CN114989190A - Macrolide compound kongjuemycins and preparation method and application thereof - Google Patents

Macrolide compound kongjuemycins and preparation method and application thereof Download PDF

Info

Publication number
CN114989190A
CN114989190A CN202210418878.1A CN202210418878A CN114989190A CN 114989190 A CN114989190 A CN 114989190A CN 202210418878 A CN202210418878 A CN 202210418878A CN 114989190 A CN114989190 A CN 114989190A
Authority
CN
China
Prior art keywords
compound
spectrum
macrolide compound
fraction
eluted
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
Application number
CN202210418878.1A
Other languages
Chinese (zh)
Other versions
CN114989190B (en
Inventor
张长生
方壮杰
张庆波
张丽萍
李洁
张文军
张海波
朱义广
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
South China Sea Institute of Oceanology of CAS
Original Assignee
South China Sea Institute of Oceanology of CAS
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by South China Sea Institute of Oceanology of CAS filed Critical South China Sea Institute of Oceanology of CAS
Priority to CN202210418878.1A priority Critical patent/CN114989190B/en
Publication of CN114989190A publication Critical patent/CN114989190A/en
Application granted granted Critical
Publication of CN114989190B publication Critical patent/CN114989190B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/08—Bridged systems
    • 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
    • A61P31/10—Antimycotics
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • 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
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/188—Heterocyclic compound containing in the condensed system at least one hetero ring having nitrogen atoms and oxygen atoms as the only ring heteroatoms
    • 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)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Oncology (AREA)
  • Microbiology (AREA)
  • Communicable Diseases (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biotechnology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

The invention discloses a macrolide compound kongjuememycins, a preparation method and application thereof. The structure of the macrolide compound is shown in any one of formula (I). The invention separates the anti-virus from the strain P.kongjuensis SCSIO 114571-8 macrolides with fungal activity, and therefore these compounds can be used for the preparation of antifungal drugs.
Figure DDA0003606063940000011

Description

Macrolide compound kongjuemycins and preparation method and application thereof
The technical field is as follows:
the invention belongs to the field of industrial microorganisms, and particularly relates to novel kongjuememycins compounds 1-8 as well as a preparation method and application thereof.
Background art:
macrolide compounds are antibiotics with various structures and broad-spectrum antibacterial activity, and are clinically important anti-infective drugs, such as erythromycin, roxithromycin, azithromycin and the like. In the face of the current increasingly clinical drug-resistant bacteria, the discovery and the modification of new macrolide antibiotics become an important strategy, and have great significance for resisting the threat of the post-antibiotic era.
The invention content is as follows:
the first object of the present invention is to provide 8 novel macrolides kongjuememycins (1-8).
The invention relates to 8 novel macrolide compounds kongjuuemycins (1-8), the structure of which is shown in formula (I):
Figure BDA0003606063920000011
wherein, the compound 2 is kongjuememycin B1, and R is CH 2 CH 2 CH 3 (ii) a The compound 3 is kongjuememycin B2, and R is CH (CH) 3 ) 2 (ii) a The compound 4 is kongjuememycin B3, and R is CH 2 CH 2 CH 2 CH 3 (ii) a The compound 5 is kongjuememycin C1, and R is CH 2 CH 3 (ii) a The compound 6 is kongjuememycin C2, and R is CH 2 CH 2 CH 3 (ii) a The compound 7 is kongjuememycin C3, and R is CH (CH) 3 ) 2 (ii) a The compound 8 is kongjuememycin C4, and R is CH 2 CH 2 CH 2 CH 3 。
The second purpose of the invention is to provide the application of the compound in preparing antifungal medicines.
An antifungal agent contains the macrolide compound kongjueumycins as an active ingredient.
The antifungal agent is an anti-Colletotrichum gloeosporioides Penz, physiosporiicola Nose and/or Bipolaris sorokiniana.
A third object of the present invention is to provide a method for preparing a compound kongjuememycins (1-8), which is characterized by comprising the steps of: the compound kongjueumycins (1-8) was isolated from a fermentation culture of Pseudomonas kongjueuensis SCSIO 11457.
Preferably, the method comprises the following specific steps:
performing fermentation culture on the strain P.kongjuensis SCSIO 11457 by using an N4 culture medium, putting macroporous resin in a culture system, collecting the macroporous resin and mycelium after culture, and eluting the macroporous resin by using acetone; leaching mycelium with acetone, ultrasonically crushing, recovering organic solvent, extracting the rest water phase with ethyl acetate, and recovering ethyl acetate to obtain crude extract;
separating the crude extract by normal phase silica gel column chromatography, performing gradient elution with chloroform/methanol as eluent, performing gradient elution from 100/0, 9/1, 4/1, 2/1, 1/1 and 0/100 at v/v, separating fraction Fr2 eluted with chloroform/methanol 9/1v/v by reverse phase silica gel column chromatography, and purifying the eluted fraction to obtain compounds 1 and 2-4; separating fraction Fr3-4 eluted with chloroform/methanol 4/1 and 2/1v/v with reverse phase silica gel column chromatography, and purifying the eluted fraction to obtain compound 5-8.
Application of the strain P.kongjuensis SCSIO 11457 in preparation of compounds 1-8.
The invention separates macrolide compounds 1-8 with antifungal activity from a strain P.kongjuensis SCSIO 11457, so that the compounds can be used for preparing antifungal medicaments.
The actinomycete Pseudomonas kongjuensis SCSIO 11457 of the present invention is disclosed in the literature: secondary metabolite study of two marine-derived actinomycetes, authors: zhuangjie, Master thesis, southern Hai Marine institute of Chinese academy of sciences, 2019. This strain is also held by the applicant and is guaranteed to be provided to the public within 20 years from the filing date.
Description of the drawings:
FIG. 1 is a high performance liquid chromatogram of a fraction Fr2-7 of a fermentation extract.
High Performance Liquid Chromatography (HPLC) conditions: the chromatographic column is Phenomenex Luna C18,150mm multiplied by 4.6mm,5 mu m; the mobile phase comprises a phase A and a phase B, wherein the phase A: 10% acetonitrile/water (v/v) + 0.1% formic acid (v/v), phase B: 90% acetonitrile/water (v/v); sample introduction procedure: 5% B-80% B (0-20min), 80% B-100% B (20-21min), 100% B (21-25min), 100% B-5% B (25-26min), 5% B (26-30min), detection wavelength of 280nm, flow rate of 1 mL/min -1 . Wherein 1 represents compound 1 and 2 represents compound 2.
FIG. 2 is a high performance liquid chromatogram of a fraction Fr2-8 of the fermentation extract. The conditions for High Performance Liquid Chromatography (HPLC) were as above, wherein 3 represents compound 3 and 4 represents compound 4.
FIG. 3 is a high performance liquid chromatogram of a fraction Fr3-4-8 of the fermentation extract. High Performance Liquid Chromatography (HPLC) conditions were as above, with 6 representing compound 6, 7 representing compound 7, and 8 representing compound 8.
FIG. 4 is a high performance liquid chromatogram of a fermentation extract fraction Fr 3-4-8. High Performance Liquid Chromatography (HPLC) conditions were as above, wherein 5 represents compound 5.
FIG. 5 is a HRESIMS spectrum of Compound 1; FIG. 6 is a drawing of Compound 1 1 H-NMR spectrum; FIG. 7 is a drawing of Compound 1 13 C-NMR spectrum; figure 8 is DEPT135 spectrum of compound 1; FIG. 9 is a COSY spectrum of compound 1; FIG. 10 is an HSQC spectrum of Compound 1; FIG. 11 is H of Compound 1MBC spectrogram;
FIG. 12 is a HRESIMS spectrum of Compound 2; FIG. 13 is a photograph of Compound 2 1 H-NMR spectrum; FIG. 14 is a photograph of Compound 2 13 A C-NMR spectrum; figure 15 is the DEPT135 spectrum of compound 2; FIG. 16 is a COSY spectrum of compound 2; figure 17 is an HSQC spectrum of compound 2; FIG. 18 is an HMBC spectrum of compound 2; FIG. 19 is a ROESY spectrum of Compound 2;
FIG. 20 is a HRESIMS spectrum of Compound 3; FIG. 21 is of Compound 3 1 H-NMR spectrum; FIG. 22 is of Compound 3 13 A C-NMR spectrum; figure 23 is DEPT135 spectrum of compound 3; FIG. 24 is a COSY spectrum of compound 3; figure 25 is an HSQC spectrum of compound 3; FIG. 26 is an HMBC spectrum of compound 3;
FIG. 27 is a HRESIMS spectrum of Compound 4; FIG. 28 is of Compound 4 1 H-NMR spectrum; FIG. 29 is of Compound 4 13 A C-NMR spectrum; figure 30 is a DEPT135 spectrum of compound 4; FIG. 31 is a COSY spectrum of compound 4; FIG. 32 is an HSQC spectrum of Compound 4; FIG. 33 is an HMBC spectrum of compound 4;
FIG. 34 is a HRESIMS spectrum of Compound 5; FIG. 35 is a drawing of Compound 5 1 H-NMR spectrum; FIG. 36 is of Compound 5 13 A C-NMR spectrum; figure 37 is a DEPT135 spectrum of compound 5; FIG. 38 is a COSY spectrum of compound 5; FIG. 39 is an HSQC spectrum of Compound 5; FIG. 40 is an HMBC spectrum of compound 5; FIG. 41 is a ROESY spectrum of Compound 5;
FIG. 42 is a HRESIMS spectrum of Compound 6; FIG. 43 is of Compound 6 1 H-NMR spectrum; FIG. 44 is of Compound 6 13 A C-NMR spectrum; figure 45 is DEPT135 spectrum of compound 6; FIG. 46 is a COSY spectrum of compound 6; FIG. 47 is an HSQC spectrum of Compound 6; FIG. 48 is an HMBC spectrum of compound 6;
FIG. 49 is a HRESIMS spectrum of Compound 7; FIG. 50 is of Compound 7 1 H-NMR spectrum; FIG. 51 is of Compound 7 13 A C-NMR spectrum; figure 52 is the DEPT135 spectrum of compound 7; FIG. 53 is a COSY spectrum of compound 7; figure 54 is an HSQC spectrum of compound 7; figure 55 is the HMBC spectrum of compound 7.
FIG. 56 is a HRESIMS spectrum of Compound 8; FIG. 57 is of Compound 8 1 H-NMR spectrum; FIG. 5The 8 being a compound of formula 8 13 A C-NMR spectrum; figure 59 is a DEPT135 spectrum of compound 8; FIG. 60 is a COSY spectrum of compound 8; figure 61 is an HSQC spectrum of compound 8; figure 62 is an HMBC spectrum of compound 8.
The specific implementation mode is as follows:
the following examples are further illustrative of the present invention and are not intended to be limiting thereof.
The wild-type strain p. kongjuuensis SCSIO 11457 produced the novel compounds 1 to 8 in the N4 medium, and analysis of hresms and NMR data confirmed the structures of 8 novel compounds kongjuuemycins (1) (fig. 5 to 11), kongjuuemycins B1(2) (fig. 12 to 19), kongjuuemycins B2(3) (fig. 20 to 26), kongjuuemycins B3(4) (fig. 27 to 33), kongjuuemycins C1(5) (fig. 34 to 41), kongjuuemycins C2(6) (fig. 42 to 48), kongjuuemycins C3(7) (fig. 49 to 55) and kongjuuemycins C4(8) (fig. 56 to 62).
The following further provides examples which are intended to aid in the understanding of the present invention and are intended to be illustrative rather than limiting.
Example 1
1. Amplified fermentation culture
The strain P.kongjuensis SCSIO 11457 is activated on a 38# culture medium solid plate, then a proper amount of spores and mycelium are scraped and inoculated into 200mLN4 fermentation medium (total 60L), and the fermentation culture is obtained after culturing for 5d at the temperature of 28 ℃ and the speed of 200rpm of a shaker.
38 # Culture medium: 5.0g of malt extract powder, 4.0g of glucose, 4.0g of yeast extract powder and 30g of sea salt, adding purified water to 1L, adjusting pH to 7.0, and sterilizing.
N4 medium: 15g of soluble starch, 8g of fish peptone, 5g of bacteriological peptone, 7.5g of glycerol, CaCO 3 2g of KBr, 0.2g of sea salt, 30g of HP20 macroporous resin 5% (mass fraction, namely 50g), and purified water is added to 1L, and the pH value is 7.0. Sterilizing to obtain the product.
2. Extraction of fermentation broth
And (4) respectively collecting the HP20 macroporous resin and fermentation liquor by using a separating funnel after the fermentation culture of 5 d. Centrifuging the fermentation liquor at 3900rpm for 20min, collecting mycelia, and eluting macroporous resin with 15L acetone; the mycelia were extracted 3 times with 1L of acetone, and the cells were disrupted by sonication for 0.5h each time. And recovering the organic solvents in the two parts by using a rotary evaporator, combining the rest water, extracting for 10 times by using 1L ethyl acetate, and recovering ethyl acetate in the ethyl acetate extract by using the rotary evaporator to obtain a crude extract.
3. Isolation of the Compound
10g of crude extract of N4 medium of the above wild type strain P. kongjuensis SCSIO 11457 was dissolved in chloroform methanol (1:1, v/v), 40mL of 100-mesh silica gel was added and stirred, the mixture was packed in a column by a 1:3 dry method in a stirred silica gel (40 mL)/separation silica gel (120mL), and gradient elution was carried out using chloroform/methanol as an eluent (100/0, 9/1, 4/1, 2/1, 1/1 and 0/100, v/v, each gradient being 800mL) to obtain fractions Fr1-Fr6 in this order. Fraction Fr2 (fraction eluted with chloroform/methanol 90/10 v/v) was subjected to medium pressure reverse phase chromatography (YMC × GEL ODS-A-HG, 12nm S-50 μm) with A phase A/B ═ water/acetonitrile (v/v) according to the following procedure: 10% B (0-20min), 10% B to 60% B (20-60min), 60% B (60-90min), 60% B to 90% B (90-120min), 90% B (120-150min), and a flow rate of 20mLmin -1 Fractions Fr2-1 to Fr2-10 were obtained in this order. Fraction Fr2-7 has the target compound according to the detection result of High Performance Liquid Chromatography (HPLC) (FIG. 1), therefore fraction Fr2-7 was purified by semi-preparative high performance liquid chromatography (Phenomenex Luna C18, 250 mm. times.10.0 mm,5 μm; phase A was water, phase B was acetonitrile, volume fraction 55% of phase B was eluted at equal rate; flow rate was 2.5 mL/min; detection wavelength was 280nm) to obtain compounds kongjueymycinA (1) (Rt 22.0min) and kongjueycin B1(2) (Rt 20.0 min). Fraction Fr2-8 has the target compound according to the detection result of High Performance Liquid Chromatography (HPLC) (FIG. 2), therefore fraction Fr2-8 is purified by semi-preparative high performance liquid chromatography (Phenomenex Luna C18, 250 mm. times.10.0 mm,5 μm; phase A is water, phase B is acetonitrile, volume fraction 60% of phase B is eluted at equal rate; flow rate is 2.5 mL/min; detection wavelength is 280nm) to obtain compounds kongjueymycin B2(3) (Rt 24.0min) and kongjueymycin B3(4) (Rt 28.0 min). Fractions Fr3 and Fr4 (fractions eluted with chloroform/methanol 4/1 and 2/1 v/v) were combined and eluted by medium pressure reverse phase chromatography (YMC × GEL ODS-A-HG, 12nm S-50 μm) with phase A/B ═ water/acetonitrile (v/v) according to the following procedure: 10% B (0-20min), 10% B to 50% B (20-60min), 50% B (60-90min), 50% Bto 90% B (90-120min), 90% B (120-150min), flow rate 20mL min -1 Fractions Fr3-4-1 to Fr3-4-12 were obtained in this order. Fraction Fr3-4-8 has the target compound according to the results of High Performance Liquid Chromatography (HPLC) (FIG. 3), and therefore fraction Fr3-4-8 was purified by semi-preparative high performance liquid chromatography (Phenomenex Luna C18, 250 mm. times.10.0 mm,5 μm; phase A was water, phase B was acetonitrile, volume fraction 40% of phase B was eluted at equal rate; flow rate was 2.5 mL/min; detection wavelength was 280nm) to give the compounds kongjueymycin C2(6) (Rt 15.0min), kongjueymycin C2(7) (Rt 20.0min) and kongjueymycin C3(8) (Rt 22.0 min). Fraction Fr3-4-7 has the target compound according to the detection result of High Performance Liquid Chromatography (HPLC) (FIG. 4), therefore fraction Fr3-4-7 is purified by semi-preparative high performance liquid chromatography (Phenomenex Luna C18, 250 mm. times.10.0 mm,5 μm; phase A is water, phase B is acetonitrile, 38% volume fraction of phase B is eluted at equal rate; flow rate is 2.5 mL/min; detection wavelength is 280nm) to obtain compound kongjuememycin C4(5) (Rt ═ 20.0 min).
1. Structural identification of compounds
The structures of the compounds 1-8 are according to HRESIMS, 1 H-NMR、 13 C-NMR, DEPT135, HSQC, HMBC and COSY spectra were identified, and the nuclear magnetic data are assigned in tables 1 and 2. The spectrum of Kongjuuemycin A (1) is shown in FIGS. 5-11, the spectrum of kongjuuemycin B1(2) is shown in FIGS. 12-19, the spectrum of kongjuuemycin B2(3) is shown in FIGS. 20-26, the spectrum of kongjuuemycin B3(4) is shown in FIGS. 27-33, the spectrum of kongjuuemycin C1(5) is shown in FIGS. 34-41, the spectrum of kongjuuemycin C2(6) is shown in FIGS. 42-48, and the spectrum of kongjuuemycin C3(7) is shown in FIGS. 49-55 and the spectrum of kongjuuemycin C4(8) is shown in FIGS. 56-62.
The structural formulae of compounds 1 to 8 were thus determined as follows:
Figure BDA0003606063920000061
of compounds 1 to 4 of Table 1 1 H-NMR (700MHz) and 13 C-NMR (175MHz) Nuclear magnetic data
Figure BDA0003606063920000062
Figure BDA0003606063920000071
Figure BDA0003606063920000081
TABLE 2 preparation of compounds 5 to 8 1 H-NMR (700MHz) and 13 C-NMR (175MHz) nuclear magnetic data
Figure BDA0003606063920000082
Figure BDA0003606063920000091
Figure BDA0003606063920000101
EXAMPLE 2 determination of antifungal Activity of Compounds 1-8
The inhibitory activities of the compounds 1 to 8 against the 3 plant pathogenic fungi Colletotrichum gloeosporioides Penz, physiosporia piricola Nose and Bipolaris sorokiniana were determined by the microculture medium dilution method. Culturing 3 plant pathogenic fungi at 28 deg.C and 200rpm for 48h in shaking table, diluting with sterile PDB culture medium to OD (600nm) of 0.04-0.06, diluting 1000 times, and adding into 96-well plate; after addition of the sample, the aliquots were diluted to final concentrations of 128, 64, 32, 16, 8, 4, 2, 1, 0.5, 0.25. mu.g mL -1 3 replicates per concentration; culturing at 28 deg.C for 48-72h, measuring absorbance of each well with microplate reader, and calculating Minimum Inhibitory Concentration (MIC) of each compound, and inhibition rate (%) (1- (sample A-sample background)/(A negative control-blank control)) × 100%, inhibition rate>80% are MIC values. The results are shown in Table 3.
TABLE 3 antibacterial Activity (MIC, μ gmL) of Compounds 1-8 -1 )
Figure BDA0003606063920000102

Claims (8)

1. A macrolide compound or a pharmaceutically acceptable salt thereof, wherein the structure of the macrolide compound is shown in any one of the following formulas (I):
Figure FDA0003606063910000011
2. use of a macrolide compound or a pharmaceutically acceptable salt thereof according to claim 1 for the preparation of an antifungal agent.
3. The use according to claim 2, wherein the antifungal agent is an agent against Colletotrichum gloeosporioides Penz, Physiospora piricola Nose and/or Bipolaris sorokiniana.
4. An antifungal agent comprising the macrolide compound or a pharmaceutically acceptable salt thereof according to claim 1 as an active ingredient.
5. The antifungal agent of claim 4 wherein the antifungal agent is an agent against Colletotrichum gloeosporioides Penz, Physalospora piricola Nose and/or Bipolaris sorokiniana.
6. A process for preparing a macrolide compound according to claim 1, comprising the steps of: the macrolide compound is isolated from the fermentation culture of Pseudonocardia kongjuensis SCSIO 11457.
7. The method of claim 6, comprising the steps of:
performing fermentation culture on the strain P.kongjuensis SCSIO 11457 by using an N4 culture medium, putting macroporous resin in a culture system, collecting the macroporous resin and mycelium after culture, and eluting the macroporous resin by using acetone; leaching mycelium with acetone, ultrasonically crushing, recovering organic solvent, extracting the rest water phase with ethyl acetate, and recovering ethyl acetate to obtain crude extract;
separating the crude extract by normal phase silica gel column chromatography, performing gradient elution with chloroform/methanol as eluent, performing gradient elution from 100/0, 9/1, 4/1, 2/1, 1/1 and 0/100 at v/v, separating fraction Fr2 eluted with chloroform/methanol 9/1v/v by reverse phase silica gel column chromatography, and purifying the eluted fraction to obtain compounds 1 and 2-4; separating fraction Fr3-4 eluted with chloroform/methanol 4/1 and 2/1v/v by reverse phase silica gel column chromatography, and purifying the eluted fraction to obtain compound 5-8.
8. Use of the strain p. kongjuensis SCSIO 11457 for the preparation of a macrolide compound according to claim 1.
CN202210418878.1A 2022-04-20 2022-04-20 Macrolide compound kongjuemycin, preparation method and application thereof Active CN114989190B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210418878.1A CN114989190B (en) 2022-04-20 2022-04-20 Macrolide compound kongjuemycin, preparation method and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210418878.1A CN114989190B (en) 2022-04-20 2022-04-20 Macrolide compound kongjuemycin, preparation method and application thereof

Publications (2)

Publication Number Publication Date
CN114989190A true CN114989190A (en) 2022-09-02
CN114989190B CN114989190B (en) 2024-02-09

Family

ID=83025449

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210418878.1A Active CN114989190B (en) 2022-04-20 2022-04-20 Macrolide compound kongjuemycin, preparation method and application thereof

Country Status (1)

Country Link
CN (1) CN114989190B (en)

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
IMRAN KHAN，ET AL.: "Cylindromicin from Arctic-Derived Fungus Tolypocladium sp. SCSIO 40433", 《MOLECULES》, vol. 26, pages 1080 *
JIE LI，ET AL.: "Detection of polyketide synthase and nonribosomal peptide synthetase biosynthetic genes from antimicrobial coral- associated actinomycetes", 《ANTONIE VAN LEEUWENHOEK》, vol. 106, pages 623 - 635, XP035387262, DOI: 10.1007/s10482-014-0233-1 *
ZHUANGJIE FANG，ET AL.: "A new uridine derivative and a new indole derivative from the coral-associated actinomycete Pseudonocardia sp. SCSIO 11457", 《NATURAL PRODUCT RESEARCH》, vol. 35, no. 2, pages 188 - 194 *

Also Published As

Publication number Publication date
CN114989190B (en) 2024-02-09

Similar Documents

Publication Publication Date Title
CN115490661B (en) Antioxidant active compound in mangrove-derived fungi and preparation method thereof
CN108753627A (en) A kind of marine aspergillus source oxa- anthraquinone analog compound and preparation method thereof and the application in preparing antitumor agent
CN106432168B (en) The anti-vibrios reactive compound and preparation method thereof in mangrove cusp sea lotus endogenetic fungus source
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
CN114989190A (en) Macrolide compound kongjuemycins and preparation method and application thereof
CN111892574A (en) Atypical keratinocyte compounds and preparation method and application thereof
CN106432169B (en) A kind of active isocoumarin class compound of anti-vibrios and its crystal
CN115109023A (en) Macrolide compound FWYZ52-A, and fermentation strain, fermentation method and application thereof
CN111808112B (en) Pratensilin D compound and preparation and application thereof
US10119158B2 (en) Process for the preparation of fidaxomicin
CN110872338B (en) Indole diterpenoid compound and preparation method and application thereof
Martin et al. Isolation, purification and properties of the hexaene macrolides candihexin I and candihexin II
CN113396214A (en) Method for producing nigericin from streptomyces sp.mcc-0151
CN107973803B (en) Seven-membered lactonofuran derivative and preparation method and application thereof
AU2016362540B2 (en) Antibiotic FIIRV 104/18 complex and the isolated individual factors thereof
CN111285828B (en) Compound proximicin and preparation method and application thereof
EP2886640A1 (en) Process for isolation of milbemycins A3 and A4
CN106957216B (en) Preparation method and antifungal application of antifungal compound
CN109320527A (en) Deer chromomycin (cervinomycin) B1, B2, B3, B4 and its production method and application
CN115504990B (en) Sugar-spiro-macrolide compound FW-5-39 and preparation method and application thereof
KR20010039119A (en) Process for the purification of Avermectin
CN108623644B (en) Paulomycin derivatives and preparation method and application thereof
CN115626942A (en) lobophorins N1-N3 and preparation method and application thereof
CN106905342B (en) Structure of two active metabolites of streptomyces roseoflavus and preparation 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