Pseudo-ceramide compound and preparation method therefor

Abstract

The present invention relates to a pseudo-ceramide compound and a preparation method therefor. According to the present invention, the pseudo-ceramide compound has a molecular structure and a function similar to those of a natural ceramide, can be readily synthesized, and has excellent solubility in an organic solvent and excellent stability, and thus the pseudo-ceramide compound can be used as an alternative to a natural ceramide. Therefore, the pseudo-ceramide compound of the present invention can be widely applied to a skin preparation for external use, a cosmetic composition, and the like for reinforcing and maintaining a skin barrier function.

Claims

1. A pseudo-ceramide compound of Chemical Formula 1: ##STR00018## wherein R.sub.1 and R.sub.2 are the same as or different from each other and are each independently a C9 to C23 saturated or unsaturated aliphatic chain.

2. The pseudo-ceramide compound according to claim 1, wherein R.sub.1 and R.sub.2 are the same as or different from each other and are each independently a C13 to C18 saturated or unsaturated aliphatic chain.

3. The pseudo-ceramide compound according to claim 1, wherein the pseudo-ceramide compound is selected from the group consisting of hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide, hexadecanoic acid (1,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide, hexadecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide, octadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide, octadecanoic acid (1,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide, octadecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide, tetradecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide, and tetradecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide.

4. A method for preparing a pseudo-ceramide compound, of Reaction Scheme 1 and comprises the steps of S1) introducing a protecting group into a compound of Chemical Formula 2 to prepare a compound of Chemical Formula 3; S2) reacting the compound of Chemical Formula 3 with a compound of Chemical Formula 4 to prepare a compound of Chemical Formula 5; S3) reacting the compound of Chemical Formula 5 with a compound of Chemical Formula 6 under a base catalyst to prepare a compound of Chemical Formula 7; and S4) removing the protecting group from the compound of Chemical Formula 7 to prepare a compound of Chemical Formula 1: ##STR00019## wherein X is selected from the group consisting of alkylidene, ethylidene, isopropylidene, cyclohexylidene, benzylidene and p-methoxybenzylidene, R.sub.1 and R.sub.2 are the same as or different from each other and are each independently a C9 to C23 saturated or unsaturated aliphatic chain, L.sub.1 is selected from the group consisting of Cl, Br, I, C1 to C4 acyloxy, and C1 to C4 alkoxy, and L.sub.2 is selected from the group consisting of Cl, Br, and I.

5. The method for preparing the pseudo-ceramide compound according to claim 4, wherein the R.sub.1 and R.sub.2 are the same as or different from each other and are each independently a C13 to C18 saturated or unsaturated aliphatic chain.

6. The method for preparing the pseudo-ceramide compound according to claim 4, wherein the compound of Chemical Formula 4 selected from the group consisting of is myristoyl chloride, palmitoyl chloride, and stearoyl chloride.

7. The method for preparing the pseudo-ceramide compound according to claim 4, wherein the compound of Chemical Formula 6 selected from the group consisting of is bromotetradecane, bromohexadecane, and bromooctadecane.

Description

EXAMPLES

Example 1: Preparation of hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide

(1) (1) Preparation of hexadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (Chemical Formula 16)

(2) ##STR00007##

(3) (5-amino-2,2-dimethyl-[1,3]dioxan-5-yl)-methanol (1.61 g), which was synthesized according to a method known in the literature (Helv. Chim. Acta 2003, 86, 2458-2470) using 2-amino-2-hydroxymethyl-propane-1,3-diol hydrochloride as starting material, was dissolved in dichloromethane (50 mL), and after adding triethylamine (1.7 mL), palmitoyl chloride (2.75 g) dissolved in dichloromethane (10 mL) while stirring at 0 C., was slowly added dropwise. The reaction solution was stirred at room temperature for 3 hours, and then washed with dilute hydrochloric acid solution and saturated sodium chloride solution. The organic solution layer was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and recrystallized from dichloromethane and hexane to obtain 2.5 g of a white solid.

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

(5) (2) Preparation of hexadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide (Chemical Formula 8)

(6) ##STR00008##

(7) The hexadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (2.0 g) prepared in the above (1) was dissolved in t-butanol (50 mL) and KOtBu (=potassium t-butoxide) (0.67 g) was slowly added thereto, followed by stirring at room temperature for 10 minutes. To this solution, bromohexadecane (1.53 g) was added, and further stirred for 12 hours. The reaction solution was neutralized with diluted hydrochloric acid to quench the reaction and extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and then concentrated under reduced pressure. The reaction mixture was dissolved in tetrahydrofuran (20 mL), a 1 M aqueous hydrochloric acid solution (4 mL) was added, and the mixture was stirred at room temperature for 12 hours. The reaction solution was diluted with dichloromethane and washed with a saturated sodium hydrogen carbonate solution. The organic solution layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The product was isolated using column chromatography to obtain 0.88 g of the desired compound as a white solid.

(8) .sup.1H NMR (300 MHz, CDCl.sub.3) 6.50 (brs, 1H), 4.34 (m, 2H), 3.71 3.45 (m, 8H), 2.55 (t, 2H, J=7.5 Hz), 1.801.20 (m, 54H), 0.88 (m, 6H).

Example 2: Preparation of hexadecanoic acid (1,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide (Chemical Formula 9)

(9) ##STR00009##

(10) 0.82 g of the desired compound was obtained using substantially the same method as in (2) of Example 1, except that bromotetradecane (1.39 g) was used instead of bromohexadecane (1.53 g).

(11) .sup.1H NMR (300 MHz, CDCl.sub.3) 6.49 (brs, 1H), 4.32 (m, 2H), 3.71 3.43 (m, 8H), 2.42 (m, 2H), 1.801.05 (m, 50H), 0.87 (m, 6H).

Example 3: Preparation of hexadecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide

(12) ##STR00010##

(13) 0.71 g of the desired compound was obtained using substantially the same method as in (2) of Example 1, except that bromooctadecane (1.67 g) was used instead of bromohexadecane (1.53 g).

(14) .sup.1H NMR (300 MHz, CDCl.sub.3) 6.50 (brs, 1H), 4.33 (m, 2H), 3.71 3.44 (m, 8H), 2.24 (t, 2H, J=7.5 Hz), 1.801.20 (m, 58H), 0.88 (m, 6H).

Example 4: Preparation of octadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide

(15) (1) Preparation of octadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (Chemical Formula 17)

(16) ##STR00011##

(17) 23 g of the desired compound as a white solid was obtained using substantially the same method as in (1) of Example 1, except that 12.8 g of (5-Amino-2,2-dimethyl-[1,3]dioxan-5-yl)-methanol was used as the starting material and stearoyl chloride (24.5 g) was used instead of palmitoyl chloride (2.75 g).

(18) .sup.1H NMR (300 MHz, CDCl.sub.3) 6.28 (brs, 1H), 5.17 (m, 1H), 3.83 (s, 4H), 3.64 (d, 2H, J=6.0 Hz), 2.28 (t, 2H, J=7.5 Hz),1.65 1.25 (m, 36H), 0.87 (t, 3H, J=6.6 Hz).

(19) (2) Preparation of octadecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide (Chemical Formula 11)

(20) ##STR00012##

(21) 1.8 g of the desired compound was obtained using substantially the same method as in (2) of Example 1, except that octadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (5.0 g) prepared in the above (1) was used instead of hexadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide, tetrahydrofuran (100 mL) was used instead of t-butanol, and KOtBu (1.73 g) and bromohexadecane (3.6 g) were used.

(22) .sup.1H NMR (500 MHz, CDCl.sub.3) 6.48 (brs, 1H), 3.683.43 (m, 8H), 2.31 (m, 2H), 2.22 (m, 2H), 1.701.20 (m, 58H), 0.85 (m, 6H).

Example 5: Preparation of octadecanoic acid (1,1-bis-hydroxymethyl-2-tetradecyloxy-ethyl)-amide (Chemical Formula 12)

(23) ##STR00013##

(24) 1.2 g of the desired compound was obtained using substantially the same method as (2) of Example 4, except that bromotetradecane (3.27 g) was used instead of bromohexadecane (3.6 g).

(25) .sup.1H NMR (500 MHz, CDCl.sub.3) 6.47 (brs, 1H), 4.32 (m, 2H), 3.68 3.31 (m, 8H), 2.22 (m, 2H), 1.611.10 (m, 54H), 0.84 (m, 6H).

Example 6: Preparation of octadecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide (Chemical Formula 13)

(26) ##STR00014##

(27) 1.1 g of the desired compound was obtained using substantially the same method as in (2) of Example 4, except that bromooctadecane (3.14 g) was used instead of bromohexadecane (3.6 g), and octadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (4.0 g) and KOtBu (1.38 g) were used.

(28) .sup.1H NMR (500 MHz, CDCl.sub.3) 6.50 (brs, 1H), 3.703.40 (m, 8H), 2.26 (m, 2H), 1.901.15 (m, 64H), 0.88 (m, 6H).

Example 7: Preparation of tetradecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide

(29) (1) Preparation of tetradecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (Chemical Formula 18)

(30) ##STR00015##

(31) 15 g of the desired compound as a white solid was obtained using substantially the same method as in (1) of Example 1, except that 12.8 g of (5-amino-2,2-dimethyl-[1,3]dioxan-5-yl)-methanol was used as the starting material and myristoyl chloride (19.5 g) was used instead of palmitoyl chloride (2.75 g).

(32) .sup.1H NMR (300 MHz, CDCl.sub.3) 6.31 (brs, 1H), 5.20 (m, 1H), 3.85 (s, 4H), 3.67 (s, 2H), 2.31 (t, 2H, J=7.2 Hz), 1.681.28 (m, 28H), 0.90 (t, 3H, J =6.6 Hz).

(33) (2) Preparation of tetradecanoic acid (2-hexadecyloxy-1,1-bis-hydroxymethyl-ethyl)-amide (Chemical Formula 14)

(34) ##STR00016##

(35) 1.2 g of the desired compound was obtained using substantially the same method as in (2) of Example 1, except that tetradecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide (3.71 g) as prepared in (1) above was used instead of hexadecanoic acid (5-hydroxymethyl-2,2-dimethyl-[1,3]dioxan-5-yl)-amide, tetrahydrofuran (100 mL) was used instead of t-butanol, and KOtBu (1.47 g) and bromohexadecane (2.74 g) were used.

(36) .sup.1H NMR (500 MHz, CDCl.sub.3) 6.47 (brs, 1H), 4.22 (m, 2H), 3.68 3.32 (m, 8H), 2.24 (m, 2H), 1.801.10 (m, 50H), 0.86 (m, 6H).

Example 8: Preparation of tetradecanoic acid (1,1-bis-hydroxymethyl-2-octadecyloxy-ethyl)-amide (Chemical Formula 15)

(37) ##STR00017##

(38) 1.05 g of the desired compound was obtained using substantially the same method as in (2) of Example 7, except that bromooctadecane (3.3 g) was used instead of bromohexadecane.

(39) .sup.1H NMR (500 MHz, CDCl.sub.3) 6.47 (brs, 1H), 4.31 (m, 2H), 3.683.43(m, 8H), 2.22 (t, 2H, J=7.0 Hz), 1.651.10 (m, 54H), 0.85 (m, 6H) .