Ceramide compound as well as preparation method and application thereof

Abstract

The invention provides a ceramide compound which has a structure as shown in a formula I. In the formula I, R1 is selected from alkylene of C6 to C18; and R2 is selected from alkyl groups of C1 to C25. The ceramide compound provided by the invention has a good effect, and the N, N '-carbonyldiimidazole is adopted as a condensation reagent, so that reaction steps and side reactions can be reduced. Meanwhile, reagents related to the method are cheap and easy to obtain, the process is easy to operate, and the method can be used for large-scale production.

Description

Technical Field

[0001] The present invention belongs to the technical field of biomedicine, and particularly relates to a ceramide compound, a preparation method thereof, and an application thereof. Background Art

[0002] Ceramide is a class of amide compounds formed by dehydration of the amino group of sphingosine and a long-chain fatty acid, and exists naturally in the skin. 40-50% of the sebum in the stratum corneum is composed of ceramide, which plays an important role in maintaining the balance of moisture in the stratum corneum.

[0003] It is reported that the evaporation of moisture from the epidermis is achieved through the moisture-maintaining effect of ceramide present in the intercellular lipids. When the concentration of ceramide in the skin decreases, the protective barrier function of the stratum corneum weakens, leading to various dermatological symptoms, such as atopic dermatitis and psoriasis symptoms. In addition, due to the decrease in the amount of ceramide, xerosis of the skin occurs, and the defensive function of the skin surface is lost, making it easier for foreign substances to invade and cause secondary skin infections, thereby causing skin rejection reactions. Specifically, the invaders cause cytokines to be released from cells such as keratinocytes, Langerhans cells, and melanocytes in the surface cells, thereby causing inflammatory phenomena. Therefore, in order to maintain and improve the skin barrier, the moisturizing effect of the skin is very important. Compared with ordinary moisturizers, a physiological lipid mixture containing ceramide compounds can promote the restoration of the damaged skin barrier function. Clinical trial results show that it has a similar effect to medium or higher-strength topical steroid preparations in improving the symptoms of atopic dermatitis patients.

[0004] However, at present, the preparation method of ceramide derivatives has many steps, low reaction conversion rate, small reaction scale, and limited purification methods, making it difficult to mass-produce on a large scale.

[0005] Therefore, considering the wide demand for functional ceramide in the market, it is very necessary to research and develop ceramide derivatives that can imitate natural ceramide, solve the problem of its insufficient supply, and enhance its efficacy. Summary of the Invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a ceramide compound, a preparation method thereof, and an application thereof. The preparation method of the ceramide compound provided by the present invention is simple, has a high conversion rate, and a simple purification method, and can be used for large-scale production.

[0007] The present invention provides a ceramide compound having the structure shown in Formula I:

[0008]

[0009] In Formula I, R 1An alkylene group selected from C6 to C18; R 2 A hydrocarbon group selected from C1 to C25.

[0010] Preferably, R 1 Is an alkylene group selected from C10 to C18; R 2 Is a hydrocarbon group selected from C15 to C25.

[0011] Preferably, the alkylene group is selected from linear alkylene groups. Preferably, the linear alkylene group is selected from straight-chain or branched-chain alkylene groups;

[0012] The hydrocarbon group is selected from linear hydrocarbon groups. Preferably, the linear hydrocarbon group is selected from straight-chain or branched-chain hydrocarbon groups;

[0013] Preferably, the hydrocarbon group is selected from saturated or unsaturated hydrocarbon groups. More preferably, the hydrocarbon group is selected from unsaturated hydrocarbon groups, and the number of unsaturated bonds in the unsaturated hydrocarbon group is 1 to 5.

[0014] Preferably, the ceramide compound is selected from any one or more of the compounds having the structures shown in Formulas Va to Vg;

[0015]

[0016]

[0017] The present invention also provides a method for preparing the above ceramide compound, comprising the following steps:

[0018] A) Reacting the compound having the structure shown in Formula II, after activation with N,N'-carbonyldiimidazole, with the compound having the structure shown in Formula III to obtain a compound having the structure shown in Formula IV;

[0019] B) Reacting the compound having the structure shown in Formula IV with the compound having the structure shown in Formula V in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, and a nitrogen-containing organic base to obtain a ceramide compound having the structure shown in Formula I;

[0020]

[0021] In Formulas III and IV, R 1 Is an alkylene group selected from C6 to C18;

[0022] In Formulas II and IV, R 2 Is a hydrocarbon group selected from C1 to C25.

[0023] Preferably, in step A), the molar ratio of the compound having the structure shown in Formula II to N,N'-carbonyldiimidazole is 1:(1.0 to 1.2);

[0024] The molar ratio of the compound having the structure shown in Formula II to the compound having the structure shown in Formula III is 1:(1.0 - 1.2);

[0025] The activation temperature is 25 - 30 °C and the time is 2 - 4 h;

[0026] The reaction temperature is 25 - 30 °C and the time is 4 - 6 h.

[0027] Preferably, in step A), after the reaction, a purification step is further included, and the purification includes the following steps:

[0028] Wash the reaction product obtained from the reaction and collect the organic phase;

[0029] Dry the organic phase, then dissolve it by heating, cool it for crystallization, and dry the obtained crystals to obtain the compound having the structure shown in Formula IV.

[0030] Preferably, in step B), the molar ratio of the compound having the structure shown in Formula IV to the compound having the structure shown in Formula V is 1:(1.0 - 1.2);

[0031] The molar ratio of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole and the nitrogen-containing organic base is (1.2 - 1.4):(1.2 - 1.4):(2.0 - 3.0);

[0032] The reaction temperature is 25 - 30 °C and the time is 10 - 12 h.

[0033] Preferably, in step B), after the reaction, a purification step is further included, and the purification includes the following steps:

[0034] Remove the solvent from the reaction product obtained from the reaction, then dissolve it by heating, wash it, and collect the organic phase;

[0035] Dry the organic phase, then crystallize it in a solvent, and dry the obtained crystals to obtain the ceramide compound having the structure shown in Formula I.

[0036] The present invention also provides an application of the above-mentioned ceramide compound in the preparation of products for preventing and treating skin diseases.

[0037] Compared with the prior art, the present invention provides a ceramide compound having the structure shown in Formula I, in Formula I, R 1 is selected from C6 - C18 alkylene; R 2An alkyl group selected from C1 to C25. The ceramide compounds provided by the present invention have good efficacy. Moreover, the present invention uses N,N'-carbonyldiimidazole as a condensation reagent, which can reduce reaction steps and side reactions. At the same time, the reagents involved in the present invention are all cheap and easily available, and the process is easy to operate and can be used for large-scale production. Description of the Drawings

[0038] Figure 1 It is a reaction flow chart of the ceramide compounds provided by the present invention;

[0039] Figure 2 It is the effect of ceramide compounds on the inflammatory factor IL-6;

[0040] Figure 3 It is the effect of ceramide compounds on the inflammatory factor TNF-α;

[0041] Figure 4 It is the ability of ceramide compounds to promote type I collagen;

[0042] Figure 5 It is the ability of ceramide compounds to inhibit MMP-1;

[0043] Figure 6 It is the ability of ceramide compounds to promote AQP3. Detailed Description of the Invention

[0044] The present invention provides a ceramide compound having the structure shown in Formula I:

[0045]

[0046] In Formula I, R 1 is selected from C6 to C18 alkylene groups; R 2 is selected from C1 to C25 alkyl groups.

[0047] Preferably, R 1 is selected from C10 to C18 alkylene groups; R 2 is selected from C15 to C25 alkyl groups; more preferably, R 2 is selected from C15 to C20 alkyl groups.

[0048] Among them, the alkylene group is selected from chain-like alkylene groups. Preferably, the chain-like alkylene group is selected from straight-chain alkylene groups or branched-chain alkylene groups;

[0049] The alkyl group is selected from chain-like alkyl groups. Preferably, the chain-like alkyl group is selected from straight-chain alkyl groups or branched-chain alkyl groups;

[0050] Preferably, the alkyl group is selected from saturated alkyl groups or unsaturated alkyl groups. Further preferably, the alkyl group is selected from unsaturated alkyl groups, and the number of unsaturated bonds in the unsaturated alkyl group is 1 to 5.

[0051] In some preferred embodiments of the present invention, the ceramide compound is selected from any one or more of the compounds having the structures shown in Formulas Va to Vg;

[0052]

[0053] The present invention also provides a method for preparing the above ceramide compound, comprising the following steps:

[0054] A) Reacting the compound having the structure shown in Formula II, after activation with N,N'-carbonyldiimidazole, with the compound having the structure shown in Formula III to obtain a compound having the structure shown in Formula IV;

[0055] B) Reacting the compound having the structure shown in Formula IV with the compound having the structure shown in Formula V in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole and a nitrogen-containing organic base to obtain a ceramide compound having the structure shown in Formula I;

[0056]

[0057] In Formulas III and IV, R 1 is selected from C6 to C18 alkylene groups;

[0058] In Formulas II and IV, R 2 is selected from C1 to C25 hydrocarbon groups.

[0059] Among them, the reaction process is as Figure 1 shown. Figure 1 is the reaction flow chart of the ceramide compound provided by the present invention.

[0060] Specifically, the present invention first dissolves the compound having the structure shown in Formula II in a solvent to obtain a mixed solution. Among them, the solvent is preferably dichloromethane (DCM).

[0061] Then, N,N'-carbonyldiimidazole (CDI) is added to the mixed solution for activation to obtain an activated product.

[0062] Among them, the molar ratio of the compound having the structure shown in Formula II to N,N'-carbonyldiimidazole is 1:(1.0 - 1.2), and can be 1:1, 1:1.05, 1:1.1, 1:1.15, 1:1.2, or any value between 1:(1.0 - 1.2).

[0063] The activation temperature is 25 - 30 °C and the time is 2 - 4 h, and can be 2, 3, 4, or any value between 2 - 4 h.

[0064] After the activation is completed, the activation product reacts with the compound having the structure shown in Formula III to obtain a compound having the structure shown in Formula IV.

[0065] Among them, the molar ratio of the compound having the structure shown in Formula II to the compound having the structure shown in Formula III is 1:(1.0 - 1.2), and can be 1:1, 1:1.05, 1:1.1, 1:1.15, 1:1.2, or any value between 1:(1.0 - 1.2).

[0066] The temperature of the reaction is 25 - 30 °C, and the time is 4 - 6 h, and can be 4, 5, 6, or any value between 4 - 6 h.

[0067] In the present invention, after the reaction, a purification step is further included, and the purification includes the following steps:

[0068] Wash the reaction product obtained from the reaction and collect the organic phase;

[0069] Dry the organic phase, then heat-dissolve and cool-crystallize it, and dry the obtained crystals to obtain a compound having the structure shown in Formula IV.

[0070] Specifically, wash the reaction product obtained from the reaction. Preferably, in the present invention, an aqueous citric acid solution with a mass concentration of 5 - 10% is used to wash the reaction product, and the number of washing times is preferably 3 times. After the washing is completed, collect the organic phase.

[0071] Then dry the organic phase. Preferably, in the present invention, rotary evaporation is used for drying. Then heat-dissolve the dried product, and the solvent for heat-dissolving is preferably methanol (MeOH). Next, cool-crystallize with methyl tert-butyl ether (MTBE). After the crystallization is completed, perform suction filtration to obtain a filter residue. Finally, dry the filter residue to obtain a compound having the structure shown in Formula IV.

[0072] After obtaining the compound having the structure shown in Formula IV, dissolve the compound having the structure shown in Formula IV in a solvent. Preferably, the solvent is preferably tetrahydrofuran (THF). Then the obtained solution reacts with the compound having the structure shown in Formula V in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide, 1-hydroxybenzotriazole, and a nitrogen-containing organic base to obtain a ceramide compound having the structure shown in Formula I.

[0073] Among them, the molar ratio of the compound having the structure shown in Formula IV to the compound having the structure shown in Formula V is 1:(1.0 - 1.2), and can be 1:1, 1:1.05, 1:1.1, 1:1.15, 1:1.2, or any value between 1:(1.0 - 1.2);

[0074] The molar ratio of the 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide (EDCI), 1-hydroxybenzotriazole (HOBt) and the nitrogen-containing organic base is (1.2 - 1.4):(1.2 - 1.4):(2.0 - 3.0), and can be 1.4:1.4:2, 1.2:1.2:3, 1.3:1.3:2.5, or any value between (1.2 - 1.4):(1.2 - 1.4):(2.0 - 3.0). In the present invention, the nitrogen-containing organic base is preferably N,N-diisopropylethylamine (DIEA).

[0075] The temperature of the reaction is 25 - 30 °C and the time is 10 - 12 h, and can be 10, 11, 12, or any value between 10 - 12 h.

[0076] After the reaction, a purification step is further included, and the purification includes the following steps:

[0077] Remove the solvent from the reaction product obtained from the reaction, then dissolve it by heating, wash it, and collect the organic phase;

[0078] Dry the organic phase and then crystallize it in a solvent, and dry the obtained crystals to obtain a ceramide compound having the structure shown in Formula I.

[0079] Specifically, in the present invention, the solvent in the reaction product is rotary evaporated and then dissolved by heating. The solvent used for the heating dissolution is preferably ethyl acetate (EA). Then, the solution after heating dissolution is washed. The solvent used for the washing is preferably water. After the washing is completed, the organic phase is collected. Then, the organic phase is dried, and the dried organic phase is added with an organic solvent for cooling crystallization. Among them, the solvent is preferably petroleum ether (PE), and the temperature of the cooling crystallization is preferably 5 - 10 °C. After the crystallization is completed, filter or centrifuge, collect the filter residue, and dry it to obtain a ceramide compound having the structure shown in Formula I.

[0080] In the present invention, the target product is directly purified by recrystallization after two-step reaction, which reduces the production cost, improves the process and is easy to operate, and can be used for large-scale production.

[0081] The present invention also provides an application of the above ceramide compound in the preparation of products for preventing and treating skin diseases.

[0082] In the present invention, the ceramide compound can be applied to the preparation of cosmetics having soothing, repairing and anti-wrinkle effects.

[0083] Among them, the ceramide compound can reduce the protein levels of inflammatory factors IL-6 and TNF-α, and can be used for the preparation of cosmetics having a soothing effect;

[0084] The ceramide compounds can significantly increase the collagen content of cells and reduce the expression of MMP-1, and can be used to prepare cosmetics with anti-wrinkle effects; further, they can be used to prepare cosmetics with repair effects; furthermore, they can be used to prepare cosmetics with the effect of repairing ultraviolet damage.

[0085] The ceramide compounds can significantly promote the expression of AQP3 and can be used to prepare cosmetics with moisturizing effects.

[0086] The protection of the carboxyl group of ω-hydroxy fatty acid in the present invention enables it to perform efficient ester condensation with carboxylic acid. The present invention uses a simple and efficient condensation reagent N,N'-carbonyldiimidazole (CDI), which can reduce the reaction steps and side reactions. Moreover, the preparation method provided by the present invention can synthesize the target product without protection, the purification method is simple, and column chromatography purification is not required. At the same time, the reagents involved in the present invention are cheap and easily available, the process is easy to operate, and it can be used for large-scale production.

[0087] To further understand the present invention, the ceramide compounds provided by the present invention, their preparation methods and applications will be described below in conjunction with examples. The protection scope of the present invention is not limited by the following examples.

[0088] Example 1

[0089] Synthesis of Compound Ⅴ a of

[0090] Dissolve 100 g of linoleic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10V), add 69.38 g of CDI (0.42 mol, 1.2 eq) for activation, stir and react at 25 - 30 °C for 2 h, monitor by TLC, and the linoleic acid is completely activated. Add 80.56 g of 10-hydroxydecanoic acid (0.42 mol, 1.2 q) to the reaction solution, stir and react at 25 - 30 °C for 6 h, monitor by TLC, when the reaction ends, wash the reaction solution three times with 3 L of 10% citric acid aqueous solution (3V), collect the organic phase, dry it with anhydrous sodium sulfate, spin-dry the reaction solution at 30 °C, add 300 ml of MeOH (3V) for hot dissolution, cool and crystallize with 300 ml of MTBE (3V), stir and crystallize at 5 - 10 °C for 30 min and then filter by suction, dry at 40 °C to obtain the intermediate solid.

[0091] Dissolve the intermediate in 1 L of THF (10V), add 124.54 g of phytosphingosine (P) (0.39 mol, 1.1 eq), add 67.45 g of HOBt (0.49 mol, 1.4 eq), cool down to 5 - 10 °C, then slowly add 77.50 g of EDCI (0.49 mol, 1.4 eq). Dropwise add 124.2 ml of DIEA (0.71 mol, 2.0 eq) into the reaction solution. After the addition is complete, restore the temperature to 25 - 30 °C and stir the reaction for 12 h. Monitor by TLC. When the reaction is completed, rotary evaporate the THF, add 500 ml of EA (5V) and dissolve it by heating at 50 °C, wash twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, dry it at 50 °C to obtain 205.3 g of a white powdery solid, with a yield of 76.75% and a purity of 96.3%.

[0092]

[0093] Example 2

[0094] Compound Ⅴ b Synthesis

[0095] Dissolve 100 g of linoleic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10V), add 69.38 g of CDI (0.42 mol, 1.2 eq) for activation, stir and react at 25 - 30 °C for 2 h. Monitor by TLC. When the linoleic acid is completely activated, add 110.57 g of 15 - hydroxypentadecanoic acid (0.42 mol, 1.2 eq) to the reaction solution, stir and react at 25 - 30 °C for 6 h. Monitor by TLC. When the reaction is completed, wash the reaction solution three times with 3 L of 10% aqueous citric acid solution (3V), collect the organic phase, dry it with anhydrous sodium sulfate, rotary evaporate the reaction solution at 30 °C, add 300 ml of MeOH (3V) and dissolve it by heating, cool and crystallize with 300 ml of MTBE (3V), stir and crystallize at 5 - 10 °C for 30 min, then filter by suction and dry at 40 °C to obtain the intermediate solid.

[0096] Dissolve the intermediate in 1 L of THF (10V), add 124.54 g of phytosphingosine (P) (0.39 mol, 1.1 eq), add 67.45 g of HOBt (0.49 mol, 1.4 eq), cool down to 5 - 10 °C, then slowly add 77.50 g of EDCI (0.49 mol, 1.4 eq), dropwise add 124.2 ml of DIEA (0.71 mol, 2.0 eq) into the reaction solution. After the addition is complete, restore the temperature to 25 - 30 °C and stir the reaction for 12 h. Monitor by TLC. When the reaction is completed, rotary evaporate the THF, add 500 ml of EA (5V) and dissolve it by heating at 50 °C, wash twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, dry it at 50 °C to obtain 208.6 g of white powdery solid, with a yield of 71.31% and a purity of 95.9%.

[0097]

[0098] Example 3

[0099] Compound Ⅴ c Synthesis

[0100] Dissolve 100 g of linoleic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10V), add 69.38 g of CDI (0.42 mol, 1.2 eq) for activation, stir and react at 25 - 30 °C for 2 h. Monitor by TLC until the linoleic acid is completely activated. Add 128.57 g of 18 - hydroxystearic acid (0.42 mol, 1.2 eq) to the reaction solution, stir and react at 25 - 30 °C for 6 h. Monitor by TLC. When the reaction is completed, wash the reaction solution three times with 3 L of 10% aqueous citric acid solution (3V), collect the organic phase, dry it with anhydrous sodium sulfate, rotary evaporate the reaction solution at 30 °C, add 300 ml of MeOH (3V) and dissolve it by heating, cool and crystallize with 300 ml of MTBE (3V), stir and crystallize at 5 - 10 °C for 30 min, then filter by suction and dry at 40 °C to obtain the intermediate solid.

[0101] Dissolve the intermediate in 1 L of THF (10 V), add 124.54 g of phytosphingosine (P) (0.39 mol, 1.1 eq), add 67.45 g of HOBt (0.49 mol, 1.4 eq), cool down to 5 - 10 °C, then slowly add 77.50 g of EDCI (0.49 mol, 1.4 eq), dropwise add 124.2 ml of DIEA (0.71 mol, 2.0 eq) into the reaction solution. After the addition is complete, restore the temperature to 25 - 30 °C and stir the reaction for 12 h. Monitor by TLC. When the reaction ends, rotary evaporate the THF, add 500 ml of EA (5 V) and dissolve it by heating at 50 °C, wash it twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10 V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, dry it at 50 °C to obtain 215.8 g of white powdery solid, with a yield of 70.18% and a purity of 96.2%.

[0102]

[0103] Example 4

[0104] Compound Ⅴ d Synthesis

[0105] Dissolve 100 g of linolenic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10 V), add 69.88 g of CDI (0.43 mol, 1.2 eq) for activation, stir and react at 25 - 30 °C for 2 h. Monitor by TLC. When the linoleic acid activation is complete, add 81.14 g of 10 - hydroxydecanoic acid (0.43 mol, 1.2 eq) to the reaction solution, stir and react at 25 - 30 °C for 6 h. Monitor by TLC. When the reaction ends, wash the reaction solution three times with 3 L of 10% citric acid aqueous solution (3 V), collect the organic phase, dry it with anhydrous sodium sulfate, rotary evaporate the reaction solution at 30 °C, add 300 ml of MeOH (3 V) and dissolve it by heating, cool and crystallize with 300 ml of MTBE (3 V), stir and crystallize at 5 - 10 °C for 30 min, then filter by suction and dry at 40 °C to obtain the intermediate solid.

[0106] Dissolve the intermediate in 1 L of THF (10V), add 125.44 g of phytosphingosine (P) (0.39 mol, 1.1 eq), add 67.94 g of HOBt (0.50 mol, 1.4 eq), cool down to 5 - 10 °C, and then slowly add 78.06 g of EDCI (0.5 mol, 1.4 eq). Dropwise add 125.1 ml of DIEA (0.71 mol, 2.0 eq) into the reaction solution. After the addition is complete, warm the solution back to 25 - 30 °C and stir the reaction for 12 h. Monitor the reaction by TLC. When the reaction is completed, rotary evaporate the THF, add 500 ml of EA (5V) and dissolve it at 50 °C, wash it twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, dry it at 50 °C to obtain 200.6 g of white powdery solid, with a yield of 74.65% and a purity of 95.6%.

[0107]

[0108] Example 5

[0109] Compound Ⅴ e Synthesis

[0110] Dissolve 100 g of oleic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10V), add 68.89 g of CDI (0.42 mol, 1.2 eq) for activation, stir the reaction at 25 - 30 °C for 2 h, monitor the reaction by TLC until the linoleic acid activation is complete. Add 79.98 g of 10 - hydroxydecanoic acid (0.42 mol, 1.2 eq) to the reaction solution, stir the reaction at 25 - 30 °C for 6 h, monitor the reaction by TLC. When the reaction is completed, wash the reaction solution three times with 3 L of 10% aqueous citric acid solution (3V), collect the organic phase, dry it over anhydrous sodium sulfate, rotary evaporate the reaction solution at 30 °C, add 300 ml of MeOH (3V) to dissolve it, cool and crystallize with 300 ml of MTBE (3V), stir and crystallize at 5 - 10 °C for 30 min and then filter by suction, dry it at 40 °C to obtain the intermediate solid.

[0111] Dissolve the intermediate in 1 L of THF (10V), add 123.65 g of phytosphingosine (P) (0.38 mol, 1.1 eq), add 66.97 g of HOBt (0.49 mol, 1.4 eq), cool down to 5 - 10 °C, and then slowly add 76.94 g of EDCI (0.49 mol, 1.4 eq). Dropwise add 123.3 ml of DIEA (0.7 mol, 2.0 eq) into the reaction solution. After the addition is complete, warm the solution back to 25 - 30 °C and stir the reaction for 12 h. Monitor the reaction by TLC. When the reaction is completed, rotary evaporate the THF, add 500 ml of EA (5V) and dissolve it by heating at 50 °C. Wash it twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, dry it at 50 °C to obtain 203.6 g of a white powdery solid with a yield of 76.45% and a purity of 96.4%.

[0112]

[0113] Example 6

[0114] Compound Ⅴ f Synthesis

[0115] Dissolve 100 g of stearic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10V), add 68.4 g of CDI (0.42 mol, 1.2 eq) for activation, and stir the reaction at 25 - 30 °C for 2 h. Monitor the reaction by TLC until the linoleic acid is completely activated. Add 79.41 g of 10 - hydroxydecanoic acid (0.42 mol, 1.2 eq) to the reaction solution and stir the reaction at 25 - 30 °C for 6 h. Monitor the reaction by TLC. When the reaction is completed, wash the reaction solution three times with 3 L of 10% aqueous citric acid solution (3V), collect the organic phase, dry it over anhydrous sodium sulfate, rotary evaporate the reaction solution at 30 °C, add 300 ml of MeOH (3V) and dissolve it by heating, cool it with 300 ml of MTBE (3V) for crystallization, stir and crystallize at 5 - 10 °C for 30 min, then filter by suction and dry it at 40 °C to obtain the intermediate solid.

[0116] Dissolve the intermediate in 1 L of THF (10 V), add 122.77 g of phytosphingosine (P) (0.38 mol, 1.1 eq), add 66.5 g of HOBt (0.49 mol, 1.4 eq), cool to 5 - 10 °C, and then slowly add 76.4 g of EDCI (0.49 mol, 1.4 eq). Dropwise add 122.4 ml of DIEA (3.1 mol, 2.0 eq) into the reaction solution. After the addition is complete, warm the reaction solution to 25 - 30 °C and stir for 12 h. Monitor the reaction by TLC. When the reaction is completed, rotary evaporate the THF, add 500 ml of EA (5 V) and dissolve it by heating at 50 °C. Wash it twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10 V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, dry it at 50 °C to obtain 201.9 g of a white powdery solid with a yield of 76.15% and a purity of 95.8%.

[0117]

[0118] Example 7

[0119] Compound Ⅴ g Synthesis

[0120] Dissolve 100 g of palmitic acid (0.35 mol, 1.0 eq) in 1 L of DCM (10 V), add 75.88 g of CDI (0.42 mol, 1.2 eq) for activation, stir and react at 25 - 30 °C for 2 h. Monitor the reaction by TLC until the linoleic acid is completely activated. Add 88.1 g of 10 - hydroxydecanoic acid (0.42 mol, 1.2 eq) to the reaction solution, stir and react at 25 - 30 °C for 6 h. Monitor the reaction by TLC. When the reaction is completed, wash the reaction solution three times with 3 L of 10% aqueous citric acid solution (3 V), collect the organic phase, dry it with anhydrous sodium sulfate, rotary evaporate the reaction solution at 30 °C, add 300 ml of MeOH (3 V) and dissolve it by heating, add 300 ml of MTBE (3 V) for cooling crystallization, stir and crystallize at 5 - 10 °C for 30 min, then filter by suction and dry at 40 °C to obtain the intermediate solid.

[0121] Dissolve the intermediate in 1 L of THF (10 V), add 138.2 g of phytosphingosine (P) (0.38 mol, 1.1 eq), add 73.77 g of HOBt (0.49 mol, 1.4 eq). After cooling to 5 - 10 °C, slowly add 84.76 g of EDCI (0.49 mol, 1.4 eq). Dropwise add 122.4 ml of DIEA (3.1 mol, 2.0 eq) into the reaction solution. After the addition is complete, restore the temperature to 25 - 30 °C and stir the reaction for 12 h. Monitor by TLC. After the reaction is completed, rotary evaporate the THF. Add 500 ml of EA (5 V) and dissolve it at 50 °C. Wash twice with 300 ml of water, collect the organic phase, dry it, add 1 L of PE (10 V) for cold precipitation, and stir and crystallize at 5 - 10 °C for 30 min. Filter by suction, collect the filter residue, and dry it at 50 °C to obtain 220 g of white powdery solid, with a yield of 77.69% and a purity of 96.2%.

[0122]

[0123] Effect Example

[0124] I. Experimental materials:

[0125] The raw materials and reagents used in the examples are all commercially available.

[0126] Among them, mouse macrophages (RAW264.7) are from Wuhan Punosai Life Science Co., Ltd.; lipopolysaccharide (LPS) is from Beijing Solarbio Science & Technology Co., Ltd.; the special medium for RAW264.7 is from Wuhan Punosai Life Science Co., Ltd. The mouse tumor necrosis factor α (TNF-α) enzyme-linked immunosorbent assay kit is from Wuhan Eiareet Biotech Co., Ltd.; the mouse interleukin 6 (IL-6) enzyme-linked immunosorbent assay kit is from Wuhan Eiareet Biotech Co., Ltd.; the CCK-8 reagent is from Beyotime Biotechnology Co., Ltd.; human foreskin fibroblasts (HFF-1) are from the Cell Bank of the Chinese Academy of Sciences Committee for Type Culture Collection; the human type I collagen enzyme-linked immunosorbent assay kit is from Wuhan Eiareet Biotech Co., Ltd.; TaKaRa MiniBEST Universal RNA Extraction Kit is from Takara Biotechnology (Beijing) Co., Ltd.; PrimeScript TM RT reagent Kit with gDNA Eraser is from Takara Biotechnology (Beijing) Co., Ltd.; PowerUp TM SYBR TM Green Master Mix is from Thermo Fisher Scientific; the MMP-1 primer is from Sangon Biotech (Shanghai) Co., Ltd.

[0127] II. Ceramides Inhibit the Levels of Inflammatory Factors IL-6 and TNF-α

[0128] The ceramide compounds provided by the present invention have a soothing effect and can reduce the protein levels of inflammatory factors IL-6 and TNF-α.

[0129] Experimental procedure: First, prepare a cell suspension. Seed 6-well plates with 2 million RAW264.7 cells (P9) per well, 2 mL per well. After 24 hours, add dexamethasone (DEX, 50 μg / mL), Compound V a (100 μg / mL), Compound V b (100 μg / mL), Compound V c (100 μg / mL), Compound V d (100 μg / mL), Compound V e (100 μg / mL), Compound V f (100 μg / mL), Compound V g (100 μg / mL). Set up three replicate wells for each group. After 1.5 h, except for the Control group, add 2 μL of 1000 μg / mL LPS. Continue culturing for 24 hours, collect the supernatant, centrifuge, take the supernatant, dilute 500-fold for the TNF-α experiment and 10-fold for the IL-6 experiment, then detect with an ELISA kit. Measure the absorbance at 450 nm within 15 minutes after adding the stop solution.

[0130] Experimental results: Lipopolysaccharide (LPS) can promote inflammation, generate a large number of inflammatory factors and promote the expression of related inflammatory proteins. Commonly, activating mouse leukemia macrophages (RAW264.7) with lipopolysaccharide is used as a cell inflammation model.

[0131] As shown in Table 1 and Figure 2 compared with the negative control group (LPS group), the IL-6 concentrations in the Compound V a group, Compound V b group, Compound V c group, Compound V d group, Compound V e group, Compound V f group, Compound V g group decreased significantly and had statistical significance. The Compound V a group, Compound V b group, Compound V c group, Compound V d group, Compound V e group, Compound V f group, Compound V gThe IL-6 concentrations of the groups decreased by 17.14%, 45.21%, 39.33%, 58.32%, 36.89%, 27.89%, and 23.63% respectively.

[0132] As shown in Table 2 and Figure 3 compared with the negative control group (LPS group), the TNF-α concentrations in the compound V a group, compound V b group, compound V c group, compound V d group, compound V e group, compound V f group, compound V g group decreased significantly and had statistical significance. The TNF-α concentrations in the compound V a group, compound V b group, compound V c group, compound V d group, compound V e group, compound V f group, compound V g group decreased by 34.77%, 56.3%, 52.44%, 63.32%, 53.02%, 46.59%, and 42.88% respectively. (P < 0.05 is considered to have statistical significance. Compared with the LPS group: "***", P < 0.001; "****", P < 0.0001). The compound V a group, compound V b group, compound V c group, compound V d group, compound V e group, compound V f group, compound V g group could significantly reduce the levels of inflammatory factors (IL-6, TNF-α) and had a soothing effect.

[0133] As shown in Table 1 and Table 2, the IL-6 level in the compound V b group was lower than that in the compound V a group, compound V c group, compound V e group, compound V f group, compound V g group, and there was a significant difference. It shows that the compound V b group had a more excellent anti-inflammatory effect than the compound V a group, compound V c group, compound V e group, compound V f group, compound V g group.

[0134] As shown in Table 1 and Table 3, the level of IL-6 in Group V of Compound V d was lower than that in Group V of Compound V a and Group V of Compound V b and Group V of Compound V c and Group V of Compound V e and Group V of Compound V f and Group V of Compound V g and there was a significant difference. This indicates that Group V of Compound V d had a more excellent anti-inflammatory effect than Group V of Compound V a and Group V of Compound V b and Group V of Compound V c and Group V of Compound V e and Group V of Compound V f and Group V of Compound V g and Group V of Compound V

[0135] As shown in Table 4 and Table 5, the level of TNF-α in Group V of Compound V b was lower than that in Group V of Compound V a and Group V of Compound V f and Group V of Compound V g and there was a significant difference. This indicates that Group V of Compound V b had a more excellent anti-inflammatory effect than Group V of Compound V a and Group V of Compound V f and Group V of Compound V g and Group V of Compound V

[0136] As shown in Table 4 and Table 6, the level of TNF-α in Group V of Compound V d was lower than that in Group V of Compound V a and Group V of Compound V b and Group V of Compound V c and Group V of Compound V e and Group V of Compound V f and Group V of Compound V g and there was a significant difference. This indicates that Group V of Compound V d had a more excellent anti-inflammatory effect than Group V of Compound V a and Group V of Compound V b and Group V of Compound V c and Group V of Compound V e and Group V of Compound V f and Group V of Compound V g and Group V of Compound V

[0137] Table 1: Soothing effect of ceramide compounds (IL-6)

[0138]

[0139]

[0140] Table 2: Statistical analysis of experimental group 2 and other experimental groups (IL-6)

[0141]

[0142] Table 3: Statistical analysis of experimental group 4 and other experimental groups (IL-6)

[0143]

[0144] Table 4: Soothing effects of ceramide compounds (TNF-ɑ)

[0145]

[0146] Table 5: Statistical analysis of experimental group 2 and other experimental groups (TNF-ɑ)

[0147]

[0148] Table 6: Statistical analysis of experimental group 4 and other experimental groups (TNF-ɑ)

[0149]

[0150] 3. Anti-wrinkle effect of ceramide compounds (type I collagen and matrix metalloproteinases).

[0151] Collagen is one of the main components of the extracellular matrix of the dermis. Dermal fibroblasts synthesize procollagen in the cells and secrete it outside the cells. Under the action of terminal procollagen peptidase, the terminal peptides are separated and polymerized to form collagen fibers. Human dermal fibroblasts can be used as a cell model to study the increase of collagen content in cosmetics. By measuring the increase rate of collagen content after administration of the test substance, the blank control and the test substance, the efficacy of the test substance in promoting collagen synthesis can be evaluated. Collagen can support the skin and keep the skin firm and smooth. However, after being stimulated by external stimuli such as ultraviolet rays, the collagen level will decrease, so the firmness of the skin can be judged by detecting the collagen level.

[0152] The degradation of the extracellular matrix mainly relies on proteolytic enzymes, and MMPs are the most important group of proteolytic enzymes, among which MMP-1 is the most important enzyme for degrading type I collagen. When MMP-1 is overexpressed, it specifically degrades extracellular matrix components, destroys the normal structure of collagen fibers and elastic fibers, and causes wrinkles and other aging manifestations on the skin. Therefore, when MMP-1 expression is inhibited, it can play an anti-wrinkle role.

[0153] Experimental procedure: In this method, a cell model was established with UVA modeling as negative and TGF-β as positive. The content of collagen secreted by cells was detected by enzyme-linked immunosorbent assay (ELISA), and the firming effect of cosmetic raw materials was judged according to the expression changes of collagen content. Fibroblasts (HFF-1) were cultured in DMEM complete medium (from Hyclone) containing 10% fetal bovine serum (FBS, from Gibco). Well-shaped HFF-1 cells were taken and prepared into a cell suspension with complete medium, inoculated into a 6-well plate at a density of 200,000 cells per well, 2 mL per well, and placed in a 5% CO 2 , and cultured in an incubator at 37°C for 24 h, irradiated with a UVA lamp (34 J / cm 2 ), and then 2 mL of TGF-β (100 ng / mL), compound V a (100 μg / mL), compound V b (100 μg / mL), compound V c (100 μg / mL), compound V d (100 μg / mL), compound V e (100 μg / mL), compound V f (100 μg / mL), compound V g (100 μg / mL), compound V

[0154] were added. Each group was set with 3 replicate wells. After incubation in a carbon dioxide incubator for 24 h, the supernatant was collected by centrifugation at 1000 rpm and 4°C for 20 min. According to the operation instructions of the ELISA kit, the concentration of type I collagen and matrix metalloproteinase was measured, and the experimental results were statistically analyzed by GraphPad Prism. Figure 4 Experimental results: As shown in a and Table 7, after UVA irradiation, the collagen content in fibroblasts decreased significantly. Compared with the negative control (UVA group), ceramide compounds could increase the collagen concentration to different extents. Compared with the negative control (UVA group), in the compound V b group, compound V c group, compound V d group, compound V e group, compound V f group, compound V g group at 100 μg / mL, the collagen concentrations increased by 21.7%, 103.51%, 87.71%, 141.21%, 83.41%, 42.24%, and 42.7% respectively, and there were significant differences (P < 0.05 was considered statistically significant. Compared with the UVA group: "**", P < 0.01; "****", P < 0.0001). Compound V aGroup, Compound V b Group, Compound V c Group, Compound V d Group, Compound V e Group, Compound V f Group, Compound V g The group can significantly increase the cellular collagen content and has the effect of anti-wrinkle.

[0155] As shown in Table 7 and Table 8, Compound V b Group and Compound V a Group, Compound V c Group, Compound V e Group, Compound V f Group, Compound V g Group has a higher level of type I collagen and there are significant differences compared with the other groups. It shows that Compound V b Group has a better anti-wrinkle effect than Compound V a Group, Compound V c Group, Compound V e Group, Compound V f Group, Compound V g Group has a more excellent anti-wrinkle effect.

[0156] As shown in Table 7 and Table 9, Compound V d Group and Compound V a Group, Compound V b Group, Compound V c Group, Compound V e Group, Compound V f Group, Compound V g Group has a higher level of type I collagen and there are significant differences compared with the other groups. It shows that Compound V d Group has a better anti-wrinkle effect than Compound V a Group, Compound V b Group, Compound V c Group, Compound V e Group, Compound V f Group, Compound V g Group has a more excellent anti-wrinkle effect.

[0157] Table 7: The effect of ceramide compounds on promoting collagen (ColⅠ)

[0158]

[0159] Table 8: Statistical analysis of experimental group 2 and other experimental groups (ColⅠ)

[0160]

[0161] Table 9: Statistical analysis of experimental group 4 and other experimental groups (ColⅠ)

[0162]

[0163] As Figure 5 shown in Table 10, after fibroblasts were irradiated with UVA, the expression of MMP-1 increased significantly. Compared with the negative control (UVA group), ceramide compounds could reduce the expression of MMP-1 to different extents. Compared with the negative control (UVA group), in groups Va, Vb, Vc, Vd, Ve, Vf, and Vg at 100 μg / mL, the MMP-1 concentrations decreased by 13.3%, 46.89%, 42.9%, 60.38%, 37.49%, 27.51%, and 20.38% respectively. And there were significant differences (P < 0.05 was considered to have statistical significance. Compared with the UVA group: "****", P < 0.0001). Compound V a group, compound V b group, compound V c group, compound V d group, compound V e group, compound V f group, compound V g group could significantly reduce the expression of MMP-1 and had the effect of anti-wrinkle.

[0164] As shown in Table 10 and Table 11, for compound V b group compared with compound V a group, compound V e group, compound V f group, compound V g group, the matrix metalloproteinase 1 level was lower and there were significant differences. It shows that compound V b group has a more excellent anti-wrinkle effect than compound V a group, compound V e group, compound V f group, compound V g group.

[0165] As shown in Table 10 and Table 12, for compound V d group compared with compound V a group, compound V b group, compound V c group, compound V e group, compound V f group, compound V g group, the matrix metalloproteinase 1 level was lower and there were significant differences. It shows that compound V d group has a more excellent anti-wrinkle effect than compound V a group, compound V b group, compound V c group.e Group, Compound V f Group, Compound V g The group has a more excellent anti-wrinkle effect.

[0166] Table 10: Inhibitory effect of ceramide compounds on matrix metalloproteinase (MMP1)

[0167]

[0168]

[0169] Table 11: Statistical analysis of experimental group 2 and other experimental groups (MMP1)

[0170]

[0171] Table 12: Statistical analysis of experimental group 4 and other experimental groups (MMP1)

[0172]

[0173] IV. Moisturizing ability of ceramide compounds - AQP3.

[0174] Skin barrier function is crucial for maintaining skin health, and hydration plays a central role in maintaining skin barrier function, regulating skin elasticity, and preventing skin dryness. Skin hydration depends not only on the action of exogenous moisturizing components but also on endogenous mechanisms. The metabolic activities and gene expressions of keratinocytes are crucial for maintaining skin hydration.

[0175] Moisturizing aims to maintain the water balance of the skin and prevent dryness and damage. Moisturizing products act on the skin through multiple mechanisms, including increasing skin water content, reducing water loss, and improving skin barrier function. AQP3 (aquaporin 3) is a channel protein located on the cell membrane, and its main function is to promote the rapid transport of water molecules. It plays an important role in skin hydration and barrier function. The expression of AQP3 is closely related to the hydration state of the skin, and its expression level in the skin is related to the degree of skin dryness. Therefore, AQP3 can directly reflect the moisturizing effect of raw materials.

[0176] This method determines the moisturizing effect of cosmetic raw materials by culturing HaCaT cells, adding cosmetic raw materials, incubating for a certain time, extracting total cellular RNA, and detecting the gene expression level of AQP3, and judging according to the change of AQP3.

[0177] Experimental procedure: Keratinocytes (Hacat) were cultured in DMEM complete medium (from Hyclone) containing 10% fetal bovine serum (FBS, from Gibco). Well-shaped Hacat cells were taken and made into a cell suspension with complete medium, and inoculated into a 6-well plate at a density of 500,000 cells per well, 2 mL per well. After inoculation into the 6-well plate, it was placed in a 5% CO 2 , 37 °C incubator for 24 h, irradiated with a UVA lamp (34 J / cm 2 ), and then 2 mL of compound V a (100 μg / mL), compound V b (100 μg / mL), compound V c (100 μg / mL), compound V d (100 μg / mL), compound V e (100 μg / mL), compound V f (100 μg / mL), compound V g (100 μg / mL) were added. Each group was set with 3 replicate wells. After incubation in a carbon dioxide incubator for 24 h, it was washed once with PBS. RNA in fibroblasts was extracted according to the instructions of the column method RNA extraction kit, and RNA was reverse transcribed into cDNA according to the reverse transcription kit. Finally, 1 μL of cDNA, 0.5 μL of AQP3 upstream primer (5'-TCTTTGACCAGTTCATAGGCAC-3'), 0.5 μL of AQP3 downstream primer (5'-GGCAGGGTTGACGGCATAG-3'), 3 μL of dd H 2 O, 5 μL of PowerUp TM SYB R TM Green Master Mix were added to the qPCR plate. The experiment was completed on a qPCR instrument, and the relative content of mRNA was analyzed by the ΔΔCt method.

[0178] Experimental results: As shown in Figure 6 and Table 13, the expression of AQP3 in the compound V a group, compound V b group, compound V c group, compound V d group, compound V e group, compound V f group, compound V g group increased significantly. Compared with the negative control (UVA group), ceramide compounds could reduce the expression of MMP-1 to different extents. Compared with the Control group, in the compound V a group, compound V b group, compound V cGroup, Compound V d Group, Compound V e Group, Compound V f Group, Compound V g For the group, at 100 μg / mL, the AQP3 concentrations increased by 15.54%, 96.58%, 85.44%, 109.06%, 76.29%, 50.79%, and 50.25% respectively. And there were significant differences (P < 0.05 is considered statistically significant. Compared with the Control group: "*", P < 0.05; "****", P < 0.0001). Compound V a Group, Compound V b Group, Compound V c Group, Compound V d Group, Compound V e Group, Compound V f Group, Compound V g The group can significantly promote the expression of AQP3 and has a moisturizing effect.

[0179] As shown in Table 13 and Table 14, Compound V b Group and Compound V a Group, Compound V e Group, Compound V f Group, Compound V g Compared with the groups, the aquaporin 3 level was higher and there were significant differences. It shows that Compound V b Group has a better moisturizing effect than Compound V a Group, Compound V e Group, Compound V f Group, Compound V g Group.

[0180] As shown in Table 13 and Table 15, Compound V d Group and Compound V a Group, Compound V c Group, Compound V e Group, Compound V f Group, Compound V g Compared with the groups, the aquaporin 3 level was higher and there were significant differences. It shows that Compound V d Group has a better moisturizing effect than Compound V a Group, Compound V c Group, Compound V e Group, Compound V f Group, Compound V g Group.

[0181] Table 13: Promoting effect of ceramide compounds on AQP3

[0182]

[0183] Table 14: Statistical Analysis of Experimental Group 2 and Other Experimental Groups (AQP3)

[0184]

[0185] Table 15: Statistical Analysis of Experimental Group 4 and Other Experimental Groups (AQP3)

[0186]

[0187] The above are only the preferred embodiments of the present invention. It should be pointed out that for those of ordinary skill in the art, without departing from the principle of the present invention, several improvements and refinements can be made, and these improvements and refinements should also be regarded as the protection scope of the present invention.

Claims

1. A ceramide compound, characterized in that: It has the structure shown in formula I: In Formula I, R 1 is selected from C6 to C18 alkylene groups; R 2 A hydrocarbon group selected from C1 to C25.

2. The ceramide compound according to claim 1, characterized in that R 1 is selected from C10 to C18 alkylene groups; R 2 A hydrocarbon group selected from C15 to C25.

3. The ceramide compound according to claim 1, characterized in that The alkylene group is selected from chain alkylene groups, and preferably, the chain alkylene group is selected from straight chain alkylene groups or branched chain alkylene groups; The hydrocarbon group is selected from a chain hydrocarbon group, preferably, the chain hydrocarbon group is selected from a straight-chain hydrocarbon group or a branched hydrocarbon group; Preferably, the hydrocarbon group is selected from a saturated hydrocarbon group or an unsaturated hydrocarbon group. More preferably, the hydrocarbon group is selected from an unsaturated hydrocarbon group, and the unsaturated bonds in the unsaturated hydrocarbon group include 1 to 5.

4. The ceramide compound according to claim 1, characterized in that The ceramide compound is selected from any one or more compounds having structures shown in formulas Va to Vg; 5. A method for preparing a ceramide compound according to any one of claims 1 to 4, characterized in that: The following steps are involved: A) activating a compound having a structure shown in formula II with N,N'-carbonyldiimidazole and reacting the compound having a structure shown in formula III to obtain a compound having a structure shown in formula IV; B) reacting a compound having a structure represented by Formula IV with a compound having a structure represented by Formula V in the presence of 1-(3-dimethylaminopropyl)-3-ethylcarbodiamine, 1-hydroxybenzotriazole and a nitrogen-containing organic base to obtain a ceramide compound having a structure represented by Formula I; In Formula III and Formula IV, R 1 A alkylene group selected from C6 to C18; In Formula II and Formula IV, R 2 A hydrocarbon group selected from C1 to C25.

6. The compound according to claim 5, characterized in that In step A), the molar ratio of the compound having the structure shown in formula II to N,N'-carbonyldiimidazole is 1:(1.0-1.2); The molar ratio of the compound having the structure represented by formula II to the compound having the structure represented by formula III is 1:(1.0-1.2); The activation temperature is 25-30°C and the activation time is 2-4h; The reaction temperature is 25-30°C and the reaction time is 4-6 hours.

7. The compound according to claim 5, characterized in that In step A), after the reaction, a purification step is also included, and the purification includes the following steps: The reaction product obtained by the reaction is washed and then the organic phase is collected; The organic phase is dried, then heat-dissolved, cooled and crystallized, and the obtained crystals are dried to obtain a compound having a structure shown in Formula IV.

8. The compound according to claim 5, characterized in that In step B), the molar ratio of the compound having the structure represented by formula IV to the compound having the structure represented by formula V is 1:(1.0-1.2); The molar ratio of 1-(3-dimethylaminopropyl)-3-ethylcarbodiamine, 1-hydroxybenzotriazole and nitrogen-containing organic base is (1.2-1.4): (1.2-1.4): (2.0-3.0); The reaction temperature is 25-30°C and the reaction time is 10-12 hours.

9. The compound according to claim 5, characterized in that In step B), after the reaction, a purification step is also included, and the purification includes the following steps: removing the solvent from the reaction product obtained by the reaction, dissolving it in water, washing it, and collecting the organic phase; The organic phase is dried and then crystallized in a solvent, and the obtained crystals are dried to obtain a ceramide compound having a structure shown in Formula I.

10. Use of the ceramide compound according to any one of claims 1 to 4 in the preparation of products for preventing and treating skin diseases.

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