2: mobile phase: 80% acetonitrile; retention time: 14min.
Example 2 ]
The embodiment provides an oxygen-containing five-membered ring derivative of a follower alkane type diterpene, 1' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L3, and the structural formula is shown as the following formula 3:
the embodiment also provides a preparation method of the oxygen-containing five-membered ring derivative of the euphorbia lathyris diterpene, and the synthetic route is shown in the following figure b:
the specific process is as follows:
EFL3 (100 mg,0.186 mmol) was dissolved in anhydrous THF, dibal (0.7mL,0.7mmol,1M in hexane,3.8equiv) was added dropwise at-78deg.C, stirred at 78deg.C under nitrogen protection to react for 2h, quenched with ethyl acetate, gradually warmed to room temperature, stirred for 1h, saturated ammonium chloride solution was added dropwise with a small amount of 1M diluted hydrochloric acid, extracted with ethyl acetate, washed with saturated saline solution, dehydrated with anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, separated by silica gel chromatography column (petroleum ether-ethyl acetate, 20-5:1) and semi-preparative HPLC to give 1 "beta-methyl-14α -hydroxy-14, 15- (1, 3-dioxypentad ring) euphorbia factor L3 (14 mg, 15% yield),
wherein, semi-preparative HPLC chromatography conditions were as follows:
chromatographic column: ODS-A (10.0X105 mm,5 μm, YMC); the flow rate is 2.5mL/min; column temperature: 25 ℃; DAD detection wavelength: 230nm and 280nm; mobile phase: the acetonitrile-water system was eluted isocratically. Mobile phase 80% acetonitrile; retention time: 25min.
< test example >
The test example comprises the steps of spotting the oxygen-containing five-membered ring derivative solution of the euphorbia lathyris diterpene in examples 1 and 2 on a silica gel thin layer plate, expanding the solution by a petroleum ether-ethyl acetate (5:1) ascending method, taking out and airing the solvent, spraying 10% sulfuric acid-ethanol solution, heating and developing the solution, wherein the sample spot is a brick red-brown spot in the silica gel thin layer plate, the Rf value of 1 ' beta-methyl-14, 15- (1, 3-dioxo five-membered ring) -13-ene euphorbia factor L1 is 0.8,1 ' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxo five-membered ring) euphorbia factor L1 is 0.4,1 ' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxo five-membered ring) euphorbia factor L3 is 0.3, the Rf value of the raw material EFL1 is 0.3, and the Rf value of EFL3 is 0.5.
NMR (600 MHz, CDCl) of oxygen-containing five-membered ring derivatives of the subsequently alkane-type diterpenes of examples 1 and 2 3 ) Analytical testing, NMR structural identification data are listed in table 1.
TABLE 1
"-" indicates no derivative peak therein.
From the NMR structural identification data, it was found that the structures of the oxygen-containing five-membered ring derivatives of the follower-alkane diterpenes of examples 1 and 2 were identical to those of formulas 1 to 3.
The present test example also carried out the evaluation of tumor cytotoxic activity on the oxygen-containing five-membered ring derivatives of the follower alkane diterpenes of examples 1 and 2, the specific procedure is as follows:
using MCF-7 and MCF-7/ADM as models, the cell culture medium was RPMI-1640 medium containing 10% fetal bovine serum. Taking cells with good logarithmic phase, blowing a culture medium after pancreatin digestion to enable adherent cells to fall off, counting to obtain cell suspensions, inoculating the cell suspensions into 96-well plates, wherein the number of the cells is 1 multiplied by 104 per well, the volume of the cell suspensions is 190 mu L per well, dividing the cell suspensions into a sample group, an ADM control group, a negative control group and a blank control group, and placing the cell suspensions into a cell incubator for conventional culture for 24 hours in each group of 3 multiple wells.
Stock solutions of samples to be tested (oxygen-containing five-membered ring derivatives of the euphorbia lathyris of examples 1 and 2) were diluted to serial concentrations of 1000.0, 500.0, 250.0 and 125.0. Mu.M (final concentrations of 50.0, 25.0, 12.5 and 6.25. Mu.M) in complete medium containing 10% FBS, and ADM stock solutions were diluted to serial concentrations of 1000.0, 500.0, 250.0 and 125.0. Mu.M (final concentrations of 50.0, 25.0, 12.5 and 6.25. Mu.M) in complete medium containing 10% FBS, respectively.
After 24h, the cells are attached, 10 mu L of sample-containing culture medium and ADM-containing culture medium with different concentrations are respectively added according to grouping and concentration setting, a complete culture solution containing 0.1% DMSO is used as a negative control group, and a hole without inoculating cells and only containing the complete culture medium is used as a blank control group. The 96-well plate was placed at 37℃in 5% CO 2 Sterile culturing in saturated humidity incubator for 48 hr, adding MTT solution 20 μl per well, culturing for 4 hr, and discarding the old culture solution. 150 μl of DMSO was added to each well and shaken on a plate shaker for 10min to allow complete dissolution of the purple crystals. The absorbance (OD) of each well was measured using a microplate reader at a detection wavelength of 570 nm. Taking the logarithm of the average cell inhibition rate of each concentration and the concentration of the sample to be tested or ADM to carry out linear regression (GGraphpad Prism V9.0.0), a standard curve of logarithmic value of sample concentration versus cell inhibition was obtained, and IC of sample or ADM to cells was calculated at 50% cell inhibition 50 . MTT experiments were repeated 3 times, IC 50 Results are expressed as mean ± variance.
The result of evaluating the cytotoxic activity of tumor shows that the oxygen-containing five-membered ring derivative of euphorbia lathyris diterpene is used for IC (integrated circuit) cytotoxicity of MCF-7 and MCF-7/ADM (tumor cell death factor) 50 27.5/17.8, 25.9/25.8 and 23.8/15.3. Mu.M, EFL1 and EFL3 for two cells, respectively 50 All are larger than 100 mu M, which indicates that the raw materials EFL1 and EFL3 have no tumor cytotoxicity, but the oxygen-containing five-membered ring derivative of the chemically modified follow-up alkane diterpene has obviously improved cytotoxicity.
The foregoing is a detailed description of the embodiments, convenient those skilled in the art are able to make and use the present invention. Those skilled in the art, based on the present invention, should not be subjected to innovative work, but rather should be able to obtain improvements or modifications by means of analysis, analogies or limited enumeration, etc. within the scope of protection defined by the following claims.
Claims (3)
1. An oxygen-containing five-membered ring derivative of euphorbia lathyris diterpene is characterized in that the oxygen-containing five-membered ring derivative of euphorbia lathyris diterpene lathyris is any one of 1 beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1,1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1 and 1 beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L3,
wherein the structural formulas of the 1 ' beta-methyl-14, 15- (1, 3-dioxy five-membered ring) -13-ene euphorbia factor L1, the 1 ' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L1 and the 1 ' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxy five-membered ring) euphorbia factor L3 are respectively shown in the following formulas 1-3:
2. a process for the preparation of an oxygen-containing five-membered ring derivative of a follower-alkane diterpene according to claim 1, wherein the synthetic routes are as shown in a and b:
the specific process of the synthetic route a is as follows:
dissolving EFL1 in anhydrous tetrahydrofuran, dropwise adding BH at-20deg.C 3 Then slowly heating to room temperature in an ice-water bath, stirring and reacting for 4 hours, adding water to quench the reaction after the reaction is completed, adding dichloromethane to extract, washing an organic layer by saturated saline water, removing water by anhydrous magnesium sulfate, filtering, concentrating the filtrate under reduced pressure, separating by a silica gel chromatographic column and semi-preparative HPLC to obtain the 1 'beta-methyl-14, 15- (1, 3-dioxygen five-membered ring) -13-ene euphorbia factor L1 and the 1' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxygen five-membered ring) euphorbia factor L1,
the specific process of the synthetic route b is as follows:
dissolving EFL3 in anhydrous THF, dropwise adding Dibal at-78 ℃, stirring under the protection of nitrogen at-78 ℃ for 2 hours, adding ethyl acetate for quenching reaction, gradually heating to room temperature, stirring for 1 hour, adding saturated ammonium chloride solution, dropwise adding a small amount of 1M diluted hydrochloric acid, adding ethyl acetate for extraction, washing with saturated saline water, dehydrating with anhydrous magnesium sulfate, filtering, concentrating the filtrate under reduced pressure, and separating by a silica gel chromatographic column and semi-preparative HPLC to obtain the 1' beta-methyl-14 alpha-hydroxy-14, 15- (1, 3-dioxygen five-membered ring) euphorbia factor L3.
3. Use of an oxygen-containing five-membered ring derivative of a euphorbia lathyris diterpene according to claim 1 for the preparation of an antitumor drug for inhibiting the activity of MCF-7 cells and MCF-7/ADM cells.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210859063.7A CN115160336B (en) | 2022-07-21 | 2022-07-21 | Oxygen-containing five-membered ring derivative of euphorbia lathyris alkane diterpene, preparation method and application thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210859063.7A CN115160336B (en) | 2022-07-21 | 2022-07-21 | Oxygen-containing five-membered ring derivative of euphorbia lathyris alkane diterpene, preparation method and application thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115160336A CN115160336A (en) | 2022-10-11 |
| CN115160336B true CN115160336B (en) | 2023-10-03 |
Family
ID=83495309
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210859063.7A Active CN115160336B (en) | 2022-07-21 | 2022-07-21 | Oxygen-containing five-membered ring derivative of euphorbia lathyris alkane diterpene, preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115160336B (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110540504A (en) * | 2018-05-29 | 2019-12-06 | 复旦大学 | Preparation method of ingenane diterpene and application thereof in pharmacy |
| CN111592462A (en) * | 2020-06-09 | 2020-08-28 | 中国科学院新疆理化技术研究所 | Macrocyclic diterpenoid compounds separated from euphorbia multocida as well as preparation method and application thereof |
| CN113200950A (en) * | 2021-05-25 | 2021-08-03 | 中国科学院成都生物研究所 | Euphorbia lathyris diterpene derivatives and application thereof |
| CN113277934A (en) * | 2021-05-25 | 2021-08-20 | 中国科学院成都生物研究所 | Euphorbia lathyris diterpene derivatives with MDR reversion activity and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2408507B1 (en) * | 2011-10-04 | 2014-04-21 | Vivacell Biotechnology España, S.L | INGENOL INSULATION METHOD. |
-
2022
- 2022-07-21 CN CN202210859063.7A patent/CN115160336B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110540504A (en) * | 2018-05-29 | 2019-12-06 | 复旦大学 | Preparation method of ingenane diterpene and application thereof in pharmacy |
| CN111592462A (en) * | 2020-06-09 | 2020-08-28 | 中国科学院新疆理化技术研究所 | Macrocyclic diterpenoid compounds separated from euphorbia multocida as well as preparation method and application thereof |
| CN113200950A (en) * | 2021-05-25 | 2021-08-03 | 中国科学院成都生物研究所 | Euphorbia lathyris diterpene derivatives and application thereof |
| CN113277934A (en) * | 2021-05-25 | 2021-08-20 | 中国科学院成都生物研究所 | Euphorbia lathyris diterpene derivatives with MDR reversion activity and application thereof |
Non-Patent Citations (3)
| Title |
|---|
| Cytotoxic Lathyrane-Type Diterpenes from Seeds of Euphorbia lathyris;Jia-Xi Wang 等;《Chem. Pharm. Bull.》;第66卷;674-677 * |
| Lathyrane-type diterpenoids from the seeds of Euphorbia lathyris;Jin Lu 等;《Phytochemistry》;第104卷;79-88 * |
| Lewis acid-mediated skeleton transformation of Euphorbia diterpenes: From lathyrane to euphoractane and myrsinane;Jia-Xi Wang 等;《Fitoterapia》;第133卷;212-218 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115160336A (en) | 2022-10-11 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108117507B (en) | Synthesis method and application of azaspiro cyclohexadienone | |
| CN109575093B (en) | Alkene estrogen compound and preparation and application thereof | |
| CN115160336B (en) | Oxygen-containing five-membered ring derivative of euphorbia lathyris alkane diterpene, preparation method and application thereof | |
| CN113173857B (en) | Cannabidiol derivative and preparation method and application thereof | |
| CN115197200B (en) | Trifluoromethyl tertiary alcohol and synthetic method and application thereof | |
| EP0736535B1 (en) | Process for the production of dihydroartemisin-hemisuccinate | |
| DE60318059T2 (en) | MANUFACTURE OF ISOFLAVONES | |
| CN111333495B (en) | (4-methoxy-3-hydroxyphenyl) (3, 5-dimethyl-2-hydroxyphenyl) ketone, and preparation method and application thereof | |
| CN117624200A (en) | Boron-containing derivative of euphorbia lathyris diterpene and application of boron-containing derivative in preparation of antitumor drugs | |
| CN108329300B (en) | Nitrobenzo [ d ] aza-quinazoline compound and preparation method and application thereof | |
| CN109096239B (en) | Preparation route of 9-anthrone lactone framework compound and application of analogue thereof in antitumor aspect | |
| CN108276384B (en) | acetaminobenzo [ d ] azepinyl quinazoline compound and preparation and application thereof | |
| CN101270119A (en) | Technique for purifying spherosinin from leguminosae pointvetch or milk vetch | |
| CN111892486B (en) | Hydroxyl-substituted benzophenone compound and preparation method and application thereof | |
| Ichihara et al. | The structure of zinnolide, a new phytotoxin from Alternaria solani | |
| CN111004145A (en) | Chiral optical amide substituted α -diamino acid derivative and preparation method and application thereof | |
| CN117209404A (en) | Rearranged derivative of skeleton structure of euphorbia factor L1 and application thereof in pharmacy | |
| CN113292573B (en) | Indolizine chromogen ketone compound with anti-tumor activity and preparation method and application thereof | |
| CN111518117B (en) | 1, 2-oxazinopyran compound and preparation method and application thereof | |
| CN112812015B (en) | Heteroditerpenoid compound containing four-membered ring, preparation method and application thereof, and pharmaceutical composition | |
| CN112062743B (en) | Resveratrol derivative and application thereof | |
| CN110684033B (en) | Tetrahydrofuran diquinoline compound and synthesis method and application thereof | |
| CN110483506B (en) | Novel method for constructing 2- (2-thienyl) imidazole [1,2-a ] pyridine-3-aldehyde by using DMF as formylation reagent | |
| CN109879873B (en) | Tetrahydrodibenzonaphthyridine compound and synthesis method and application thereof | |
| CN108078993B (en) | Application of 6-nitroquinazoline compound in preparation of medicine for treating lung cancer |
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 |