A polyketide compound, its preparation method and application in cox2 enzyme inhibition and anti-inflammatory drugs

Abstract

The application discloses a polyketone compound, a preparation method thereof and application of the polyketone compound in Cox2 enzyme inhibition and anti-inflammatory drugs, and has the characteristics that the structural formula of the compound is shown as I, the preparation method steps include obtaining a fermentation product containing the polyketone compound through fermentation culture of a strain, then soaking the fermentation product with ethyl acetate to obtain a crude extract, and on the basis, obtaining the crude extract through normal-phase silica gel column chromatography, reverse-phase medium-pressure column chromatography and semi-preparative high performance liquid chromatography separation and purification, and the polyketone compound has obvious anti-inflammatory activity; and the polyketone compound can significantly inhibit the generation of nitric oxide, active oxygen and prostaglandin E2 and inhibit COX-2 enzyme activity, and is expected to become an active drug molecule for inflammation treatment.

Description

Technical Field

[0001] This invention relates to polyketides, and more particularly to a polyketide compound, its preparation method, and its application in Cox2 enzyme inhibitors and anti-inflammatory drugs. Background Technology

[0002] Inflammation, as a defensive response of the body to infection, injury, or abnormal stimuli, can lead to the development of various diseases if excessive or persistently activated. Traditional treatments for inflammation mainly include nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, and antibiotics, but these generally have limitations in efficacy: NSAIDs may cause gastrointestinal or cardiovascular risks, long-term use of glucocorticoids can easily lead to immunosuppression, and antibiotics are only effective against bacterial infections. Therefore, there is an urgent need to find and develop novel anti-inflammatory molecular structures for targeted treatment.

[0003] Microorganisms provide a wealth of lead compounds for drug development. Macrocyclic polyketides, due to their novel structures and potential pharmacological activity, are widely found in microorganisms. The inventors isolated microorganisms from mangrove sediments in Haikou. Guided by genome mining techniques, we preferentially screened from hundreds of microbial strains a strain carrying a macrocyclic polyketide biosynthesis gene cluster— Hahella Sp. NBU794 was isolated, and chemical analysis of its organic extracts successfully identified a novel 17-membered polyketide compound. Currently, there are no reports on the chemical structure and anti-inflammatory activity of this compound, therefore, no related drugs are available on the market. Summary of the Invention

[0004] The technical problem to be solved by the present invention is to provide a polyketide compound that can significantly inhibit the generation of nitric oxide, reactive oxygen species and prostaglandin E2 and inhibit the activity of COX-2 enzyme, as well as its preparation method and its application in Cox2 enzyme inhibition and anti-inflammatory drugs, which is expected to become an active drug molecule for the treatment of inflammation.

[0005] The technical solution adopted by the present invention to solve the above-mentioned technical problem is: a polyketide compound, which is derived from *Heterobacter*. Hahella The compound was isolated from the secondary metabolites of sp. and its structural formula is shown in I: I.

[0006] The specific steps for preparing the above-mentioned polyketide compounds are as follows: (1) Fermentation production The *Heterococcus* strain with accession number CGMCC No. 17574 was... Hahellastreak the sp. on ISP4 solid medium plates, incubate upside down in an incubator at 26-30℃ for 4-6 days, then pick a single colony and inoculate it into ISP4 liquid medium. Incubate on a shaker at 26-30℃ and 200-250 rpm for 5-8 days, and then collect the fermentation broth. (2) Extraction of extract Add an equal volume of ethyl acetate to the fermentation broth obtained in step (1), extract repeatedly 2 to 4 times, and then vacuum evaporate the ethyl acetate extract to obtain a crude extract. (3) Isolation and preparation of compounds The crude extract obtained in step (2) was first dissolved in a 1:1 mixture of dichloromethane and methanol, then mixed with 200-300 mesh silica gel and subjected to normal-phase medium-pressure column chromatography. Isocratic elution was performed using a petroleum ether-ethyl acetate solution containing 40% ethyl acetate as the eluent at a flow rate of 80 mL / min. The eluent was collected. The eluent was then subjected to reverse-phase medium-pressure column chromatography, using a linear gradient elution with methanol-water as the eluent. Elution was performed with 10% methanol for 20 min, 10-100% methanol for 90 min, and 100% methanol for 30 min at a flow rate of 20 mL / min. The fractions were arranged in descending order of polarity and combined to obtain 10 fractions. The fifth fraction was purified by semi-preparative reversed-phase high-performance liquid chromatography using acetonitrile-water at a volume ratio of 65:35 as the mobile phase to obtain a 17-membered polyketide compound, the structure of which is shown in Figure I. I.

[0007] Further, the preparation method of the ISP4 solid culture medium in step (1) is as follows: Dissolve 10g of soluble starch, 2g of (NH4)2SO4, 1g of K2HPO4, 2g of CaCO3, 1g of MgSO4·7H2O, 1g of NaCl, 0.001g of FeSO4·7H2O, 0.001g of MnCl2·7H2O, and 15g of agar powder in 1000 mL of distilled water, adjust the pH to 7.4-7.6, autoclave at 121℃ for 20 min, cool to 60℃, and then pour into plates; The preparation method of the ISP4 liquid culture medium is as follows: Dissolve 10g of soluble starch, 2g of (NH4)2SO4, 1g of K2HPO4, 2g of CaCO3, 1g of MgSO4·7H2O, 1g of NaCl, and 15g of FeSO4·7H2O It is prepared by dissolving 0.001g of MnCl2•7H2O in 1000 mL of distilled water.

[0008] Furthermore, the separation column used in the normal phase medium-pressure column chromatography in step (3) is a Silica Flash Column 330 g; the separation column used in the reverse phase medium-pressure column chromatography is a SEPAFLASH SW040.

[0009] Furthermore, the compound separation column for the semi-preparative reversed-phase high-performance liquid chromatography described in step (3) is a YMCC column. 18 (10 × 250 mm, 5 μm), flow rate 2.0 mL / min.

[0010] The present invention also provides the use of the above-mentioned polyketide compounds in the preparation of anti-inflammatory drugs.

[0011] Furthermore, the anti-inflammatory drug is a nitric oxide and / or reactive oxygen species inhibitor.

[0012] The present invention also provides the application of the above-mentioned polyketide compounds in the preparation of COX-2 enzyme activity inhibitors.

[0013] The present invention also provides the use of the above-mentioned polyketide compounds in the preparation of prostaglandin E2 inhibitors.

[0014] Compared with the prior art, the advantages of the present invention are: the present invention provides a polyketide compound, its preparation method, and its application in Cox2 enzyme inhibition and anti-inflammatory drugs, through *Helicobacter pylori*. Hahella The fermentation broth was obtained by sp. fermentation culture, and then extracted by soaking the fermentation broth in ethyl acetate to obtain a crude extract. The crude extract was then purified by medium-pressure normal-phase column chromatography, medium-pressure reversed-phase column chromatography, and semi-preparative high-performance liquid chromatography to obtain a polyketide compound. This compound has significant anti-inflammatory activity and can inhibit COX-2 enzyme activity.

[0015] The aforementioned *Helicobacter pylori* strain, HK-22, is classified and named *Helicobacter pylori*. Hahella sp., with accession number CGMCC No.17574, was deposited on April 17, 2019, at the China General Microbiological Culture Collection Center, located at No.3, No.1 Beichen West Road, Chaoyang District, Beijing. Attached Figure Description

[0016] Figure 1 The HR-ESI-MS spectra of the compounds of this invention are shown below. Figure 2 The nuclear magnetic resonance UV spectrum of the compound of this invention; Figure 3 The nuclear magnetic resonance (IR) spectrum of the compound of this invention; Figure 4 The proton NMR spectrum of the compound of this invention; Figure 5The carbon NMR spectrum of the compound of this invention; Figure 6 The DEPT-135 NMR spectrum of the compound of this invention; Figure 7 The HSQC nuclear magnetic resonance spectrum of the compound of this invention; Figure 8 Nuclear magnetic resonance of the compound of the present invention 1 H- 1 H COSY spectrum; Figure 9 The nuclear magnetic resonance HMBC spectrum of the compound of this invention; Figure 10 The NMR NOESY spectrum of the compound of this invention; Figure 11 The compound of this invention was determined by the modified Mosher method. S 1H NMR spectrum of )-MTPA derivatives; Figure 12 The compound of this invention was determined by the modified Mosher method. S Nuclear magnetic resonance of )-MTPA derivatives 1 H- 1 H COSY spectrum; Figure 13 The compound of this invention was determined by the modified Mosher method. R 1H NMR spectrum of )-MTPA derivatives; Figure 14 The compound of this invention was determined by the modified Mosher method. R Nuclear magnetic resonance of )-MTPA derivatives 1 H- 1 H COSY spectrum; Figure 15 Comparison of ECD spectra of the compounds of this invention; Figure 16 This is a single-crystal diffraction pattern of the compound of the present invention; Figure 17 The diagrams show intuitive examples of the COSY, HMBC, NOESY, and modified Mosher reactions of the compounds of this invention. Figure 18The anti-inflammatory activity of compound I was evaluated, where A is the chemical structural formula of compound I; B is the inhibition curve of compound I against COX-2; CE represents the effects of compound I at concentrations of 2 μM, 10 μM, and 30 μM on the production levels of nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E2 (PGE2) in RAW264.7 macrophages induced by lipopolysaccharide (LPS); Con indicates the negative control group (DMSO) and Dic indicates the positive drug diclofenac (10 μM). Detailed Implementation

[0017] The present invention will be further described in detail below with reference to the accompanying drawings and embodiments.

[0018] Example 1: Through *Hypericum* Hahella The structural formula of the polyketide compound extracted from sp. is shown in Figure I: I.

[0019] Example 2: The preparation method of the polyketide compound shown in Example 1 above includes the following steps: Step 1, Fermentation Production: The *Lithotridium* strain with preservation number CGMCC No. 17574 (…) Hahella (sp.) Streak the bacteria on ISP4 solid medium plates and incubate upside down in an incubator at 28℃ for 5 days. Then, pick a single colony and inoculate it into ISP4 liquid medium. Incubate on a shaker at 28℃ and 220 rpm for 7 days, then collect the fermentation broth. The preparation method of ISP4 solid medium is as follows: Dissolve 10g of soluble starch, 2g of (NH4)2SO4, 1g of K2HPO4, 2g of CaCO3, 1g of MgSO4·7H2O, 1g of NaCl, 0.001g of FeSO4·7H2O, 0.001g of MnCl2•7H2O, and 15g of agar powder in 1000mL of distilled water, adjust the pH to 7.4-7.6, and autoclave at 121℃ for 20 minutes. After cooling to 60℃, pour the solution into plates. The preparation method of ISP4 liquid culture medium is as follows: Dissolve 10g of soluble starch, 2g of (NH4)2SO4, 1g of K2HPO4, 2g of CaCO3, 1g of MgSO4·7H2O, 1g of NaCl, 0.001g of FeSO4·7H2O, and 0.001g of MnCl2•7H2O in 1000 mL of distilled water. Step 2, Extraction of Extract: Add an equal volume of ethyl acetate to the fermentation broth obtained in Step 1, and extract repeatedly 3 times. Then, evaporate the ethyl acetate extract under vacuum to obtain crude extract. Step 3, Separation and Preparation of Compounds: The crude extract obtained in Step 2 was first dissolved in a 1:1 mixture of dichloromethane and methanol, then mixed with 200-300 mesh silica gel and subjected to normal-phase medium-pressure column chromatography. The separation column was a Silica Flash Column 330 g (Santai Technologies, Inc.), with isocratic elution using a petroleum ether-ethyl acetate solution containing 40% ethyl acetate as the eluent at a flow rate of 80 mL / min. The eluent was collected. The eluent was then subjected to reverse-phase medium-pressure column chromatography using a SEPAFLASH SW040 column (serial number: SW-5222-040-SP; Santai Technologies, Inc.), with linear gradient elution using methanol-water as the eluent. Elution was performed with 10% methanol (v / v) for 20 min, 10-100% methanol (v / v) for 90 min, and 100% methanol (v / v) for 30 min at a flow rate of 20 mL / min. The fractions were collected at a rate of mL / min, arranged in descending order of polarity. Each 100 mL fraction was labeled as a separate fraction, and the fractions were combined to obtain 10 fractions. The fifth fraction was then treated with acetonitrile-water at a ratio of 65:35. v / v The mixture of the two solutions was used as the mobile phase and subjected to semi-preparative reversed-phase high-performance liquid chromatography (where the separation column was YMC C). 18 Polyketide compounds were obtained by separation and purification using a flow meter (10 × 250 mm, 5 μm, at a flow rate of 2.0 mL / min), the structure of which is shown in Figure I. I.

[0020] Example 3: Structural analysis of polyketide compound I prepared in Example 2 above.

[0021] The aforementioned polyketide compound I is a white solid powder. Figure 1 This is the high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) spectrum of the compound of this invention. This figure shows the quasi-molecular ion peak. m / z 388.2497 [M + H] + Its molecular formula was determined to be C 23 H 33 NO4. This compound 1 H and 13 The C13 NMR data are shown in Table 1.

[0022] Table 1. Compound I 1 H and 13 C NMR data (DMSO-d) 6 )

[0023] Note 1: s—single peak, d—double peak, t—triple peak, q—quartet, m—multiple peak.

[0024] Note 2: 1 The H spectrum was obtained by 600 MHz NMR; 13 The C spectrum was obtained by 150 MHz NMR.

[0025] Figure 2 This is the ultraviolet (UV) absorption spectrum of the compound of the present invention. Figure 3 The infrared absorption (IR) spectrum of the compound of this invention is shown below. Figure 2 The absorption at 204.47 nm and 229.41 nm in the ultraviolet spectrum and Figure 3 3463 cm⁻¹ in the infrared spectrum -1 and 1656cm -1 The absorption at the site together revealed the presence of hydroxyl groups and double bonds.

[0026] Figure 4 The proton NMR spectrum of the compound of this invention is obtained by... Figure 4 It can be seen that, 1 H NMR spectra showed the presence of 5 methyl groups (H3-18, H3-19, H3-21, H3-22, H3-23), 2 methylene groups (H2-9, H2-15), and 11 methine groups (H-2, H-3, H-4, H-6, H-7, H-8, H-10, H-12, H-13, H-14, H-16).

[0027] Figure 5 The carbon NMR spectrum of the compound of this invention is shown below. Figure 6 This is the DEPT-135 NMR spectrum of the compound of this invention. Figure 7 The HSQC nuclear magnetic resonance spectrum of the compound of this invention; by Figure 5 middle 13 C spectrum Figure 6 DEPT-135 spectrum and Figure 7 Data analysis of the HSQC spectrum revealed a total of 23 carbon signals (Table 1), including 5 methyl groups, 2 methylene groups, 11 methine groups, and 2 oxygen-containing tertiary carbons. δ C 69.0, 73.0) and 7 olefin carbons ( δ C 126.9, 128.9, 130.0, 131.5, 133.0, 133.6, 138.7), 3 aprotonated carbons ( δ C 133.7, 134.1, 137.8), 1 ketone carbonyl group ( δC 206.2) and 1 acetyl carbonyl group ( δ C 168.8).

[0028] Figure 8 Nuclear magnetic resonance of the compound of the present invention 1 H- 1 H COSY spectrum, Figure 9 Nuclear magnetic resonance of the compound of the present invention 1 H- 13 C HMBC spectrum. (From) Figure 8 It can be seen that there are three proton-proton coupling systems, corresponding to the three substructures C-19 / C-2 / C-3 / C-4, C-6 / C-7 / C-8 / C-9 / C-10, and C-12 / C-13 / C-14 / C-15 / C-16, respectively; from Figure 9 It can be seen that H-3 ( δ H 4.81), H-16 ( δ H 6.53), H3-18 ( δ H 1.74), H3-19 ( δ H The HMBC correlation signal of 0.95 / C-1 indicates that the ketone group (C-1) is located between C-2 and C-17. Furthermore, H3-22 ( δ H 1.67) / C-5 ( δ C 134.1), H3-22 ( δ H 1.67) / C-6 ( δ C 133.6) and H-4 ( δ H 4.98) / C-6 ( δ C 133.6) indicates the connection between C-5 and C-6. Meanwhile, H3-23 ( δ H 1.53) / C-10 ( δ C 126.9), H3-23 ( δ H 1.53) / C-11 ( δ C 133.7) and H3-23 ( δ H 1.53) / C-12 ( δ CThe HMBC correlation of 133.0 clarified the connection between C-11 and C-12. Therefore, the planar structure of compound I was established.

[0029] Figure 10 Nuclear magnetic resonance of the compound of the present invention 1 H- 1 1H NOESY spectrum. The coupling constant (J) values ​​in Table 1 were used to determine the compounds. Z , E Configuration. Based on the coupling constants of H-6 and H-7 ( J H-6 / H-7 =15.7 Hz) and the coupling constants of H-12 and H-13 ( J H-12 / H-13 =15.6 Hz), the configurations of the C-6 / C-7 and C-12 / C-13 double bonds were determined as follows: E Type. Using the NOESY correlation signals of H-3 and H3-22, and H-15 and H3-18, the C-4 / C-5 and C-16 / C-17 double bonds were determined to be... E Based on the NOESY correlation signals of H-10 and H-12, and H-13 and H3-23, the configuration of the C-11 / C-12 double bond is determined to be... Z type.

[0030] Figure 11 To improve the determination of compounds by the Mosher method ( S 1H NMR spectrum of )-MTPA derivatives; Figure 12 To improve the determination of compounds by the Mosher method ( S )-MTPA derivatives 1 H- 1 H COSY spectrum; Figure 13 To improve the determination of compounds by the Mosher method ( R 1H NMR spectrum of )-MTPA derivatives; Figure 14 To improve the determination of compounds by the Mosher method ( R Nuclear magnetic resonance of )-MTPA derivatives 1 H- 1 H COSY spectrum. Analysis of... Figure 11-14 It is pointed out that the absolute configurations of C-8 and C-14 are respectively R , S . Figure 15 This is the ECD spectrum of the compound of the present invention. Figure 16 The image shows the single-crystal diffraction pattern of the compound of this invention. The single-crystal data has been uploaded to the Cambridge Crystallography Data Centre (CCDC login number: CCDC 2393439). Figure 15 and 16It is known that the stereoconfiguration of compound I of the present invention is 2. S , 3 S , 8 R , 14 S .

[0031] In summary, the structure of compound I was established. A CAS Scifinder search confirmed it as a novel configuration compound.

[0032] Figure 17 The diagrams provided are visual examples of the COSY, HMBC, NOESY, and modified Mosher reactions of the compounds of this invention. Figure 17 This provides all the information from the aforementioned nuclear magnetic resonance spectrum.

[0033] Example 4: Determination of the anti-inflammatory ability of polyketide compounds.

[0034] Cell culture and viability assay: Mouse macrophage line RAW264.7 was purchased from the American Type Culture Collection (ATCC, Rockville, Maryland, USA). Cells were cultured at 37°C in a 5% CO2 saturated humidity incubator using high-glucose Dalberg modified Eagle medium (DMEM, Nisshin Pharmaceutical Co., Ltd., Tokyo, Japan), supplemented with 100 mg / mL streptomycin, 2.5 mg / L amphotericin B, and 10% heat-inactivated fetal bovine serum (FBS). The test cell suspension (approximately 1.0 × 10⁶ cells / mL) was... 4 Cells (10 cells / well) were seeded into 96-well plates and cultured for 12 h. Then, compound I at serially diluted concentrations was added, and the plates were cultured for another 24 h. The untreated control wells contained only complete culture medium. Compound solutions were prepared using a two-fold serial dilution method, with the highest concentration set at 50 μM. Cell viability was assessed using the MTT assay, and absorbance was measured at 450 nm using a SpectraMaxPro 7.1 microplate reader (Molecular Devices, San Jose, California, USA). All experiments used cells in the logarithmic growth phase.

[0035] Determination of nitric oxide (NO) and cytokine production levels released into the culture medium: RAW264.7 macrophages (approximately 1 × 10⁻⁶ cells) were used. 4Cells were seeded at 1000 cells / well in 96-well plates and cultured for 12 h. Subsequently, cells were pretreated with escalating concentrations of the test drug for 1 h, followed by co-incubation with 25 ng / mL lipopolysaccharide (LPS) for 24 h. Nitric oxide (NO) levels in the cell culture supernatant were quantified using the Griess reaction. The simplified procedure is as follows: 80 μL of Griess reagent was mixed with 80 μL of supernatant and incubated at 37°C in the dark for 15 min; absorbance was measured at 520 nm using a SpectraMax Pro 7.1 microplate reader (Molecular Devices, San Jose, California, USA). NO concentration was calculated using a standard curve plotted with 0–100 μM sodium nitrite solution. For the detection of prostaglandin E2 (PGE2), the procedure was strictly followed according to the kit instructions. The supernatant was detected using the prostaglandin E2 enzyme-linked immunosorbent assay kit (Jiangsu Meizheng Industrial Co., Ltd., China), and the absorbance value was read at a wavelength of 415 nm.

[0036] Detection of reactive oxygen species (ROS): RAW264.7 macrophages (approximately 1 × 10⁻⁶ cells) were analyzed. 4 Cells were seeded (1 cell / well) in black 96-well plates and cultured for 12 h. Subsequently, cells were pretreated with the test compound for 1 h, followed by co-incubation with 1 μg / mL lipopolysaccharide (LPS) for 24 h. After compound I treatment, the culture medium was discarded, and cells were washed with phosphate-buffered saline (PBS). 100 μL of dichlorofluorescein diacetate (DCFH-DA) solution (diluted to a final concentration of 100 μM with fetal bovine serum-free medium) was added to each well, and the plates were incubated at 37°C for 30 min. After incubation, the culture medium was discarded, and 100 μL of PBS was added to each well. Fluorescence intensity was detected using a SpectraMax Pro 7.1 microplate reader (Molecular Devices, San Jose, California, USA), with excitation and emission wavelengths set to 485 nm and 520 nm, respectively.

[0037] Test results: The collected data show that compound I ( Figure 18 A) It exhibits significant cyclooxygenase-2 (COX-2) inhibitory activity, with a half-maximal inhibitory concentration (IC50) of [missing information]. 50 The value was 3.87 μM. Figure 18 B). In addition, the enzymatic activities of inducible nitric oxide synthase (iNOS) and COX-2 can mediate the generation of downstream effector molecules, specifically nitric oxide (NO) and reactive oxygen species (ROS), which play a key role in the body's response to inflammatory stimuli.

[0038] Previous studies have confirmed that elevated levels of NO and ROS significantly affect the pathogenesis of various inflammatory diseases. This invention detected the secretion levels of NO and ROS in the supernatant of RAW264.7 cells pretreated with compound I, using the clinically approved drug diclofenac as a control. The results showed that compound I had a concentration-dependent inhibitory effect on the production of NO and ROS. Figure 18 C and D). Furthermore, the inhibitory effect of compound I on prostaglandin E2 (PGE2) was evaluated using enzyme-linked immunosorbent assay (EIA), revealing that this compound effectively inhibited PGE2 secretion. Figure 18 E).

[0039] The foregoing description is not intended to limit the invention, nor is the invention limited to the examples given. Any changes, modifications, additions, or substitutions made by those skilled in the art within the scope of the invention should also be considered within the protection scope of the invention.

Claims

1. A polyketide compound, characterized in that... The structural formula of the compound is shown in Figure I: I。 2. A method for preparing the polyketide compound according to claim 1, characterized in that... The specific steps are as follows: (1) Fermentation production The *Heterococcus* strain with accession number CGMCC No. 17574 was... Hahella streak the sp. on ISP4 solid medium plates, incubate upside down in an incubator at 26-30℃ for 4-6 days, then pick a single colony and inoculate it into ISP4 liquid medium. Incubate on a shaker at 26-30℃ and 200-250 rpm for 5-8 days, and then collect the fermentation broth. (2) Extraction of extract Add an equal volume of ethyl acetate to the fermentation broth obtained in step (1), extract repeatedly 2 to 4 times, and then vacuum evaporate the ethyl acetate extract to obtain a crude extract. (3) Isolation and preparation of compounds The crude extract obtained in step (2) was first dissolved in a 1:1 mixture of dichloromethane and methanol, then mixed with 200-300 mesh silica gel and subjected to normal-phase medium-pressure column chromatography. Isocratic elution was performed using a petroleum ether-ethyl acetate solution containing 40% ethyl acetate as the eluent, and the eluent was collected. The eluent was then subjected to reverse-phase medium-pressure column chromatography, using methanol-water as the eluent for linear gradient elution. Elution was performed with 10% methanol for 20 min, 10-100% methanol for 90 min, and 100% methanol for 30 min. The fractions were arranged in descending order of polarity and combined to obtain 10 fractions. The fifth fraction was purified by semi-preparative reversed-phase high-performance liquid chromatography using acetonitrile-water at a volume ratio of 65:35 as the mobile phase to obtain a 17-membered polyketide compound, the structure of which is shown in Figure I. I。 3. The method for preparing a polyketide compound according to claim 2, characterized in that... The preparation method of the ISP4 solid culture medium in step 1 is as follows: Dissolve 10g of soluble starch, 2g of (NH4)2SO4, 1g of K2HPO4, 2g of CaCO3, 1g of MgSO4·7H2O, 1g of NaCl, 0.001g of FeSO4·7H2O, 0.001g of MnCl2•7H2O, and 15g of agar powder in 1000 mL of distilled water, adjust the pH to 7.4-7.6, autoclave at 121℃ for 20 min, cool to 60℃, and then pour into plates. The preparation method of the ISP4 liquid culture medium is as follows: Dissolve 10g of soluble starch, 2g of (NH4)2SO4, 1g of K2HPO4, 2g of CaCO3, 1g of MgSO4·7H2O, 1g of NaCl, 0.001g of FeSO4·7H2O, and 15g of MnCl2•7H2O. It is prepared by dissolving 0.001g in 1000mL of distilled water.

4. The method for preparing a polyketide compound according to claim 2, characterized in that: The flow rate for isocratic elution with the petroleum ether-ethyl acetate solution in step 3 is 80 mL / min.

5. The method for preparing a polyketide compound according to claim 2, characterized in that: The separation column used in the normal phase medium-pressure column chromatography in step (3) is Silica Flash Column 330 g; the separation column used in the reverse phase medium-pressure column chromatography is SEPAFLASH SW040.

6. The method for preparing a polyketide compound according to claim 2, characterized in that: The flow rate for the semi-preparative reversed-phase high-performance liquid chromatography (RP-HPLC) preparation of compounds described in step 3 is 2.0 mL / min.

7. The use of the polyketide compound of claim 1 in the preparation of an anti-inflammatory drug.

8. The application according to claim 7, characterized in that: The anti-inflammatory drugs mentioned are nitric oxide and / or reactive oxygen species inhibitors.

9. The use of the polyketide compound of claim 1 in the preparation of COX-2 enzyme activity inhibitors.

10. The use of the polyketide compound of claim 1 in the preparation of a prostaglandin E2 inhibitor.

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