CN108727169B - Preparation method of marine fungus-derived diphenyl ether compound and application of compound as antibacterial agent - Google Patents
Preparation method of marine fungus-derived diphenyl ether compound and application of compound as antibacterial agent Download PDFInfo
- Publication number
- CN108727169B CN108727169B CN201710275997.5A CN201710275997A CN108727169B CN 108727169 B CN108727169 B CN 108727169B CN 201710275997 A CN201710275997 A CN 201710275997A CN 108727169 B CN108727169 B CN 108727169B
- Authority
- CN
- China
- Prior art keywords
- chromatographic separation
- culture
- compounds
- fermentation
- gel column
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
- C07C43/295—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/38—Separation; Purification; Stabilisation; Use of additives by liquid-liquid treatment
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
- C12P7/00—Preparation of oxygen-containing organic compounds
- C12P7/02—Preparation of oxygen-containing organic compounds containing a hydroxy group
- C12P7/22—Preparation of oxygen-containing organic compounds containing a hydroxy group aromatic
-
- 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
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Wood Science & Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Health & Medical Sciences (AREA)
- General Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Biotechnology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention belongs to the field of secondary metabolites of marine fungi, and particularly relates to a preparation method of a biphenyl ether compound derived from marine fungi and application of the biphenyl ether compound as an antibacterial agent. The biphenyl ether compound provided by the invention has a structure shown as a compound 1 or 2:
Description
Technical Field
The invention belongs to the field of secondary metabolites of marine fungi, and particularly relates to a preparation method of a biphenyl ether compound derived from marine fungi and application of the biphenyl ether compound as an antibacterial agent.
Background
In recent years, the resistance of bacteria has become an extremely serious problem due to the unjustified use of antibacterial drugs. The World Health Organization (WHO) states that the appearance of "superbacteria" in 2010 indicates a rapid development of bacterial resistance, posing a great threat to human life health. In order to reduce the generation of bacterial drug resistance, the development of new high-sensitivity antibacterial drugs is urgently needed to improve the effectiveness of clinical drugs. Under the conditions of high salt, high pressure, low light and the like of the sea, the marine microorganisms can generate a large amount of secondary metabolites with novel structures and unique activities, and a plurality of compounds have antibacterial activity and provide an important source for searching potential antibacterial drug lead compounds. Cephalosporin (Cephalosporin) is an antibiotic widely used clinically after penicillin, and its originally discovered source is just a secondary metabolite of marine microorganisms. In recent years, with the development of marine natural medicinal chemistry, more and more antibacterial active compounds are continuously separated from marine microorganisms, and a material basis is provided for searching for novel antibacterial agents. The method of artificial culture fermentation is adopted to obtain secondary metabolites with important antibacterial activity from marine microorganisms, has the characteristics of environmental friendliness, sustainable development and the like, and can effectively solve key problems of medicine sources and the like in the process of medicine development, thereby having unique advantages.
Disclosure of Invention
The invention provides a marine fungus Phoma sp, which is separated from two-branch bud of juncus effusury, wherein the two-branch bud of juncus effusury is collected from the West Islands of south China sea in 2008 in 9 months by an inventor. The strain preservation information of the marine fungus Phoma sp: the name of the depository: china general microbiological culture Collection center; the address of the depository: western road No.1, north west city of township, beijing, institute of microbiology, china academy of sciences; the preservation date is as follows: year 2017, month 4 and day 1; the preservation number is: CGMCC No. 13881; and (3) classification and naming: phoma sp.
The present invention provides a biphenyl ether compound or a pharmaceutically acceptable salt thereof, characterized in that the biphenyl ether compound has a structure represented by compound 1 or 2:
the invention provides a method for simultaneously preparing compounds 1 and 2, which is characterized by comprising the following steps: firstly, carrying out strain culture on marine fungi Phoma sp in a strain culture medium, then carrying out fermentation culture on the marine fungi in a fermentation culture medium to obtain a fermentation product, leaching the fermentation product for 2-6 times by using ethyl acetate, merging ethyl acetate leaching liquor, carrying out reduced pressure concentration to obtain a crude extract, and carrying out chromatographic separation to obtain compounds 1 and 2; wherein the strain culture medium contains glucose, yeast extract, peptone, agar, crude sea salt and water; the fermentation culture medium contains rice, crude sea salt and water; the chromatographic separation is sequentially carried out by normal phase silica gel column chromatographic separation, gel column chromatographic separation and high performance liquid chromatographic separation.
The culture medium of the strain in the preparation method preferably contains 0.10-10% (weight percentage, the same below) of glucose, 0.01-4.0% of yeast extract, 0.01-4.0% of peptone, 0.10-6.0% of agar, 0.05-10% of crude sea salt and the balance of water; the culture temperature is preferably 5-45 ℃; the culture time is preferably 3-10 days; the fermentation culture medium preferably contains 50-150 g of rice, 0.05-10 g of crude sea salt and 50-150 mL of water in each 500mL conical flask; the culture temperature is preferably 5-45 ℃; the culture time is preferably 5-50 days; the normal phase silica gel column chromatographic separation adopts a mixed solvent of ethyl acetate-petroleum ether with a stationary phase of 200-300 meshes and a mobile phase of 30-40% (volume percentage, the same below); the stationary phase adopted by the gel column chromatographic separation is sephadex LH-20, and the mobile phase is petroleum ether: dichloromethane: a mixed solvent of methanol 2:1:1 (volume ratio); the high performance liquid chromatography adopts a semi-preparative C18 chromatographic column (Kromasil,7 mu m,10 multiplied by 250mm) and a mobile phase of 60-65% (volume percent) of methanol-water mixed solvent.
The present invention provides an antibacterial agent characterized by containing a compound 1 and/or 2 or a pharmaceutically acceptable salt thereof as an active ingredient; other antibacterial active ingredients and/or pharmaceutically acceptable carriers or excipients may also be included.
The present invention provides the use of compound 1 and/or 2 or a pharmaceutically acceptable salt thereof for the manufacture of a medicament for the prevention and/or treatment of a disease caused by Staphylococcus albus (Staphylococcus albus), Staphylococcus aureus (s.aureus), Escherichia coli (Escherichia coli), or Vibrio parahaemolyticus (Vibrio parahaemolyticus).
The term "pharmaceutically acceptable salts" as used herein refers to non-toxic inorganic or organic acid and/or base addition salts, as described in "Salt selection for basic drugs", int.J.pharm. (1986),33, 201-217.
Detailed Description
In order to facilitate a further understanding of the invention, the following examples are provided to illustrate it in more detail. However, these examples are only for better understanding of the present invention and are not intended to limit the scope or the principle of the present invention, and the embodiments of the present invention are not limited to the following.
Example 1
(1) Culture of marine fungus Phoma sp
The culture medium used for culturing the strain of fungus Phoma sp contains 1.0% of glucose (weight percentage, the same below), 0.1% of yeast extract, 0.2% of peptone, 1.0% of agar, 3.0% of crude sea salt, and the balance of water, and is prepared into a test tube slant when in use, and the fungus strain is cultured for 5 days at 28 ℃.
(2) Fermentation of marine fungi Phoma sp
The fermentation culture medium used for the fermentation culture of the fungus Phoma sp is that each 500mL conical flask contains 80g of rice, 2g of crude sea salt and 120mL of water, and the fungus strain is kept stand for fermentation culture for 28 days at 25-28 ℃ to obtain a fermentation product; a total of 50 500mL Erlenmeyer flasks were used for fermentation.
(3) Isolation and extraction of Compounds 1 and 2 of the invention
Taking the fermentation product obtained in the step (2), leaching for 3 times by using ethyl acetate, decompressing and concentrating the leaching liquor to obtain a crude extract, and firstly carrying out normal phase silica gel column chromatographic separation, wherein the stationary phase is as follows: 200-300 mesh silica gel, mobile phase: eluting 5 column volumes by using 30 percent (volume percentage) of ethyl acetate-petroleum ether mixed solvent, concentrating the eluent, and then carrying out Sephadex LH20 gel column chromatographic separation, wherein the mobile phase is as follows: petroleum ether: dichloromethane: eluting 3 column volumes with a mixed solvent of methanol 2:1:1 (volume ratio), concentrating the eluent, and separating by high performance liquid chromatography, wherein the stationary phase: semi-preparative C18 chromatography column (Kromasil,7 μm,10 × 250mm), mobile phase: 60% -65% of methanol-water mixed solvent, and preparing to obtain the compounds 1 and 2, which are white powder.
Compound 1:
structure confirmation data:1H NMR(CD3OD,600MHz)δ:6.49(1H,s,H-3),6.24(1H,brs,H-4′),6.15(1H,brs,H-6′),6.02(1H,brs,H-2′),3.81(3H,s,4-OMe),3.70(3H,s,5-OMe),2.18(3H,s,5′-Me),1.98(3H,s,6-Me)；13C NMR(CD3OD,150MHz)δ:160.8(C,C-1′),159.4(C,C-3′),151.7(C,C-4),147.5(C,C-2),141.4(C,C-5′),141.3(C,C-5),134.7(C,C-1),127.2(C,C-6),110.4(CH,C-4′),108.1(CH,C-6′),100.3(CH,C-2′),100.0(CH,C-3),61.0(CH3,5-OMe),56.4(CH3,4-OMe),21.6(CH3,5′-Me),9.8(CH3,6-Me).HRESIMS m/z291.1168[M+H]+(calcd for C16H19O5,291.1227).
compound 2
Structure confirmation data: ESIMS M/z 261.8[ M + H ]]+543.3,[2M+Na]+,559.3[2M+K]+.
Example 2
(1) Culture of marine fungus Phoma sp
The strain culture medium contains glucose 0.10-10 wt%, yeast extract 0.01-4.0 wt%, peptone 0.01-4.0 wt%, agar 0.10-6.0 wt%, coarse sea salt 0.05-10 wt%, and water in balance; the culture temperature is 5-45 ℃; the culture time is 3-10 days.
(2) Fermentation of marine fungi Phoma sp
The fermentation medium is that each 500mL conical flask contains 50-150 g of rice, 0.05-10 g of crude sea salt and 50-150 mL of water; the fermentation culture temperature is 5-45 ℃; fermenting and culturing for 20-50 days to obtain fermented product.
(3) Isolation and extraction of Compounds 1 and 2 of the invention
Taking the fermentation product obtained in the step (2), leaching for 2-6 times by using ethyl acetate to obtain an ethyl acetate leaching liquor, concentrating the leaching liquor under reduced pressure to obtain a crude extract, performing normal phase silica gel column chromatographic separation, wherein the adopted stationary phase is 200-300 meshes of silica gel, and the adopted mobile phase is 30-40% (volume percentage) of ethyl acetate-petroleum ether mixed solvent to obtain a crude component A, and performing gel column chromatographic separation, wherein the selected stationary phase is sephadex LH-20, and the mobile phase is petroleum ether: dichloromethane: the crude fraction B was obtained by mixing 2:1:1 (vol.%) methanol in a mixed solvent, and the crude fraction B was finally subjected to high performance liquid chromatography using a semi-preparative C18 column (Kromasil,7 μm,10 × 250mm) and a 60% -65% (vol.%) methanol/water mixed solvent as the mobile phase to give compounds 1 and 2. The structural confirmation data for compounds 1 and 2 are consistent with the corresponding data in example 1.
The conditions for culturing and fermenting other strains and other experimental operating conditions such as normal phase silica gel column chromatographic separation, high performance liquid chiral chromatographic separation and the like which are not specifically indicated in the examples 1-2 are all conventional experimental operating conditions in the field, and a person skilled in the art can reasonably select the conditions according to actual needs.
Example 3
Carrying out strain culture on marine fungi Phoma sp in a strain culture medium, carrying out fermentation culture on the marine fungi in a fermentation culture medium, leaching a fermentation product with ethyl acetate for 2-6 times, carrying out reduced pressure distillation on the leaching solution to obtain a crude extract, carrying out chromatographic separation to obtain 2 white powdery compounds, namely compounds 1 and 2, wherein the structure confirmation data of the compounds are consistent with the corresponding data in the example 1. Wherein the strain culture medium contains glucose, yeast extract, peptone, agar, crude sea salt and water, and the fermentation culture medium contains rice, crude sea salt and water; the chromatographic separation is sequentially carried out by adopting normal phase silica gel column chromatographic separation, gel column chromatographic separation and high performance liquid chromatographic separation.
In order to search for more widely applicable methods for preparing the compounds 1 and 2 of the present invention, the components of the strain culture medium and the fermentation medium in this example are added in the conventional ratio in the art or in any ratio, and the specifications of silica gel and gel used in chromatographic separation, the type of chromatographic column and the choice of elution solvent are all conventional choices in the art. The experimental results show that the compounds 1 and 2 of the present invention can be obtained by the above conventionally selected preparation methods, and the structure confirmation data are consistent with the corresponding data in example 1, but only slight differences exist in the purity and yield of the compounds.
The results of examples 1-3 show that compounds 1 and 2 of the present invention can be obtained by culturing, fermenting, separating and purifying marine fungi Phoma sp according to the conventional culture and fermentation conditions of the strain in the art, and the conventional conditions of normal phase silica gel column chromatography, gel column chromatography and high performance liquid chromatography. The method for producing the compounds 1 and 2 of the present invention is preferably the method described in example 1-2.
Example 4
Determination of antibacterial Activity of Compounds 1 and 2 of the present invention
(1) Compounds 1 and 2 of the invention were tested against 2 gram-positive bacteria according to literature methods (Pierce c.g.; Uppuluri p.; teisan a.r.; Wormley jr.f.l.; Mowat e.; Ramage g.; Lopez-ribot j.l.nat. protoc.2008,3, 1494-: staphylococcus aureus (s.aureus), staphylococcus albus (s.albus), and 3 gram-negative bacteria: antibacterial activity of Escherichia coli (E.coli), Vibrio parahaemolyticus (V.parahaemolyticus), and Vibrio anguillarum (V.anguillarum).
(2) Antibacterial Activity of Compounds 1 and 2 of the present invention
The compounds of the present invention have significant antibacterial activity against staphylococcus albus (s. albus), staphylococcus aureus (s. aureus), escherichia coli (e. coli), vibrio parahaemolyticus (v. parahaemolyticus), and vibrio anguillarum (v. anguillarum), as shown in table 1.
TABLE 1 inhibitory Activity of Compounds 1 and 2 of the present invention against bacteria
The invention provides an antibacterial agent, which is characterized in that compounds 1 and 2 are used as effective components for preventing or treating related diseases caused by staphylococcus albus (S.albus), staphylococcus aureus (S.aureus), escherichia coli (E.coli), vibrio parahaemolyticus (V.parahaemolyticus) or vibrio anguillarum (V.anguillarum), and raw materials can be produced in a large scale through fungal fermentation and are not limited by resources, so the antibacterial agent has wide application prospect.
Claims (1)
1. A process for the simultaneous preparation of compounds 1 and 2, characterized by comprising the steps of: firstly, carrying out strain culture on marine fungi Phoma sp in a strain culture medium, then carrying out fermentation culture on the marine fungi in a fermentation culture medium to obtain a fermentation product, leaching the fermentation product for 2-6 times by using ethyl acetate, merging ethyl acetate leaching liquor, carrying out reduced pressure concentration to obtain a crude extract, and carrying out chromatographic separation to obtain compounds 1 and 2;
the strain culture medium contains 0.10-10% of glucose, 0.01-4.0% of yeast extract, 0.01-4.0% of peptone, 0.10-6.0% of agar, 0.05-10% of crude sea salt and the balance of water, wherein the percentages are weight percentages; the culture temperature is 5-45 ℃; the culture time is 3-10 days;
the fermentation medium is that each 500mL conical flask contains 50-150 g of rice, 0.05-10 g of crude sea salt and 50-150 mL of water; the culture temperature is 5-45 ℃; the culture time is 5-50 days;
the chromatographic separation is to sequentially carry out normal phase silica gel column chromatographic separation, gel column chromatographic separation and high performance liquid chromatographic separation; the normal phase silica gel column chromatographic separation adopts silica gel with a fixed phase of 200-300 meshes and a mobile phase of 30-40% of ethyl acetate-petroleum ether mixed solvent; the stationary phase adopted by the gel column chromatographic separation is sephadex LH-20, and the mobile phase is petroleum ether: dichloromethane: a mixed solvent of methanol 2:1: 1; the chromatographic column adopted for the high performance liquid chromatography is a semi-preparative C18 chromatographic column Kromasil,7 mu m,10 multiplied by 250mm, and the mobile phase is 60-65% of methanol-water mixed solvent; the proportion of the mixed solvent is volume ratio;
the structures of the compounds 1 and 2 are as follows:
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710275997.5A CN108727169B (en) | 2017-04-25 | 2017-04-25 | Preparation method of marine fungus-derived diphenyl ether compound and application of compound as antibacterial agent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710275997.5A CN108727169B (en) | 2017-04-25 | 2017-04-25 | Preparation method of marine fungus-derived diphenyl ether compound and application of compound as antibacterial agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108727169A CN108727169A (en) | 2018-11-02 |
| CN108727169B true CN108727169B (en) | 2021-06-22 |
Family
ID=63934370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201710275997.5A Active CN108727169B (en) | 2017-04-25 | 2017-04-25 | Preparation method of marine fungus-derived diphenyl ether compound and application of compound as antibacterial agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108727169B (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112898161B (en) * | 2021-01-25 | 2022-03-25 | 华南农业大学 | 18-hydroxy octadecanoic carbonate containing diphenyl ether unit and preparation method and application thereof |
| CN114853581B (en) * | 2021-02-03 | 2023-01-10 | 华南农业大学 | Diphenyl ether phenol and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103589757A (en) * | 2013-02-04 | 2014-02-19 | 中国海洋大学 | Preparation method for bromo-diphenyl ether derivatives and applications as antibacterial agents |
| CN104230874A (en) * | 2013-09-11 | 2014-12-24 | 中国海洋大学 | Preparation method of isocoumarin compound and application of isocoumarin compound as antibacterial agent |
-
2017
- 2017-04-25 CN CN201710275997.5A patent/CN108727169B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103589757A (en) * | 2013-02-04 | 2014-02-19 | 中国海洋大学 | Preparation method for bromo-diphenyl ether derivatives and applications as antibacterial agents |
| CN104230874A (en) * | 2013-09-11 | 2014-12-24 | 中国海洋大学 | Preparation method of isocoumarin compound and application of isocoumarin compound as antibacterial agent |
Non-Patent Citations (2)
| Title |
|---|
| Barceloneic acid C, a new polyketide from an endophytic fungus Phoma sp. JS752 and its antibacterial activities;Xuekui Xia等;《The Journal of Antibiotics》;20151231;第139-141页 * |
| Synthesis and Herbicidal activity of cyperin;Philip M.Harrington等;《J.Agric.Food Chem.》;19951231;第804-808页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN108727169A (en) | 2018-11-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106834160B (en) | Streptomyces erythropolis for producing keratin compound | |
| CN107827805B (en) | Indole diterpenoid compound derived from mangrove plant xylocarpus meliloti fungi as well as preparation method and application thereof | |
| CN115490661B (en) | Antioxidant active compound in mangrove-derived fungi and preparation method thereof | |
| CN110527629B (en) | Marine fungus-derived brefeldin A, preparation method and application thereof in resisting agricultural pathogenic bacteria | |
| CN115806881B (en) | Penicillium fungus and application thereof in preparation of antibacterial drugs | |
| CN108727169B (en) | Preparation method of marine fungus-derived diphenyl ether compound and application of compound as antibacterial agent | |
| CN103172507B (en) | Ophiobollin sesterterpine compound as well as preparation method and application thereof | |
| CN109134574B (en) | Steroid compound, preparation method and application thereof, and anti-tumor drug | |
| CN109486685B (en) | Mangrove cuspid and sea lotus endophytic fungus and application thereof in preparation of anti-insect active terpenoid crystal compound | |
| CN112300243B (en) | Cyclopeptide compound and preparation method and application thereof | |
| CN107828663B (en) | Indole diterpenoid compound crystal and application thereof as antitumor drug | |
| CN115403556B (en) | Pentylketothiophene compound, preparation method thereof and application thereof in anti-inflammatory drugs | |
| CN115724816B (en) | Chromone crystal form in mangrove-derived fungi and preparation and application thereof | |
| CN108441427B (en) | Arthriospora fungi and pyridone alkaloid compound produced by same | |
| CN114409627B (en) | Anti-inflammatory compound Dalditone A and preparation method and application thereof | |
| CN108728367B (en) | Marine fungus from dichotomous juncus effusum and application of marine fungus in preparation of antibacterial drugs | |
| CN111808015B (en) | Phenylalanine-derived cytochalasin as well as preparation method and application thereof | |
| CN114940667A (en) | Diterpenoid compound and preparation method and application thereof | |
| CN110698441B (en) | 2-methyl-4- (1-glycerol) -furan compounds and preparation method and application thereof | |
| CN107226800A (en) | A kind of xanthone classes compound and its preparation method of monocrystalline and the application as anti-Mycobacterium marinum medicine | |
| CN103214449A (en) | Chloro benzophenone compound and preparation method and application thereof | |
| CN104230874B (en) | Preparation method of isocoumarin compound and application of isocoumarin compound as antibacterial agent | |
| CN108929857B (en) | Salicornia europaea-derived marine fungus and application thereof in preparation of topoisomerase I inhibitor | |
| CN110527631B (en) | Unsaturated fatty acid compound from marine fungus HK1-22, preparation method and application thereof | |
| CN107973803B (en) | Seven-membered lactonofuran derivative and preparation 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 |