Polyketone compound and application thereof in preparation of osteoclast differentiation inhibitor

Abstract

The invention provides a polyketone compound and application thereof in preparation of an osteoclast differentiation inhibitor, and relates to the technical field of marine natural products. The compound is obtained by separation and purification from a fermentation culture of a marine fungus talaromyces sp. GMIMD 02524 (the preservation number is GDMCC No. 66968), the compound is named as talaromyces furanone A, and the structure of the compound is as shown in the formula (I) in the specification. The compound can effectively inhibit RANKL-induced osteoclast differentiation by inhibiting an NF-kappa B signal channel in vitro, and has no obvious cytotoxicity at an effective concentration. Therefore, the compound talaromyfuranone A can be used for developing medicines for preventing and treating osteoclast-related osteolytic diseases such as osteoporosis and the like, and has a good application prospect.

Description

Technical Field

[0001] This invention relates to the field of marine natural products, and in particular to a polyketide compound and its application in the preparation of osteoclast differentiation inhibitors. Background Technology

[0002] Osteoporosis is a systemic skeletal disease characterized by decreased bone mass, deterioration of bone microstructure, increased bone fragility, and a significantly elevated risk of fractures. With the accelerating aging of the global population, this disease has become a major public health challenge that urgently needs to be addressed. Although osteoclast-targeting therapies such as denosumab, bisphosphonates (e.g., zoledronic acid), and estrogen replacement therapy have been introduced into clinical use, these drugs generally carry risks such as osteonecrosis of the mandible, atypical femoral fractures, or kidney damage, and their long-term safety and tolerability need to be improved.

[0003] Osteoclast differentiation is primarily regulated by the synergistic action of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB (RANKL). In recent years, the RANKL signaling pathway has been clearly defined as a core therapeutic target for inhibiting osteoclast differentiation and alleviating excessive bone resorption. However, the known sources of RANKL signaling pathway inhibitors remain relatively limited, particularly the discovery of novel, highly active, and low-toxicity polyketide RANKL inhibitors from marine fungal resources, which requires further investigation.

[0004] Marine natural products, with their novel structures, diverse types, and varied biological activities, demonstrate enormous potential in innovative drug development. Among them, marine fungi, due to their unique habitat, are an important treasure trove for discovering novel polyketide bioactive molecules. In recent years, studies have confirmed that various marine-derived compounds can effectively inhibit osteoclast differentiation, further revealing the broad prospects of marine natural products as lead compounds for the treatment of osteoclast-related osteolytic diseases.

[0005] However, the discovery of novel polyketide compounds from specific marine fungal resources that can efficiently inhibit the RANKL signaling pathway remains a valuable but under-researched area. Summary of the Invention

[0006] This invention aims to overcome the shortcomings of existing drugs (such as RANKL inhibitors) for treating osteolytic diseases like osteoporosis, which have strong side effects. To this end, this invention provides a novel polyketide compound derived from marine fungi, its producing strain, its preparation method, and its application in the preparation of osteoclast differentiation inhibitors.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: In a first aspect, the present invention provides a polyketide compound, named talaromyfuranone A, the chemical structural formula of which is shown in formula (I): Equation (Ⅰ).

[0008] Secondly, the present invention provides a strain for producing the above-mentioned polyketide compounds, which is a marine fungus. Talaromyces sp GMIMD 02524. This strain was deposited at the Guangdong Provincial Center for Microbial Culture Collection on September 17, 2025, with accession number GDMCC No. 66968.

[0009] Thirdly, the present invention provides a method for preparing the above-mentioned polyketide compound, the method comprising: taking the strain Talaromyces sp. GMIMD 02524 was fermented, and then the compound talaromyfuranone A was isolated and purified from the fermentation culture.

[0010] To further explain, the specific steps of the method for preparing polyketide compounds are as follows: (1) Preparation of inoculum: culture the strain Talaromyces sp. GMIMD 02524 was used to obtain the fermentation inoculum. (2) Solid fermentation: The inoculum obtained in step (1) is inoculated into a solid culture medium and allowed to ferment statically; (3) Extraction and separation: After fermentation, the fermentation culture was extracted with organic solvent to obtain crude extract. Then, the crude extract was separated by normal phase silica gel column chromatography, reverse phase silica gel column chromatography and semi-preparative high performance liquid chromatography to obtain compound talaromyfuranone A.

[0011] Further, the preparation of inoculum in step (1) includes: inoculating the strain from the preservation slant onto a solid plate culture medium for activation, and after mycelium grows, transferring it to a liquid seed culture medium for shaker expansion culture.

[0012] Further, the solid culture medium in step (2) is a rice culture medium.

[0013] Furthermore, the rice culture medium comprises rice, sea salt, methionine, and corn steep liquor.

[0014] Furthermore, in step (3), the organic solvent is ethyl acetate.

[0015] Further, in step (3), after the crude extract is eluted by gradient elution using normal-phase silica gel column chromatography, the fraction containing the compound talaromyfuranone A is collected for reverse-phase silica gel column chromatography; after gradient elution using reverse-phase silica gel column chromatography, the fraction containing the compound talaromyfuranone A is collected for semi-preparative high-performance liquid chromatography separation.

[0016] Fourthly, the present invention provides the application of the polyketide compound talaromyfuranone A in the preparation of osteoclast differentiation inhibitors.

[0017] Furthermore, the present invention provides the use of the polyketide compound in the preparation of a medicament for the prevention and / or treatment of osteoporosis or other osteoclast-related osteolytic diseases.

[0018] The present invention has at least the following beneficial effects: 1. This invention is the first to utilize marine fungi Talaromyces sp. A novel polyketide compound, talaromyfuranone A, was isolated from GMIMD 02524. Its chemical structure was confirmed by comprehensive spectroscopic analysis and single-crystal X-ray diffraction, enriching the structural types of marine natural products and providing a new chemical entity for drug development. At the same time, this invention provides the production strain and complete preparation process for this compound, ensuring its availability and reproducibility, and laying a material foundation for subsequent development.

[0019] 2. Compound talaromyfuranone A exhibits significant anti-osteoclast differentiation activity in vitro, effectively inhibiting RANKL-induced osteoclast formation in a dose-dependent manner within the concentration range of 1–15 μM. Moreover, it shows no significant toxicity to normal bone marrow macrophages at effective concentrations and even higher concentrations, demonstrating good activity and safety, and has the potential to become a high-quality lead compound.

[0020] 3. Mechanism of action studies have shown that this compound can block key signal transduction of osteoclast differentiation at the molecular level by inhibiting transcriptional activation of the NF-κB signaling pathway and downregulating the phosphorylation level of key proteins in the MAPK pathway, thus providing a clear mechanistic basis for its role as an osteoclast differentiation inhibitor.

[0021] In summary, compound talaromyfuranone A possesses multiple advantages, including novel structure, significant activity, clear mechanism, good safety profile, and feasible preparation, making it of significant value in the development of novel drugs for the prevention and / or treatment of osteoclast-related osteolytic diseases such as osteoporosis. Attached Figure Description

[0022] Figure 1 The chemical structural formula (left) and two-dimensional (HMBC and) of talaromyfuranone A in the embodiments of the present invention are shown in the embodiments. 1 H- 1 HCOSY NMR correlation diagram (right); Figure 2 The 1H NMR spectrum (Chloroform-) of talaromyfuranone A in this embodiment of the invention d ); Figure 3 In this embodiment of the invention, the carbon nuclear magnetic resonance spectrum (CNMR spectrum) of talaromyfuranone A was obtained. d ); Figure 4 The HSQC spectrum (Chloroform-) of talaromyfuranone A in this embodiment of the invention d ); Figure 5 The HMBC spectrum (Chloroform-) of talaromyfuranone A in this embodiment of the invention d ); Figure 6 In the embodiments of the present invention, talaromyfuranone A 1 H- 1 H COSY spectrum (Chloroform- d ); Figure 7 The NOESY spectrum (Chloroform-) of talaromyfuranone A in this embodiment of the invention d ); Figure 8 This is a crystal structure diagram of talaromyfuranone A in an embodiment of the present invention; Figure 9 These are the measured and calculated ECD spectra of talaromyfuranone A in this embodiment of the invention; Figure 10 This refers to the quantitative count of TRAP-positive multinucleated cells in this embodiment of the invention; BAY 11-7082 is a positive control. ### express p < 0.001 vs. control group; * indicates p < 0.05 vs. LPS group; Figure 11This is a bar chart showing the effect of compound talaromyfuranone A on BMM cell viability as determined by the CCK-8 assay in this embodiment of the invention.

[0023] Figure 12 These are representative microscopic images of talaromyfuranone A inhibiting RANKL-induced osteoclast differentiation in BMMs in a dose-dependent manner, as described in this embodiment of the invention.

[0024] Figure 13 This is a graph showing the results of detecting the expression of NF-κB pathway proteins in RAW264.7 cells at different RANKL stimulation times, as described in this embodiment of the invention.

[0025] Figure 14 This is a graph showing the results of detecting the expression of MAPK pathway proteins in RAW264.7 cells at different RANKL stimulation times using talaromyfuranone A in an embodiment of the present invention. Detailed Implementation

[0026] To make the above-mentioned objectives, features, and advantages of the present invention clearer and more intuitive, the specific embodiments of the present invention will be described in detail below with reference to the accompanying drawings. Although many specific details are listed herein to aid in a comprehensive understanding of the present invention, the embodiments of the present invention are not limited thereto. Those skilled in the art can make equivalent improvements without departing from the core essence of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0027] Example 1: Marine fungi Talaromyces sp. Separation and Preservation of GMIMD 02524 Fungi were isolated from mangrove sediment samples in the Beibu Gulf of Guangxi using a standard dilution-spreading method on PDA medium (containing 2% sea salt). Single colonies were picked and purified to obtain a pure culture strain. Genomic DNA was extracted from this strain, and its endogenous transcriptional spacer (ITS) sequence was amplified by PCR and sequenced. The obtained sequence was compared and analyzed in the GenBank database of the National Center for Biotechnology Information (NCBI) in the United States, and identified as... Talaromyces sp. and named Talaromyces sp GMIMD 02524.

[0028] To ensure the long-term and stable preservation and provision of this biological material, the strain was deposited on September 17, 2025, at the Guangdong Microbial Culture Collection Center (GDMCC), located on the fifth floor of Building 59, Guangdong Institute of Microbiology, No. 100 Xianlie Middle Road, Guangzhou, Guangdong Province, China, with accession number GDMCC No. 66968.

[0029] Example 2: Preparation, isolation and structural identification of compound talaromyfuranone A (1) Fermentation culture The strains preserved on the slant Talaromyces sp. GMIMD 02524 was inoculated onto MB solid plates (containing 1.5% malt extract, 1.8% agar, and 2% sea salt) and activated by incubation at 28°C for 5 days. Mycelial blocks were then inoculated into 250 mL Erlenmeyer flasks containing 100 mL of MB liquid seed medium (1.5% malt extract, 2% sea salt, pH 7.4) and cultured on a shaker at 28°C and 180 rpm for 3 days to obtain the seed culture.

[0030] The above seed culture was inoculated into sterilized rice solid culture medium at an inoculation rate of 5% (v / v). The rice culture medium formula was as follows: 120 g of rice was added to each 1 L Erlenmeyer flask, followed by 150 mL of an aqueous solution containing sea salt (final concentration 2%), methionine (final concentration 0.1%), and corn steep liquor (final concentration 0.2%). The flasks were sterilized at 121°C for 30 minutes. A total of 100 flasks were inoculated and incubated statically at 25-28°C for 30 days.

[0031] (2) Extraction and separation After fermentation, 300 mL of ethyl acetate was added to each bottle of fermentation product, and the mixture was extracted three times by sonication at room temperature for one hour each time. All ethyl acetate extracts were combined and concentrated under reduced pressure to remove the solvent, yielding approximately 282 g of dark brown crude extract.

[0032] The crude extract was initially separated by normal-phase silica gel (200-300 mesh) column chromatography. Gradient elution was performed using petroleum ether-dichloromethane-methanol (volume ratio gradually changed from 100:0 to 0:100) as the mobile phase. Similar components were combined based on the results of thin-layer chromatography (TLC) to obtain a total of 7 fractions (Fr.1 ~ Fr.7).

[0033] Activity tracking showed that fraction Fr.2 (the eluent of petroleum ether:ethyl acetate = 80:20, approximately 12.5 g) possessed the target activity. Fr.2 was further separated by reversed-phase silica gel (ODS-A, 50 μm) column chromatography, with a gradient elution of methanol-water (volume ratio varying from 10:90 to 100:0) as the mobile phase, yielding a total of 19 sub-fractions (Fr.2-1 ~ Fr.2-19).

[0034] The fraction Fr.2-17 (methanol:water = 70:30 elution fraction, approximately 320 mg) was finally purified by semi-preparative high-performance liquid chromatography (HPLC). Chromatographic conditions: YMC-Pack ODS-A column (250 × 10 mm, 5 μm); mobile phase: 76% acetonitrile aqueous solution (isocratic elution); flow rate: 2 mL / min; detection wavelength: 254 nm. The retention time was... t R The target component was collected at 20 minutes, concentrated and dried to obtain approximately 4.2 mg of talaromyfuranone A, a white amorphous powder.

[0035] (3) Structural identification The obtained compound was subjected to systematic spectroscopic analysis to confirm its chemical structure.

[0036] Compound talaromyfuranone A: a white solid, its molecular formula can be deduced to be C according to HRESIMS. 30 H 30 O 10 ( m / z 573.1735 [M + Na] + The degree of unsaturation is 16.

[0037] 1 H NMR (500 MHz, Chloroform- d The spectrum gives signals of 6 olefin protons. δ H 5.52 (d, J =15.5 Hz, H-6), 6.27 (dd, J = 15.5, 10.2 Hz, H-7), 5.97 (m, H-8), 5.87 (m, H-9), 6.58 (d, J = 2.1 Hz, H-20), 6.97 (d, J = 2.2 Hz, H-22); 1 methylene hydrogen signal δ H 2.11 (m, H2-10); 3 methine hydrogen signals δ H 4.09 (d, J = 5.6 Hz, H-15), 2.86 (m, H-16), 5.16 (d, J = 3.5 Hz, H-17); 6 methyl hydrogen signals δ H 1.01 (t,J = 7.4 Hz, H-11), 3.82(s, H-13), 1.55 (s, H-14), 1.86 (s, H-25), 1.12 (d, J = 7.1 Hz, H-26), 3.89(s, H-27); 13 C NMR (125 MHz, Chloroform- d The spectrum gives signals for 6 methyl carbons. δ C 13.4 (C-11), 52.2 (C-13), 22.6 (C-14), 17.1 (C-25), 18.1 (C-26), 56.1 (C-27); 1 methylene carbon signal δ C 25.9 (C-10); 9 methylene carbon signals δ C 124.6 (C-6), 132.9 (C-7), 127.6 (C-8), 140.5 (C-9), 48.4 (C-15), 39.4 (C-16), 76.7 (C-17), 100.6 (C-20), 103.0 (C-22); 14 seasonal carbon signals δ C193.2 (C-2), 100.2 (C-3), 197.6 (C-4), 92.4 (C-5), 163.4(C-12), 134.9 (C-17a), 164.5 (C-18), 110.1 (C-18a), 166.0 (C-19), 167.3 (C-21), 153.0 (C-22a), 112.9 (C-23a), 48.0 (C-23), 171.6 (C-24). Analysis of 1D and 2D NMR spectra revealed that the structure of compound talaromyfuranone A consists of part A and part B. Through COSY correlations of H-6 / H-7 / H-8 / H-9 / H-10 / H-11, and HMBC correlations of H-6 to C-4 / C-5, H-7 to C-5, H-14 to C-4 / C-5, and H-13 to C-12, part A exhibits structural features similar to those of the known polyketide compound aspertetronin A. The structure of part B was determined by COSY correlations of H-15 / H-16 / H-17 / H-26, and HMBC correlations of H-17 to C-17a / C-23a / C-24, H-25 to C-15 / C-23a / C-24, H-20 to C-19 / C-22, H-22 to C-20 / C-21 / C-23a, and H-27 to C-21. Finally, HMBC correlations of H-15 to C-2 confirmed that part A and part B of compound talaromyfuranone A are connected via C-2 / C-15. Figure 1 The one-dimensional and two-dimensional NMR spectra of compound talaromyfuranone A are shown below. Figures 2-7 .

[0038] The absolute configuration of compound talaromyfuranone A is mainly determined by single crystal analysis. Figure 8 ), and then calculate using ECD ( Figure 9 Furthermore, the absolute configuration of talaromyfuranone A was determined to be 5. S , 15 S , 16 S , 17 R , twenty three S .

[0039] Physicochemical data of compound talaromyfuranone A: [α]25 D −110.1 ( c 0.1, MeOH); ECD(0.25 mg / mL, MeOH) λ max(Δε) 203 (27.34), 226 (14.15), 254 (−37.37), 320(7.16) nm. 1 H and 13 The C NMR data are shown in Table 1; HR-ESIMS m / z 573.1735 [M + Na] + (calcd forC 30 H 30 O 10 Na 573.1737).

[0040] compound talaromyfuranone A 1 H (500 MHz) and 13 C (125 MHz) NMR data (Chloroform- d As shown in Table 1: Table 1

[0041] “ s " indicates a single peak; d " indicates a double peak; " t " " indicates a triplet; "m" indicates a multiplet.

[0042] In summary, the isolated compound was identified as a novel polyketide compound, named talaromyfuranone A, with its chemical structure shown in formula (I).

[0043] Equation (Ⅰ).

[0044] Example 3: The effect of talaromyfuranone A on inhibiting osteoclast differentiation (1) The inhibitory activity of talaromyfuranone A on lipopolysaccharide (LPS)-induced NF-κB activation in RAW264.7 cells was evaluated using luciferase reporter gene technology. RAW264.7 cells stably transfected with the NF-κB luciferase reporter gene were co-incubated for 4 hours with either talaromyfuranone A (final concentration 20 μM) or the NF-κB inhibitor BAY11-7082 (final concentration 5 μM). Cells were then stimulated with 100 ng / mL LPS for 6 hours. Results showed that, compared with the LPS model group, 20 μM talaromyfuranone A significantly inhibited NF-κB luciferase activity, with a statistically significant difference. P <0.05). (See) Figure 10 ).

[0045] (2) The effect of talaromyfuranone A on cell differentiation into osteoclasts was detected by using osteoclast precursors BMMs as experimental subjects.

[0046] Take bone marrow macrophages (BMMs) in good growth condition, at a ratio of 1×10⁻⁶ 3 Cells were seeded at a density of [number] cells / well in 96-well plates and incubated overnight at 37°C with 5% CO2. After complete cell adhesion and stable growth, different concentration gradients of talaromyfuranone A were added to each well, resulting in final concentrations of 0 (solvent control), 5 μM, 10 μM, and 15 μM, with three replicates per group. Incubation continued for 4 h. Subsequently, receptor activator of nuclear factor κB (RANKL) ligand was added to each well to a final concentration of 100 ng / mL. The culture medium was changed every two days for 4–5 days. After culture, cells were stained for tartrate-resistant acid phosphatase (TRAP). Cell photography and counting were performed using an inverted microscope. TRAP-positive cells with more than 5 nuclei were identified as osteoclasts. Results showed that talaromyfuranone A significantly inhibited RANKL-induced osteoclast formation in a dose-dependent manner, with the most significant inhibitory effect observed at a concentration of 15 μM (see [link to relevant documentation]). Figure 10 and Figure 12 ).

[0047] (3) CCK-8 assay to detect cell viability Take BMMs at 1×10 5Cells were seeded at a density of [number] cells / well in 96-well plates. Each well was then filled with phenol red-free α-MEM medium containing 10% fetal bovine serum, 100 IU / mL penicillin, and 100 IU / mL streptomycin, bringing the total volume to 200 μL. Macrophage colony-stimulating factor (M-CSF) was added to each well to a final concentration of 50 ng / mL. The 96-well plates were incubated overnight at 37°C in a 5% CO2 cell culture incubator. After cell adhesion and stable growth, different concentrations of talaromyfuranone A were added to the wells, resulting in final concentrations of 0 (solvent control), 5 μM, 10 μM, and 15 μM, respectively. Each group was in triplicate, and incubation continued for 72 hours. After incubation, 100 μL of supernatant was discarded from each well, and 5 μL of CCK-8 reagent (CellCounting Kit-8) was added to each well. The plates were thoroughly mixed and then incubated again at 37°C in a 5% CO2 incubator for 3 hours. The optical density (OD) value of each well was detected at a wavelength of 450 nm using an ELISA reader, and the cell viability of each group was calculated.

[0048] The results showed that, compared with the solvent control group, talaromyfuranone A had no significant effect on the cell viability of BMMs at concentrations of 5, 10, and 15 μM (see [link to study]). Figure 11 ).

[0049] (4) Regulatory effect on RANKL-induced osteoclast differentiation-related signaling pathways RAW264.7 cells were used for relevant assays. First, in the NF-κB luciferase reporter gene assay, NF-κB-luc-RAW264.7 cells transfected at passages 3–8 were selected at a concentration of 1 × 10⁻⁶ cells. 4 Cells / wells were seeded into 96-well plates, and after adhesion, culture medium containing different intervention drugs was added (experimental groups: 0 μM and 20 μM target compound; positive control group: 5 μM BAY11-7082 or 1 μM Cyclosporin A; blank group: drug-free culture medium). The plates were pre-incubated at 37°C and 5% CO2 for 6 h. Except for the blank group, 100 ng / mL RANKL was added to each group and incubated for another 6 h. Subsequently, lysis and fluorescence detection were performed according to the kit instructions.

[0050] Secondly, to detect changes in pathway proteins, RAW264.7 cells were cultured at a concentration of 9 × 10⁻⁶. 5Cells / wells were seeded into six-well plates. After cell adhesion, the experimental group was pretreated with 15 μM of the target compound, and the blank group was pretreated with 15 μL of DMEM for 6 h. The cells were then stimulated with 100 ng / mL RANKL for 0, 5, 10, 15, 30, and 60 min, respectively, before protein extraction. Protein expression was analyzed using Western blotting. The main steps included: protein extraction using RIPA lysis buffer containing the inhibitor, quantification using the BCA method, separation by SDS-PAGE electrophoresis (first at 80 V, then at 120 V), transfer to a PVDF membrane (300 mA constant current for 90 min, ice bath throughout), blocking, overnight incubation with primary antibody at 4°C, 1 h incubation with secondary antibody at room temperature, multiple TBST washings, and detection using a Li-cor near-infrared imaging system.

[0051] The above experimental results indicate that talaromyfuranone A can inhibit RANKL-induced NF-κB luciferase activity and regulate the phosphorylation levels of key proteins in the NF-κB and MAPK signaling pathways (see...). Figure 13 and Figure 14 ).

[0052] The results of the above embodiments demonstrate that the compound talaromyfuranone A of the present invention can: 1) significantly inhibit LPS-induced NF-κB transcriptional activation at a concentration of 20 μM; 2) effectively inhibit RANKL-induced osteoclast differentiation in a dose-dependent manner within the range of 1–15 μM, and show no significant cytotoxicity at concentrations up to 15 μM; 3) its inhibitory effect is related to the regulation of NF-κB and MAPK signaling pathways. These results fully demonstrate that the compound talaromyfuranone A has the potential to be developed into a drug for the prevention or treatment of osteoclast-related osteolytic diseases such as osteoporosis.

[0053] The above content details the use of the compound talaromyfuranone A provided by this invention in the preparation of osteoclast differentiation inhibitors and in the prevention and treatment of osteoclast-related osteolytic diseases. This application illustrates the working principle and implementation methods of the invention through specific embodiments. The description of the above embodiments is intended to help those skilled in the art understand the technical methods and core ideas of this invention. It should be noted that those skilled in the art can still make several improvements and modifications to this invention without departing from the principles of this invention, and these improvements and modifications also fall within the protection scope defined by the claims of this invention.

Claims

1. A polyketide compound, characterized in that, The compound is named talaromyfuranone A, and its chemical structural formula is shown in formula (Ⅰ). Equation (Ⅰ).

2. A strain for producing the polyketide compound as described in claim 1, characterized in that, The strain is Talaromyces sp. GMIMD 02524 was deposited at the Guangdong Provincial Center for Microbial Culture Collection on September 17, 2025, with accession number GDMCC No. 66968.

3. A method for preparing the polyketide compound as described in claim 1, characterized in that, Includes the following steps: (1) Preparation of inoculum: culture the strain Talaromyces sp. GMIMD 02524 was used to obtain the fermentation inoculum. (2) Solid fermentation: The inoculum obtained in step (1) is inoculated into a solid culture medium and allowed to ferment statically; (3) Extraction and separation: After fermentation, the fermentation culture was extracted with organic solvent to obtain crude extract. Then, the crude extract was separated by normal phase silica gel column chromatography, reverse phase silica gel column chromatography and semi-preparative high performance liquid chromatography to obtain compound talaromyfuranone A.

4. The method according to claim 3, characterized in that, Step (1) involves preparing the inoculum by inoculating the strain from the preservation slant onto a solid plate culture medium for activation, and after mycelium growth, transferring it to a liquid seed culture medium for shaker expansion culture.

5. The method according to claim 3, characterized in that, In step (2), the solid culture medium is rice culture medium.

6. The method according to claim 5, characterized in that, The rice culture medium contains rice, sea salt, methionine, and corn steep liquor.

7. The method according to claim 3, characterized in that, In step (3), the organic solvent is ethyl acetate.

8. The method according to claim 3, characterized in that, In step (3), after the crude extract is eluted by gradient elution using normal-phase silica gel column chromatography, the fraction containing the compound talaromyfuranone A is collected for reverse-phase silica gel column chromatography; after gradient elution using reverse-phase silica gel column chromatography, the fraction containing the compound talaromyfuranone A is collected for semi-preparative high-performance liquid chromatography separation.

9. The use of the polyketide compound as described in claim 1 in the preparation of osteoclast differentiation inhibitors.

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