An amide compound having a pyrrolidine skeleton and its preparation method and application

Abstract

The present invention discloses an amide compound having a pyrrolidine skeleton, and a preparation method and application thereof. The amide compound provided by the present invention has a structural formula shown in formula (I) or formula (II). The present invention separates and purifies the ethanol extract of Panax notoginseng by normal phase silica gel column chromatography, reverse phase ODS column chromatography and preparative HPLC separation and purification to obtain two new amide components, namely, physolamide A shown in formula (I) and physolamide B shown in formula (II). Through the activity study of the new amide compound, it is found that it has anti-inflammatory activity and has the potential to be prepared into anti-inflammatory drugs.

Description

Technical Field

[0001] The invention belongs to the field of natural drug chemistry, and specifically relates to an amide compound with a pyrrolidine skeleton and a preparation method and application thereof. Background Art

[0002] Chinese ginseng (Physochlainae Radix) is the dried root of Physochlainae Radix, a plant of the Solanaceae family. It is named after the Huashan Mountain where it is mainly produced. It is distributed in Shaanxi, Henan, Shanxi and other provinces. Chinese ginseng is warm in nature, sweet and slightly bitter in taste. It has the effects of warming the lungs and removing phlegm, relieving asthma and cough, and calming the nerves. It is mainly used to treat asthma and cough caused by cold phlegm, palpitations and insomnia. It is often used to treat cough, asthma and tuberculosis in the folk. In addition, Chinese ginseng also has certain therapeutic effects on stomach and abdominal pain, neurasthenia, schizophrenia, etc.

[0003] CN111848436A discloses a novel type I or II amide compound found from the Chinese medicinal herb Panax notoginseng, and finds that it can be used to prepare CREB activator drugs, promote neuron development, regeneration, synapse formation and repair, promote learning and memory, and has the prospect of anti-anxiety or anti-depression drugs.

[0004] However, there are not many studies on the active substances in Chinese ginseng, and the active substances that exert various functions need to be further developed. Summary of the invention

[0005] The purpose of the present invention is to provide a new amide compound and its preparation method and application. The amide compound has a pyrrolidine skeleton structure and has anti-inflammatory activity, and can be used to prepare drugs for treating inflammatory diseases.

[0006] To achieve the above object, the present invention provides the following technical solutions:

[0007] In a first aspect, the present invention provides an amide compound having a structural formula shown in formula (I) or formula (II):

[0008]

[0009] Compound represented by formula (I):

[0010] Molecular formula: C 19 H 22 N 2 O 5 ;

[0011] ESI-MS m / z: 357.1473 [MH] - ;

[0012] State: light yellow oil;

[0013] Specific rotation:

[0014]

[0015] The compound represented by formula (II):

[0016] Molecular formula: C 20 H 24 N 2 O 5 ;

[0017] ESI-MS m / z: 371.1607 [MH] - ;

[0018] State: light yellow oil;

[0019] Specific rotation:

[0020] In a second aspect, the present invention provides a method for preparing the amide compound, comprising the following steps:

[0021] S1. Extracting the crushed Chinese ginseng with ethanol, and concentrating the obtained extract to obtain a crude extract;

[0022] S2, after the crude extract is dispersed in water, petroleum ether, ethyl acetate, and water-saturated n-butanol are used for extraction in sequence to obtain an n-butanol extract;

[0023] S3. The n-butanol extract is sequentially separated and purified by normal phase silica gel column chromatography, reverse phase ODS column chromatography and preparative HPLC to obtain an amide compound represented by formula (I) or formula (II).

[0024] In step S1, the volume concentration of the ethanol is 50%-95%; preferably, the volume concentration is 70%, and the amount of the ethanol used is 10-20 times the weight of the Chinese ginseng.

[0025] The extraction temperature is room temperature; the extraction times are 1-3 times.

[0026] The extract is concentrated under reduced pressure to obtain a crude extract; the temperature of the reduced pressure concentration is 30-50°C.

[0027] In step S2, the extraction conditions are as follows:

[0028] The volume ratio of water to the petroleum ether, the ethyl acetate and the water-saturated n-butanol is 1:1-3:1-3:1-3; preferably 1:1:1:1.

[0029] The number of extractions with each solvent is 2-5 times. For example, the crude extract is evenly dispersed by adding distilled water, then extracted twice with petroleum ether in sequence, the extracts are combined, and concentrated by rotary evaporator under reduced pressure to obtain a petroleum ether extract extract; then extracted three times with ethyl acetate, the extracts are combined, and concentrated by rotary evaporator under reduced pressure to obtain an ethyl acetate extract extract; then extracted five times with water-saturated n-butanol, the extracts are combined, and concentrated by rotary evaporator under reduced pressure to obtain an n-butanol extract extract; the volume ratio of distilled water to petroleum ether, ethyl acetate, and water-saturated n-butanol is 1:1:1:1.

[0030] In step S3, the n-butanol extract is separated by normal phase silica gel column chromatography, and gradient elution is performed with dichloromethane-methanol as the mobile phase, and the elution ratios are 50:0, 50:1, 20:1, 10:1, 5:1, 3:1, 2:1, 1:1, 0:1, and each eluent is identified by thin layer chromatography and similar fractions are combined. According to the detection results and the elution order, 15 components are obtained in sequence, which are marked as Fr.1-15;

[0031] Component Fr.9 was separated and purified by reverse phase ODS column chromatography and preparative HPLC to obtain an amide compound represented by formula (I);

[0032] Component Fr.8 was separated and purified by the reverse phase ODS column chromatography and the preparative HPLC in turn to obtain an amide compound represented by formula (II).

[0033] Furthermore, in the normal phase silica gel column chromatography separation process, the amount of the mobile phase used for each elution ratio is 2 to 4 column volumes, and each portion of the eluate is collected as 1 / 4 of the column volume to obtain 120 portions of the eluate;

[0034] In the thin layer chromatography identification, 10% sulfuric acid-ethanol is used as a color developer, and each eluent is detected by thin layer chromatography under 254nm, 365nm ultraviolet light and sunlight. The 1st to 4th, 5th to 9th, 10th to 14th, 15th to 22nd, 23rd to 31st, 32nd to 47th, 48th to 56th, 57th to 68th, 69th to 86th, 87th to 94th, 95th to 102nd, 103rd to 108th, 109th to 113th, 114th to 118th, and 119th to 120th eluents with similar chromatographic behaviors are combined to obtain components Fr.1-15 in sequence.

[0035] Preferably, before performing the normal phase silica gel column chromatography separation, the n-butanol extract is firstly added with an appropriate amount of methanol for redissolution, and then mixed with 80-120 mesh silica gel, and wet packed into the column and dry loaded into a chromatographic column filled with 200-300 mesh silica gel.

[0036] Furthermore, the preparation conditions of the amide compound represented by formula (I) are as follows:

[0037] The component Fr.9 is separated by reverse phase ODS column chromatography, and gradient elution is performed with methanol-water as the mobile phase, and the elution concentration is 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% methanol in sequence, and each eluent is identified by thin layer chromatography and similar fractions are combined, and components Fr.9A to 9I are obtained in sequence according to the detection results and the elution order;

[0038] Component Fr.9E was separated and purified by the preparative HPLC, with methanol-water as the mobile phase and an elution ratio of 47:53, to obtain an amide compound represented by formula (I).

[0039] In the reversed phase ODS column chromatography separation, the amount of the mobile phase used for each elution concentration is 1 to 3 column volumes, and each portion of the eluate is collected as 1 / 5 of the column volume, to obtain 118 portions of eluate;

[0040] In the thin layer chromatography identification, 10% sulfuric acid-ethanol is used as a color developer, and each eluate is detected by thin layer chromatography under 254nm, 365nm ultraviolet light and sunlight, and the 1st to 4th, 5th to 19th, 20th to 44th, 45th to 57th, 58th to 62nd, 63rd to 89th, 90th to 99th, 100th to 112th, and 113th to 118th eluates with similar chromatographic behaviors are combined to obtain a total of 9 components in order, which are marked as components Fr.9A to 9I;

[0041] Furthermore, the preparation conditions of the amide compound represented by formula (II) are as follows:

[0042] The Fr.8 component is separated by reverse phase ODS column chromatography, and gradient elution is performed with methanol-water as the mobile phase, and the concentrations are 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, and each eluent is detected by thin layer chromatography and similar fractions are combined. According to the detection results and the elution order, components Fr.8A to 8J are obtained in sequence;

[0043] Component Fr.8E was separated and purified by the preparative HPLC, with methanol-water as the mobile phase and an elution ratio of 57:43, to obtain an amide compound represented by formula (II).

[0044] Furthermore, in the reversed-phase ODS column chromatography separation, the amount of the mobile phase used for each elution concentration is 1 to 3 column volumes, and each portion of the eluate is collected as 1 / 4 of the column volume, and 98 portions of the eluate are obtained in sequence;

[0045] In the thin layer chromatography identification, 10% sulfuric acid-ethanol is used as a color developer, and each eluate is detected by thin layer chromatography at 254nm, 365nm and sunlight, and the 1st to 3rd, 4th to 16th, 17th to 29th, 30th to 47th, 48th to 54th, 55th to 62nd, 63rd to 78th, 79th to 85th, 86th to 91st, and 92nd to 98th eluates with similar chromatographic behaviors are combined to obtain a total of 10 components in order, which are marked as components Fr.8A to 8J;

[0046] In the present invention, the chromatographic column of the preparative liquid chromatography is a C18 column.

[0047] In a third aspect, the present invention also provides use of the amide compounds in the preparation of drugs for treating inflammatory diseases; the drugs are prodrugs or pharmaceutically acceptable salts.

[0048] Preferably, the drug is a drug having the function of inhibiting LPS-induced macrophage secretion of inflammatory factor NO.

[0049] Compared with the prior art, the beneficial effects achieved by the present invention are as follows:

[0050] 1. The present invention separates and identifies two new amide compounds from Panax notoginseng for the first time, namely physolamide A and physolamide B. The new compounds physolamide A and physolamide B have a pyrrolidine skeleton, which is the first time that amide compounds with this skeleton type have been found in Solanaceae plants.

[0051] 2. The present invention separates new compounds physolamide A and physolamide B by combining three separation methods and optimizing the elution ratio.

[0052] 3. The present invention found through in vitro anti-inflammatory tests that compounds physolamide A and physolamide B have an inhibitory effect on the NO release of RAW264.7 inflammatory cells induced by LPS. Therefore, compounds physolamide A and physolamide B have potential in being developed into anti-inflammatory drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0053] Figure 1 This is the hydrogen spectrum of compound physolamide A.

[0054] Figure 2 This is the carbon spectrum of compound physolamide A.

[0055] Figure 3 This is the mass spectrum of compound physolamide A.

[0056] Figure 4 This is the DEPT-135 spectrum of compound physolamide A.

[0057] Figure 5 This is the HSQC spectrum of compound physolamide A.

[0058] Figure 6 For the compound physolamide A 1 H- 1 H COSY spectrum.

[0059] Figure 7 This is the HMBC spectrum of compound physolamide A.

[0060] Figure 8 For physolamide A 1 H- 1 H COSY is related to the key HMBC.

[0061] Fig. 9 This is the hydrogen spectrum of compound physolamide B.

[0062] Fig.10 This is the carbon spectrum of compound physolamide B.

[0063] Fig.11 This is the mass spectrum of compound physolamide B.

[0064] Fig.12 This is the DEPT-135 spectrum of compound physolamide B.

[0065] Fig.13 This is the HSQC spectrum of compound physolamide B.

[0066] Fig.14 For the compound physolamide B 1 H- 1 H COSY spectrum.

[0067] Fig.15 This is the HMBC spectrum of compound physolamide B. DETAILED DESCRIPTION

[0068] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0069] Instruments and Materials:

[0070] The Chinese ginseng medicinal materials were purchased from Queshan City, Henan Province in September 2021.

[0071] Bruker Ascend-600 MHz NMR spectrometer (Bruker, Germany).

[0072] Q Exactive Focus LC-MS / MS liquid chromatography-mass spectrometry (Thermo Fisher, USA).

[0073] Büchi pump Manager C-610 medium pressure chromatograph (Büchi, Switzerland).

[0074] Waters 2695-2998-2414 analytical high performance liquid chromatograph (Waters Company, USA).

[0075] Shimadzu Essentia LC-16P preparative high performance liquid chromatograph (Shimadzu Co., Ltd., Japan).

[0076] Sharpsil-U C18 preparative chromatographic column (21.2 mm × 250 mm, 5 μm, Kelanmu Experimental Technology (Shanghai) Co., Ltd.).

[0077] Sharpsil-U C18 analytical chromatography column (4.6 mm × 250 mm, 5 μm, Kelanmu Experimental Technology (Shanghai) Co., Ltd.).

[0078] Column chromatography silica gel (200-300 mesh, 80-120 mesh, Qingdao Ocean Chemical Plant).

[0079] Column chromatography ODS (YMC, Japan).

[0080] Chromatographic grade methanol (OCEANPAK, Sweden).

[0081] Other reagents were of analytical grade (Tianjin Zhiyuan Chemical Reagent Co., Ltd.).

[0082] Example 1. Preparation and structural confirmation of compounds physolamide A and physolamide B

[0083] The preparation method comprises the following steps:

[0084] (1) Extraction:

[0085] Take 10 kg of dried Chinese ginseng, crush it into uniform small pieces, and extract it with 20 times 70% ethanol at room temperature for 3 times, each time for 7 days. Combine the extracts, and use a rotary evaporator to concentrate under reduced pressure (40°C) to obtain 2.05 kg of crude extract.

[0086] (2) Extraction:

[0087] The crude extract was evenly dispersed by adding 20 L of distilled water, then extracted twice with 20 L of petroleum ether, the extracts were combined, and concentrated under reduced pressure on a rotary evaporator to obtain 112.6 g of petroleum ether extract extract; extracted three times with 20 L of ethyl acetate, the extracts were combined, and concentrated under reduced pressure on a rotary evaporator to obtain 347.2 g of ethyl acetate extract extract; extracted five times with 20 L of water-saturated n-butanol, the extracts were combined, and concentrated under reduced pressure on a rotary evaporator to obtain 545.2 g of n-butanol extract extract.

[0088] (3) Separation and purification:

[0089] Take 400 g of n-butanol extract, add appropriate amount of methanol for redissolution, then mix the sample in 500 g of 80-120 mesh silica gel, wet-pack it into the column, and dry-load it into the silica gel chromatographic column (2.5 kg of 200-300 mesh silica gel is loaded into the glass chromatographic column).

[0090] The silica gel chromatographic column is gradient eluted with dichloromethane-methanol as the mobile phase, and the elution ratio is 50:0-0:50 (the ratios are: dichloromethane-methanol=50:0, 50:1, 20:1, 10:1, 5:1, 3:1, 2:1, 1:1, 0:1, v / v), the amount of the mobile phase for each elution ratio is 2-4 column volumes, and each eluent is collected as a bottle according to 1 / 4 of the column volume, and the 1st to 120th bottles of eluent are obtained in sequence;

[0091] Using 10% sulfuric acid-ethanol as a color developer, each eluent was detected by thin layer chromatography under 254nm, 365nm ultraviolet light and sunlight, and the eluents from bottles 1 to 4, 5 to 9, 10 to 14, 15 to 22, 23 to 31, 32 to 47, 48 to 56, 57 to 68, 69 to 86, 87 to 94, 95 to 102, 103 to 108, 109 to 113, 114 to 118, and 119 to 120 with similar chromatographic behaviors were combined to obtain component Fr.1-15 in sequence.

[0092] (4) Component Fr.9 (eluate from bottles 69 to 86) was subjected to reverse phase ODS column chromatography with methanol-water as the mobile phase for gradient elution, and the elution concentration was 10%-100% methanol (the concentrations were: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% methanol), the amount of the mobile phase for each elution concentration was 1 to 3 column volumes, and 1 / 5 of the column volume was collected as one bottle, and 118 eluates were obtained in sequence;

[0093] Using 10% sulfuric acid-ethanol as the color developer, each eluate was detected by thin layer chromatography under 254nm, 365nm ultraviolet light and sunlight, and the eluates from bottles 1 to 4, 5 to 19, 20 to 44, 45 to 57, 58 to 62, 63 to 89, 90 to 99, 100 to 112, and 113 to 118 with similar chromatographic behaviors were combined to obtain a total of 9 components in sequence, which were marked as components Fr. 9A to 9I.

[0094] (5) Component Fr.9E (eluent from bottles 58 to 62) was purified by preparative HPLC using methanol-water (47:53) as the mobile phase to obtain compound physolamide A (11.4 mg).

[0095] (6) Component Fr.8 (eluate from bottles 57 to 68) was subjected to reverse phase ODS column chromatography with methanol-water as the mobile phase for gradient elution, the elution concentration being 10%-100% methanol (the concentrations being: 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% methanol in sequence), the amount of the mobile phase used for each elution concentration being 1 to 3 column volumes, each portion of the eluate being collected as a bottle at 1 / 4 of the column volume, and bottles 1 to 98 of the eluate were obtained in sequence;

[0096] Using 10% sulfuric acid-ethanol as the color developer, each eluent was detected by thin layer chromatography at 254nm, 365nm and sunlight, and the eluents from bottles 1 to 3, 4 to 16, 17 to 29, 30 to 47, 48 to 54, 55 to 62, 63 to 78, 79 to 85, 86 to 91, and 92 to 98 with similar chromatographic behaviors were combined to obtain a total of 10 components in sequence, which were marked as components Fr. 8A to 8J.

[0097] (7) Fraction Fr.8E (eluent from bottles 48 to 54) was purified by preparative HPLC using methanol-water (57:43) as the mobile phase to obtain compound physolamide B (11.1 mg).

[0098] Structure confirmation:

[0099] Physolamide A is a light yellow oil. HRESIMS gives [MH] at m / z 357.1473 - Ion peak (calculated value is 357.1451), the molecular formula is estimated to be C 19 H 22 N 2 O 5 .

[0100] 1In the H-NMR spectrum (Table 1), a group of mutually coupled olefin proton signals [δ H 6.35 (1H, d, J = 15.7 Hz, H-2) and 7.38 (1H, d, J = 15.7 Hz, H-3)] and a typical set of aromatic proton signals in the ABX coupling system [δ H 7.00 (1H, d, J = 2.1 Hz, H-5), 6.76 (1H, d, J = 8.2 Hz, H-8) and 6.91 (1H, dd, J = 8.2, 2.1 Hz, H-9)], suggesting that the structure contains a trans-caffeoyl structural fragment.

[0101] Combination 13 C-NMR and DEPT spectra clearly show 19 carbon signals, including 9 carbon signals of caffeoyl fragments (δ C 169.3,118.4,142.2,128.3,115.0,146.7,148.7,116.4,122.1), 4 adjacent methylene carbon signals (δ C 40.0, 27.7, 29.8, 46.3), and one aldehyde carbon signal (δ C 180.9), 1 hydroxymethyl carbon signal (δ C 56.5) and four pyrrole ring carbon signals (δ C 133.5,126.4,111.5,144.5). 1 H- 1 H COSY and HMBC spectra can further confirm the structure. 1 H- 1 The H COSY spectrum clearly shows Figure 8 The directly connected fragments are marked by the thick lines in the middle, and then the above fragments are linked by HMBC spectrum, such as Figure 8 The arrow in the middle indicates: H-6′(δ H 6.98) and C-5′(δ C 133.5), C-8′(δ C 144.5), C-10′(δ C 180.9) is related; H 2 -9′(δ H 4.63) and C-7′(δ C 111.5), C-8′(δ C 144.5) is related; H 2 -4′(δ H 4.39) and C-5′(δ C 133.5), C-8′(δ C144.5). The above correlation spectrum constructs a (2-formyl-5-hydroxymethyl)-pyrrolidine structure fragment. In addition, H 2 -1′(δ H 6.35) and C-1(δ C 169.3) and further connected the above-mentioned caffeoyl fragment and (2-formyl-5-hydroxymethyl)-pyrrolidine fragment. Therefore, its structure was finally determined and named physolamide A.

[0102] The structure of the compound physolamide A is shown in formula (I):

[0103]

[0104] Molecular formula: C 19 H 22 N 2 O 5

[0105] ESI-MS m / z: 357.1473 [MH] -

[0106] State: Pale yellow oil

[0107] Specific rotation:

[0108] Physolamide B is a light yellow oil. HRESIMS gives a [MH]-ion peak at m / z 371.1628 (calculated value 371.1607), and the molecular formula is estimated to be C 20 H 24 N 2 O 5 . Analysis found that it has highly similar one-dimensional NMR spectral data with physolamide A, so it is speculated that the two have the same skeleton. The main difference between them is that physolamide B has an additional methoxy group [δ H 3.34(3H,s),δ C 58.2], and by δ H 3.34 and C-9′(δ C The HMBC correlation between 66.4) and 1,4-dihydropyridine could link the methoxy group to the C-9′ position. Therefore, its structure was finally determined and named physolamide B.

[0109] The structure of compound physolamide B is shown in formula (II):

[0110]

[0111] Molecular formula: C 20 H 24 N 2 O 5

[0112] ESI-MS m / z: 371.1607 [MH] -

[0113] State: Pale yellow oil

[0114] Specific rotation:

[0115] Table 1. 1 H-NMR (600MHz,methanol-d 4 )and 13 C-NMR (150MHz,methanol-d 4 )data

[0116]

[0117]

[0118] Example 2. Anti-inflammatory activity of physolamide A and physolamide B

[0119] In this study, the LPS-induced RAW264.7 inflammatory cell model was used to investigate the anti-inflammatory activity of compounds physolamide A and physolamide B.

[0120] The specific method is as follows:

[0121] (1) Cytotoxicity:

[0122] RAW264.7 cells were revived by conventional methods and placed in DMEM medium containing 10% fetal bovine serum and 100 U / mL penicillin / streptomycin at 37°C and 5% CO 2 Take 100 μL of cells in the logarithmic growth phase and culture them at a density of 1×10 5 cell / mL were inoculated in a 96-well plate, with 3 replicates per group. After the cells were completely attached, the culture medium was removed, the drug group was given 50 μM drug-containing culture medium, the control group was given 100 μL normal culture medium, and the blank group contained only normal culture medium. After continuing to culture under the above culture conditions for 24 hours, 10 μL CCK-8 was added and cultured for 2 hours, and then the absorbance value of each well was detected at 450 nm using an ELISA reader to calculate the cytotoxicity of compounds physolamide A and physolamide B to RAW264.7 cells.

[0123] (2) Anti-inflammatory activity:

[0124] Take 100 μL of RAW264.7 cells in the logarithmic growth phase and plate them at a density of 1×10 5 cell / mL were inoculated in a 96-well plate, with 3 replicates per group. The culture medium was aspirated, and 100 μL of DMEM medium containing 1 μg / mL LPS was added to the rest except the blank group. After incubation for 24 hours, 100 μL of DMEM medium was added to the blank group and the model group, and 100 μL of DMEM medium containing drugs of various concentrations (final concentrations of 5, 10, 20, 30, 50 μM / L) was added to the drug-treated group, and indomethacin was used as a positive drug. After the culture was completed, 100 μL of the supernatant was transferred to another 96-well plate, and 50 μL of Griess reagent A solution and B solution were added respectively. The color was protected from light for 30 minutes, and the absorbance value of each well was detected at 540 nm.

[0125] The inhibition rate was calculated according to the formula: inhibition rate = (absorbance value of the model group - absorbance value of the drug administration group) / (absorbance value of the model group - absorbance value of the blank group) × 100%.

[0126] Table 2. Inhibitory effects of physolamide A and physolamide B on LPS-induced NO release in RAW264.7 cells

[0127]

[0128] Experimental conclusion:

[0129] (1) Cytotoxicity assay results showed that compounds physolamide A and physolamide B had no cytotoxic effects on RAW264.7 cells at concentrations between 1 and 50 μM / mL;

[0130] (2) Compounds physolamide A and physolamide B have an inhibitory effect on LPS-induced NO release in RAW264.7 inflammatory cells. 50 The results show that the physolamide A and physolamide B have a certain potential in developing anti-inflammatory drugs.

[0131] Although the present invention has been described in detail above with general descriptions and specific embodiments, it is obvious to those skilled in the art that some modifications or improvements may be made thereto based on the present invention. Therefore, these modifications or improvements made without departing from the spirit of the present invention all fall within the scope of protection claimed by the present invention.

Claims

1. A method for preparing an amide compound, characterized in that: The amide compound has a structural formula shown in formula (I) or formula (II): （I） (II) The preparation method comprises the following steps: S1. Extracting the crushed Chinese ginseng with ethanol, and concentrating the obtained extract to obtain a crude extract; S2, after the crude extract is dispersed in water, petroleum ether, ethyl acetate, and water-saturated n-butanol are used for extraction in sequence to obtain an n-butanol extract; In step S2, the extraction conditions are as follows: the volume ratio of water to the petroleum ether, the ethyl acetate and the water-saturated n-butanol is 1:1-3:1-3:1-3; S3, the n-butanol extract is sequentially separated by normal phase silica gel column chromatography, reverse phase ODS column chromatography and preparative HPLC separation and purification to obtain an amide compound represented by formula (I) or formula (II); In step S3, the n-butanol extract is separated by normal phase silica gel column chromatography, and gradient elution is performed with dichloromethane-methanol as the mobile phase, and the elution ratios are 50:0, 50:1, 20:1, 10:1, 5:1, 3:1, 2:1, 1:1, 0:1, and each eluent is identified by thin layer chromatography and similar fractions are combined. According to the detection results and the elution order, 15 components are obtained in sequence, marked as Fr. 1-15; The component Fr.9 is separated and purified by the reverse phase ODS column chromatography and the preparative HPLC in turn to obtain an amide compound represented by formula (I); The preparation conditions of the amide compound represented by formula (I) are as follows: The component Fr.9 is separated by reverse phase ODS column chromatography, and gradient elution is performed with methanol-water as the mobile phase, and the elution concentrations are 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 100% methanol, respectively. Each eluent is identified by thin layer chromatography and similar fractions are combined. According to the detection results and the elution order, components Fr. 9A~9I are obtained in sequence; The component Fr.9E was separated and purified by the preparative HPLC, with methanol-water as the mobile phase and an elution ratio of 47:53, to obtain an amide compound represented by formula (I); The Fr.8 component is separated by reverse phase ODS column chromatography, and gradient elution is performed with methanol-water as the mobile phase, and the concentrations are 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 100% methanol, respectively. Each eluent is detected by thin layer chromatography and similar fractions are combined. According to the detection results and the elution order, components Fr. 8A~8J are obtained in sequence; The component Fr.8E was separated and purified by the preparative HPLC, with methanol-water as the mobile phase and an elution ratio of 57:43, to obtain an amide compound represented by formula (II).

2. The method for preparing an amide compound according to claim 1, characterized in that: In step S1, the volume concentration of ethanol is 50%-95%; The amount of ethanol used is 10-20 times the weight of the Chinese ginseng; The extraction temperature is room temperature; The number of extractions is 1-3 times; The extract is concentrated under reduced pressure to obtain a crude extract; the temperature of the reduced pressure concentration is 30-50°C.

3. The method for preparing an amide compound according to claim 1 or 2, characterized in that: In step S2, the number of extractions with each solvent is 2-5 times.

4. The method for preparing an amide compound according to claim 1, characterized in that: During the normal phase silica gel column chromatography separation process, the amount of the mobile phase used for each elution ratio is 2 to 4 column volumes, and each portion of the eluate is collected as 1 / 4 of the column volume to obtain 120 portions of the eluate; In the thin layer chromatography identification, 10% sulfuric acid-ethanol is used as a color developer, and each eluent is detected by thin layer chromatography under 254nm, 365nm ultraviolet light and sunlight. The 1st to 4th, 5th to 9th, 10th to 14th, 15th to 22nd, 23rd to 31st, 32nd to 47th, 48th to 56th, 57th to 68th, 69th to 86th, 87th to 94th, 95th to 102nd, 103rd to 108th, 109th to 113th, 114th to 118th, and 119th to 120th eluents with similar chromatographic behaviors are combined to obtain component Fr. 1-15 in order.

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