CN105968122A - 16-membered ring macrolides compound as well as preparation method and application thereof - Google Patents
16-membered ring macrolides compound as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN105968122A CN105968122A CN201610311954.3A CN201610311954A CN105968122A CN 105968122 A CN105968122 A CN 105968122A CN 201610311954 A CN201610311954 A CN 201610311954A CN 105968122 A CN105968122 A CN 105968122A
- Authority
- CN
- China
- Prior art keywords
- compound
- membered ring
- preparation
- ring macrolides
- fermentation
- 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.)
- Granted
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
- C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
-
- 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
- C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
- C12P17/02—Oxygen as only ring hetero atoms
- C12P17/08—Oxygen as only ring hetero atoms containing a hetero ring of at least seven ring members, e.g. zearalenone, macrolide aglycons
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Zoology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Microbiology (AREA)
- General Chemical & Material Sciences (AREA)
- Biotechnology (AREA)
- Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Genetics & Genomics (AREA)
- Agricultural Chemicals And Associated Chemicals (AREA)
Abstract
The invention provides a 16-membered ring macrolides compound as well as a preparation method and application thereof, belonging to the technical field of pesticides. The structural formula of the compound is described in the description. The compound is obtained by carrying out enlarged culture on Streptomyces bingchenggensis BC-120-4, then filtering ferment liquor, leaching by using methyl alcohol, extracting by using ethyl acetate, concentrating, then carrying out silica gel column chromatography, and carrying out RP-18 column chromatography. The compound is applied to preparation of medicines for killing mites and nematodes. The compound provided by the invention has higher mite and nematode killing activity.
Description
Technical field
The invention belongs to technical field of pesticide, be specifically related to a class and there is the macrolide antibiotics of insecticidal activity, and system
Preparation Method.
Background technology
1967, Sankyo company of Japan sending out from Streptomyces hygroscopicus subsp.aureolacrimosus
Finding mibemycin in ferment liquid, research is so far, separated to mibemycin more than 20 kind.In long-term research, logical
Cross the multiple components to mibemycin and carry out modifying for chemical structure, define a series of derivant.Commercialization at present is most
Be mibemycin A3/A4, moxidectin, milbemycin oxime.Parasite type is had preferably in farming and animal husbandry by such medicine
Prevention effect, and there is broad-spectrum insecticidal activity, such as demodicid mite class, aphid, malacosoma neustria, Enterozoa and other harm
Agricultural and the parasite of animal husbandry.Its action character includes that consumption is few, strong reaction and evil safe and nontoxic to people, does not pollutes
Environment, harmless to natural enemy, it is not easy to produce resistance.As antiparasitic, mibemycin mechanism of action is, it is as one
Plant the agonist of γ-aminobutyric acid (GABA), and then cause presynaptic GABA to discharge, affect Cl-The permeability of passage,
And then the conduction of block nerves mediator, thus cause polypide neuromuscular paralysis till death.
Harbin streptomycete Streptomyces bingchenggensis is this laboratory mibemycin of isolated from soil
Producing strains.With other mibemycin producing strains Streptomyces hygroscopicus subsp.aureolacrimosus and
Streptomyces griseochromogenes is the same, and Harbin streptomycete Streptomyces bingchenggensis is except producing
Outside mibemycin A3/A4, also produce other mibemycin series compound and other secondary metabolite.Pass through
Streptomyces bingchenggensis is carried out normal temperature and pressure plasma mutation, we obtain a strain mibemycin
A3/A4 superior strain Streptomyces bingchenggensis BC-120-4 (Hai-Yan Wang, Ji Zhang, Yue-Jing
Zhang,Bo Zhang,Chong-Xi Liu,Hai-Rong He,Xiang-Jing Wang,Wen-Sheng Xiang.
Combined application of plasma mutagenesis and gene engineering leads to 5-oxomilbemycins
A3/A4 as main components from Streptomyces bingchenggensis[J].Applied Microbiology and
Biotechnology,2014,98:9703-9712).Therefore, isolated and purified permissible to this mutant strain fermentating metabolism product
Finding novel, the mibemycin analog of more high bioactivity, the research for mibemycin biosynthesis mechanism carries
For new visual angle, also the drug development for novel mibemycin provides abundant experiment material.
Summary of the invention
The invention mainly relates to be obtained by Harbin streptomycete mutant strain (Streptomyces bingchenggensis BC-120-4)
The new mibemycin compounds arrived, and their preparation method and application.
It is an object of the invention to provide a class and there is 16-membered ring macrolides's compound of strong insecticidal activity.
It is a further object to provide the preparation method of this kind of 16-membered ring macrolides's compound.
In the present invention, the structural formula of 16-membered ring macrolides's compound is:
The preparation method of above-mentioned 16-membered ring macrolides's compound be by Harbin streptomycete mutant strain after amplification culture
The most isolated and purified；Wherein said amplification culture is divided into slant culture, seed culture and last three steps of fermentation.
Wherein, described Harbin streptomycete mutant strain is Streptomyces bingchenggensis BC-120.
Described slant culture is: slant medium forms: glucose 10-12g/L, maltose 3-4g/L, extraction from yeast
Powder 3-4g/L, K2HPO4·3H2O 0.5-0.6g/L, MgSO4·7H2O 0.5-0.6g/L, NaCl 0.5-0.6g/L, KNO3
1.0-1.2g/L, agar powder 20-25g/L, pH 7.0-7.2, prepare with deionized water, sterilizing, connect bacterium and be placed on 28 DEG C of trainings
Supporting in case, cultivate 8-9 days, spore sterilized water cultivation obtained is configured to 107-108c.f.u.ml-1Spore suspension standby
With.
Described seed culture is: seed culture medium forms: glucose 5-6g/L, maltodextrin 5-6g/L, and solubility is formed sediment
Powder 1.0-1.2g/L, yeast powder 5-6g/L, Carnis Bovis seu Bubali cream 1.0-1.2g/L, casein peptone 1.0-1.2g/L, pH 7.0-7.2, uses
Distilled water is prepared, and sterilizing takes slant culture gained 107-108c.f.u.ml-1Spore suspension is inoculated in seed culture medium, puts
In rotary shaker, cultivate 46-52h for 28 DEG C.
Described fermentation: fermentation medium forms: glucose 10-12g/L, lactose 25-30g/L, cottonseed meal 25-30g/L,
CaCO30.3-0.4g/L, pH 7.0-7.2, prepares with distilled water, sterilizing, seed culture gained seed liquor is linked into fermentation
In culture medium, put rotary shaker, 28 DEG C of fermentation culture 7-8 days.
Described isolated and purified method is: after fermentation liquor 100～200 eye mesh screen filters, filtering residue is by 3-4 times of volumes methanol
Extracting, extracting solution extracts 3-4 time by equal-volume ethyl acetate after concentrating, and carries out silica gel column chromatography successively after being concentrated by extract
After RP-18 column chromatography, obtain two kinds of white powder compounds 1 and compound 2.
The filler that described silica gel column chromatography is used is the silica gel of 100～200 mesh, and flowing is petroleum ether mutually: ethyl acetate
=(100:0)-(50:50) (V/V) carries out gradient elution, flow velocity 10-20ml/min, collects eluent, thin layer chromatography (TLC) successively
Combining data detection same composition；Described RP-18 column chromatography uses mixed solvent, i.e. methanol: water=(80:20)-(95:5) (V/V)
Carry out gradient elution, flow velocity 3-5ml/min, thin layer chromatography (TLC) combining data detection same composition.
The application in preparation mite killing worm medicine, nematicide of the described 16-membered ring macrolides's compound.
The present invention has obtained 16-membered ring macrolides's compound has stronger insecticidal activity to Tetranychus cinnabarinus and Bursaphelenchus xylophilus,
Can be used for the exploitation of insecticide.
Detailed description of the invention
Detailed description of the invention one: the fermented bacterium that present embodiment uses is Harbin streptomycete mutant strain, this bacterial strain is open
In Hai-Yan Wang, Ji Zhang, Yue-Jing Zhang, Bo Zhang, Chong-XiLiu, Hai-Rong He,
Xiang-Jing Wang,Wen-Sheng Xiang.Combined application of plasma mutagenesis and gene
engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces
Bingchenggensis [J] .Applied Microbiology and Biotechnology, the Harbin chain of 2014,98:9703-9712
Mycete Streptomyces bingchenggensis BC-120-4.
The preparation method of 16-membered ring macrolides's compound is carried out in the steps below:
One, amplification culture:
(1) slant culture: culture medium composition (g/L): glucose 10, maltose 3, extraction from yeast powder 3, K2HPO4·3H2O
0.5, MgSO4·7H2O 0.5, NaCl 0.5, KNO31, agar powder 20, pH 7.0, prepares with deionized water, in 121 DEG C
Lower sterilizing 20min.Connect bacterium to be placed in 28 DEG C of incubators, cultivate 8 days.
(2) seed culture: seed culture medium composition (g/L): glucose 5, maltodextrin 5, soluble starch 1, ferment
Female powder 5, Carnis Bovis seu Bubali cream 1, casein peptone 1, pH 7.0, prepares with distilled water, sterilizing 20min at 121 DEG C.To bacterium
Plant and on inclined-plane, add 10ml sterilized water, scrape spore with sterilized inoculating loop and make spore suspension so that it is concentration is 107
c.f.u.ml-1.Then taking 2ml spore suspension to be inoculated in seed culture shaking flask, seed flask liquid amount is 25ml/250ml,
It is placed in 250rpm rotary shaker, cultivates 46h for 28 DEG C.
(3) fermentation: fermentation medium composition (g/L): glucose 10, lactose 25, cottonseed meal 25, CaCO30.3,
PH 7.0-7.2, prepares with distilled water, sterilizing 20min at 121 DEG C.By 8% (V/V) inoculum concentration, seed liquor is connect
Entering in 1L fermentation shake flask, the liquid amount of fermentation shake flask is 100ml/L.It is placed in 250rpm rotary shaker, sends out for 28 DEG C
Ferment is cultivated 8 days.
2, compound separates:
30L fermentation liquor 200 eye mesh screen is filtrated to get mycelium filter cake 3L.Filter cake uses 10L work after being washed with deionized water again
Industry methanol soaked overnight, filters to obtain methanol extract liquid.Gained extracting solution removes methanol phase at 45 DEG C of concentrating under reduced pressure until remaining
About 2L, then extracts three times to obtain acetic acid ethyl acetate extract respectively by equal-volume ethyl acetate, and extract is the denseest
It is reduced to do, obtains 25g oily mater.
Silicagel column on the oily mater of gained (particle diameter 100～200 mesh) is chromatographed, with petroleum ether: ethyl acetate
=100:0-50:50 (V/V) carries out gradient elution, flow velocity 10ml/min, collects eluent successively by 250ml conical flask,
Every part of 250ml, merges same composition after thin layer chromatography (TLC) detection (petroleum ether: ethyl acetate=2:1), obtains
Component one (RF=0.72-0.78), component two (RF=0.63-0.71), component three (RF=0.48-0.62).By component two
Upper RP-18 post chromatographs, and carries out gradient elution, flow velocity 3ml/min with methanol with water=80:20-95:5 (V/V), uses
10ml test tube collects eluent, every part of 10ml successively, and thin layer chromatography (TLC) detects (petroleum ether: ethyl acetate=2:1),
The component merging RF=0.66 obtains compound 1:7.6mg, and the component merging RF=0.70 obtains compound 2:9.3mg.
3, Structural Identification
Compound 1
Character: white powder
Dissolubility: be soluble in chloroform, acetone, methanol, water insoluble
Molecular formula: C33H44O7
Specific optical rotation:(c 0.16,EtOH)
High resolution mass spectrum (HRESI-MS): 553.3142 [M+H]+(calcd C33H45O7for 553.3160)
Ultra-violet absorption spectrum (UV absorption spectrum) λmax(EtOH) nm (log ε): 260 (4.44), 200 (4.34)
Infrared absorption spectroscopy (IR absorption spectrum) Vmaxcm-1: 3348,2977,1710,1613,1456,
1268,1182,1099,1029,907
Compound 2
Character: white powder
Dissolubility: be soluble in chloroform, acetone, methanol, water insoluble
Molecular formula: C32H40O7
Specific optical rotation:(c 0.04,EtOH)
High resolution mass spectrum (HRESI-MS): 537.2827 [M+H]+(calcd C32H41O7for 537.2847)
Ultra-violet absorption spectrum (UV absorption spectrum) λmax(EtOH) nm (log ε): 363 (4.24), 274 (4.33),
218 (4.35), 200 (4.40)
Infrared absorption spectroscopy (IR absorption spectrum) Vmaxcm-1: 3348,2960,2926,1774,1711,
1609,1455,1364,1209,1068,984
Compound 1 and compound 21H and13C NMR(CDCl3) data are shown in Table 1.
Table 1 compound 1 and compound 21H and13C NMR(CDCl3) data
The structural formula of compound 1 is:
The structural formula of compound 2 is:
4, insecticidal activity assay
(1) miticidal activities is killed
By the methanol solution containing the single pure compound of 1g/ml with containing 0.01% (w/v) surfactant alkylphenol polyoxyethylene
Water dilute 10 times, make the solution of 100mg/ml, then make 0.1,0.05,0.025,0.01,0.005mg/l through dilution
Dilute solution as sample solution.The Tetranychus cinnabarinus that organic phosphates parasite killing is sensitive will be inoculated on the acrospire of Semen vignae sinensis.
After inoculating one day, by the leaf immersion of Semen vignae sinensis 1-2s in sample solution.After leaf is placed 3 days at 25 DEG C, with micro-
The number of sem observation survival adult, calculates mortality rate (%).
(2) eelworm-killing activity
By the methanol solution dilute with water 10 times containing the single pure compound of 1g/ml, make the solution of 100mg/ml, then depend on
Secondary dilution obtains the solution of 1,0.5,0.25,0.1 and 0.05mg/ml.Take each 10 μ l of above-mentioned variable concentrations solution to be separately added into
To 90 μ l containing living in Bursaphelenchus xylophilus aqueous suspensions.15h is placed at 25 DEG C after mixed liquor concussion.Count not moving-wire under the microscope
The quantity of worm and the sum of test nematicide.Calculate the mortality rate (%) of test nematicide.
Compound 1 and compound 2 have stronger mite killing and eelworm-killing activity, are shown in Table 2.
Table 2 compound 1 and the mite killing of compound 2 and eelworm-killing activity
aMibemycin A3 and A4 mixes (30:70)
Test result indicate that, compound 1 and 2 is demonstrated by higher insecticidal activity, has potential Development volue.
Detailed description of the invention two: the fermented bacterium that present embodiment uses is Harbin streptomycete mutant strain, this bacterial strain is open
In Hai-Yan Wang, Ji Zhang, Yue-Jing Zhang, Bo Zhang, Chong-XiLiu, Hai-Rong He,
Xiang-Jing Wang,Wen-Sheng Xiang.Combined application of plasma mutagenesis and gene
engineering leads to 5-oxomilbemycins A3/A4 as main components from Streptomyces
Bingchenggensis [J] .Applied Microbiology and Biotechnology, the Harbin chain of 2014,98:9703-9712
Mycete Streptomyces bingchenggensis BC-120-4.
The preparation method of 16-membered ring macrolides's compound is carried out in the steps below:
One, amplification culture:
(1) slant culture: culture medium composition (g/L): glucose 12, maltose 4, extraction from yeast powder 4, K2HPO4·3H2O
0.6, MgSO4·7H2O 0.6, NaCl 0.6, KNO31.2, agar powder 20, pH 7.2, prepare with deionized water, in
Sterilizing 20min at 121 DEG C.Connect bacterium to be placed in 28 DEG C of incubators, cultivate 8 days.
(2) seed culture: seed culture medium composition (g/L): glucose 6, maltodextrin 6, soluble starch 1.2,
Yeast powder 6, Carnis Bovis seu Bubali cream 1.2, casein peptone 1.2, pH 7.2, prepares with distilled water, sterilizing 20min at 121 DEG C.
On strain inclined plane, add 10ml sterilized water, scrape spore with sterilized inoculating loop and make spore suspension so that it is concentration is
108c.f.u.ml-1.Then taking 2ml spore suspension to be inoculated in seed culture shaking flask, seed flask liquid amount is 25ml/250
Ml, is placed in 250rpm rotary shaker, cultivates 46h for 28 DEG C.
(3) fermentation: fermentation medium composition (g/L): glucose 12, lactose 30, cottonseed meal 30, CaCO30.4,
PH 7.2, prepares with distilled water, sterilizing 20min at 121 DEG C.By 8% (V/V) inoculum concentration, seed liquor is accessed
In 1L fermentation shake flask, the liquid amount of fermentation shake flask is 100ml/L.It is placed in 250rpm rotary shaker, 28 DEG C of fermentations
Cultivate 8 days.
2, compound separates
30L fermentation liquor 200 eye mesh screen is filtrated to get mycelium filter cake 3L.Filter cake uses 12L after being washed with deionized water again
Industrial methanol soaked overnight, filters to obtain methanol extract liquid.Gained extracting solution removes methanol phase at 45 DEG C of concentrating under reduced pressure until remaining
More than about 2L, then with equal-volume ethyl acetate extract respectively four times acetic acid ethyl acetate extract, extract is at reduced pressure conditions
It is concentrated to dryness, obtains 25g oily mater.
Silicagel column on the oily mater of gained (particle diameter 100～200 mesh) is chromatographed, with petroleum ether: ethyl acetate
=100:0-50:50 (V/V) carries out gradient elution, flow velocity 20ml/min, collects eluent successively by 250ml conical flask,
Every part of 250ml, thin layer chromatography (TLC) detection (petroleum ether: ethyl acetate=2:1) merges same composition, obtains component
One (RF=0.72-0.78), component two (RF=0.63-0.71), component three (RF=0.48-0.62).By in component two
RP-18 post chromatographs, and carries out gradient elution with methanol with water=80:20-95:5 (V/V), and flow velocity 5ml/min, with 10
Ml test tube collects eluent, every part of 10ml successively, and thin layer chromatography (TLC) detects (petroleum ether: ethyl acetate=2:1),
The component merging RF=0.66 obtains compound 1:8.0mg, and the component merging RF=0.70 obtains compound 2:9.0mg.
Claims (10)
1. 16-membered ring macrolides's compound, it is characterised in that the structural formula of this compound is:
2. 16-membered ring macrolides's compound, it is characterised in that the structural formula of this compound is:
3. the preparation method of 16-membered ring macrolides's compound as claimed in claim 1 or 2, it is characterised in that described
The preparation method of compound be by Harbin streptomycete mutant strain after amplification culture the most isolated and purified.
The preparation method of 16-membered ring macrolides's compound the most according to claim 3, it is characterised in that described
Harbin streptomycete mutant strain is Streptomyces bingchenggensis BC-120, and described amplification culture is divided into inclined-plane
Cultivation, seed culture and last three steps of fermentation.
The preparation method of 16-membered ring macrolides's compound the most according to claim 4, it is characterised in that described is oblique
Face is cultivated: slant medium forms: glucose 10-12g/L, maltose 3-4g/L, extraction from yeast powder 3-4g/L,
K2HPO4·3H2O 0.5-0.6g/L, MgSO4·7H2O 0.5-0.6g/L, NaCl 0.5-0.6g/L, KNO31.0-1.2g/L,
Agar powder 20-25g/L, pH 7.0-7.2, prepares with deionized water, sterilizing, connects bacterium and be placed in 28 DEG C of incubators, cultivates
8-9 days, spore sterilized water cultivation obtained was configured to 107-108c.f.u.ml-1Spore suspension standby.
The preparation method of 16-membered ring macrolides's compound the most according to claim 4, it is characterised in that described kind
Son is cultivated: seed culture medium forms: glucose 5-6g/L, maltodextrin 5-6g/L, soluble starch 1.0-1.2g/L,
Yeast powder 5-6g/L, Carnis Bovis seu Bubali cream 1.0-1.2g/L, casein peptone 1.0-1.2g/L, pH 7.0-7.2, prepares with distilled water, goes out
Bacterium, takes slant culture gained 107-108c.f.u.ml-1Spore suspension is inoculated in seed culture medium, is placed in rotary shaker, 28 DEG C
Cultivate 46-52h.
The preparation method of 16-membered ring macrolides's compound the most according to claim 4, it is characterised in that described sends out
Ferment: fermentation medium forms: glucose 10-12g/L, lactose 25-30g/L, cottonseed meal 25-30g/L, CaCO3 0.3-0.4
G/L, pH 7.0-7.2, prepares with distilled water, sterilizing, seed culture gained seed liquor is linked in fermentation medium, puts rotation
Rotatable shaking table, 28 DEG C of fermentation culture 7-8 days.
The preparation method of 16-membered ring macrolides's compound the most according to claim 3, it is characterised in that described
Isolated and purified method is: after fermentation liquor 100～200 eye mesh screen filters, filtering residue extracts by 3-4 times of volumes methanol, extracts
Liquid extracts 3-4 time by equal-volume ethyl acetate after concentrating, and carries out silica gel column chromatography and RP-18 post successively after being concentrated by extract
After chromatography, obtain two kinds of compounds.
The preparation method of 16-membered ring macrolides's compound the most according to claim 8, it is characterised in that described
The filler that silica gel column chromatography is used is the silica gel of 100～200 mesh, flowing be petroleum ether mutually: ethyl acetate=(100:0)～
(50:50) (V/V) carries out gradient elution, flow velocity 10-20ml/min, collects eluent successively, and thin layer chromatography combining data detection is identical
Component；Described RP-18 column chromatography uses mixed solvent, i.e. methanol: water=(80:20)～(95:5) (V/V) to carry out gradient
Eluting, flow velocity 3-5ml/min, thin layer chromatography combining data detection same composition.
10. the 16-membered ring macrolides's compound described in claim 1 or 2 is in preparation mite killing worm medicine, nematicide
Application.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610311954.3A CN105968122B (en) | 2016-05-12 | 2016-05-12 | 16-membered ring macrolides compound and preparation method and application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610311954.3A CN105968122B (en) | 2016-05-12 | 2016-05-12 | 16-membered ring macrolides compound and preparation method and application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105968122A true CN105968122A (en) | 2016-09-28 |
| CN105968122B CN105968122B (en) | 2018-01-30 |
Family
ID=56992369
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610311954.3A Active CN105968122B (en) | 2016-05-12 | 2016-05-12 | 16-membered ring macrolides compound and preparation method and application |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105968122B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114634518A (en) * | 2022-04-02 | 2022-06-17 | 台州职业技术学院 | Two new macrolide compounds, pharmaceutical composition, preparation method and application thereof |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0710006A2 (en) * | 1994-10-28 | 1996-05-01 | Nec Corporation | Image forming apparatus capable of producing a pseudo half-tone image by using dither patterns |
| CN101037441A (en) * | 2007-01-17 | 2007-09-19 | 东北农业大学 | Macrolide compound and preparation method thereof |
| CN101037442A (en) * | 2007-01-17 | 2007-09-19 | 东北农业大学 | New compound prepared by ice city streptomyces and preparation method |
-
2016
- 2016-05-12 CN CN201610311954.3A patent/CN105968122B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0710006A2 (en) * | 1994-10-28 | 1996-05-01 | Nec Corporation | Image forming apparatus capable of producing a pseudo half-tone image by using dither patterns |
| CN101037441A (en) * | 2007-01-17 | 2007-09-19 | 东北农业大学 | Macrolide compound and preparation method thereof |
| CN101037442A (en) * | 2007-01-17 | 2007-09-19 | 东北农业大学 | New compound prepared by ice city streptomyces and preparation method |
Non-Patent Citations (2)
| Title |
|---|
| JOHN D.STONG: "Determination of Ivermectin by Fluorescence Derivatization", 《ANAL.CHEM.》 * |
| XIANG-JING WANG，等: "Three new milbemycin derivatives from Streptomyces bingchenggensis", 《JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114634518A (en) * | 2022-04-02 | 2022-06-17 | 台州职业技术学院 | Two new macrolide compounds, pharmaceutical composition, preparation method and application thereof |
| CN114634518B (en) * | 2022-04-02 | 2023-10-24 | 台州职业技术学院 | Two macrolide new compounds, pharmaceutical composition, and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105968122B (en) | 2018-01-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106432264B (en) | Two kinds of macrolides compounds and preparation method and application | |
| CN105906650B (en) | Macrolide new compounds and preparation method and application | |
| CN106754498B (en) | Bacillus aryabhattai, microbial inoculum thereof, preparation method and application | |
| CN107119088A (en) | A kind of molten bacillus OH11 production active antibacterial materials HSAF of response phase method optimization producing enzyme method | |
| CN103740606B (en) | Plant raw streptomycete and produce antibiotic promise and irrigate method and the application of nest mycin | |
| CN101720772B (en) | Macrolide composition for preventing and controlling fungal disease of crop and preparation process thereof | |
| CN111004252B (en) | Sixteen-membered macrolide compound and preparation method and application thereof | |
| CN110776518A (en) | Azaphilone spiro compounds and preparation method and application thereof | |
| CN111303184B (en) | Macrolide compound and preparation method and application thereof | |
| US5126265A (en) | Ab-021 antibiotics and process for producing them | |
| CN103242338A (en) | Macrolide compound as well as preparation method and application thereof | |
| CN104098585B (en) | Mibemycin analogue, its preparation method and application | |
| CN101720781B (en) | New phosphorus and nitrogen mycin A for preventing and controlling fungal disease of crop and preparation process thereof | |
| CN105968122B (en) | 16-membered ring macrolides compound and preparation method and application | |
| CN112961168B (en) | Macrolide new compound and preparation method and application thereof | |
| CN109180593B (en) | Phenolic oxazine alkaloid secondary metabolite and application thereof | |
| CN113248516B (en) | Seventeen-membered macrolide compound and preparation method and application thereof | |
| CN114634518B (en) | Two macrolide new compounds, pharmaceutical composition, and preparation method and application thereof | |
| CN115124582B (en) | Derivatives containing 2,9-dimethyl hexadecanoic macrolide parent nucleus for resisting rhizoctonia solani, and preparation method and application thereof | |
| CN103361276A (en) | Saccharopolyspora spinosa HBERC-25376, culturing method thereof as well as separation method and application of active substances thereof | |
| EP0472186B1 (en) | Antibiotics AB-023 and process for preparing them | |
| CN109536399A (en) | A kind of high-throughput screening method of virginiamycin superior strain | |
| CN111909166B (en) | Two new milbemycins, preparation method and application thereof | |
| US5171836A (en) | Antibiotics plusbacin | |
| CN107827950A (en) | A kind of Trichomide classes Cyclopeptide derivatives and its preparation method and application |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |