KR20170100906A - Ceramide compound, a process of preparing the ceramide compound, an intermediate compound and a process of preparing the intermediate compound - Google Patents

Abstract

Disclosed is a novel ceramide-like compound having structural features of natural ceramide. More specifically, disclosed is a method for producing a compound having a similar structure as natural ceramide by bonding various alkyl groups and acyl groups onto an -hydroxy fatty acid having a hydroxyl(alcohol) group at a terminal end of fatty acid, especially an -hydroxyl group which is a part of alcohol. The use of the method can overcome shortcomings of natural ceramide with regard to cleanliness and purity of products and expensive price while being hard to obtain. In addition, the ceramide-like compound of the present invention also shows higher effects than natural ceramide.

Description

TECHNICAL FIELD The present invention relates to a ceramide compound, a process for preparing the same, an intermediate compound for preparing the same, and a process for preparing the intermediate compound,

New ceramide analogues having structural properties of native ceramides are disclosed herein. More specifically, a compound similar to a natural ceramide structure is attached to an? -Hydroxy group having an alcohol (? A method for providing the same is disclosed.

Anyone will want to make themselves beautiful and beautiful. In particular, it is almost absolutely everyone's wish to keep your skin elastic and hydrated.

The most damaging of human skin is due to skin dryness caused by the evaporation of water in the cells, and the second is due to external stimuli such as ultraviolet rays and deterioration of exfoliation of keratinocytes.

As the person gets older, the content of various ceramides in the stratum corneum of the skin is reduced, and the skin becomes rough due to damage to the skin surface due to reduction of moisture in the skin, external stimulation, exfoliation of the keratinocyte, and the like.

As shown in Figs. 1 and 2, various ceramides exist in the skin. Previously, they were classified according to the difference in polarity of ceramides, but now they are classified according to the structural difference of ceramides. (Cer 2), NP (Cer 3), NH (Cer 8), Nds (Cer 10) and non-hydroxy fatty acid-bonded sphingoid skeletons. Ceramide, ω-esterified ceramide, EOS (Cer 1), EOP (Cer 9), ω-hydroxy fatty acid ), EOH (Cer 4), and non-hydroxy ceramide fatty acids are present in various lengths. However, only NP (Cer 3), AP (Cer 6) and NS (Cer 2) can be produced commercially. Many recent studies have reported that there are various ceramides in the skin and that the skin barrier function varies depending on the fatty acid length of the ceramide. This is due to the fact that the use of various types of ceramide is more effective than using a single ceramide Suggesting that it helps with barrier function.

When ceramide content in the stratum corneum is reduced, damage to the stratum corneum is accelerated by skin aging or external stimulation as well as water content in the skin cells. However, when the ceramide is supplemented from the outside, the lamella structure of the skin is restored, Can be restored to a normal state. Natural ceramides, however, are difficult to obtain, are expensive, and natural ceramides are not only available in small quantities at the end of a horse but also have problems in refining and hygiene.

Therefore, the efficacy of natural ceramide is similar to that of natural ceramide.

First, in relation to ceramide derivatives, Korean Patent Laid-Open No. 10-1997-0070014 synthesized differently from natural ceramide structures. In particular, it was claimed that the carbon chain in the amide group was a new substance with a small alcohol. Korean Patent Laid-Open No. 10-1998-0002056 also discloses a novel compound synthesized differently from the natural ceramide structure. Korean Patent Laid-Open No. 10-2003-0065991 discloses a novel compound synthesized by changing the chemical structure of a sphingosine moiety which becomes a skeleton in a ceramide structure. Korean Registration No. 10-1051812 discloses a skin moisturizing and anti-aging cosmetic composition by esterifying a primary alcohol moiety of phytosphingosine with L-proline and replacing a fatty acid moiety with an unsaturated fatty acid. Korean Patent No. 10-1288776 discloses a cosmetic composition in which a novel compound having a short carbon chain in which an amide moiety of phytosphingosine is chemically reacted with maleic anhydride can prevent and improve inflammatory skin diseases. Korean Patent Laid-Open No. 10-2011-0097866 also discloses a method for dispersing various natural and synthetic ceramides, and a method which can be used in a cosmetic composition is proposed.

However, ceramide-like compounds according to the prior art have been proposed in which the carbon chain or structure is too different from natural ceramides, and some compounds are not easy to synthesize.

Korean Patent Publication No. 10-1997-0070014 Korean Patent Publication No. 10-1998-0002056 Korean Patent Publication No. 10-2003-0065991 Korean Registration No. 10-1051812 Korea Registration No. 10-1288776 Korean Patent Publication No. 10-2011-0097866

In one aspect, the present invention provides ceramides having a structure similar to natural ceramides.

In another aspect, the present invention aims to provide a skin damaging resilience effect that is similar or rather similar to that of natural ceramides.

In another aspect, the present invention aims to provide a novel ceramide-like compound that contains moisture in the skin to prevent skin aging.

In another aspect, the present invention aims at providing a method for producing ceramides that is simple, simple, and inexpensive.

In another aspect, the present invention provides an intermediate compound for producing ceramides in an easy, simple, and inexpensive manner.

In one aspect, the present invention is a pentadecanoic acid compound represented by the following formula (1), a salt thereof, an isomer thereof, a hydrate thereof or a solvate thereof:

[Chemical Formula 1]

In the above formulas,

R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group.

In another aspect, the present invention is a ceramide represented by the following formula (2), a salt thereof, an isomer thereof, a hydrate thereof, or a solvate thereof:

(2)

In Formula 2,

R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,

R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group.

In another aspect, the present invention is a ceramide represented by the following formula (3), a salt thereof, an isomer thereof, a hydrate thereof, or a solvate thereof:

(3)

In Formula 3,

R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,

R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group.

In another aspect, the present invention is a ceramide represented by the following formula (4), a salt thereof, an isomer thereof, a hydrate thereof, or a solvate thereof:

[Chemical Formula 4]

R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,

R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group.

In the present invention in another aspect is, formula (1) (In the formula, R ₁ is C ₁ ~ C ₂₀ alkyl group, C ₁ ~ is selected from an alkenyl group of C _20.) To the compound represented by the 15-penta Kano ripening A method for producing an acid ether compound, comprising the steps of: reacting a 15-hydroxypentadecanoic acid represented by the formula (1) wherein R ₁ is H with a halogen compound to convert the hydroxy moiety of the 15-hydroxypentadecanoic acid into a halogen Substituting; And reacting the halogen-substituted pentadecanoic acid compound with an alkanol (R ₁ -OH) compound to obtain an ether compound.

To the present invention In one aspect the formula (1) (In the formula, R ₁ is C ₁ to C ₂₀ alkyl group, C is selected from _one or alkenyl group of C _20. In) the compound having a 15-penta Kano ripening acid represented by A method for producing an ether compound, which comprises the step of reacting a 15-hydroxypentadecanoic acid of formula (1) wherein R ₁ is H with an alkyl halide (R ₁ -X) to obtain an ether compound .

In one aspect, the present invention provides a process for producing a 15-acetoxypentadecanoic acid compound represented by the following formula (1) (wherein R ₁ is an acetyl group) Hydroxypentadecanoic acid, wherein R < ₁ > is H, with acetic acid to obtain 15-acetoxypentadecanoic acid.

In one aspect, the present invention provides a compound of formula I wherein R ₁ is a C ₁ -C ₂₀ acyl group (R-CO-), R is H or a C ₁ -C ₁₉ alkyl group or C ₁ -C ₁₉ Pentadecanoic acid ester compound which is a compound represented by the general formula (1): wherein R ₁ is a group represented by the general formula ; And a second step of reacting the fatty acid having been subjected to the first step with 15-hydroxypentadecanoic acid having R ₁ in the formula (1) to obtain an ester compound.

In one embodiment, the second step comprises reacting ethoxymethyl 15 hydroxypentadecanoate with a fatty acid that has undergone the first step and then obtaining a 15-pentadecanoic acid ester compound of Formula 1 from the reactant can do.

In one aspect, the present invention provides a method for producing ceramides, wherein the ceramide is any one of the formulas (2) to (4) above, and reacting 15- (acetoxy) pentadecanoic acid with phytosphingosine, sphingosine or sphinganine To obtain 15- (acetoxy) pentadecanoic acid ceramide; And obtaining 15 (hydroxy) pentadecanoic acid from the obtained 15- (acetoxy) pentadecanoic acid ceramide.

In one aspect, the present invention relates to a method for producing ceramide, wherein the ceramide is any one of the above-mentioned formulas 2 to 4, and the 15-pentadecanoic acid ether compound of the formula (1) or the 15-pentadecanoic acid ester compound of the formula With phytosphingosine, sphingosine or sphinganine to obtain a ceramide.

The ceramide compounds and their intermediate compounds disclosed in this specification are expensive, difficult to obtain, pointed out as disadvantages of natural ceramide, can overcome the purity and hygienic problems of the product, and are effective in overcoming natural ceramide . Accordingly, the present invention relates to a novel ceramide-like compound having an effect of restoring the skin damage better than natural ceramide, and containing moisture in the skin to prevent aging of the skin, and an intermediate compound for preparation thereof.

Figures 1 and 2 show various ceramides present in the skin.
3 is NMR data showing the synthesis of 15- (hydroxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide of Structural Formula 15. FIG.
4 is NMR data showing the synthesis of 15- (nonyloxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide of structural formula 17. FIG.
5 is NMR data showing the synthesis of 15- (9Z, 12Z-octadecadienyloxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide of structural formula 25. FIG.
FIG. 6 is a graph illustrating a damaged skin barrier recovery effect of ceramides according to an embodiment of the present invention.
7 is a graph showing the skin moisturizing effect of ceramides according to an embodiment of the present invention.

As mentioned earlier, natural ceramides are useful as a compound that maintains skin elasticity by keeping moisture in the stratum corneum, which is difficult and expensive to obtain in general, and many researchers are continuing to research new natural pseudoceramide.

The present inventors have found that 15-hydroxypentadecanoic acid (15-hydroxypentadecanoic acid), a kind of ω-hydroxy fatty acid having a carbon number of 15, which is comparatively inexpensive and easily obtainable in order to make a material having a similar structural form to natural ceramide, ) Was used as a starting material and various alkyl groups and acyl groups were attached to the hydroxyl group at the 15th position to make the length and structure of the fatty acid similar to that of the natural ceramide. The fatty acid was converted into naturally occurring sphingosine, The present invention has been completed on the basis of the reaction and synthesis with high-purity and sphinganine.

Hereinafter, the present invention will be described in detail.

As used herein, "pentadecanoic acid compound" means any compound in which the pentadecanoic acid residue is contained in the compound. For example, it is possible to use pentadecanoic acid or 15-hydroxypentadecanoic acid having a hydroxy group attached thereto, or 15-acetoxypentadecanoic acid having an acetoxy group instead of a hydroxy group, A 15-pentadecanoic acid ether compound in which an alkyl group is bonded in place of the hydrogen in the hydroxyl group of the canoic acid, or a 15-pentadecanoic acid ester compound in which an acyl group is bonded instead of hydrogen in the hydroxyl group of the penta-decanoic acid However, the present invention is not limited thereto.

In one embodiment, the pentadecanoic acid compound may be a pentadecanoic acid compound represented by the following formula (1)

[Chemical Formula 1]

In the above formulas,

R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group.

If R ₁ is hydrogen (H) 15-hydroxy-penta to Kano ripening acid, R ₁ is an acetyl group is 15-acetoxy-penta to Kano ripening acid, R ₁ is a is an acyl group of C ₁ ~ C ₂₀ 15- penta having When R ₁ is a C ₁ -C ₂₀ alkyl or alkenyl group, it is a 15-pentadecanoic acid ether compound.

As used herein, "alkyl" means a monovalent saturated aliphatic hydrocarbon chain. The hydrocarbon chain may be linear or branched. In one aspect of the invention "alkyl" may have from 1 to 20 carbon atoms ("C ₁ to C ₂₀ alkyl"). In one aspect of the present invention, "alkyl" may have 1 to 6 carbon atoms ("C 1 to C 6 alkyl") and in another aspect, 1 to 5 carbon atoms May have four carbon atoms ("C1 to C4 alkyl"), and in yet another aspect may have one to three carbon atoms ("C1 to C3 alkyl"). Specifically, "alkyl" includes but is not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, tert-butyl or t-amyl.

", "R₁-CO-" 를 의미할 수 있다. 예컨대, C₁ ~ C₂₀의 아실기일 수 있다. 여기서 R₁은 알킬 또는 알케닐일 수 있다. 즉, 탄소원자들이 모두 단일결합을 할 수도 있고, 하나 이상의 이중결합을 포함할 수 도 있다. As used herein, "acyl group" may mean a functional group from which one or more hydroxyl groups have been removed from oxo-acid. For example,

"," It may refer to a R ₁ -CO- ". For example, it may acyl date of C ₁ ~ C _20. Wherein R ₁ may be imidazol-alkyl or alkenyl, that is, the carbon atoms are all also be a single bond And may contain one or more double bonds.

As used herein, "alkoxy" means an -OR group, wherein R is an alkyl group as defined above. Specific examples of "alkoxy" include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy or 1,2- But is not limited thereto.

As used herein, "halogen" includes fluorine, chloride, bromine or iodine. In one aspect of the present invention, halo may be bromine or chloride.

As used herein, the term "alkenyl" refers to a linear or branched aliphatic hydrocarbon chain containing at least one carbon-carbon double bond.

The compounds disclosed herein, or salts thereof, may contain one or more asymmetric centers and thus may exist as enantiomers, diastereomers and other stereoisomeric forms (in terms of absolute stereochemistry, as (R) - or (S) - Or (D) - or (L) -) may be generated. Unless otherwise specified, it is intended that the compound includes both E and Z geometric isomers (e. G., Cis or trans). Likewise, it is intended that not only all possible isomers but also their racemates and optionally pure forms, and all tautomeric forms are also included.

"Stereoisomer" refers to a compound having a different three-dimensional structure that is made up of the same atom bound by the same bond, but which is not exchangeable. Therefore, various stereoisomers and mixtures thereof are contemplated and include "enantiomers" (which refers to two stereoisomers whose enantiomers do not overlap each other with a mirror image). A "tautomer" refers to a proton shifted from one atom of a molecule to another atom of the same molecule. The compounds provided herein may exist as tautomers. Tautomers are compounds that are interconverted by the transfer of hydrogen atoms following the conversion of single bonds and adjacent double bonds.

As used herein, the term " pharmaceutically acceptable "refers to the approval of a government or equivalent regulatory agency that can be used on animals, and more specifically on humans, by avoiding significant toxic effects when used in conventional medicinal dosage Received, approved, or listed in pharmacopoeia or other general pharmacopoeia.

As used herein, "salt thereof" or "pharmaceutically acceptable salt thereof" means a salt according to one aspect of the present invention which is pharmaceutically acceptable and has the desired pharmacological activity of the parent compound. The salt may be (1) formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like; (3-hydroxybenzoyl) benzoic acid, or an acetic acid, propionic acid, hexanoic acid, cyclopentenepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, Benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4- chlorobenzenesulfonic acid, 2- 4-methylbicyclo [2,2,2] -oct-2-en-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert Acid addition salts formed with organic acids such as butylacetic acid, laurylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid; Or (2) salts formed when the acidic proton present in the parent compound is substituted.

As used herein, "hydrate " means a compound to which water is bound, and is a broad concept that includes an inclusion compound having no chemical bonding force between water and the compound.

As used herein, "solvate" means a higher order compound formed between a molecule or ion of a solute and a molecule or ion of a solvent.

In another aspect, the present invention provides a compound represented by the formula (1) (wherein R ₁ is selected from a C ₁ -C ₂₀ alkyl group and a C ₁ -C ₂₀ alkenyl group), 15-pentadecano A step of reacting a 15-hydroxypentadecanoic acid represented by the formula (1) wherein R ₁ is H with a halogen compound to replace the hydroxy moiety of the 15-hydroxypentadecanoic acid with a halogen; And reacting the halogen-substituted pentadecanoic acid compound with an alkanol (R ₁ -OH) compound to obtain an ether compound.

In one aspect, the present invention relates to a compound represented by the formula (1) (wherein R ₁ is selected from a C ₁ -C ₂₀ alkyl group and a C ₁ -C ₂₀ alkenyl group), 15-pentadecanoic acid A step of reacting 15-hydroxypentadecanoic acid of formula (1) wherein R ₁ is H with an alkyl halide (R ₁ -X) to obtain an ether compound.

For example, an intermediate required for the preparation (synthesis) of a ceramide compound was synthesized through the following synthesis procedure. The reaction in each step is as shown in the following Reaction Schemes 1a or 1b.

The following Reaction Schemes 1a and 1b describe the preparation of an intermediate compound that produces a ceramide from ether compounds by reacting an alkyl group to the alcohol moiety of a compound (ω-hydroxy fatty acid) having a hydroxy (alcohol group) at the terminal of the fatty acid .

First, the alcohol part of an omega -hydroxy fatty acid is substituted with a bromine compound, and an alcohol compound having an alkyl group attached thereto is reacted to form a fatty acid having a desired ether compound attached thereto (Scheme 1a ).

The second method is to remove hydrogen from the alcohol moiety of the ω-hydroxy fatty acid and react with an alkyl halide compound to form a fatty acid with desired ether compounds. For example, R1 may be an alkyl group such as pentyl (C5H11-), heptyl (C7H15-), nonyl (C9H19-), undecyl (C11H23-), dodecyl (C12H25-), octadecyl (C18H37-)

In one aspect, the present invention provides a process for producing a 15-acetoxypentadecanoic acid compound represented by the formula (1) (wherein R ₁ is an acetyl group) Hydroxypentadecanoic acid, wherein R < ₁ > is H, with acetic acid to obtain 15-acetoxypentadecanoic acid. It was reacted with an acetyl group to protect the hydroxy (alcohol group) at the end of the fatty acid as shown in Scheme 1c (Scheme 1c).

[Reaction Scheme 1a]

[Reaction Scheme 1b]

[Reaction Scheme 1c]

The long-chain ether-fatty acid compounds represented by the following Structural Formulas 1 to 7 synthesized through the above Reaction Scheme 1 were synthesized to obtain the final natural pseudoceramide.

In one aspect,

In Formula 1

Wherein R ₁ is selected from C ₁ -C ₂₀ acyl groups (R-CO-) and R is H or a C ₁ -C ₁₉ alkyl group or a C ₁ -C ₁₉ alkenyl group,

As a method for producing a 15-pentadecanoic acid ester compound,

In the above manufacturing method,

A first step of subjecting a fatty acid, which is the parent of R ₁ , to an acid halide reaction or an acid anhydride reaction; And

The second step of reacting the fatty acid obtained in the first step with 15-hydroxypentadecanoic acid of formula (1) wherein R ₁ is H to obtain an ester compound

.

In one embodiment, the second step is a step of reacting ethoxymethyl 15 hydroxypentadecanoate with the fatty acid through the first step, and then obtaining a 15-pentadecanoic acid ester compound of formula (1) from the reaction product .

In the following Scheme 2, long-chain ester-fatty acid compounds similar to natural ceramide were synthesized as follows. 1) in the following Reaction Scheme 2 is a method in which stearic acid or palmitic acid, which is a saturated fatty acid, is subjected to an acid chloride reaction or an acid anhydride reaction, and then 15- The desired compound was synthesized by reacting with decanoic acid.

2) in the following reaction formula 2) is a method in which an unsaturated fatty acid such as oleic acid, linoleic acid or palmitoleic acid is reacted with an acid chloride or an acid anhydride, After the reaction, the desired compound was synthesized by reacting with 15-hydroxypentadecanoic acid.

[Reaction Scheme 2]

In one aspect, the present invention provides a method for producing ceramides, wherein the ceramide is any one of the formulas (2) to (4) above, and reacting 15- (acetoxy) pentadecanoic acid with phytosphingosine, sphingosine or sphinganine To obtain 15- (acetoxy) pentadecanoic acid ceramide; And obtaining 15 (hydroxy) pentadecanoic acid from the obtained 15- (acetoxy) pentadecanoic acid ceramide.

In one aspect, the present invention relates to a method for producing ceramide, wherein the ceramide is any one of the above-mentioned formulas 2 to 4, and the 15-pentadecanoic acid ether compound of the formula (1) or the 15-pentadecanoic acid ester compound of the formula With phytosphingosine, sphingosine or sphinganine to obtain a ceramide.

For example, a ceramide can be prepared according to the following Reaction Scheme 3. The naturally occurring ceramide derivatives, which are the final compounds, were prepared by using the naturally occurring compounds obtained in the above Reaction Schemes 1 and 2, phytosphingosine represented by Formula 5, sphingosine represented by Formula 6, and sphinganine represented by Formula 7, respectively .

[Chemical Formula 5]

Phytosphingosine

[Chemical Formula 6]

Sphingosine

(7)

Sphinganine

In the following scheme 3 R1 is R ₁ is hydrogen (H), acetyl group, C ₁ ~ C ₂₀ of the acyl group (R-CO-), selected from an alkenyl group of C ₁ ~ C ₂₀ alkyl group and a C ₁ ~ C ₂₀ of and, said R is an alkenyl group of H or C ₁ ~ C ₁₉ alkyl group or a C ₁ ~ C ₁₉ of.

For example, R ₁ is an alkyl group such as palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid and the like, (C5H11-), heptyl (C7H15-), nonyl (C9H19-), undecyl (C11H23-), dodecyl (C12H25-), octadecyl (C18H37-) and the like.

[Reaction Scheme 3]

In Scheme 3, novel compounds of phytosphingosine derivative 3-1 were prepared by the following method to prepare ceramide compounds of Structural Formulas 13 to 25.

Hereinafter, examples and comparative examples of the present invention will be exemplified. The following examples are provided to aid understanding of the present invention, and thus the technical scope of the present invention is not limited thereto.

(1) 15- Hydroxypentadecanoic acid  The acid (15- hydroxypentadecanoic  acid)

100 g of 15-hydroxypentadecanoic acid phthalocyanine salt was dissolved in 150 ml of water and THF (2: 1 ratio) in a reaction vessel. The temperature of the reaction vessel was adjusted to 0 ° C, the pH was adjusted to 2 with H 2 SO 4, the solvent was removed by vacuum, and recrystallized with ether to obtain a solid compound with a yield of 93%.

1H NMR (400MHz, CDCl3): δ (ppm) 12.15 (s, 1H), 3.65 (t, 2H), 2.35 (t, 2H), 1.52-1.68 (m, 4H), 1.23-1.41 (m, 20H)

(2) 15- Acetoxypentadecanoic acid  The acid (15- acetoxypentadecanoic  acid)

(Represented by the following structural formula 1)

[Structural formula 1]

(0.41 mol) of the 15-hydroxypentadecanoic acid obtained in the above step (1) was dissolved in 700 ml of dichloromethane (CH2Cl2), and then 50.9 g (0.49 mol) of acetic anhydride at room temperature, And pyridine (35.7 g) were added thereto, followed by stirring at 35-40 占 폚 for 8 hours. When the reaction is complete, cool to room temperature and adjust the pH to 3-4 with 10% aqueous phosphoric acid solution. The solvent was removed under reduced pressure, and 105 g of white powder 15-acetoxypentadecanoic acid was obtained in a yield of 85% using methanol and water.

1H NMR (400MHz, CDCl3): δ (ppm) 12.03 (s, 1H), 4.03 (t, 2H), 2.34 (t, 2H), 2.03 (s, 3H), 1.62-1.01 (m, 24H)

(3) 15- Bromopentadecanoic acid  The acid (15- bromopentadecanoic  acid)

177 g (0.69 mol) of the 15-hydroxypentadecanoic acid obtained in the above step (1) was placed in a reaction vessel and 577.4 g (3.43 mol) of 48% HBr / AcOH was added. 240 ml of concentrated sulfuric acid was added at room temperature, and the mixture was refluxed for 6 hours. After cooling to room temperature, the organic layer separated with dichloromethane was washed with water, dried over magnesium sulfate (MgSO4) and concentrated in vacuo. 195 g of white powder 15-bromopentadecanoic acid was obtained in a yield of 88%.

1H NMR (400MHz, CDCl3): [ delta] (ppm) 12.06 (s, IH), 3.34 (t, 2H), 2.15

(4) 15- ( Pentyloxy ) Pentadecanoi  Acid [15- ( pentyloxy ) pentadecanoic  acid]

(Represented by the following structural formula 2)

[Structural formula 2]

(Method 1) 32.0 g (0.80 mol) of 60% sodium hydride (NaH) was added to 1 L of toluene, 32.8 g (0.37 mol) of pentanol was slowly added dropwise and the mixture was stirred at 50 캜 for 1 hour. 100 g (0.31 mol) of 15-bromopentadecanoic acid was added dropwise to 250 ml of toluene, and the mixture was heated to reflux for 48 hours. When the reaction was completed, the reaction was quenched with water and the organic layer was extracted with ethyl acetate and recrystallized in n-hexane. The obtained solid was dried under reduced pressure to obtain 78.4 g of a white powder of 15- (pentyloxy) pentadecanoic acid in a yield of 77%.

(Method 2) 100 g (0.31 mol) of 15-hydroxypentadecanoic acid is dissolved in 150 ml of THF and 150 ml of HMPA, and 32 g (0.80 mol) of 60% sodium hydride (NaH) is slowly added at a reaction temperature of 0 ° C or lower. After stirring for 1 hour, add 46.8 g (0.31 mol) of pentylbromide in 50 ml of THF and slowly add it. When the reaction is complete, the reaction is quenched with water, the THF is firstly removed under reduced pressure, the organic layer extracted with ethyl acetate is washed with water three times, treated with anhydrous Na2SO4, filtered and the ethyl acetate is removed by distillation under reduced pressure. Recrystallization from n-hexane and drying under reduced pressure at 40 [deg.] C yielded 69.3 g of white powder 15- (pentyloxy) pentadecanoic acid in 68% yield.

1H NMR (400MHz, CDCl3): δ (ppm) 12.13 (s, 1H), 3.37 (t, 4H), 2.15 (t, 2H), 1.51-1.12 (m, 30H), 0.91 (t, 3H)

(5) Synthesis of 15- (heptyloxy) pentadecanoic acid [15- (heptyloxy) pentadecanoic acid]

(Represented by the following structural formula 3)

[Structural Formula 3]

(Method 1) 32 g (0.80 mol) of 60% sodium hydride (NaH) was added to 1 L of toluene, 43.0 g (0.37 mol) of heptanol was slowly added dropwise and the mixture was stirred at 50 캜 for 1 hour. 100 g (0.31 mol) of 15-bromopentadecanoic acid are mixed with 250 ml of toluene, and the mixture is slowly added dropwise, and the mixture is refluxed for 48 hours. When the reaction was completed, the reaction was quenched with water and the organic layer was extracted with ethyl acetate and recrystallized in n-hexane. The obtained solid was dried under reduced pressure to obtain 88.4 g of a white powder of 15- (heptyloxy) pentadecanoic acid in a yield of 80%.

(Method 2) 100 g (0.31 mol) of 15-hydroxypentadecanoic acid is dissolved in 150 ml of THF and 150 ml of HMPA, and 32 g (0.80 mol) of 60% sodium hydride (NaH) is slowly added at a reaction temperature of 0 ° C or lower. After stirring for 1 hour, add 55.5g (0.31mol) of heptylbromide in 50ml of THF and slowly add it. When the reaction is complete, the reaction is quenched with water, the THF is firstly removed under reduced pressure, the organic layer extracted with ethyl acetate is washed three times with water, treated with anhydrous Na2SO4, filtered and the ethyl acetate is removed by distillation under reduced pressure. The resulting solid was recrystallized from n-hexane and dried under reduced pressure at 40 캜 to obtain a yield of 69%, and as a white powder, 76.3 g of 15- (heptyloxy) pentadecanoic acid was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 12.15 (s, 1H), 3.36 (t, 4H), 2.15 (t, 2H), 1.51-1.12 (m, 34H), 0.90 (t, 3H)

(6) Synthesis of 15- (nonyloxy) pentadecanoic acid [15- (nonyloxy) pentadecanoic acid]

(Represented by the following structural formula 4)

[Structural Formula 4]

(Method 1) 32 g (0.80 mol) of 60% sodium hydride (NaH) was added to 1 L of toluene, and 53.4 g (0.37 mol) of nonanol was slowly added dropwise. After stirring at 50 ° C for 1 hour, 100 g (0.31 mol) of bromopentadecanoic acid was slowly mixed with 250 ml of toluene, and the mixture was heated under reflux for 48 hours. When the reaction was completed, the reaction was quenched with water and the reaction was quenched with water. The organic layer was extracted with ethyl acetate and dried under reduced pressure to obtain 91.8 g of a white powder of 15- (nonyloxy) pentadecanoic acid in 77% yield.

(Method 2) 100 g (0.31 mol) of 15-hydroxypentadecanoic acid is dissolved in 150 ml of THF and 150 ml of HMPA, and 32 g (0.80 mol) of 60% sodium hydride (NaH) is slowly added at a reaction temperature of 0 ° C or lower. After stirring for 1 hour, add 64.2 g (0.31 mol) of nonylbromide in 50 ml of THF and slowly add it. When the reaction is complete, the reaction is quenched with water, the THF is firstly removed under reduced pressure, the organic layer extracted with ethyl acetate is washed three times with water, treated with anhydrous Na2SO4, filtered and the ethyl acetate is removed by distillation under reduced pressure. The resulting solid was recrystallized from n-hexane and dried under reduced pressure at 40 占 폚 to obtain 57.4 g of a white powder of 15- (nonyloxy) pentadecanoic acid in a yield of 65%.

1H NMR (400MHz, CDCl3): δ (ppm) 12.10 (s, 1H), 3.34 (t, 4H), 2.15 (t, 2H), 1.51-1.12 (m, 38H), 0.92 (t, 3H)

(7) Synthesis of 15- (undecyloxy) pentadecanoic acid [15- (undecyloxy) pentadecanoic acid]

(Represented by the following structural formula 5)

[Structural Formula 5]

(Method 1) 32 g (0.80 mol) of 60% sodium hydride (NaH) was added to 1 L of toluene, 63.8 g (0.37 mol) of undecanol was slowly added dropwise and the mixture was stirred at 50 캜 for 1 hour. 100 g (0.31 mol) of 15-bromopentadecanoic acid are mixed with 250 ml of toluene, and the mixture is slowly added dropwise, and the mixture is refluxed for 48 hours. When the reaction was completed, the reaction was quenched with water and the organic layer was extracted with ethyl acetate and recrystallized in n-hexane. The resulting solid was dried under reduced pressure to obtain 103.6 g of a white powder of 15- (undecyloxy) pentadecanoic acid in a yield of 81%.

(Method 2) 100 g (0.31 mol) of 15-hydroxypentadecanoic acid is dissolved in 150 ml of THF and 150 ml of HMPA, and 32 g (0.80 mol) of 60% sodium hydride (NaH) is slowly added at a reaction temperature of 0 ° C or lower. After stirring for 1 hour, add 72.9 g (0.31 mol) of undecanylbromide in 50 ml of THF and slowly add it. When the reaction is complete, the reaction is quenched with water, the THF is firstly blown off under reduced pressure, the organic layer extracted with ethyl acetate is washed three times with water, treated with anhydrous Na2SO4, filtered and the ethyl acetate is removed by distillation under reduced pressure. The obtained solid was recrystallized from n-hexane and dried under reduced pressure at 40 캜 to obtain a yield of 67.5%, and as a white powder, 86.4 g of 15- (undecyloxy) pentadecanoic acid was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 12.12 (s, 1H), 3.34 (t, 4H), 2.15 (t, 2H), 1.51-1.12 (m, 42H), 0.91 (t, 3H)

(8) Synthesis of 15- (dodecyloxy) pentadecanoic acid [15- (dodecyloxy) pentadecanoic acid]

(Represented by the following structural formula 6)

[Structural Formula 6]

(Method 1) 32 g (0.80 mol) of 60% sodium hydride (NaH) was added to 1 L of toluene, 68.9 g (0.37 mol) of dodecanol was slowly added dropwise and the mixture was stirred at 50 캜 for 1 hour. 100 g (0.31 mol) of 15-bromopentadecanoic acid are mixed with 250 ml of toluene, and the mixture is slowly added dropwise, and the mixture is refluxed for 48 hours. When the reaction was completed, the reaction was quenched with water and the organic layer was extracted with ethyl acetate and recrystallized in n-hexane. The obtained solid was dried under reduced pressure to obtain 110.1 g of a white powder of 15- (dodecyloxy) pentadecanoic acid in a yield of 83.2%.

(Method 2) 100 g (0.31 mol) of 15-hydroxypentadecanoic acid is dissolved in 150 ml of THF and 150 ml of HMPA, and 32 g (0.80 mol) of 60% sodium hydride (NaH) is slowly added at a reaction temperature of 0 ° C or lower. After stirring for 1 hour, add 77.3g (0.31mol) of dodecylbromide in 50ml of THF and slowly add it. When the reaction is complete, the reaction is quenched with water, the THF is firstly blown off under reduced pressure, the organic layer extracted with ethyl acetate is washed three times with water, treated with anhydrous Na2SO4, filtered and the ethyl acetate is removed by distillation under reduced pressure. The resulting solid was recrystallized from n-hexane and dried under reduced pressure at 40 占 폚 to obtain a yield of 59.2% and a white powder of 78.3 g of 15- (dodecyloxy) pentadecanoic acid as a white powder.

1H NMR (400MHz, CDCl3): δ (ppm) 12.10 (s, 1H), 3.34 (t, 4H), 2.15 (t, 2H), 1.53-1.12 (m, 44H), 0.92 (t, 3H)

(9) Synthesis of 15- (octadecyloxy) pentadecanoic acid [15- (octadecyloxy) pentadecanoic acid]

(Represented by the following structural formula 7)

[Structural Formula 7]

(Method 1) 32 g (0.80 mol) of 60% sodium hydride (NaH) was added to 1 L of toluene, 100 g (0.37 mol) of octadecanol was slowly added dropwise and the mixture was stirred at 50 캜 for 1 hour. -Bromopentadecanoic acid (100 g, 0.31 mol) are mixed with 250 ml of toluene and slowly added dropwise, and the mixture is heated under reflux for 48 hours. When the reaction was completed, the reaction was quenched with water and the organic layer was extracted with ethyl acetate and recrystallized in n-hexane. The obtained solid was dried under reduced pressure to obtain 136.2 g of a white powder of 15- (octadecyloxy) pentadecanoic acid in a yield of 86.0%.

(Method 2) 100 g (0.31 mol) of 15-hydroxypentadecanoic acid is dissolved in 150 ml of THF and 150 ml of HMPA, and 32 g (0.80 mol) of 60% sodium hydride (NaH) is slowly added at a reaction temperature of 0 ° C or lower. After stirring for 1 hour, add 100 g (0.30 mol) of octadecylbromide in 50 ml of THF and slowly add it. When the reaction is complete, the reaction is quenched with water, the THF is firstly blown off under reduced pressure, the organic layer extracted with ethyl acetate is washed three times with water, treated with anhydrous Na2SO4, filtered and the ethyl acetate is removed by distillation under reduced pressure. The obtained solid was recrystallized from n-hexane and dried under reduced pressure at 40 캜 to obtain a yield of 68.4% and a white powder of 108.3 g of 15- (octadecyloxy) pentadecanoic acid as a white powder.

1H NMR (400MHz, CDCl3): δ (ppm) 11.94 (s, 1H), 3.34 (t, 4H), 2.15 (t, 2H), 1.53-1.12 (m, 56H), 0.89 (t, 3H)

(10) Synthesis of 15- (hexadecanyloxy) pentadecanoic acid [15- (Hexadecanyloxy) pentadecanoic acid]

(Represented by the following structural formula 8)

[Structural formula 8]

50 g (0.169 mol) of 15-hydroxypentadecanoic acid phthalocyanine salt are mixed with 500 ml of N, N-dimethylformamide (DMF), 85 ml of pyridine is added, and the internal temperature is lowered to 0 ° C. 20 ml (0.22 mol) of chloromethyl ethyl ether was added dropwise at 0 占 폚 for 30 minutes, and the mixture was stirred at the same temperature for 1 hour, followed by natural heating and stirring at room temperature for 8 hours or more. After completion of the reaction, 600 ml of water was added, and the mixture was extracted three times with 200 ml of ethyl acetate. The organic layer was washed with water several times, dried over anhydrous Na2SO4, filtered and concentrated. Ethyl acetate was recrystallized from n-hexane, dried, 48.1 g (yield: 90%) of a hydroxypentadecanoate white powder was obtained.

30 g (0.117 mol) of pamitic acid are mixed in 200 ml of dichloromethane and 12.2 m (0.14 mol) of oxalyl chloride are introduced. After stirring at room temperature for 4 hours and the reaction is complete, dichloromethane and excess oxalyl chloride are removed by distillation under reduced pressure, and the obtained hexadecanoyl chloride is diluted with 100 ml of dichloromethane and placed in a dropping funnel. To the reactor were added 35.2 g (0.111 mol) of ethoxymethyl 15-hydroxypentadecanoate, 250 ml of dichloromethane and 15.7 g of triethylamine, and the mixture was cooled to 0 deg. C with stirring. Hexadecanoyl chloride was added thereto at a temperature of 5 ° C or lower for about 1 hour, stirred at the same temperature for 1 hour, then heated to room temperature, and stirred for 12 hours. After completion of the reaction, the dichloromethane was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with water, and then dried with anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized with n-hexane to obtain ethoxymethyl 15- Hexadecanyloxy) pentadecanoate (yield: 72.2%).

(0.07 mol) of ethoxymethyl 15- (hexadecanyloxy) pentadecanoate were added to 200 ml of ethanol and 7.5 g (0.07 mol) of hydrochloric acid (35%) and the mixture was stirred at 40 占 폚 for 10 hours. When the reaction was completed, the reaction mixture was cooled to 10 ° C, 500 ml of water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized from n-hexane to obtain 15- Decanyloxy) pentadecanoic acid (yield: 93.0%).

1H NMR (400MHz, CDCl3): δ (ppm) 12.11 (s, 1H), 4.13 (t, 2H), 2.32-2.28 (tt, 4H), 1.83-1.22 (m, 50H), 0.88 (t, 3H)

(11) Synthesis of 15- (octadecanyloxy) pentadecanoic acid [15- (Octadecanyloxy) pentadecanoic acid]

(Represented by the following structural formula 9)

[Structural Formula 9]

30 g (0.105 mol) of stearic acid are mixed in 200 ml of dichloromethane and 11 ml of oxalyl chloride are introduced. After stirring at room temperature for 4 hours and the reaction is complete, dichloromethane and excess oxalyl chloride are removed by distillation under reduced pressure, octadecanoyl chloride is diluted with 100 ml of dichloromethane and placed in a dropping funnel. To the reactor was added 31.7 g (0.10 mol) of ethoxymethyl 15-hydroxypentadecanoate, 250 ml of dichloromethane and 14.2 g of triethylamine, and the mixture was cooled to 0 deg. C with stirring. The octadecanoyl chloride solution was added thereto at a reaction temperature of 5 占 폚 for 1 hour and stirred at the same temperature for 1 hour. The mixture is heated to room temperature and stirred for 12 hours. After completion of the reaction, the dichloromethane was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with water, and then dried with anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized with n-hexane to obtain ethoxymethyl 15- Octadecanyloxy) pentadecanoate (yield: 73.4%).

40 g (0.069 mol) of ethoxymethyl 15- (octadecanyloxy) pentadecanoate were added to 250 ml of ethanol and 7.5 g of hydrochloric acid (35%), and the mixture was stirred at 40 占 폚 for 10 hours. After completion of the reaction, the reaction mixture was cooled to 10 ° C, 500 ml of water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and dried over anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized from n-hexane to obtain 15- Decanyloxy) pentadecanoic acid (yield: 92.5%).

1H NMR (400MHz, CDCl3): δ (ppm) 12.12 (s, 1H), 4.15 (t, 2H), 2.31-2.29 (tt, 4H), 1.72-1.12 (m, 54H), 0.88 (t, 3H)

(12) Synthesis of 15- (9Z-hexadecenyloxy) pentadecanoic acid [15- (9Z-Hexadecenyloxy) pentadecanoic acid]

(Represented by the following structural formula 10)

[Structural Formula 10]

30 g (0.118 mol) of palmitoleic acid are mixed with 200 ml of dichloromethane and 12.3 ml of oxalyl chloride are introduced. After stirring at room temperature for 4 hours and the reaction is complete, dichloromethane and excess oxalyl chloride are removed by distillation under reduced pressure, and 9Z-hexadecenoyl chloride is diluted in 100 ml of dichloromethane and placed in a dropping funnel. To the reactor were added 35.5 g (0.112 mol) of ethoxymethyl 15-hydroxypentadecanoate, 250 ml of dichloromethane and 15.9 g of triethylamine, and the mixture was cooled to 0 DEG C while stirring. The solution of 9Z-hexadecenoic acid chloride was added thereto for about 1 hour while adjusting the temperature to 5 占 폚 or less, and the mixture was stirred at the same temperature for 1 hour. The mixture is heated to room temperature and stirred for 12 hours. After completion of the reaction, the dichloromethane was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with water, and then dried with anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized with n-hexane to obtain ethoxymethyl 15- (9S-hexadecenyloxy) pentadecanoate (yield: 75.0%).

40 g (0.072 mol) of ethoxymethyl 15- (9Z-hexadecenyloxy) pentadecanoate were added to 250 ml of ethanol and 7.5 g of hydrochloric acid (35%), and the mixture was stirred at 40 占 폚 for 10 hours. When the reaction was completed, the reaction mixture was cooled to 10 ° C, 500 ml of water was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was recrystallized from n-hexane to obtain 15- (Hexadecenyloxy) pentadecanoic acid (yield: 94.1%).

1H NMR (400MHz, CDCl3): δ (ppm) 12.17 (s, 1H), 5.43 (m, 2H), 4.13 (t, 2H), 2.30-2.28 (tt, 4H), 2.21-2.12 (m, 4H) , 1.82-1.22 (m, 42H), 0.89 (t, 3H)

(13) 15- (9Z- Octadecenyloxy ) Pentadecanoi  Synthesis of acid [15- (9Z-Octadecenyloxy) pentadecanoic acid]

(Represented by the following structural formula 11)

[Structural Formula 11]

30 g (0.106 mol) of oleic acid are mixed with 200 ml of dichloromethane and 11.1 ml of oxalyl chloride are introduced. After stirring at room temperature for 4 hours and the reaction is complete, dichloromethane and excess oxalyl chloride are removed by distillation under reduced pressure, and 9Z-octadecenoyl chloride is diluted in 100 ml of dichloromethane and placed in a dropping funnel. 32.0 g (0.101 mol) of ethoxymethyl 15-hydroxypentadecanoate, 250 ml of dichloromethane and 14.3 g of triethylamine were added to the reactor, and the mixture was cooled to 0 deg. C with stirring. The solution of 9Z-octadecenoic acid chloride was added thereto for about 1 hour while adjusting the temperature to 5 占 폚 or lower, and the mixture was stirred at the same temperature for 1 hour. The mixture is heated to room temperature and stirred for 12 hours. After completion of the reaction, the dichloromethane was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with water, and then dried with anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized with n-hexane to obtain ethoxymethyl 15- Octadecenyloxy) pentadecanoate (yield: 72.0%) was obtained.

(0.069 mol) of ethoxymethyl 15- (9Z-octadecenyloxy) pentadecanoate were added to 250 ml of ethanol and 7.2 g of hydrochloric acid (35%), and the mixture was stirred at 40 ° C for 10 hours. When the reaction was completed, the reaction mixture was cooled to 10 ° C, 500 ml of water was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was recrystallized from n-hexane to obtain 15- (Octadecenyloxy) pentadecanoic acid (yield: 91.2%).

1H NMR (400MHz, CDCl3): δ (ppm) 12.18 (s, 1H), 5.45 (m, 2H), 4.13 (t, 2H), 2.35-2.32 (tt, 4H), 2.20-2.17 (m, 4H) , 1.78-1.20 (m, 46H), 0.89 (t, 3H)

(14) 15- (9Z, 12Z- Octadecadienyloxy ) Pentadecanoi  Synthesis of acid [15- (9Z, 12Z-Octadecadienyloxy) pentadecanoic acid]

(Represented by Structural Formula 12 below)

[Structural Formula 12]

30 g (0.107 mol) of linoleic acid are mixed in 200 ml of dichloromethane and 11.2 ml of oxalyl chloride are introduced. After stirring at room temperature for 4 hours and the reaction is complete, dichloromethane and excess oxalyl chloride are removed by distillation under reduced pressure, and 9Z, 12Z-octadecadienyl chloride is diluted in 100 ml of dichloromethane and placed in a dropping funnel. To the reactor were added 32.2 g (0.102 mol) of ethoxymethyl 15-hydroxypentadecanoate, 250 ml of dichloromethane and 14.4 g of triethylamine, and the mixture was cooled to 0 deg. C with stirring. The solution of 9Z, 12Z-octadecadienyl acid chloride was added thereto at a temperature of 5 ° C or lower for about 1 hour, and the mixture was stirred at the same temperature for 1 hour. The mixture is heated to room temperature and stirred for 12 hours. After completion of the reaction, the dichloromethane was removed by distillation under reduced pressure. The residue was dissolved in ethyl acetate, washed twice with water, and then dried with anhydrous Na2SO4. Ethyl acetate was concentrated and recrystallized with n-hexane to obtain ethoxymethyl 15- 9Z, 12Z-octadecadienyloxy) pentadecanoate (yield: 73.9%).

(0.069 mol) of ethoxymethyl 15- (9Z, 12Z-octadecadienyloxy) pentadecanoate are added to 250 ml of ethanol and 7.2 g of hydrochloric acid (35%), and the mixture is stirred at 40 ° C for 10 hours. When the reaction was completed, the reaction mixture was cooled to 10 ° C, 500 ml of water was added, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous Na2SO4, filtered and concentrated. The residue was recrystallized from n-hexane to obtain 15- , 12Z-octadecadienyloxy) pentadecanoic acid (yield: 90.6%).

1H NMR (400MHz, CDCl3): δ (ppm) 12.10 (s, 1H), 5.41-5.45 (m, 4H), 4.15 (t, 2H), 2.65 (m, 2H), 2.36-2.34 (tt, 4H) , 2.24-2.22 (m, 4H), 1.78-1.20 (m, 40H), 0.88 (t, 3H)

(15) 15- ( Acetoxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( acetoxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by the following structural formula 13)

[Structural Formula 13]

30 g (0.1 mol) of 15- (acetoxy) pentadecanoic acid was dissolved in 300 ml of dichloromethane, and 21.0 g (0.208 mol) of triethylamine and 19.5 g (0.10 mol) of p- 31.7 g (0.1 mol) of phytosphingosine represented by the formula (3) was added thereto, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 55.1 g of a white powder of 15- (acetoxy) pentadecanoic acid 2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 4.32 (d, 1H), 4.15 (t, 1H), 4.12 (m, 3H), 3.76-3.24 (m, 6H), 2.23 (s, 3H), 2.13 (t, 2H), 1.60-1.25 (m, 50H), 0.89

(16) 15- (hydroxy) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( hydroxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by Structural Formula 14 below)

[Structural Formula 14]

40 g (0.067 mol) of 15- (acetoxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was placed in a reaction vessel and 500 ml of methanol and 10% And the mixture was refluxed for 4 hours. When the reaction is complete, the temperature is cooled to 25 ° C, the pH is adjusted to neutral, filtered, washed with water and dried to yield 31.8 g of white powder 15- (hydroxy) pentadecanoic acid (2,3 -Dihydro-1-hydroxymethyl-heptadecyl) amide. Figure 3 shows NMR data.

1H NMR (400MHz, CDCl3) :? (Ppm) 6.90 (d, IH), 4.18 (d, IH), 4.09 (t, 2H), 1.60-1.29 (m, 50H), 0.89 (t, 3H)

(17) 15- ( Pentyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( pentyloxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by Structural Formula 15 below)

[Structural Formula 15]

50 g (0.15 mol) of 15- (pentyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 30.4 g (0.30 mol) of triethylamine, 28.6 g (0.15 mol) 47.6 g (0.15 mol) of phytosphingosine represented by the formula (3) was added thereto, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 84.8 g of white powder of 15- (pentyloxy) pentadecanoic acid 2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 4.12 (m, 1H), 3.93-3.54 (m, 6H), 3.52 (tt, 4H), 2.26 (t, 2H), 1.75 -1.22 (m, 56H), 0.85 (m, 6H)

(18) 15- ( Heptyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( heptyloxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by Structural Formula 16 below)

[Structural Formula 16]

50 g (0.14 mol) of 15- (heptyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 28.3 g (0.28 mol) of triethylamine, 26.7 g (0.14 mol) 44.5 g (0.14 mol) of phytosphingosine represented by the formula (3) was added thereto, followed by reflux stirring for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 84.0 g of white powder of 15- (heptyloxy) pentadecanoic acid 2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.29 (d, 1H), 4.11 (m, 1H), 3.94-3.55 (m, 6H), 3.53 (tt, 4H), 2.31 (t, 2H), 1.75 -1.22 (m, 60H), 0.86 (m, 6H)

(19) 15- ( Nonyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( nonyloxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by Structural Formula 17 below)

[Structural Formula 17]

50 g (0.13 mol) of 15- (nonyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 26.3 g (0.26 mol) of triethylamine and 24.8 g (0.13 mol) of p- 41.3 g (0.13 mol) of phytosphingosine represented by the formula (3) was added thereto, followed by stirring under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 82.8 g of a white powder of 15.1 g (nonyloxy) pentadecanoic acid 2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained. The results of compound synthesis can be confirmed from the NMR data of FIG.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 4.10 (m, 1H), 3.92-3.55 (m, 6H), 3.53 (tt, 4H), 2.31 (t, 2H), 1.75 -1.22 (m, 64H), 0.85 (m, 6H)

(20) 15- ( Undecyox ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( undecyloxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by Structural Formula 18 below)

[Structural Formula 18]

50 g (0.12 mol) of 15- (undecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 24.3 g (0.24 mol) of triethylamine, 22.9 g (0.12 mol) of p- 38.1 g (0.12 mol) of phytosphingosine represented by the formula (3) was added, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 79.3 g of white powder 15- (undecyloxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): [ delta] (ppm) 6.32 (d, IH), 4.09 (m, IH), 3.96-3.55 -1.22 (m, 68H), 0.86 (m, 6H)

(21) 15- ( Dodecyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( dodecyloxy ) pentadecanoic  acid (2,3- dihydro -One- hidroxymethyl -heptadecyl) amide]

(Represented by the following structural formula 19)

[Structural Formula 19]

50 g (0.117 mol) of 15- (dodecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 23.7 g (0.234 mol) of triethylamine and 22.3 g (0.117 mol) of p- 37.1 g (0.117 mol) of phytosphingosine represented by the formula (3) was added, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 77.1 g of white powder of 15- (dodecyloxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.29 (d, 1H), 4.08 (m, 1H), 3.88-3.54 (m, 6H), 3.52 (tt, 4H), 2.31 (t, 2H), 1.75 -1.22 (m, 70H), 0.85 (m, 6H)

(22) 15- ( Octadecyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( octadecyloxy ) pentadecanoic  acid (2,3- dihydro -1-hydroxymethyl-heptadecyl) amide]

(Represented by Structural Formula 20 below)

[Structural Formula 20]

(0.10 mol) of 15- (octadecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , 31.8 g (0.10 mol) of phytosphingosine represented by the general formula (3), and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 72.9 g of a white powder of 15- (octadecyloxy) pentadecanoate Acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.28 (d, 1H), 4.07 (m, 1H), 3.90-3.54 (m, 6H), 3.51 (tt, 4H), 2.30 (t, 2H), 1.75 -1.22 (m, 82H), 0.87-0.85 (m, 6H)

(23) 15- ( Hexadecanyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( hexadecanyloxy ) pentadecanoic  acid (2,3- dihydro -1-hydroxymethyl-heptadecyl) amide]

(Represented by the following structural formula 21)

[Structural Formula 21]

49.7 g (0.10 mol) of 15- (hexadecanyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 31.8 g (0.10 mol) of phytosphingosine represented by the formula (3) were placed, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 72.9 g of a white powder of 15- (hexadecanyloxy) pentadecanoate Acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.32 (d, 1H), 4.16 (t, 2H), 4.07 (m, 1H), 3.90-3.50 (m, 6H), 2.30-2.20 (m, 4H) , 1.75-1.22 (m, 76H), 0.87-0.86 (m, 6H)

(24) Synthesis of 15- (octadecanyloxy) pentadecanoic acid (2,3-dihydro-1 (3-dihydro-1-hydroxymethyl-heptadecyl) - hydroxymethyl-heptadecyl) amide]

(Represented by the following structural formula 22)

[Structural Formula 22]

52.5 g (0.10 mol) of 15- (octadecanyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 31.8 g (0.10 mol) of phytosphingosine represented by the formula (3) were placed, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 75.9 g of white powder of 15- (octadecanyloxy) pentadecanoate Acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 4.15 (t, 2H), 4.08 (m, 1H), 3.90-3.51 (m, 6H), 2.30-2.20 (m, 4H) , 1.75-1.22 (m, 80H), 0.87-0.86 (m, 6H)

(25) Synthesis of 15- (9Z-hexadecenyloxy) pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) -dihydro-1-hydroxymethyl-heptadecyl) amide]

(Represented by the following structural formula 23)

[Structural Formula 23]

49.5 g (0.10 mol) of 15- (9Z-hexadecenyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g 0.10 mol), and 31.8 g (0.10 mol) of phytosphingosine represented by the formula (3) were placed, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 72.5 g of white powder of 15- (9Z-hexadecenyloxy) pentade (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3) :? (Ppm) 6.30 (m, 1H), 5.32 (m, 2H), 4.15 (M, 4H), 2.18-2.10 (m, 4H), 1.75-1.22 (m, 68H), 0.88-0.87

(26) 15- (9Z- Octadecenyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl -Heptadecyl) amide [15- (9Z- octadecenyloxy ) pentadecanoic  acid (2,3- dihydro -1-hydroxymethyl-heptadecyl) amide]

(Represented by Structural Formula 24 below)

[Structural Formula 24]

52.3 g (0.10 mol) of 15- (9Z-octadecenyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g 0.10 mol), and 31.8 g (0.10 mol) of phytosphingosine represented by the formula (3) were placed, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 73.8 g of white powder of 15- (9Z-octadecenyloxy) pentade (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.29 (d, 1H), 5.31 (m, 2H), 4.15 (t, 2H), 4.08 (m, 1H), 3.90-3.51 (m, 6H), 2.30 (M, 4H), 2.18-2.10 (m, 4H), 1.75-1.22 (m, 72H), 0.88-0.87

(27) 15- (9Z, 12Z- Octadecadienyloxy ) Pentadecanoi  Acid (2,3- Dihydro -One- Hydroxymethyl -Heptadecyl) amide [15- (9Z, 12Z- octadecadienyloxy ) pentadecanoic  acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide]

 [Structural Formula 25]

52.1 g (0.10 mol) of 15- (9Z, 12Z-octadecadienyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, to which 20.2 g (0.20 mol) of triethylamine and p-TsCl (0.10 mol) of phytosphingosine and 31.8 g (0.10 mol) of phytosphingosine represented by the formula (3) are placed in a flask, and the mixture is refluxed for 8 hours. When the reaction was complete, the temperature was lowered and the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to yield 74.9 g of white powder, 15- (9Z, 12Z-octadecadienyloxy ) Pentadecanoic acid (2,3-dihydro-1-hydroxymethyl-heptadecyl) amide was obtained. The results of compound synthesis can be confirmed from the NMR data of FIG.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 5.41-5.38 (m, 4H), 4.15 (t, 2H), 4.12 (t, 2H), 4.08 (m, 1H), 3.90 (M, 6H), 2.30-2.20 (m, 4H), 2.18-2.10 (m, 4H), 1.74-1.23

In the above scheme 3, the novel compounds 3-2, which are sphingosine derivatives, were prepared by the following method.

(23) 15- (acetoxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-ene-heptadecyl) 3-ene-heptadecyl) amide]

(Represented by Structural Formula 26 below)

[Structural Formula 26]

30.1 g (0.10 mol) of 15- (acetoxy) pentadecanoic acid was dissolved in 1.5 L of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , And 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added and stirred at reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 54.1 g of white powder of 15- (acetoxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): [ delta] (ppm) 6.35 (m, 2H), 5.63 (m, 2H), 4.52 (m, 2H), 2.31 (m, 2H), 2.23 (s, 3H)

(24) 15- (hydroxy) Pentadecanoi  The acid (2- Heathrow -One- Hydroxymethyl -3-en- Heptadecyl ) Amide [15- hydroxypentadecanoic  acid (2-hydro-1- hidroxymethyl -3- ene -heptadecyl) amide]

(Represented by the following structural formula 27)

[Structural Formula 27]

50 g (0.086 mol) of 15- (acetoxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide was placed in a reaction vessel, and 500 ml of methanol and 10 ml of 10% And the mixture was refluxed for 4 hours. When the reaction was completed, the temperature was cooled to 25 DEG C, the pH was adjusted to neutral, filtered, washed with water and dried to obtain 39.5 g of a white powder of 15- (hydroxy) pentadecanoic acid -1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3) :? (Ppm) 6.35 (m, 2H), 5.65 (m, 2H), 4.56 (m, 5H), 2.31 (m, 2H), 1.62-1.25 (m, 46H)

(25) 15- ( Pentyloxy ) Pentadecanoi  The acid (2- Heathrow -One- Hydroxymethyl -3-en- Heptadecyl ) Amide [15- ( pentyloxy ) pentadecanoic  acid (2-hydro-1- hidroxymethyl -3- ene -heptadecyl) amide]

(Represented by the following structural formula 28)

[Structural Formula 28]

32.9 g (0.10 mol) of 15- (pentyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- 30.0 g (0.10 mol) of sphingosine represented by the formula (4) was added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 56.2 g of white powder of 15- (pentyloxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3) :? (Ppm) 6.30 (m, 1H), 5.65 (m, 2H), 4.56 (t, 4H), 2.31 (m, 2H), 2.26 (t, 2H), 1.75-1.22 (m,

(26) Synthesis of 15- (heptyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-ene-heptadecyl) 3-ene-heptadecyl) amide]

(Represented by the following structural formula 29)

[Structural Formula 29]

35.7 g (0.10 mol) of 15- (heptyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- 30.0 g (0.10 mol) of sphingosine represented by the formula (4) was added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 57.6 g of white powder of 15- (heptyloxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.31 (d, 1H), 5.63 (m, 2H), 4.52 (m, 1H), 4.12 (m, 1H), 3.93-3.54 (m, 4H), 3.51 2H), 1.75-1.22 (m, 56H), 0.89 (m, 6H)

(27) Synthesis of 15- (nonyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-ene-heptadecyl) 3-ene-heptadecyl) amide]

(Represented by the following structural formula 30)

[Structural Formula 30]

38.5 g (0.10 mol) of 15- (nonyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine, 19.1 g (0.10 mol) of p- 30.0 g (0.10 mol) of sphingosine represented by the formula (4) was added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 60.6 g of white powder 15.0% (nonyloxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3) :? (Ppm) 6.32 (d, 1H), 5.65 (m, 2H), 4.50 2H), 1.75-1.21 (m, 60H), 0.88 (m, 6H)

(28) Synthesis of 15- (undecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) -3-ene-heptadecyl) amide]

(Represented by the following structural formula 31)

[Structural Formula 31]

(0.10 mol) of 15- (undecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , And 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added and stirred at reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 63.6 g of white powder of 91.6% yield, 15- (undecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.31 (d, 1H), 5.64 (m, 2H), 4.50 (m, 1H), 4.11 (m, 1H), 3.90-3.52 (m, 4H), 3.48 (m, 6H), 2.80 (m, 2H), 2.25 (t, 2H)

(29) Synthesis of 15- (dodecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl) thiophenecarboxylic acid (2-hydro-1-hydroxymethyl- -3-ene-heptadecyl) amide]

(Represented by the following structural formula 32)

[Structural Formula 32]

42.7 g (0.10 mol) of 15- (dodecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , And 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added and stirred at reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 65.4 g of white powder of 15- (dodecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 5.63 (m, 2H), 4.49 (m, 1H), 4.10 (m, 1H), 3.91-3.52 (m, 4H), 3.48 2H), 1.75-1.20 (m, 62H), 0.88 (m, 6H)

(30) A mixture of 15- (octadecyloxy) pentadecanoic acid (2-hydro-1- hydroxymethyl-3-ene-heptadecyl) amide]

(Represented by the following structural formula 33)

[Structural Formula 33]

(0.10 mol) of 15- (octadecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 73.9 g of white powder of 15- (octadecyloxy) pentadecanoic acid Acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.29 (d, 1H), 5.57 (m, 2H), 4.40 (m, 1H), 4.08 (m, 1H), 3.89-3.52 (m, 4H), 3.47 (m, 2H), 2.20 (t, 2H), 1.70-1.20 (m, 78H), 0.88

(31) Synthesis of 15- (hexadecanyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-ene-heptadecyl) hydroxymethyl-3-ene-heptadecyl) amide]

(Represented by Structural Formula 34 below)

[Structural Formula 34]

49.7 g (0.10 mol) of 15- (hexadecanyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 70.6 g of white powder 15- (hexadecanyloxy) pentadecanoate Acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.32 (d, 1H), 5.56 (m, 2H), 4.45 (m, 2H), 4.40 (m, 1H), 4.16 (t, 2H), 4.07 (m (M, 4H), 1.95-1.22 (m, 72H), 0.87-0.86 (m, 6H)

(32) To a solution of 15- (octadecanyloxy) pentadecanoic acid (2-hydro-1- (2-hydroxy-3-heptadecyl) hydroxymethyl-3-ene-heptadecyl) amide]

(Represented by Structural Formula 35 below)

[Structural Formula 35]

52.5 g (0.10 mol) of 15- (octadecanyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 72.6 g of white powder of 15- (octadecanyloxy) pentadecanoate Acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.32 (d, 1H), 5.57 (m, 2H), 4.43 (m, 2H), 4.35 (m, 1H), 4.16 (t, 2H), 4.07 (m (M, 4H), 1.95-1.22 (m, 76H), 0.87-0.86 (m, 6H)

(33) Synthesis of 15- (9Z-hexadecenyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) hydro-1-hydroxymethyl-3-ene-heptadecyl) amide]

(Represented by Structural Formula 36 below)

[Structural Formula 36]

49.5 g (0.10 mol) of 15- (9Z-hexadecenyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g 0.10 mol), and 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added and stirred at reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 70.5 g of white powder 15- (9Z-hexadecenyloxy) pentade (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.31 (d, 1H), 5.55 (m, 2H), 5.32 (m, 2H), 4.22 (m, 2H), 4.12 (m, 1H), 4.07 (m 4H), 2.18-2.10 (m, 6H), 1.95-1.22 (m, 64H), 0.88-0.86 (m, 6H)

(34) Synthesis of 15- (9Z-octadecenyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) hydro-1-hydroxymethyl-3-ene-heptadecyl) amide]

(Represented by the following structural formula 37)

[Structural Formula 37]

52.3 g (0.10 mol) of 15- (9Z-octadecenyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g 0.10 mol), and 30.0 g (0.10 mol) of sphingosine represented by the formula (4) were added and stirred at reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, and the organic layer was removed under reduced pressure and dried to obtain 74.1 g of white powder of 15- (9Z-octadecenyloxy) pentade (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.34 (d, 1H), 5.52 (m, 2H), 5.32 (m, 2H), 4.22 (m, 2H), 4.12 (m, 1H), 4.07 (m (M, 4H), 2.18-2.10 (m, 6H), 1.95-1.22 (m, 68H), 0.88-0.86

(35) Synthesis of 15- (9Z, 12Z-octadecadienyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) pentadecanoic acid (2-hydro-1-hydroxymethyl-3-ene-heptadecyl) amide]

(Represented by Structural Formula 38 below)

[Structural Formula 38]

52.1 g (0.10 mol) of 15- (9Z, 12Z-octadecadienyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, to which 20.2 g (0.20 mol) of triethylamine and p-TsCl , And 30.0 g (0.10 mol) of sphingosine represented by the general formula (4) were placed, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 74.9 g of white powder 15- (9Z, 12Z-octadecadienyloxy ) Pentadecanoic acid (2-hydro-1-hydroxymethyl-3-en-heptadecyl) amide.

1H NMR (400MHz, CDCl3) :? (Ppm) 6.35 (m, 2H), 5.53 (m, 2H), 5.31 (M, 6H), 1.95-1.22 (m, 68H), 0.88-0.86 (m, 6H)

In the above scheme 3, the novel compounds of 3-3, which are sphinganine derivatives, were prepared as follows.

(36) 15- ( Acetoxy ) Pentadecanoi  The acid (2- Heathrow -One- Hydroxymethyl - Heptadecyl ) Amide [15- ( acetoxy ) pentadecanoic  acid (2-hydro-1- hidroxymethyl - heptadecyl ) amide]

(Represented by Structural Formula 39 below)

[Structural Formula 39]

30.1 g (0.10 mol) of 15- (acetoxy) pentadecanoic acid was dissolved in 1.5 L of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , 30.2 g (0.10 mol) of sphinganine represented by the general formula (4), and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 53.9 g of white powder of 15- (acetoxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): [ delta] (ppm) 6.35 (d, IH), 4.32 (d, IH), 4.15 (m, 2H), 3.78-3.42 (s, 3H), 2.13 (t, 2H), 1.66-1.20 (m, 52H)

(37) Synthesis of 15- (hydroxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide [15-hydroxypentadecanoic acid

(Represented by Structural Formula 40 below)

[Structural Formula 40]

50 g (0.0856 mol) of 15- (acetoxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide was added to the reaction vessel and the mixture was adjusted to pH 10 with 500 ml of methanol and 10% Reflux stirring is carried out. When the reaction was completed, the temperature was lowered, the pH was adjusted to neutral and the work-up was carried out. The organic layer was removed under reduced pressure and dried to obtain 40.4 g of white powder 15- (hydroxy) pentadecanoic acid (2 -Hydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.70 (d, 1H), 4.14 (d, 1H), 4.12-3.40 (m, 5H), 2.13 (t, 2H), 1.66-1.20 (m, 52H) , 0.90 (t, 3 H)

(38) 15- (pentyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide [15- (pentyloxy) pentadecanoic acid] Synthesis of

(Represented by the following structural formula 41)

[Structural Formula 41]

32.9 g (0.10 mol) of 15- (pentyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- 30.2 g (0.10 mol) of sphinganine represented by the formula (4) was added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 56.4 g of white powder of 15- (pentyloxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.32 (d, 1H), 4.10 (m, 1H), 3.98-3.56 (m, 5H), 3.48 (tt, 4H), 2.22 (t, 2H), 1.75 -1.22 (m, 58H), 0.88 (m, 6H)

(39) A mixture of 15- (heptyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide [ Synthesis of

(Represented by the following structural formula 42)

[Structural Formula 42]

35.7 g (0.10 mol) of 15- (heptyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- 30.2 g (0.10 mol) of sphinganine represented by the formula (4) was added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 57.7 g of a white powder of 15- (heptyloxy) pentadecanoic acid 2-hydroxy-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.31 (d, 1H), 4.12 (m, 1H), 4.01-3.46 (m, 5H), 3.44 (tt, 4H), 2.21 (t, 2H), 1.72 -1.22 (m, 62H), 0.89 (m, 6H)

(40) 15- (Nonyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide [ Synthesis of

(Represented by the following structural formula 43)

[Structural Formula 43]

38.5 g (0.10 mol) of 15- (nonyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine, 19.1 g (0.10 mol) of p- 30.2 g (0.10 mol) of sphinganine represented by the formula (4) was added, and the mixture was stirred under reflux for 8 hours. When the reaction was complete, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 60.8 g of white powder 15- (nonyloxy) pentadecanoic acid (91.0% 2-hydroxy-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 4.11 (m, 1H), 4.00-3.47 (m, 5H), 3.42 (tt, 4H), 2.20 (t, 2H), 1.70 -1.22 (m, 66H), 0.89 (m, 6H)

(41) 15- (undecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide [15- (undecyloxy) pentadecanoic acid ] Synthesis of

(Represented by the following structural formula 44)

[Structural Formula 44]

(0.10 mol) of 15- (undecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , 30.2 g (0.10 mol) of sphinganine represented by the general formula (4), and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 63.8 g of a white powder of 91.6% yield of 15- (undecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.29 (d, 1H), 4.10 (m, 1H), 3.98-3.45 (m, 5H), 3.42 (tt, 4H), 2.20 (t, 2H), 1.70 -1.22 (m, 70H), 0.89 (m, 6H)

(42) Synthesis of 15- (dodecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide ] Synthesis of

(Represented by the following structural formula 45)

[Structural Formula 45]

42.7 g (0.10 mol) of 15- (dodecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- , 30.2 g (0.10 mol) of sphinganine represented by the general formula (4), and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 65.9 g of white powder of 15- (dodecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide.

1H NMR (400MHz, CDCl3): δ (ppm) 6.28 (d, 1H), 4.10 (m, 1H), 3.99-3.43 (m, 5H), 3.41 (tt, 4H), 2.20 (t, 2H), 1.68 -1.20 (m, 72H), 0.88 (m, 6H)

(43) 15- (octadecyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) 15- (octadecyloxy) pentadecanoic acid (2-hydro- amide]

(Represented by Structural Formula 46 below)

[Structural Formula 46]

(0.10 mol) of 15- (octadecyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 30.2 g (0.10 mol) of sphinganine represented by the formula (4) were added, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered and the dichloromethane layer was worked up with water. The organic layer was removed under reduced pressure and dried to obtain 74.2 g of white powder of 15- (octadecyloxy) pentadecanoic acid Acid (2-hydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.26 (d, 1H), 4.07 (m, 1H), 3.86-3.43 (m, 5H), 3.40 (tt, 4H), 2.15 (t, 2H), 1.65 -1.15 (m, 84H), 0.88 (m, 6H)

(44) 15- (hexadecanyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) 15- (hexadecanyloxy) pentadecanoic acid amide]

(Represented by the following structural formula 47)

[Structural Formula 47]

49.7 g (0.10 mol) of 15- (hexadecanyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 30.0 g (0.10 mol) of sphinganine represented by the formula (4) were added, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 71.2 g of a white powder of 15- (hexadecanyloxy) pentadecanoic acid Acid (2-hydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.31 (d, 1H), 4.26 (t, 2H), 4.07 (m, 1H), 3.86-3.43 (m, 4H), 2.21-2.15 (m, 4H) , 1.78-1.15 (m, 78H), 0.89 (m, 6H)

(45) 15- (octadecanyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) 15- (octadecanyloxy) pentadecanoic acid amide]

(Represented by the following structural formula 48)

[Structural Formula 48]

52.5 g (0.10 mol) of 15- (octadecanyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g (0.10 mol) of p- ), And 30.2 g (0.10 mol) of sphinganine represented by the formula (4) were added, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure, and dried to obtain 74.6 g of a white powder of 15- (octadecanyloxy) pentadecanoic acid Acid (2-hydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.30 (d, 1H), 4.24 (t, 2H), 4.08 (m, 1H), 3.88-3.41 (m, 4H), 2.20-2.15 (m, 4H) , 1.78-1.14 (m, 82H), 0.89 (m, 6H)

(46) Synthesis of 15- (9Z-hexadecenyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) hydroxymethyl-heptadecyl) amide]

(Represented by the following structural formula 49)

[Structural Formula 49]

49.5 g (0.10 mol) of 15- (9Z-hexadecenyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g 0.10 mol), and 30.2 g (0.10 mol) of sphinganine represented by the formula (4) were added, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered, the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 70.2 g of white powder 15- (9Z-hexadecenyloxy) pentade (2-hydroxy-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.29 (d, 1H), 5.42 (m, 2H), 4.24 (t, 2H), 4.08 (m, 1H), 3.98-3.41 (m, 4H), 2.20 (M, 4H), 2.15-2.10 (m, 4H), 1.78-1.14 (m, 70H), 0.89

(47) Synthesis of 15- (9Z-octadecenyloxy) pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) hydroxymethyl-heptadecyl) amide]

(Represented by Structural Formula 50 below)

[Structural Formula 50]

52.3 g (0.10 mol) of 15- (9Z-octadecenyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, and 20.2 g (0.20 mol) of triethylamine and 19.1 g 0.10 mol), and 30.2 g (0.10 mol) of sphinganine represented by the formula (4) were added, and the mixture was refluxed for 8 hours. When the reaction was completed, the temperature was lowered and the dichloromethane layer was worked up with water, and the organic layer was removed under reduced pressure and dried to obtain 74.6 g of white powder of 15- (9Z-octadecenyloxy) pentade (2-hydroxy-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.28 (d, 1H), 5.45 (m, 2H), 4.31 (t, 2H), 4.05 (m, 1H), 3.98-3.41 (m, 4H), 2.21 2H), 2.18-2.11 (m, 4H), 1.78-1.14 (m, 74H), 0.89 (m, 6H)

(48) A mixture of 15- (9Z, 12Z-octadecadienyloxy) pentadecanoic acid (2-hydroxymethyl-heptadecyl) -hydro-1-hydroxymethyl-heptadecyl) amide]

(Represented by Structural Formula 51 below)

[Structural Formula 51]

52.1 g (0.10 mol) of 15- (9Z, 12Z-octadecadienyloxy) pentadecanoic acid was dissolved in 750 ml of dichloromethane, to which 20.2 g (0.20 mol) of triethylamine and p-TsCl , And 30.2 g (0.10 mol) of sphinganine represented by the general formula (4) were placed in a flask, and the mixture was stirred under reflux for 8 hours. When the reaction was completed, the temperature was lowered and the dichloromethane layer was worked up with water, the organic layer was removed under reduced pressure and dried to obtain 74.6 g of white powder 15- (9Z, 12Z-octadecadienyloxy ) Pentadecanoic acid (2-hydro-1-hydroxymethyl-heptadecyl) amide was obtained.

1H NMR (400MHz, CDCl3): δ (ppm) 6.28 (d, 1H), 5.45-5.43 (m, 4H), 4.29 (t, 2H), 4.05 (m, 1H), 3.98-3.41 (m, 5H) , 2.20-2.18 (m, 4H), 2.14-2.12 (m, 4H), 1.75-1.10 (m, 68H), 0.89

(Formulation Example 1) Preparation of cream for evaluating skin efficacy

The composition of the cream for skin efficacy evaluation is as follows. The water phase was prepared by dissolving purified water, glycerin, and hydrogenated lecithin. Cera to C12 triglyceride was added with ceramide and compound of the structural formula of the present specification, followed by heating and dissolution to prepare an oily portion.

The oil phase was added to the upper part of the water and stirred to prepare a white cream.

Vehicle Comparison group 1 Test group 2 Test group 3 Test group 4 Test group 5 Purified water 88 87 87 87 87 87 glycerin 5 5 5 5 5 5 C8-C12 triglyceride 5 5 5 5 5 5 Hydrogenated lecithin 2 2 2 2 2 2 Ceramide NP 0 One 0 0 0 0 Compound 17 Compound 0 0 One 0 0 0 Compound 21 Compound 0 0 0 One 0 0 Compound 23 Compound 0 0 0 0 One 0 Compound 25 Compound 0 0 0 0 0 One

( Experimental Example  1) Restoration effect of skin barrier

Basal TEWL (Trans Epidermal Water Loss) was measured using a Tewameter (MPA580, Courage & Khazaka, Germany) after marking the test site on the forearm of the subjects (5).

Each experimental site was severely damaged by continuous stripping with 22mm D-squame tape (Cuderm corporation, USA) to damage the skin barrier so that TEWL was at least 40g / hr / m2. Measure TEWL immediately after damage (0 h). After the initial TEWL measurement, the same amount of each sample was applied to each test site, and TEWL was measured at 3, 6, 9, 12, and 24 hours to assess skin barrier recovery. During the test period, the temperature of the test site (23 ± 4 ° C) and humidity (40 ~ 60%) were kept constant.

The method of calculating the barrier recovery rate after tape-stripping induced acute skin barrier damage was as follows.

TEWL after barrier damage: TEWLa

TEWL for each hour: TEWLb

(1)

The results are shown in Fig. As shown in FIG. 6, it was confirmed that the recovered function of the damaged skin barrier was superior to that of the existing ceramide.

( Experimental Example  2) Skin moisturizing effect

After the test site was marked on the forearm of the subjects (5), the skin moisture was measured using a Corneometer (MPA580, Courage & Khazaka, Germany).

The moisture content of the skin was evaluated by measuring the corneometer value of each sample at the same time, 30 min, 1 hr and 2 hr. During the test period, the temperature of the test site (23 ± 4 ° C) and humidity (40 ~ 60%) were kept constant. The result is shown in Fig. As shown in Fig. 7, it was confirmed that the present composition has superior moisturizing effect to the existing ceramide.

Claims (11)

A pentadecanoic acid compound represented by the following formula (1), a salt thereof, an isomer thereof, a hydrate thereof or a solvate thereof:
[Chemical Formula 1]

In the above formulas,
R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, or C ₁ ~ C ₁₉ alkyl group or a C ₁ ~ C ₁₉ alkenyl giim of a.) A salt thereof, an isomer thereof, a hydrate thereof, or a solvate thereof;
(2)

In Formula 2,
R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,
R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group. A salt thereof, an isomer thereof, a hydrate thereof, or a solvate thereof;
(3)

In Formula 3,
R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,
R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group. A salt thereof, an isomer thereof, a hydrate thereof or a solvate thereof;
[Chemical Formula 4]

In Formula 4,
R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,
R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, Or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group. A process for producing a 15-pentadecanoic acid ether compound represented by the following formula (1)
[Chemical Formula 1]

(In the above formula,
R ₁ is selected from a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group.)
In the above manufacturing method,
Reacting a 15-hydroxypentadecanoic acid of formula (1) wherein R ₁ is H with a halogen compound to replace the hydroxy moiety of the 15-hydroxypentadecanoic acid with a halogen; And
And reacting the halogen-substituted pentadecanoic acid compound with an alkanol (R ₁ -OH) compound to obtain an ether compound. A process for producing a 15-pentadecanoic acid ether compound represented by the following formula (1)
[Chemical Formula 1]

(In the above formula,
R ₁ is selected from a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group.)
In the above manufacturing method,
Of 15-hydroxy-penta to Kano acid the alkyl halide (R ₁ -X) and the reaction of process for producing a 15-penta to Kano ripening acid ether compound containing ether to afford a compound R ₁ H in the formula (I). A process for producing a 15-acetoxypentadecanoic acid compound represented by the following formula (1)
[Chemical Formula 1]

(In the above formula,
R ₁ is an acetyl group.)
In the above manufacturing method,
Acetoxypentadecanoic acid comprising reacting 15-hydroxypentadecanoic acid of formula (1) wherein R ₁ is H with acetic acid to obtain 15-acetoxypentadecanoic acid, ≪ / RTI > A process for producing a 15-pentadecanoic acid ester compound represented by the following formula (1)
[Chemical Formula 1]

(In the above formula,
R ₁ is selected from a C ₁ to C ₂₀ acyl group (R-CO-), and R is H or a C ₁ to C ₁₉ alkyl group or a C ₁ to C ₁₉ alkenyl group.
In the above manufacturing method,
A first step of subjecting a fatty acid, which is the parent of R ₁ , to an acid halide reaction or an acid anhydride reaction; And
And a second step of reacting the fatty acid having been subjected to the first step with 15-hydroxypentadecanoic acid having R ₁ in H in the formula (1) to obtain an ester compound. 9. The method of claim 8,
The second step comprises:
Reacting ethoxymethyl 15 hydroxypentadecanoate with a fatty acid obtained in the first step, and then obtaining a 15-pentadecanoic acid ester compound of the formula (1) from the reaction product. As a method for producing ceramides,
The ceramide is any one of the following formulas (2) to (4)
(2)

(3)

[Chemical Formula 4]

(In the above formula (2), (3) or (4)
R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,
R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, or C ₁ ~ C ₁₉ alkyl group or a C ₁ ~ C ₁₉ alkenyl giim of a.),
Reacting 15- (acetoxy) pentadecanoic acid with phytosphingosine, sphingosine or sphinganine to obtain 15- (acetoxy) pentadecanoic acid ceramide; And
And obtaining 15 (hydroxy) pentadecanoic acid from the obtained 15- (acetoxy) pentadecanoic acid ceramide. As a method for producing ceramides,
The ceramide is any one of the following formulas (2) to (4)
(2)

(3)

[Chemical Formula 4]

(In the above formula (2), (3) or (4)
R ₂ to R ₃ are selected from hydrogen (H), C ₁ -C ₄ alkyl,
R ₁ is selected from hydrogen (H), an acetyl group, an acyl group of C ₁ to C ₂₀ (R-CO-), a C ₁ to C ₂₀ alkyl group and a C ₁ to C ₂₀ alkenyl group, or C ₁ ~ C ₁₉ alkyl group or a C ₁ ~ C ₁₉ alkenyl giim of a.),
A process for producing a ceramide comprising the step of reacting a 15-pentadecanoic acid ether compound of the formula (1) or a 15-pentadecanoic acid ester compound of the formula (1) with phytosphingosine, sphingosine or sphinganine to obtain a ceramide .

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