KR20210026336A - Method for preparing pseudoceramide compound - Google Patents

Abstract

The present invention relates to a method for preparing a pseudo-ceramide compound. The method for preparing a pseudo-ceramide compound according to the present invention increases the yield by using a base and a quaternary ammonium compound in an etherification step of a starting material, and then increases the yield without side reactions by using a Lewis acid catalyst in a deprotection step, and thus is suitable for mass production of pseudo-ceramide compounds.

Description

Method for producing pseudo ceramide compound {METHOD FOR PREPARING PSEUDOCERAMIDE COMPOUND}

The present invention relates to a method for preparing a similar ceramide compound.

The surface of human skin is protected by the stratum corneum, and among the components of the stratum corneum, lipids between keratinocytes form a layered structure, contributing to maintaining the basic functions of the skin.

Lipids between keratinocytes are composed of ceramide, cholesterol, and free fatty acids, among which ceramide plays a central role in water retention and barrier function of the stratum corneum as a main component. It is known that when the content of ceramide in the stratum corneum decreases, the protective barrier function of the stratum corneum decreases and various skin diseases are worsened.

Meanwhile, it has been reported that when the ceramide content in the stratum corneum is reduced due to skin aging or external irritation, the skin can be restored to a normal state by restoring the lamella structure of the skin by supplementing ceramide from the outside. Accordingly, for the purpose of restoring and maintaining the skin barrier function and enhancing moisturizing power, development of cosmetic compositions including ceramides has been actively made.

These ceramides are extracted from various animals and plants containing ceramides, and are also referred to as natural ceramides.

Natural ceramides have various physiological activities and advantages obtained from nature, but are difficult to mass-produce and are difficult to commercialize due to high prices.

In addition, natural ceramides have a low solubility in various solvents used in cosmetics, so the amount that can be used when making a product is limited, so there is a limit in showing efficacy.

Accordingly, research and development on similar ceramide compounds having a structure similar to that of natural ceramide, usable in cosmetics, and improved physical properties to replace natural ceramide are continuing.

However, conventionally, only a laboratory method of manufacturing similar ceramides in small quantities has been reported, and mass production of similar ceramides is practically impossible.

Korea Patent Publication No. 2014-0070474

In order to solve the above problems, the present inventors have tried to mass synthesize similar ceramides in high yield by optimizing the reaction conditions of a similar ceramide compound having a structure similar to that of natural ceramide and improving physical properties such as solubility. The present invention has been completed.

Accordingly, it is an object of the present invention to provide a method for preparing a similar ceramide compound.

In order to achieve the above object, the present invention is represented by the following Scheme 1, (S1) preparing a compound of Formula 3 by introducing a protecting group into the compound of Formula 2; (S2) preparing a compound of Formula 5 by reacting the compound of Formula 3 with a compound of Formula 4; (S3) preparing a compound of Formula 7 by reacting the compound of Formula 5 with a compound of Formula 6 and a quaternary ammonium compound under a base; And (S4) preparing a compound of Formula 1 by removing a protecting group from the compound of Formula 7 under a Lewis acids catalyst. Provides:

[Scheme 1]

In Scheme 1 above,

X is the protecting group, alkylidene, ethylidene, isopropylidene, cyclohexylidene, benzylidene or p-methoxybenzylidene,

R ₁ and R ₂ are the same as or different from each other, and each independently a C ₉ to C ₂₃ saturated or unsaturated aliphatic chain,

L ₁ is Cl, Br, I, C ₁ to C ₄ acyloxy or C ₁ to C ₄ alkoxy group,

L ₂ is Cl, Br, or I.

According to the method for preparing a similar ceramide compound according to the present invention, it is possible to produce a similar ceramide compound in a large amount without side reactions, and it may be advantageous for commercialization.

In addition, the similar ceramide compound can be widely applied to external skin preparations and cosmetic compositions for strengthening and maintaining the skin barrier function, and thus the method of preparing the similar ceramide compound can be applied to the production of cosmetics.

Hereinafter, it will be described in detail so that those of ordinary skill in the art can easily implement the present invention. However, the present invention may be implemented in various different forms, and is not limited to the embodiments described herein.

Method for producing pseudo ceramide compound

The present invention relates to a method for preparing a similar ceramide compound represented by the following Scheme 1, comprising the steps of: (S1) preparing a compound of Formula 3 by introducing a protecting group into the compound of Formula 2; (S2) preparing a compound of Formula 5 by reacting the compound of Formula 3 with a compound of Formula 4; (S3) preparing a compound of Formula 7 by reacting the compound of Formula 5 with a compound of Formula 6 and a quaternary ammonium compound under a base; And (S4) removing a protecting group from the compound of Formula 7 under a Lewis acids catalyst to prepare the compound of Formula 1.

[Scheme 1]

In Scheme 1 above,

X is the protecting group, alkylidene, ethylidene, isopropylidene, cyclohexylidene, benzylidene or p-methoxybenzylidene,

R ₁ and R ₂ are the same as or different from each other, and each independently a C ₉ to C ₂₃ saturated or unsaturated aliphatic chain,

L ₁ is Cl, Br, I, C ₁ to C ₄ acyloxy or C ₁ to C ₄ alkoxy group,

L ₂ is Cl, Br, or I.

Hereinafter, a method for preparing a similar ceramide compound according to the present invention will be described in more detail step by step with reference to Scheme 1 above.

In the method for preparing the pseudo ceramide compound, step (S3) may be an etherification step, and step (S4) may be classified into a deprotection step.

Step (S1)

In the present invention, in the step (S1), a protecting group may be introduced into the compound of Formula 2 to prepare the compound of Formula 3. At this time, a protecting group may be introduced into the compound of Formula 2 according to a method known in the literature (Helv. Chim. Acta 2003, 86, 2458 to 2470).

The compound of Formula 2 may be a starting material, and may be 2-amino-2-hydroxymethyl-propane-1,3-diol.

The protecting group may be used without limitation as long as it is used as a protecting group for a hydroxy group, but it is recommended to use a protecting group used as a protecting group for a diol so that two of the three hydroxy groups of tris(hydroxymethyl)aminomethane can be protected at the same time. desirable. Specifically, methylidene acetal, ethylidene acetal, isopropylidene ketal, cyclohexylidene ketal, benzylidene ketal, or p-methoxybenzylidene acetal protecting group may be used.

Specifically, since the carbon chain needs to be connected to only one of the three hydroxy groups (-OH) contained in the compound of Formula 2, the two -OH are temporarily bound using the protecting group, and then only the remaining one -OH is reacted. It may be a process of linking the carbon chains and dehousing after that.

The solvent used in this step is preferably an organic solvent, for example, chloroform, dimethylformamide (DMF), dichloromethane, acetonitrile, diisopropyl ether, diethyl ether, tetrahydrofuran (THF), dimethylacetamide. One selected from the group consisting of (DMA), dimethyl sulfoxide (DMSO), chlorobenzene, toluene, benzene, acetone, and a mixed solvent thereof may be used.

In this step, if necessary, a known acid or base catalyst may be used. In addition, reaction conditions, temperature, pressure, time, and the like are not particularly limited in the present invention, and known conditions are followed.

According to a preferred embodiment of the present invention, the protecting group is an isopropylidene ketal protecting group. The method of introducing the isopropylidene ketal protecting group is not particularly limited in the present invention, and a method known in the art may be used. For example, an isopropylidene ketal protecting group may be introduced by reacting tris(hydroxymethyl)aminomethane with 2,2-dimethoxypropane under weakly acidic conditions as shown in Scheme 2 below.

[Scheme 2]

In the reaction of Scheme 2, an organic solvent as described above may be used, and an acid catalyst may be used. Preferably, it is possible to use DMF as a solvent and p-toluenesulfonic acid (TsOH) as an acid catalyst.

Step (S2)

In the present invention, in the step (S2), the compound of Formula 5 may be prepared by reacting the compound of Formula 3 with the compound of Formula 4.

The compound of Formula 3 is a compound formed by introducing a protecting group into the compound of Formula 2 in the step (S1).

The compound of Formula 5 having an amide group may be prepared by reacting the compound of Formula 3 with the compound of Formula 4.

The compound of Formula 4 _{is an acyl compound having a leaving group (L 1} ), and may be an acyl halide, an acid anhydride, or an ester. Any compound of Formula 4 may be used as long as it satisfies the definition of Scheme 1, for example, palmitoyl chloride (CH ₃ (CH ₂ ) ₁₄ COCl), myristoyl chloride (CH ₃ (CH ₂ ) ₁₂ COCl), stearoyl chloride (CH ₃ (CH ₂ ) ₁₆ COCl), and the like can be used.

The solvent used in this step is preferably an organic solvent as described above in step (S1), and if necessary, such as triethylamine, N,N'-diisopropylethylamine, pyridine, and N-methylmorpholine. Bases can be used. At this time, the reaction conditions, temperature, pressure, time, etc. are not particularly limited, and known conditions are followed.

According to a preferred embodiment of the present invention, dichloromethane as a solvent and triethylamine as a base may be used, and a base is added to the compound of Formula 3 at 0°C, and the compound of Formula 4 is slowly added dropwise thereto, and then at room temperature. By stirring for 2 to 4 hours in the compound of formula 5 can be prepared.

Step (S3)

In the present invention, in the step (S3), the compound of Formula 7 may be prepared by reacting the compound of Formula 5 with the compound of Formula 6 and a quaternary ammonium compound under a base. Specifically, the compound of Formula 7 having a ceramide-like structure can be prepared by introducing an aliphatic chain into the hydroxy group of the compound of Formula 5 above.

In this step, a solvent and a base used in the nucleophilic substitution reaction may be used.

THF, t-butanol, or 1,4-dioxane may be used as the solvent.

As the base, at least one selected from the group consisting of potassium t-butoxide, potassium hydroxide, sodium hydroxide, lithium hydroxide, and sodium hydride may be used.

The quaternary ammonium compound may be a material having a phase change catalyst function. For example, the quaternary ammonium compound is TBAHSO ₄ (Tetrabutylammonium hydrogensulfate, (n-Bu ) 4 N + HSO 4 -) - selected from the group consisting of, TBAI (Tetrabutylammonium iodide) and TBAC (Tetrabutylammonium chloride), TBAB ( Tetrabutylammonium Bromide, (n-Bu) 4 N + Br) It may contain one or more of which are.

At this time, the reaction conditions, temperature, pressure, time, etc. are not particularly limited in the present invention, and may be appropriately adjusted according to the reaction material used.

Specifically, in an embodiment of the present invention, THF was used as a solvent and potassium hydroxide (KOH) was used as a base, and the compound of Formula 7 was prepared by reacting at room temperature for 10 to 14 hours.

Step (S4)

In the present invention, in the step (S4), the compound of Formula 1 may be prepared by removing the protecting group of the compound of Formula 7 under a Lewis acids catalyst.

The step (S4) is a step of removing the diol protecting group introduced in step (S1), and the reaction conditions, temperature, pressure, time, etc. are not particularly limited and may vary depending on the protecting group used. Specifically, removal of the protecting group may be performed in the presence of a Lewis acid catalyst, an acidic aqueous solution, or a metal catalyst, and hydrogen gas or the like may be added if necessary.

According to a preferred embodiment of the present invention, a Lewis acids catalyst is used to remove the isopropylidene protecting group. The Lewis acid used at this time is AlCl ₃ , BiCl ₃ . It may be one or more selected from the group consisting of _{FeCl 3} and ZnCl _{2 , and BiCl 3} is preferably used.

In addition, when water is mixed with the Lewis acid catalyst, the production yield of a similar ceramide compound may be further improved. At this time, the water may be used in a small amount, for example, 0.5 to 3 parts by weight, preferably 0.5 to 2 parts by weight, based on 100 parts by weight of the solvent used in step (S1) to improve the manufacturing yield. I can.

The conditions for such a protecting group removal reaction are not particularly limited in the present invention, and are performed in the range of -30 to 60°C, preferably -30 to 40°C for 0.5 to 72 hours, preferably 1 to 12 hours.

The solvent may be a polar solvent capable of dissolving an acid, _{and one selected from the group consisting of water, C 1} -C ₄ lower alcohol, tetrahydrofuran (THF), and a mixed solvent thereof may be used. Hydrofuel (THF) column can be used.

Pseudo ceramide compounds

The present invention provides a novel similar ceramide compound represented by the following formula (1). A novel pseudo ceramide compound represented by the following Formula 1 may be prepared in large quantities by the method for preparing a similar ceramide compound as described above.

[Formula 1]

(In Chemical Formula 1,

R ₁ and R ₂ are the same as or different from each other, and each independently a C9 to C23 saturated or unsaturated aliphatic chain)

The saturated aliphatic chain of C9 to C23 mentioned in the present specification is a carbon-to-carbon bond consisting only of a single bond, for example, nonanyl group (C9:0, nonanyl), decanyl group (C10:0, decanyl), unde Canyl group (C11:0, undecanyl), dodecanyl group (C12:0, dodecanyl), tridecanyl group (C13:0, tridecanyl), tetradecanyl group (C14:0, tetradecanyl), pentadecanyl group (C15:0 , pentadecanyl), hexadecanyl group (C16:0, hexadecanyl), heptadecanyl group (C17:0, heptadecanyl), octadecanyl group (C18:0, octadecanyl), nonadecanyl group (C19:0, nonadecanyl), icosan Diary (C20:0, icosanyl), henaikosanyl group (C21:0, henicosanyl) docosanyl group (C22:0, docosanyl), or tricosanyl group (C23:0, tricosanyl), but is not limited thereto. .

In addition, the C9 to C23 unsaturated aliphatic chain mentioned in the present specification is one containing one or more carbon-carbon double bonds or triple bonds, for example, nonenyl group (C9:1, nonenyl), decenyl group (C10:1, decenyl), undecenyl group (C11:1, undecenyl), dodecenyl group (C12:1, dodecenyl), tridecenyl group (C13:1, tridecenyl), tetradecenyl group (C14:1, tetradecenyl), pentadecenyl group (C15:1, pentadecenyl), hexadecenyl group (C16:1, hexadecenyl), heptadecenyl group (C17:1, heptadecenyl), octadecenyl group (C18:1, octadecenyl), nonadecenyl group (C19:1, nonadecenyl) ), icosenyl group (C20:1, icosenyl), henicosenyl group (C21:1, henicosenyl) docosenyl group (C22:1, docosenyl), or tricosenyl group (C23:1, tricosenyl), but this It is not limited.

Preferably, the R ₁ and R ₂ are the same as or different from each other, and each independently may be a C13 to C18 saturated or unsaturated aliphatic chain.

More preferably, R ₁ and R ₂ are the same as or different from each other, and each independently may be a tridecanyl group, a tetradecanyl group, a pentadecanyl group, a hexadecanyl group, a heptadecanyl group, or an octadecanyl group.

Even more preferably, R ₁ may be a tridecanyl group, a pentadecanyl group, or a heptadecanyl group, and R ₂ may be a tetradecanyl group, a hexadecanyl group, or an octadecanyl group.

Specific examples of the compound represented by Formula 1 include hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide (Chemical Formula 8), hexadecanoic acid (1 ,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide (Chemical Formula 9), hexadecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl) -Amide (Formula 10), octadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl) -amide (Formula 11), octadecanoic acid (1,1-bis -Hydroxymethyl-2-tetradecyloxy-ethyl)-amide (Chemical Formula 12), octadecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide (Chemical Formula 13), tetradecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide (Formula 14), or tetradecanoic acid (1,1-bis-hydroxy Methyl-2-octadecyloxy-ethyl)-amide (Chemical Formula 15) is mentioned.

[Formula 8]

[Formula 9]

[Formula 10]

[Formula 11]

[Formula 12]

[Formula 13]

[Formula 14]

[Formula 15]

The similar ceramide compound of Formula 1 as described above is structurally and functionally similar to natural ceramide, and thus may be used as a raw material component of a skin external preparation or cosmetic composition for protecting the skin barrier.

The compound of Formula 1 prepared through the above-described method can be applied to various fields, and can be applied in various fields such as cosmetics, pharmaceutical preparations, external preparations, and food fields to which natural ceramides, synthetic ceramides or similar ceramides are applied.

Hereinafter, the present invention will be described in more detail by the following examples. However, the following examples are for illustrative purposes only, and the contents of the present invention are not limited by the following examples.

Example One: Hexadecanoic acid (2- Hexadecyloxy -1,1- Vis - Hydroxymethyl -Ethyl)-amide ( Hexadecanoic acid (2- hexadecyloxy -1,1-bis- hydroxymethyl -ethyl)-amide)

According to the following Scheme 1-1, hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide, which is a compound of the following formula 1, was prepared as a similar ceramide compound.

[Reaction Scheme 1-1]

(One) Preparation of the compound of formula 3

Using (5-amino-2,2-dimethyl-[1,3]dioxan-5-yl)-methanol, which is the compound of Formula 2 as a starting material, see Helv. Chim. Acta 2003, 86, 2458 ~ 2470), the compound of Formula 3 (5-amino-2,2-dimethyl-[1,3]dioxan-5-yl)-methanol was prepared.

(2) Preparation of compound of formula 5

The compound of Formula 3, (5-amino-2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (86.3g) was dissolved in dichloromethane (1L) and triethylamine (89.3mL). After adding, while stirring at 0° C., palmitoyl chloride (161.89 mL), which is a compound of Formula 4, was slowly added dropwise. The reaction solution was stirred at room temperature (25°C) for 3 hours and 30 minutes, and then washed with a diluted hydrochloric acid solution and a saturated sodium chloride solution. The organic solution layer was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and recrystallized using dichloromethane and hexane to obtain a white solid (168 g, yield: 78%).

The white solid was 2-amino-2-hydroxymethyl-propane-1,3-diol hydrochloride, which is a compound of Formula 5, and was confirmed by the following NMR analysis results.

¹ H NMR (300MHz, CDCl ₃ ) δ 6.28 (brs, 1H), 5.18 (m, 1H), 3.83 (s, 4H), 3.65 (d, 2H, J = 6.3Hz), 2.28 (t,2H, J = 7.2Hz), 1.65 ~ 1.25 (m, 32H), 0.88 (t, 3H, J = 6.9Hz).

(3) Preparation of compound of formula 7-etherification step

After dissolving bromohexadecane (91.6g), the compound of Formula 6, in tetrahydrofuran (750mL), potassium hydroxide (73.3g) and tetrabutylammonium hydrogen sulfate [TBAHSO ₄ =(n-Bu) ₄ N ⁺ HSO ₄ ^-] (10.2g) was added to the above-mentioned (2) the hexahydro compounds of the formula (5) prepared to Kano acid (5-hydroxymethyl-2,2-dimethyl-in with stirring [l, 3] dioxan -5 -Yl)-amide (119.82g) was slowly added and stirred at room temperature for 6 hours. The reaction solution was crudely neutralized using 1M hydrochloric acid aqueous solution, and then extracted with water (1L) and dichloromethane (1L). The collected organic layers were dried under anhydrous magnesium sulfate, filtered, concentrated, and recrystallized under dichloromethane/hexane to obtain a white solid (127.33g, 68%).

The white solid is hexadecanoic acid (5-hexadecyloxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide, which is a compound of Chemical Formula 7, as a result of the following NMR analysis. Confirmed.

¹ H NMR (300MHz, CDCl ₃ ) δ 5.67 (brs, 1H), 4.34 ~ 4.30 (m, 2H), 3.79 ~ 3.70 (m, 4H), 3.44 (t, 2H, J = 6.6Hz), 2.16 (t , 2H, J = 7.5Hz), 1.57-1.24 (m, 60H), 0.87 (m, 6H).

(4) Preparation of compound of formula 1-deprotection step

Hexadecanoic acid (5-hexadecyloxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (11g), the compound of Formula 7 above, was added to dichloromethane (100 mL) and aceto. After dissolving in nitrile (50 mL), water (1 mL) was added, and a Lewis acid catalyst, BiCl ₃ and bismuth chloride (0.7 g) were added while stirring, followed by stirring at room temperature for 5 hours. After completion of the reaction, the reaction solution was washed with an aqueous sodium hydrogen carbonate solution (200 mL), the organic layer was dried over anhydrous sodium hydrogen sulfate, and then concentrated under reduced pressure. A white solid compound (7.62g, yield: 74%) was obtained by recrystallization under dichloromethane/hexane conditions.

The white solid compound was hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide, which is the compound of Formula 1, and was confirmed by the following NMR analysis results.

¹ H NMR (300MHz, CDCl ₃ ) δ 6.50 (brs, 1H), 4.34 (m, 2H), 3.71 ~ 3.45 (m, 8H), 2.55 (t, 2H, J = 7.5Hz), 1.80 ~ 1.20 (m , 54H), 0.88 (m, 6H).

Comparative example One: Hexadecanoic acid (2- Hexadecyloxy -1,1- Vis - Hydroxymethyl -Ethyl)-amide ( Hexadecanoic acid (2- hexadecyloxy -1,1-bis- hydroxymethyl -ethyl)-amide)

Conducted in the same manner as in Example 1, except that KOtBu (=potassium t-butoxide) was used instead of potassium hydroxide as a reaction catalyst in step (3), and tetrabutylammonium hydrogen sulfate was not added, and in step (4) Using a 1M aqueous hydrochloric acid solution, which is a dilute hydrochloric acid containing a large amount of water, instead of a Lewis acid catalyst and water, the hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl) of the formula 1, a similar ceramide compound. -Ethyl)-amide was prepared.

Experimental Example 1: Yield comparison

In the preparation process of the similar ceramide compound in Example 1 and Comparative Example 1, the yields of the etherification step (3) and the deprotection step (4) were calculated and are shown in Table 1 below.

yield Example 1 Comparative Example 1 Step (3) Formula 7 compound production yield 68% 41% Step (4) Formula 1 compound production yield 74% 73%

Referring to Table 1, in the case of the production yield of the compound of Formula 7 prepared in step (3), which is an etherification step in the production process of a similar ceramide compound, 68% and 41 in Example 1 and Comparative Example 1, respectively. Since it is expressed as %, it can be seen that the yield of preparing the compound of Formula 1 in Example 1 is good.

In addition, in the case of the production yield of the compound of Formula 1, which is a similar ceramide compound prepared in step (4), which is the deprotection step, it was found to be similar to 74% and 73% in Example 1 and Comparative Example 1, respectively. However, in the case of Example 1, by using Lewis acid and a small amount of water in step (4), it was confirmed that there were fewer side reactions compared to the case of using diluted hydrochloric acid containing a large amount of water in Comparative Example 1.

At this time, the degree of side reaction was measured using thin layer chromatography, and when diluted hydrochloric acid was used in the reaction of step (4) of Comparative Example 1, the chromatogram of the side reaction was confirmed.

In the above, although the present invention has been described by a limited embodiment and drawings, the present invention is not limited thereto, and the technical idea of the present invention and the following description by those of ordinary skill in the art to which the present invention pertains. It goes without saying that various modifications and variations are possible within the equivalent range of the claims to be made.

Claims (9)

It is represented by the following scheme 1,
(S1) preparing a compound of Formula 3 by introducing a protecting group into the compound of Formula 2;
(S2) preparing a compound of Formula 5 by reacting the compound of Formula 3 with a compound of Formula 4;
(S3) preparing a compound of Formula 7 by reacting the compound of Formula 5 with a compound of Formula 6 and a quaternary ammonium compound under a base; And
(S4) A method for producing a similar ceramide compound represented by Formula 1, comprising the step of preparing a compound of Formula 1 by removing a protecting group from the compound of Formula 7 under a catalyst of Lewis acids:
[Scheme 1]

In Scheme 1 above,
X is the protecting group, alkylidene, ethylidene, isopropylidene, cyclohexylidene, benzylidene or p-methoxybenzylidene,
R ₁ and R ₂ are the same as or different from each other, and are independently C ₉ to C ₂₃ saturated or unsaturated aliphatic chains,
L ₁ is Cl, Br, I, C ₁ to C ₄ acyloxy or C ₁ to C ₄ alkoxy group,
L ₂ is Cl, Br, or I. The method of claim 1,
The R ₁ and R ₂ are the same as or different from each other, and each independently a C ₁₃ to C ₁₈ saturated or unsaturated aliphatic chain. The method of claim 1,
The compound of Formula 4 is myristoyl chloride, palmitoyl chloride, or a method for producing a similar ceramide compound, characterized in that stearoyl chloride. The method of claim 1,
The method for producing a similar ceramide compound, characterized in that the compound of Formula 6 is bromotetradecane, bromohexadecane, or bromooctadecane. The method of claim 1,
The base is potassium t-butoxide, potassium hydroxide, sodium hydroxide, lithium hydroxide, and sodium hydride. The method of claim 1,
The quaternary ammonium compound is TBAHSO ₄ (Tetrabutylammonium hydrogensulfate, (n-Bu ) 4 N + HSO 4 -) - selected from the group consisting of, TBAI (Tetrabutylammonium iodide) and TBAC (Tetrabutylammonium chloride), TBAB ( Tetrabutylammonium Bromide, (n-Bu) 4 N + Br) The method for producing a similar ceramide compound that includes one or more of which are. The method of claim 1,
The Lewis acids catalyst is AlCl ₃ , BiCl ₃ . FeCl ₃ and ZnCl _{2 The} method for producing a similar ceramide compound comprising at least one selected from the group consisting of. The method of claim 1,
The method for producing a similar ceramide compound, wherein water is mixed with the Lewis acid catalyst. The method of claim 1,
The yield of the production method is 50% or more, a method for producing a similar ceramide compound.