Guaiane type sesquiterpene lactone compound as well as preparation method and application thereof

Abstract

The invention relates to a guaiane type sesquiterpene lactone compound as well as a preparation method and application thereof. The guaiane type sesquiterpene lactone compound is prepared by the following steps: extracting from the whole herb of Achillea millefolium L by adopting an organic solvent, extracting, concentrating and drying, thereby obtaining the guaiane type sesquiterpene lactone compound. Then separating by two to three methods of normal phase silica gel column chromatography, medium and low pressure rapid preparative chromatography and semi-preparative high performance liquid chromatography to obtain two new guaiane type sesquiterpene lactone monomeric compounds; the two compounds are determined to be new guaiane type sesquiterpene lactone compounds through methods such as high-resolution mass spectrum and nuclear magnetic resonance spectrum, and the structures of the guaiane type sesquiterpene lactone compounds are identified. In addition, related activity determination of neuroinflammation treatment is carried out on the two guaiane type sesquiterpene lactone compounds by using microglial cells BV2, and the result shows that the guaiane type sesquiterpene lactone compounds can be used for treating neuroinflammation and can be used for anti-neuroinflammation drugs.

Description

Technical Field

[0001] The invention relates to the field of medical technology, and in particular to a guaiacyl sesquiterpene lactone compound and a preparation method and use thereof. Background Art

[0002] Neuroinflammation is a complex phenomenon that has both protective and damaging effects on various neurological diseases. Inflammation is a natural defense mechanism for initial insults such as infection and trauma, but in chronic diseases, persistent neuroinflammation leads to a continued cycle of neuronal damage and degeneration. Chronic neuroinflammation is characterized by excessive activation of glial cells, including microglia and astrocytes, which release proinflammatory cytokines, chemokines, and reactive oxygen species, exacerbating neuronal damage and leading to the progressive neurodegeneration seen in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, and others.

[0003] Guaiane-type sesquiterpene lactone compounds are important naturally occurring active compounds, and their structural characteristics are that the molecular skeleton is a typical [5,7] ring structure. So far, a few natural guaiacane-type sesquiterpene lactone compounds have been found to have the effect of inhibiting neuroinflammation, such as the 2,3-opened guaiacane-type sesquiterpene lactone compounds discovered by our research group from Achillea millefolium and the guaiacane-type sesquiterpene lactone compounds discovered from chicory. These findings provide new insights into the treatment of neuroinflammation-related diseases with guaiacane-type sesquiterpene lactone compounds. Summary of the invention

[0004] The present invention aims to provide a guaiacyl sesquiterpene lactone compound, a preparation method and a use thereof, wherein the guaiacyl sesquiterpene lactone compound is extracted from the whole plant of Achillea millefolium L. by using an organic solvent to extract the solvent, and then separated by two or three of normal phase silica gel column chromatography, medium and low pressure rapid preparative chromatography, and semi-preparative high performance liquid chromatography to obtain two new guaiacyl sesquiterpene lactone monomer compounds, which are determined to be new guaiacyl sesquiterpene lactone compounds by high resolution mass spectrometry, nuclear magnetic resonance spectroscopy and the like, and their structures are identified. The use of the guaiacyl sesquiterpene lactone compound described in the present invention in the preparation of a drug for treating neuroinflammation has been tested.

[0005] The guaiacyl sesquiterpene lactone compound of the present invention has the structural formula:

[0006]

[0007] Wherein: the compound of formula (I) is (1R,5R,6S,7R,8S,10S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone;

[0008] The compound of formula (II) is (1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0009] The preparation method of the guaiacyl sesquiterpene lactone compound is carried out according to the following steps:

[0010] a. Take the whole herb of Achillea millefolium as raw material, crush it, and use 4-8 times the volume of 50-95% ethanol aqueous solution or 50-95% methanol aqueous solution to perform percolation or cold soaking extraction at room temperature, and evaporate the solvent under reduced pressure at 45°C to obtain a crude extract of Achillea millefolium;

[0011] b. Dispersing the crude extract obtained in step a with water, sequentially adding petroleum ether or n-hexane, ethyl acetate, dichloromethane or chloroform to extract 3-5 times, concentrating the ethyl acetate, dichloromethane or chloroform extract to obtain an ethyl acetate, dichloromethane or chloroform extract extract;

[0012] c. Separate the ethyl acetate, dichloromethane or chloroform extract obtained in step b by two or three methods selected from normal phase silica gel column chromatography, medium and low pressure rapid preparative chromatography and semi-preparative high performance liquid chromatography to obtain the compound of formula (I) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0013] The normal phase silica gel column chromatography used in step c is normal pressure or pressurized column chromatography, and the filler used is normal phase silica gel; the medium and low pressure preparative chromatography used is pressurized column chromatography, and the column chromatography filler used is reversed phase ODS silica gel; the semi-preparative high performance liquid chromatography used is a pressurized column layer.

[0014] Two separation methods in step c:

[0015] c. The ethyl acetate, dichloromethane or chloroform extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was chloroform-methanol or dichloromethane-methanol with a volume ratio of 100:1-0:1 for gradient elution, and 20:1-50:1 fraction F was collected. Fraction F was subjected to semi-preparative high performance liquid chromatography with a concentration of 20%-99% methanol-water solution or a concentration of 10%-99% acetonitrile-water solution Gradient elution to obtain a compound of formula (I) ( 1R,5R,6S,7R,8S,10S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0016] Three separation methods in step c:

[0017] c. The ethyl acetate, dichloromethane or chloroform extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was chloroform-methanol or dichloromethane-methanol with a volume ratio of 100:1-0:1 for gradient elution, and the 20:1-50:1 fraction F was collected. The fraction F was subjected to medium and low pressure rapid preparative chromatography with a concentration of 20%-99% methanol-water solution or 10%-99% acetonitrile-water solution gradient elution, and the 30-70% methanol-water solution or acetonitrile-water solution elution fraction F30-70 was collected. The F30-70 fraction was subjected to semi-preparative high performance liquid chromatography with a concentration of 2 Gradient elution with 0%-99% methanol-water solution or 10%-99% acetonitrile-water solution can give the compound of formula (Ⅰ) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (Ⅱ) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0018] Use of the guaiacyl sesquiterpene lactone compound in preparing a drug for treating neuroinflammation.

[0019] The guaiacyl sesquiterpene lactone compound of the present invention can be obtained by separation and purification from plants, or synthesized by a chemical modification method well known to those skilled in the art.

[0020] The structure of the guaiacyl sesquiterpene lactone compound described in the present invention is determined by modern spectroscopy methods such as high-resolution mass spectrometry, one-dimensional and two-dimensional nuclear magnetic resonance spectroscopy, and the structural identification process is as follows:

[0021] The compound of formula (I) is (1R,5R,6S,7R,8S,10S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone, colorless needle-shaped crystals, [α] 20 D -8 (concentration 0.1, methanol); UV (methanol) 218.1 nm; circular dichroism absorption (methanol) 230 (Δε-4.19); through its quasi-molecular ion peak [M+H] in high-resolution mass spectrum + m / z 279.1224 (calculated value 279.1227) confirmed its molecular formula to be C 15 H 18 O5; according to 1 H, 13 C NMR and 2D NMR data confirmed that its structural skeleton type is a guaiacyl sesquiterpene lactone compound, named (1R,5R,6S,7R,8S,10S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiacyl-3-ene-12,6-lactone; 1 H and 13 C NMR assignments are shown in Table 1 [600 MHz ( 1 H), 150MHz( 13 C), deuterated chloroform].

[0022] The compound of formula (II) is (1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone, a white amorphous powder, [α] 20 D -8 (concentration 0.1, methanol); UV (methanol) 218.1 nm; circular dichroism absorption (methanol) 230 (Δε-4.19); through its quasi-molecular ion peak [M+Na] in high-resolution mass spectrum + m / z 437.1330 (calculated value 437.1338) confirmed its molecular formula to be C 20 H 27 O7Cl; according to 1 H, 13C NMR and two-dimensional nuclear magnetic resonance data confirmed that its structural skeleton type is a guaiacyl sesquiterpene lactone compound, named 1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiacyl-1-ene-12,6-lactone; 1 H and 13 C NMR assignments are shown in Table 1 [600 MHz ( 1 H), 150MHz( 13 C), deuterated chloroform].

[0023] Table 1. Compounds of formula (I) and (II) 1 H and 13 C NMR data [δ(ppm), J(Hz)]

[0024]

[0025] BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 The compound of formula (I) of the present invention 1 H NMR (600MHz, CDCl3) spectrum;

[0027] Figure 2 The compound of formula (I) of the present invention 13 C NMR (150MHz,CDCl3) spectrum;

[0028] Figure 3 The compound of formula (II) of the present invention 1 H NMR (600MHz, CDCl3) spectrum;

[0029] Figure 4 The compound of formula (II) of the present invention 13 C NMR (150 MHz, CDCl3) spectrum. DETAILED DESCRIPTION

[0030] All reagents used were analytically pure, and acetonitrile in HPLC was HPLC grade (Merck, Germany). Normal phase silica gel for column chromatography (100-200 mesh, 200-300 mesh): produced by Qingdao Ocean Chemical Plant; reversed phase silica gel ODS: produced by Merck, Germany; medium and low pressure preparative chromatography Sepacore (Buch, Switzerland, with the following configuration): C-620 control system, C-660 fraction collector, C-640 UV detector, C-605 pump; HPLC (Dionex, USA) with the following configuration: P680HPLC pump, ASI-100 autosampler, TCC-100 column oven, UVD170U UV detector (four wavelengths), quaternary solvent system, online degasser, Chameleon chromatography workstation. The preparative high performance liquid chromatography (Dionex, USA) was configured as follows: P680HPLC pump, UVD170U ultraviolet detector (four wavelengths), quaternary solvent system, online degasser, Chameleon chromatography workstation; mass spectra were measured using a quadrupole-time-of-flight hybrid mass spectrometer (Applied Biosystems, USA); nuclear magnetic resonance was measured using a VARIAN VNMRS 600 MHz nuclear magnetic resonance spectrometer; and ECD spectral data were obtained using a Chirascan circular dichroism spectrometer (UK).

[0031] The whole herb of Achillea millefolium was collected from Changji area of ​​Xinjiang Uygur Autonomous Region and was identified as Achillea millefolium L. by Associate Researcher Lu Chunfang from Xinjiang Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences.

[0032] Example 1

[0033] Two separation methods:

[0034] a. Take 5 kg of Achillea millefolium whole herb raw material, crush it, and use 4 times the volume of 95% ethanol aqueous solution for cold soaking extraction at room temperature, and evaporate the solvent under reduced pressure at 45°C to obtain a crude extract of Achillea millefolium;

[0035] b. Dispersing the crude extract obtained in step a with water, adding petroleum ether and ethyl acetate in turn for extraction three times, combining the ethyl acetate layers, and evaporating under reduced pressure to obtain an ethyl acetate layer extract;

[0036] c. The ethyl acetate extract obtained in step b is sequentially chromatographed on a normal phase silica gel column with a gradient elution of 100:1-0:1 chloroform-methanol as the eluent, and a 20:1-50:1 fraction F is collected; fraction F is subjected to semi-preparative high performance liquid chromatography with a gradient elution of 20%-99% methanol-water solution to obtain a compound of formula (I) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and a compound of formula (II) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0037] Example 2

[0038] Two separation methods:

[0039] a. Take 5 kg of Achillea millefolium whole herb raw material, crush it, and use 8 times the volume of 50% ethanol aqueous solution for percolation extraction at room temperature, and evaporate the solvent under reduced pressure at 45°C to obtain a crude extract of Achillea millefolium;

[0040] b. Dispersing the crude extract obtained in step a with water, sequentially adding n-hexane and dichloromethane to extract 4 times, combining the dichloromethane layers and evaporating under reduced pressure to obtain a dichloromethane extract;

[0041] c. The dichloromethane extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was a dichloromethane-methanol solution with a volume ratio of 100:1-0:1, and gradient elution was performed to collect 20:1-50:1 fraction F, and fraction F was subjected to semi-preparative high performance liquid chromatography with a gradient elution of 10%-99% acetonitrile-water solution to obtain the compound of formula (I) (1R, 5R, 6S, 7R, 8S, 1 0S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0042] Example 3

[0043] Three separation methods:

[0044] a. Take 5 kg of Achillea millefolium whole herb raw material, crush it, and use 4 times the volume of 95% methanol aqueous solution for percolation extraction, and evaporate the solvent under reduced pressure at 45°C to obtain a crude extract of Achillea millefolium;

[0045] b. Dispersing the crude extract obtained in step a with water, adding petroleum ether and chloroform in turn for extraction 5 times, combining the chloroform layers and evaporating under reduced pressure to obtain a chloroform extract;

[0046] c. The chloroform extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was a chloroform-methanol solution with a volume ratio of 100:1-0:1, and gradient elution was performed to collect 20:1-50:1 fraction F, and fraction F was subjected to medium and low pressure semi-preparative chromatography with a concentration of 20%-99% methanol-water solution gradient elution, and 30-70% methanol-water solution elution fraction F30-70 was collected, and F30-70 was subjected to semi-preparative high performance liquid chromatography with a concentration of 30%-80% methanol-water gradient elution. The mixture was eluted at a certain degree to obtain the compound of formula (I) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0047] Example 4

[0048] Three separation methods:

[0049] a. Take 5 kg of Achillea millefolium whole herb raw material, crush it, and use 8 times the volume of 50% methanol aqueous solution for percolation extraction at room temperature, and evaporate the solvent under reduced pressure to obtain a crude extract of Achillea millefolium;

[0050] b. Disperse the crude extract obtained in step a with water, add n-hexane and dichloromethane successively for extraction 5 times, combine the dichloromethane layers, and evaporate to dryness under reduced pressure to obtain a dichloromethane extract;

[0051] c. The dichloromethane extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was dichloromethane-methanol with a volume ratio of 100:1-0:1 for gradient elution, and the 20:1-50:1 fraction F was collected. The fraction F was subjected to medium and low pressure semi-preparative chromatography with a gradient elution of 10%-99% acetonitrile-water solution, and the 30-70% acetonitrile-water solution elution fraction F30-70 was collected. F30-70 was subjected to semi-preparative high performance liquid chromatography with a gradient elution of 40%-70% acetonitrile-water solution. The mixture was eluted at a certain degree to obtain the compound of formula (I) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0052] Example 5

[0053] Three separation methods:

[0054] a. Take 5 kg of Achillea millefolium whole herb raw material, crush it, soak it in 6 times the volume of 70% ethanol aqueous solution for extraction, evaporate the solvent under reduced pressure to obtain a crude extract of Achillea millefolium;

[0055] b. Dispersing the crude extract obtained in step a with water, adding petroleum ether and ethyl acetate for 3 times, combining the ethyl acetate layers, and evaporating under reduced pressure to obtain an ethyl acetate extract;

[0056] c. The ethyl acetate extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was chloroform-methanol with a volume ratio of 100:1-0:1 for gradient elution, and the 20:1-50:1 fraction F was collected. The fraction F was subjected to medium-low pressure semi-preparative chromatography with a concentration of 10%-99% methanol-water solution gradient elution, and the 30-70% methanol-water solution elution fraction F30-70 was collected. F30-70 was subjected to semi-preparative high performance liquid chromatography with a concentration of 30-80% methanol-water solution gradient elution. The mixture was eluted at a certain degree to obtain the compound of formula (I) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

[0057] Example 6

[0058] The use of the guaiacyl sesquiterpene lactone compounds isolated from the whole herb of Achillea millefolium in the preparation of a drug for treating neuroinflammation, taking microglia (BV2) as an example;

[0059] Cell culture:

[0060] Microglial cells (BV2) (purchased from BeNa Culture Collection, BNCC) were cultured in Dulbecco's modified eagle medium (DMEM) high glucose medium (purchased from Hyclone, USA) containing 10% fetal bovine serum (FBS) (purchased from Giboco, USA) and 1% penicillin and streptomycin in an incubator at 37°C and 5% carbon dioxide;

[0061] 1. Test of the effect of the compounds of the present invention on cell viability:

[0062] When the revived BV2 cells grow to 80-90%, they are passaged according to the cell status, and the cells in better condition are taken and stained with trypan blue. 10 μl trypan blue is added to 10 μl cell suspension, mixed thoroughly, and added to the cell counting plate. The cells are counted with a cell counter. The cells are evenly spread in a 96-well plate at a density of 5×10 3 / well. Culture in a 37°C, 5% carbon dioxide constant temperature incubator overnight. The next day, add samples of different concentrations, set up 3 replicates, incubate for 2 hours, add 1 μg / ml lipopolysaccharide, and incubate for 22 hours in a 37°C, 5% carbon dioxide constant temperature incubator. Aspirate the liquid in the well, add 100 μl of 0.5 mg / ml (3-(4,5-dimethylthiazole-2)-2,5-diphenyltetrazolium bromide) (MTT) to each well, and continue incubating for 3-4 hours in a 37°C, 5% carbon dioxide incubator before terminating the culture. Aspirate the liquid in the well, add 150 μl of dimethyl sulfoxide (DMSO) to each well, shake for 10 minutes to fully dissolve the crystals in the cells, and measure the absorbance of each well at a wavelength of 490 nm using an enzyme reader. The cell survival rate is calculated according to the following formula:

[0063] Cell proliferation activity (%) = (A 样品 -A 零孔 ) / (A 对照 -A 零孔 )×100%;

[0064] 2. Determination of nitric oxide (NO) content:

[0065] The amount of nitric oxide released in microglia was tested using the Bio-Tech method. After confirming that the drug concentration had no significant effect on cell viability, samples with concentrations of 100, 50, 25, 12.5 and 6.25 μmol were added and incubated for 2 hours, and then 1 μg / ml of lipopolysaccharide was added and incubated for 22 hours. After the incubation was completed, the cell supernatant was collected and the nitric oxide content in the cell supernatant was determined by the Bio-Tech method. Before the determination, Bio-Tech reagents I and II were removed and restored to room temperature. Complete culture medium was used. Dilute the standard (1-100 micromolar); the concentration of the standard can be 0, 1, 2, 5, 10, 20, 40, 60, 100 micromolar, add the standard and the collected culture supernatant to a 96-well plate at 50 microliters / well, add 50 microliters of Biyuntian reagent I and 50 microliters of Biyuntian reagent II restored to room temperature to each well in turn, shake and mix for 5 minutes, measure the absorbance at 540 nanometers, make a standard curve, and calculate the nitric oxide content in the culture supernatant according to the standard curve;

[0066] 3. Experimental results:

[0067] The compounds of formula (I) and (II) obtained by the present invention have no obvious cytotoxicity to microglia at the tested concentration; the compounds of formula (I) and (II) can significantly inhibit the nitric oxide content in microglia induced by lipopolysaccharide, and the half inhibition rate of nitric oxide content is IC 50 The values ​​were 4.01 ± 0.19 and 46.10 ± 0.52 μmol, respectively;

[0068] The above results indicate that the compounds of formula (I) and formula (II) can reduce the release of nitric oxide in microglia induced by lipopolysaccharide, have the effect of treating neuroinflammation, and can be used as drugs for treating diseases related to neuroinflammation.

Claims

1. A guaiacyl sesquiterpene lactone compound, characterized in that The structural formula of the compound is: Wherein: the compound of formula (I) is (1R,5R,6S,7R,8S,10S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone; The compound of formula (II) is (1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

2. The method for preparing a guaiacyl sesquiterpene lactone compound according to claim 1, characterized in that Follow these steps: a. Take the whole herb of Achillea millefolium as raw material, crush it, and use 4-8 times the volume of 50-95% ethanol aqueous solution or 50-95% methanol aqueous solution to perform percolation or cold soaking extraction at room temperature, and evaporate the solvent under reduced pressure at 45°C to obtain a crude extract of Achillea millefolium; b. Dispersing the crude extract obtained in step a with water, sequentially adding petroleum ether or n-hexane, ethyl acetate, dichloromethane or chloroform to extract 3-5 times, concentrating the ethyl acetate, dichloromethane or chloroform extract to obtain an ethyl acetate, dichloromethane or chloroform extract extract; c. Separate the ethyl acetate, dichloromethane or chloroform extract obtained in step b by two or three methods selected from normal phase silica gel column chromatography, medium and low pressure rapid preparative chromatography and semi-preparative high performance liquid chromatography to obtain the compound of formula (I) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

3. The method for preparing the guaiacyl sesquiterpene lactone compound according to claim 2, characterized in that The normal phase silica gel column chromatography used in step c is normal pressure or pressurized column chromatography, and the filler used is normal phase silica gel; the medium and low pressure preparative chromatography used is pressurized column chromatography, and the column chromatography filler used is reversed phase ODS silica gel; the semi-preparative high performance liquid chromatography used is pressurized column chromatography.

4. The method for preparing a guaiacyl sesquiterpene lactone compound according to claim 2, characterized in that Two separation methods in step c: c. The ethyl acetate, dichloromethane or chloroform extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was chloroform-methanol or dichloromethane-methanol with a volume ratio of 100:1-0:1 for gradient elution, and 20:1-50:1 fraction F was collected. Fraction F was subjected to semi-preparative high performance liquid chromatography with a concentration of 20%-99% methanol-water solution or a concentration of 10%-99% acetonitrile-water solution Gradient elution to obtain a compound of formula (I) ( 1R,5R,6S,7R,8S,10S,11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (II) (1S,2R,3S,4R,5R,6S,7R,8S,10S,11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

5. The method for preparing a guaiacyl sesquiterpene lactone compound according to claim 2, characterized in that Three separation methods in step c: c. The ethyl acetate, dichloromethane or chloroform extract obtained in step b was subjected to normal phase silica gel column chromatography, and the eluent was chloroform-methanol or dichloromethane-methanol with a volume ratio of 100:1-0:1 for gradient elution, and the 20:1-50:1 fraction F was collected. The fraction F was subjected to medium and low pressure rapid preparative chromatography with a concentration of 20%-99% methanol-water solution or 10%-99% acetonitrile-water solution gradient elution, and the 30-70% methanol-water solution or acetonitrile-water solution elution fraction F30-70 was collected. The F30-70 fraction was subjected to semi-preparative high performance liquid chromatography with a concentration of 2 Gradient elution with 0%-99% methanol-water solution or 10%-99% acetonitrile-water solution can give the compound of formula (Ⅰ) (1R, 5R, 6S, 7R, 8S, 10S, 11S)-2-keto-8-hydroxy-1,10-epoxy-guaiac-3-ene-12,6-lactone and the compound of formula (Ⅱ) (1S, 2R, 3S, 4R, 5R, 6S, 7R, 8S, 10S, 11S)-1,10-epoxy-2,3-dihydroxy-4-chloro-8-[(Z)-2-methyl-2-butenoyloxy]-guaiac-1-ene-12,6-lactone.

6. Use of the guaiacyl sesquiterpene lactone compound according to claim 1 in the preparation of a drug for treating neuroinflammation.

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