WO2023063466A1 - Method for preparing ceramide compound - Google Patents
Method for preparing ceramide compound Download PDFInfo
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- WO2023063466A1 WO2023063466A1 PCT/KR2021/015416 KR2021015416W WO2023063466A1 WO 2023063466 A1 WO2023063466 A1 WO 2023063466A1 KR 2021015416 W KR2021015416 W KR 2021015416W WO 2023063466 A1 WO2023063466 A1 WO 2023063466A1
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- WIPO (PCT)
- Prior art keywords
- formula
- ceramide
- substituted
- unsubstituted
- phytosphingosine
- Prior art date
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- 229940106189 ceramide Drugs 0.000 title claims abstract description 52
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 title claims abstract description 46
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 title claims abstract description 46
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 title claims abstract description 46
- -1 ceramide compound Chemical class 0.000 title claims abstract description 24
- 238000000034 method Methods 0.000 title claims abstract description 20
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 claims abstract description 43
- 229940033329 phytosphingosine Drugs 0.000 claims abstract description 25
- 150000001875 compounds Chemical class 0.000 claims abstract description 24
- AERBNCYCJBRYDG-UHFFFAOYSA-N D-ribo-phytosphingosine Natural products CCCCCCCCCCCCCCC(O)C(O)C(N)CO AERBNCYCJBRYDG-UHFFFAOYSA-N 0.000 claims abstract description 20
- AERBNCYCJBRYDG-KSZLIROESA-N phytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@@H](N)CO AERBNCYCJBRYDG-KSZLIROESA-N 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 18
- 150000004702 methyl esters Chemical class 0.000 claims abstract description 18
- 239000000126 substance Substances 0.000 claims abstract description 15
- FVKFHMNJTHKMRX-UHFFFAOYSA-N 3,4,6,7,8,9-hexahydro-2H-pyrimido[1,2-a]pyrimidine Chemical compound C1CCN2CCCNC2=N1 FVKFHMNJTHKMRX-UHFFFAOYSA-N 0.000 claims description 15
- 125000003118 aryl group Chemical group 0.000 claims description 7
- OEBXWWBYZJNKRK-UHFFFAOYSA-N 1-methyl-2,3,4,6,7,8-hexahydropyrimido[1,2-a]pyrimidine Chemical compound C1CCN=C2N(C)CCCN21 OEBXWWBYZJNKRK-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000000217 alkyl group Chemical group 0.000 claims description 6
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 4
- SGUVLZREKBPKCE-UHFFFAOYSA-N 1,5-diazabicyclo[4.3.0]-non-5-ene Chemical compound C1CCN=C2CCCN21 SGUVLZREKBPKCE-UHFFFAOYSA-N 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 125000001072 heteroaryl group Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 10
- 230000015572 biosynthetic process Effects 0.000 abstract description 7
- 238000003786 synthesis reaction Methods 0.000 abstract description 7
- 230000002194 synthesizing effect Effects 0.000 abstract description 7
- 239000007858 starting material Substances 0.000 abstract description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 23
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- KBHSAMYHDBBRKS-QTJGBDASSA-N 2-hydroxy-n-[(2s,3s,4r)-1,3,4-trihydroxyoctadecan-2-yl]benzamide Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@H](CO)NC(=O)C1=CC=CC=C1O KBHSAMYHDBBRKS-QTJGBDASSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 7
- ATGQXSBKTQANOH-UWVGARPKSA-N N-oleoylphytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@H](CO)NC(=O)CCCCCCC\C=C/CCCCCCCC ATGQXSBKTQANOH-UWVGARPKSA-N 0.000 description 6
- 150000001783 ceramides Chemical class 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 5
- 210000003491 skin Anatomy 0.000 description 5
- 210000000434 stratum corneum Anatomy 0.000 description 5
- VJVMYHSATVCCRM-GHKJEYBUSA-N (2S,3S,4R)-2-[[(Z)-octadec-9-enyl]amino]octadecane-1,3,4-triol Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@H](CO)NCCCCCCCC\C=C/CCCCCCCC VJVMYHSATVCCRM-GHKJEYBUSA-N 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical group COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- 230000008901 benefit Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000011259 mixed solution Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- FLIACVVOZYBSBS-UHFFFAOYSA-N Methyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC FLIACVVOZYBSBS-UHFFFAOYSA-N 0.000 description 2
- HPEUJPJOZXNMSJ-UHFFFAOYSA-N Methyl stearate Chemical group CCCCCCCCCCCCCCCCCC(=O)OC HPEUJPJOZXNMSJ-UHFFFAOYSA-N 0.000 description 2
- NGPJDSJKORHGMX-LXQNXJGFSA-N N-dodecanoylphytosphingosine Chemical compound CCCCCCCCCCCCCC[C@@H](O)[C@@H](O)[C@H](CO)NC(=O)CCCCCCCCCCC NGPJDSJKORHGMX-LXQNXJGFSA-N 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- DIBHLCJAJIKHGB-UHFFFAOYSA-N dec-5-ene Chemical compound [CH2]CCCC=CCCCC DIBHLCJAJIKHGB-UHFFFAOYSA-N 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- QYDYPVFESGNLHU-UHFFFAOYSA-N elaidic acid methyl ester Natural products CCCCCCCCC=CCCCCCCCC(=O)OC QYDYPVFESGNLHU-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- UQDUPQYQJKYHQI-UHFFFAOYSA-N methyl laurate Chemical compound CCCCCCCCCCCC(=O)OC UQDUPQYQJKYHQI-UHFFFAOYSA-N 0.000 description 2
- QYDYPVFESGNLHU-KHPPLWFESA-N methyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC QYDYPVFESGNLHU-KHPPLWFESA-N 0.000 description 2
- 229940073769 methyl oleate Drugs 0.000 description 2
- 229960001047 methyl salicylate Drugs 0.000 description 2
- 230000003020 moisturizing effect Effects 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229940077859 salicyloyl phytosphingosine Drugs 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
- ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- IVBULNXGVIHEKN-MVIDNBQJSA-N N-hexadecanoylphytosphingosine Chemical compound CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)[C@H](O)CCCCCCCCCCCCCC IVBULNXGVIHEKN-MVIDNBQJSA-N 0.000 description 1
- IEZRNEGTKRQRFV-LFBNJJMOSA-N N-octadecanoyl-4-hydroxysphinganine Chemical compound CCCCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)[C@H](O)CCCCCCCCCCCCCC IEZRNEGTKRQRFV-LFBNJJMOSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 125000005035 acylthio group Chemical group 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 125000000852 azido group Chemical group *N=[N+]=[N-] 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- BGRWYRAHAFMIBJ-UHFFFAOYSA-N diisopropylcarbodiimide Natural products CC(C)NC(=O)NC(C)C BGRWYRAHAFMIBJ-UHFFFAOYSA-N 0.000 description 1
- CAMHHLOGFDZBBG-UHFFFAOYSA-N epoxidized methyl oleate Natural products CCCCCCCCC1OC1CCCCCCCC(=O)OC CAMHHLOGFDZBBG-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 235000021588 free fatty acids Nutrition 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 230000003278 mimic effect Effects 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 230000008591 skin barrier function Effects 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C235/08—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/26—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being saturated and containing rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
- C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
- C07C235/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and unsaturated
Definitions
- the present invention relates to a method for preparing a ceramide compound.
- Ceramide is a component that occupies a large portion of lipids between keratinocytes constituting the stratum corneum of the skin, and functions to suppress moisture evaporation and maintain the structure of the stratum corneum.
- This stratum corneum acts as a barrier to protect harmful substances or microorganisms from the external environment from penetrating into the skin tissue.
- Lipids between keratinocytes are composed of ceramide, cholesterol, free fatty acids, etc. It is known to play a central role in barrier function. It is known that when the content of ceramide in the stratum corneum is reduced, water evaporation increases and various skin diseases are aggravated.
- natural ceramide was synthesized by refluxing stirring of fatty acid and phytosphingosine in an organic solvent under an acid catalyst, and was obtained in a low yield of about 30%.
- activated ester intermediates are prepared using fatty acids, 1-hydroxybenzotriazol, and diisopropyl carbodiimide under a nitrogen atmosphere, and phytosphingosine Natural ceramides were prepared by combining.
- the yield of natural ceramide is low, and expensive raw materials are used in an amount of 1 equivalent or more compared to phytosphingosine.
- the present inventors of the present invention researched and developed a method for synthesizing natural ceramide without using a purification method using chromatography, and when using a cyclic amine base-based catalyst, high yield even under relatively mild conditions
- the present invention was completed by finding that ceramide can be synthesized.
- the present invention specifically aims to provide a method for synthesizing ceramide by reacting phytosphingosine as a starting material with a methyl ester-based compound represented by Formula 2 in the presence of a cyclic amine base-based catalyst.
- the present invention provides a method for preparing ceramide represented by Chemical Formula 1 by reacting phytosphingosine with a methyl ester-based compound represented by Chemical Formula 2 in the presence of a cyclic amine base-based catalyst. .
- ceramide in the method for preparing ceramide of the present invention, can be synthesized in high yield even under relatively mild conditions by reacting phytosphingosine as a starting material with a methyl ester-based compound represented by Formula 2 in the presence of a cyclic amine base-based catalyst. .
- Ceramides synthesized in this way can be helpful for skin health, such as strengthening the skin barrier and moisturizing effect when applied to cosmetics.
- Effects of the present invention are not limited to the effects mentioned above, and various effects may be included within a range apparent to those skilled in the art from the contents to be described below.
- Figure 1 shows the 1 H-NMR results of N-oleyl-phytosphingosine (ceramide NP) synthesized in Example 1.
- Figure 2 shows the 1 H-NMR results of N-salicyloyl-phytosphingosine synthesized in Example 2.
- Figure 3 shows the 1 H-NMR results of N-oleyl-phytosphingosine (ceramide NP) synthesized in Comparative Example 1.
- Figure 4 shows the 1 H-NMR results of N-salicyloyl-phytosphingosine synthesized by Comparative Example 2.
- the present invention provides a method for preparing ceramide represented by Chemical Formula 1 by reacting phytosphingosine with a methyl ester-based compound represented by Chemical Formula 2 in the presence of a cyclic amine base-based catalyst.
- R is a substituted or unsubstituted C 8 to C 25 alkyl, a substituted or unsubstituted C 8 to C 25 alkenyl, a substituted or unsubstituted C 8 to C 25 alkynyl, a substituted or unsubstituted C 6 to C 12 aryl, or substituted or unsubstituted C 6 to C 12 heteroaryl.
- the term "phytosphingosine” is a compound having the following structure and is used as a starting material for synthesizing ceramide.
- substituted means that one or more hydrogen atoms are replaced with an atom other than hydrogen, that is, a substituent.
- substituents include, but are not limited to, halogen, nitro, amino, azido, oxo, hydroxyl, thiol, carboxy, carboxy ester, carboxamide, alkylamino, alkyldithio, alkylthio, alkoxy, acylamido, acyl It may be oxy or acylthio, but is not limited thereto.
- aryl refers to an aromatic ring compound having 6 to 12 carbon atoms, and specifically may be phenyl, naphthyl, or anthracenyl, but is not limited thereto.
- cyclic amine base-based catalyst is in the form of a bulky, fused ring, and includes at least one nitrogen atom (N) to serve as a base catalyst.
- cyclic amine base-based catalysts include 1,8-diazabicyclo[5,4,0]undec-7-ene; DBU ⁇ , 1,5-Diazabicyclo[4,3,0]non-5-ene; DBN ⁇ , 1,5,7-Triazabicyclo[4,4,0]dec-5-ene ⁇ 1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD ⁇ and 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene ⁇ 1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD ⁇ may be any one or more selected from the group consisting of, preferably 1,5,7-triazabicyclo[4,4,0]dec-5-ene ⁇ 1,5,7-Triaza
- the cyclic amine base-based catalyst combines with an ester compound during ceramide synthesis to generate an activated intermediate and converts it to ceramide, so that reaction by-products are minimized in ceramide synthesis and relatively mild reaction conditions It has the advantage of being able to generate ceramide.
- R is substituted or unsubstituted C 8 to C 25 alkyl, substituted or unsubstituted C 8 to C 25 alkenyl, or substituted or unsubstituted C 6 to C 12 aryl It may be any one of, but is not limited thereto.
- R is substituted or unsubstituted C 8 to C 17 alkyl, substituted or unsubstituted C 8 to C 17 alkenyl, or substituted or unsubstituted C 6 to C 8 aryl It may be any one of, specifically R is , , , or It may be, but is not limited thereto. (as shown in the R substituent above means the part to be joined.)
- the methyl ester-based compound represented by Chemical Formula 2 may be any one or more of the compounds represented by Chemical Formulas 2-1 to 2-5 below, but is not limited thereto.
- the methyl ester-based compound represented by Chemical Formula 2-1 is methyl laurate
- the methyl ester-based compound represented by Chemical Formula 2-2 is methyl palmitate
- Chemical Formula 2-3 The methyl ester-based compound represented by is methyl stearate
- the methyl ester-based compound represented by Formula 2-4 is methyl oleate
- the methyl ester-based compound represented by Formula 2-5 is It is methyl salicylate.
- the method for preparing ceramide may be performed at 40 to 80 ° C. for 16 to 32 hours, but is not limited thereto.
- the temperature range as described above is a mild condition, and when using a cyclic amine base-based catalyst, there is an advantage in synthesizing ceramide with a high yield even if the reaction temperature is progressed under mild conditions.
- the ceramide represented by Chemical Formula 1 may be any one or more of the compounds represented by Chemical Formulas 1-1 to 1-5 below, but is not limited thereto.
- the ceramide represented by Formula 1-1 is N-Lauroyl Phytosphingosine
- the ceramide represented by Formula 1-2 is N-palmitoyl-phytosphingosine (N-Lauroyl Phytosphingosine).
- ceramide represented by Formula 1-3 is N-Stearoyl-phytosphingosine
- ceramide represented by Formula 1-4 is N-oleyl-phytosine.
- It is phingosine (N-Oleayl-phytosphingosine, ceramide NP)
- the ceramide represented by Formula 1-5 is N-salicyloyl-phytosphingosine.
- phytosphingosine and the methyl ester-based compound represented by Formula 2 may be reacted in a weight ratio of 1: 0.5 to 1.5, specifically 1: 0.7 to 1.25. It is not limited.
- the cyclic amine base-based catalyst may be added in an amount of 3.5 to 10% by weight based on the total sum of phytosphingosine and the methyl ester-based compound represented by Formula 2, specifically 5 to 8% by weight % can be added, but is not limited thereto.
- the method may be carried out under dichloromethane solvent or solventless conditions, but is not limited thereto.
- the ceramide synthesized according to the present invention is applied to the skin when applied to cosmetics, and effects such as moisturizing power, elasticity, and wrinkle whitening can be expected.
- N-oleyl-phytosphingosine N- Oleayl-phytosphingosine, ceramide NP was obtained (30 g, yield: 85%).
- N-salicyloyl-phytosphingosine N-salicyloyl-phytosphingosine, an example of ceramide. Salicyloyl-phytosphingosine was obtained (4 g, yield: 15%).
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Disclosed is a method for preparing a ceramide compound. Specifically, provided is a method for synthesizing ceramide by reaction of phytosphingosine and a methyl ester-based compound represented by chemical formula 2, as starting materials, in the presence of a cyclic amine base-based catalyst. The use of the cyclic amine base-based catalyst enables the synthesis of ceramide at high yield even under relatively mild conditions.
Description
본 발명은 세라마이드 화합물의 제조방법에 관한 것이다.The present invention relates to a method for preparing a ceramide compound.
세라마이드는 피부 각질층을 구성하는 각질세포간 지질의 많은 부분을 차지하는 구성성분으로서 수분증발을 억제하고 각질층의 구조를 유지하는 기능을 한다. 이러한 각질층은 외부 환경으로부터의 유해물이나 미생물들이 피부의 조직으로 침투하지 않도록 보호하는 방어막 역할을 하며 각질세포간 지질은 세라마이드, 콜레스테롤, 유리 지방산 등으로 이루어지고, 이중 세라마이드는 주성분으로서 각질층의 수분 유지와 장벽기능에 중심적 역할을 하는 것으로 알려져 있다. 각질층에서 세라마이드의 함량이 감소하게 되면, 수분증발이 증가하고 다양한 피부질환이 악화되는 것으로 알려져 있다.Ceramide is a component that occupies a large portion of lipids between keratinocytes constituting the stratum corneum of the skin, and functions to suppress moisture evaporation and maintain the structure of the stratum corneum. This stratum corneum acts as a barrier to protect harmful substances or microorganisms from the external environment from penetrating into the skin tissue. Lipids between keratinocytes are composed of ceramide, cholesterol, free fatty acids, etc. It is known to play a central role in barrier function. It is known that when the content of ceramide in the stratum corneum is reduced, water evaporation increases and various skin diseases are aggravated.
또한, 피부의 노화가 진행되거나 외적인 자극에 의해 각질층 내의 세라마이드 함량이 감소하면, 외부에서 세라마이드를 보충하여 피부를 정상상태로 회복시킬 수 있는 것으로 알려져 있다.In addition, it is known that when the aging of the skin progresses or the ceramide content in the stratum corneum decreases due to external stimulation, the skin can be restored to a normal state by replenishing ceramide from the outside.
따라서 천연으로부터 세라마이드를 얻기 위하여, 세라마이드를 함유하는 다양한 동식물에 대한 연구가 진행되었다. Therefore, in order to obtain ceramide from nature, studies on various animals and plants containing ceramide have been conducted.
종래에는 산 촉매 하에서 지방산과 피토스핑고신(Phytosphingosine)을 유기 용매에서 환류 교반하여 천연 세라마이드를 합성하였으며, 약 30% 수준의 낮은 수율로 수득하였다.Conventionally, natural ceramide was synthesized by refluxing stirring of fatty acid and phytosphingosine in an organic solvent under an acid catalyst, and was obtained in a low yield of about 30%.
또한, 다른 방법으로는 질소분위기 하에서 지방산과 1-히드록시벤조트리아졸 (1-hydroxybenzotriazol), 디이소프로필 카보디아미드(diisopropyl carbodiimide)를 사용하여 활성화된 에스테르 중간체를 만든 후 피토스핑고신과의 결합으로 천연 세라마이드를 제조하였다.In addition, as another method, activated ester intermediates are prepared using fatty acids, 1-hydroxybenzotriazol, and diisopropyl carbodiimide under a nitrogen atmosphere, and phytosphingosine Natural ceramides were prepared by combining.
상기와 같은 반응들의 경우 천연 세라마이드의 수율이 낮으며, 고가의 원료가 피토스핑고신 대비 1 당량 이상으로 사용되는 문제점이 있다.In the case of the above reactions, the yield of natural ceramide is low, and expensive raw materials are used in an amount of 1 equivalent or more compared to phytosphingosine.
이에 따라, 천연 세라마이드의 단점을 보완하고 상용화가 가능한 천연 유래의 세라마이드를 모방하고, 또한 보다 개선된 물성과 성질을 갖으며, 대량생산이 가능한 유사 세라마이드에 대한 연구가 진행되고 있다.Accordingly, research is being conducted on similar ceramides that compensate for the disadvantages of natural ceramides, mimic commercially available natural ceramides, have more improved physical properties and properties, and can be mass-produced.
하지만, 크로마토그래피를 사용한 정제를 해야 하므로 생성 수율이 매우 낮은 문제가 있다.However, there is a problem in that the production yield is very low because purification using chromatography must be performed.
따라서, 경제적인 방법으로 천연 세라마이드를 합성할 수 있는 방법에 대한 연구 및 개발이 필요한 상황이다.Therefore, it is necessary to research and develop a method for synthesizing natural ceramide in an economical way.
이에, 본 발명의 본 발명자들은 크로마토그래피를 사용한 정제방법을 사용하지 않으면서도 천연 세라마이드를 합성할 수 있는 방법에 대해 연구 개발하던 중, 고리형 아민 염기계열 촉매를 사용할 경우 비교적 온화한 조건에서도 고수율로 세라마이드를 합성할 수 있음을 밝혀내어 본 발명을 완성하였다.Accordingly, the present inventors of the present invention researched and developed a method for synthesizing natural ceramide without using a purification method using chromatography, and when using a cyclic amine base-based catalyst, high yield even under relatively mild conditions The present invention was completed by finding that ceramide can be synthesized.
따라서, 본 발명은 구체적으로 고리형 아민 염기계열 촉매 존재 하에 출발물질로 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 반응시켜 세라마이드를 합성하는 방법을 제공하는 것을 구체적인 해결과제로 한다.Accordingly, the present invention specifically aims to provide a method for synthesizing ceramide by reacting phytosphingosine as a starting material with a methyl ester-based compound represented by Formula 2 in the presence of a cyclic amine base-based catalyst.
상기한 목적을 달성하기 위하여, 본 발명은 고리형 아민 염기계열 촉매 존재 하에 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 반응시켜 화학식 1로 표시되는 세라마이드를 제조하는 방법을 제공하는 것이다. In order to achieve the above object, the present invention provides a method for preparing ceramide represented by Chemical Formula 1 by reacting phytosphingosine with a methyl ester-based compound represented by Chemical Formula 2 in the presence of a cyclic amine base-based catalyst. .
본 발명의 세라마이드를 제조하는 방법은 고리형 아민 염기계열 촉매 존재 하에 출발물질로 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 반응시킴으로써 비교적 온화한 조건에서도 고수율로 세라마이드를 합성할 수 있다.In the method for preparing ceramide of the present invention, ceramide can be synthesized in high yield even under relatively mild conditions by reacting phytosphingosine as a starting material with a methyl ester-based compound represented by Formula 2 in the presence of a cyclic amine base-based catalyst. .
이렇게 합성된 세라마이드는 화장품 분야에 적용 시 피부장벽 강화, 보습 효과 등 피부 건강에 도움이 될 수 있다.Ceramides synthesized in this way can be helpful for skin health, such as strengthening the skin barrier and moisturizing effect when applied to cosmetics.
본 발명의 효과는 이상에서 언급한 효과들로 제한되지 않으며, 이하에서 설명할 내용으로부터 통상의 기술자에게 자명한 범위 내에서 다양한 효과들이 포함될 수 있다.Effects of the present invention are not limited to the effects mentioned above, and various effects may be included within a range apparent to those skilled in the art from the contents to be described below.
도 1은 실시예 1에 의해 합성된 N-올레일-피토스핑고신(세라마이드 NP)의 1H-NMR 결과를 나타낸 것이다.Figure 1 shows the 1 H-NMR results of N-oleyl-phytosphingosine (ceramide NP) synthesized in Example 1.
도 2는 실시예 2에 의해 합성된 N-살리실로일-피토스핑고신의 1H-NMR 결과를 나타낸 것이다.Figure 2 shows the 1 H-NMR results of N-salicyloyl-phytosphingosine synthesized in Example 2.
도 3은 비교예 1에 의해 합성된 N-올레일-피토스핑고신(세라마이드 NP)의 1H-NMR 결과를 나타낸 것이다.Figure 3 shows the 1 H-NMR results of N-oleyl-phytosphingosine (ceramide NP) synthesized in Comparative Example 1.
도 4는 비교예 2에 의해 합성된 N-살리실로일-피토스핑고신의 1H-NMR 결과를 나타낸 것이다.Figure 4 shows the 1 H-NMR results of N-salicyloyl-phytosphingosine synthesized by Comparative Example 2.
이하 본 명세서에 대하여 더욱 상세히 설명한다.Hereinafter, the present specification will be described in more detail.
이를 구체적으로 설명하면 다음과 같다. 한편, 본 발명에서 개시된 각각의 설명 및 실시형태는 각각에 대한 다른 설명 및 실시형태에도 적용될 수 있다. 즉, 본 발명에 개시된 다양한 요소들의 모든 조합이 본 발명의 범주에 속한다. 또한, 하기에 기술된 구체적인 서술에 의하여 본 발명의 범주가 제한된다고 볼 수 없다.A detailed description of this is as follows. Meanwhile, each description and embodiment disclosed in the present invention may also be applied to other descriptions and embodiments for each. That is, all combinations of the various elements disclosed herein fall within the scope of the present invention. In addition, it cannot be seen that the scope of the present invention is limited by the specific descriptions described below.
본 명세서에서 사용되는 「포함하는」과 같은 표현은, 해당 표현이 포함되는 문구 또는 문장에서 특별히 다르게 언급되지 않는 한, 다른 실시예를 포함할 가능성을 내포하는 개방형 용어(open-ended terms)로 이해되어야 한다.Expressions such as “comprising” used in this specification are understood as open-ended terms that include the possibility of including other embodiments, unless specifically stated otherwise in a phrase or sentence in which the expression is included. It should be.
본 발명의 설명 및 청구범위에서 사용된 용어나 단어는, 통상적이거나 사전적인 의미로 한정해서 해석되어서는 아니되며, 발명자는 그 자신의 발명을 가장 최선을 방법으로 설명하기 위해 용어의 개념을 적절하게 정의할 수 있다는 원칙에 입각하여, 본 발명의 기술적 사상에 부합하는 의미와 개념으로 해석되어야만 한다.The terms or words used in the description and claims of the present invention should not be construed as being limited to ordinary or dictionary meanings, and the inventors use the concept of terms appropriately in order to explain their invention in the best way. Based on the principle that it can be defined, it should be interpreted as meaning and concept consistent with the technical spirit of the present invention.
세라마이드의 제조방법Manufacturing method of ceramide
본 발명은 고리형 아민 염기계열 촉매 존재 하에 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 반응시켜 화학식 1로 표시되는 세라마이드를 제조하는 방법을 제공한다.The present invention provides a method for preparing ceramide represented by Chemical Formula 1 by reacting phytosphingosine with a methyl ester-based compound represented by Chemical Formula 2 in the presence of a cyclic amine base-based catalyst.
[화학식 1][Formula 1]
[화학식 2][Formula 2]
상기 화학식 1 및 2에서,In Formulas 1 and 2,
R은 치환 또는 비치환된 C8 내지 C25 알킬, 치환 또는 비치환된 C8 내지 C25 알케닐, 치환 또는 비치환된 C8 내지 C25 알키닐, 치환 또는 비치환된 C6 내지 C12 아릴, 또는 치환 또는 비치환된 C6 내지 C12 헤테로아릴임.R is a substituted or unsubstituted C 8 to C 25 alkyl, a substituted or unsubstituted C 8 to C 25 alkenyl, a substituted or unsubstituted C 8 to C 25 alkynyl, a substituted or unsubstituted C 6 to C 12 aryl, or substituted or unsubstituted C 6 to C 12 heteroaryl.
구체적인 본 발명의 세라마이드 제조방법에 대한 반응 메커니즘은 하기 반응식 1에 기재된 바와 같다.The specific reaction mechanism for the ceramide production method of the present invention is as described in Reaction Scheme 1 below.
[반응식 1][Scheme 1]
본 발명에 있어서, 용어 「피토스핑고신」이란, 하기 구조를 갖는 화합물로서, 세라마이드를 합성하기 위한 출발물질로 이용된다.In the present invention, the term "phytosphingosine" is a compound having the following structure and is used as a starting material for synthesizing ceramide.
본 발명에 있어서, 용어 「치환된」이란, 하나 이상의 수소 원자가 수소 이외의 원자, 즉 치환기로 대체되는 것을 의미한다. 바람직한 치환기로는 비-제한적으로 할로겐, 니트로, 아미노, 아지도, 옥소, 하이드록실, 티올, 카르복시, 카르복시 에스테르, 카르복사미드, 알킬아미노, 알킬다이티오, 알킬티오, 알콕시, 아실아미도, 아실옥시 또는 아실티오 일 수 있고, 이에 한정되는 것은 아니다.In the present invention, the term "substituted" means that one or more hydrogen atoms are replaced with an atom other than hydrogen, that is, a substituent. Preferred substituents include, but are not limited to, halogen, nitro, amino, azido, oxo, hydroxyl, thiol, carboxy, carboxy ester, carboxamide, alkylamino, alkyldithio, alkylthio, alkoxy, acylamido, acyl It may be oxy or acylthio, but is not limited thereto.
본 발명에 있어서, 용어 「아릴」이란, 탄소수 6 내지 12개의 방향족 고리 화합물을 의미하며, 구체적으로 페닐, 나프틸, 안트라세닐 일 수 있고, 이에 한정되는 것은 아니다.In the present invention, the term "aryl" refers to an aromatic ring compound having 6 to 12 carbon atoms, and specifically may be phenyl, naphthyl, or anthracenyl, but is not limited thereto.
본 발명에 있어서, 용어 「고리형 아민 염기계열 촉매」란, 벌키(Bulky)한 Fused된 고리 형태의 것으로서, 적어도 질소원자(N)를 하나 이상 포함하여 염기 촉매로서의 역할을 수행할 수 있는 것을 의미한다. 구체적으로, 고리형 아민 염기계열 촉매는 1,8-디아자비시클로[5,4,0]운데크-7-엔{1,8-Diazabicyclo[5,4,0]undec-7-ene; DBU}, 1,5-디아자비시클로[4,3,0]논-5-엔{1,5-Diazabicyclo[4,3,0]non-5-ene; DBN}, 1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD} 및 7-메틸-1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD}로 이루어진 군에서 선택된 어느 하나 이상일 수 있으며, 바람직하게는 1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD} 및 7-메틸-1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD}, 보다 바람직하게는 1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD} 일 수 있고, 이에 한정되는 것은 아니다.In the present invention, the term "cyclic amine base-based catalyst" is in the form of a bulky, fused ring, and includes at least one nitrogen atom (N) to serve as a base catalyst. do. Specifically, cyclic amine base-based catalysts include 1,8-diazabicyclo[5,4,0]undec-7-ene; DBU}, 1,5-Diazabicyclo[4,3,0]non-5-ene; DBN}, 1,5,7-Triazabicyclo[4,4,0]dec-5-ene {1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD} and 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene {1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD} may be any one or more selected from the group consisting of, preferably 1,5,7-triazabicyclo[4,4,0]dec-5-ene{1,5,7-Triazabicyclo[4.4.0] dec-5-ene; TBD} and 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene {1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD}, more preferably 1,5,7-triazabicyclo[4,4,0]dec-5-ene {1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD}, but is not limited thereto.
본 발명에 있어서, 상기 고리형 아민 염기계열 촉매는 세라마이드 합성 시 에스터 화합물과 결합하여 활성화된 중간체를 생성하여 세라마이드로 전환시켜주는 역할을 수행하므로, 세라마이드 합성에 있어서 반응 부산물을 최소화하고 비교적 온화한 반응조건에서 세라마이드를 생성할 수 있는 이점이 있다.In the present invention, the cyclic amine base-based catalyst combines with an ester compound during ceramide synthesis to generate an activated intermediate and converts it to ceramide, so that reaction by-products are minimized in ceramide synthesis and relatively mild reaction conditions It has the advantage of being able to generate ceramide.
본 발명에 있어서, 상기 화학식 1 및 2에서, R은 치환 또는 비치환된 C8 내지 C25 알킬, 치환 또는 비치환된 C8 내지 C25 알케닐 또는 치환 또는 비치환된 C6 내지 C12 아릴 중 어느 하나일 수 있으며, 이에 한정되는 것은 아니다.In the present invention, in Formulas 1 and 2, R is substituted or unsubstituted C 8 to C 25 alkyl, substituted or unsubstituted C 8 to C 25 alkenyl, or substituted or unsubstituted C 6 to C 12 aryl It may be any one of, but is not limited thereto.
본 발명에 있어서, 상기 화학식 1 및 2에서, R은 치환 또는 비치환된 C8 내지 C17 알킬, 치환 또는 비치환된 C8 내지 C17 알케닐 또는 치환 또는 비치환된 C6 내지 C8 아릴 중 어느 하나일 수 있으며, 구체적으로 R은 , , , 또는 일 수 있고, 이에 한정되는 것은 아니다. (위 R 치환기에서 표시한 란, 결합되는 부분을 지칭하는 것이다.)In the present invention, in Formulas 1 and 2, R is substituted or unsubstituted C 8 to C 17 alkyl, substituted or unsubstituted C 8 to C 17 alkenyl, or substituted or unsubstituted C 6 to C 8 aryl It may be any one of, specifically R is , , , or It may be, but is not limited thereto. (as shown in the R substituent above means the part to be joined.)
본 발명에 있어서, 상기 화학식 2로 표시되는 메틸 에스터계 화합물은, 하기 화학식 2-1 내지 화학식 2-5로 표시되는 화합물 중 어느 하나 이상일 수 있으며, 이에 한정되는 것은 아니다.In the present invention, the methyl ester-based compound represented by Chemical Formula 2 may be any one or more of the compounds represented by Chemical Formulas 2-1 to 2-5 below, but is not limited thereto.
[화학식 2-1][Formula 2-1]
[화학식 2-2][Formula 2-2]
[화학식 2-3][Formula 2-3]
[화학식 2-4][Formula 2-4]
[화학식 2-5][Formula 2-5]
구체적으로, 화학식 2-1로 표시되는 메틸 에스터계 화합물은 메틸 라우릴레이트(Methyl laurate)이고, 화학식 2-2로 표시되는 메틸 에스터계 화합물은 메틸 팔미테이트(Methyl palmitate)이며, 화학식 2-3으로 표시되는 메틸 에스터계 화합물은 메틸 스테아레이트(Methyl stearate)이고, 화학식 2-4로 표시되는 메틸 에스터계 화합물은 메틸 올레이트(Methyl oleate)이며, 화학식 2-5로 표시되는 메틸 에스터계 화합물은 메틸 살리실레이트(Methyl salicylate)이다.Specifically, the methyl ester-based compound represented by Chemical Formula 2-1 is methyl laurate, the methyl ester-based compound represented by Chemical Formula 2-2 is methyl palmitate, and Chemical Formula 2-3 The methyl ester-based compound represented by is methyl stearate, the methyl ester-based compound represented by Formula 2-4 is methyl oleate, and the methyl ester-based compound represented by Formula 2-5 is It is methyl salicylate.
본 발명에 있어서, 세라마이드를 제조하는 방법은 40 내지 80℃에서 16 내지 32시간 동안 수행될 수 있으며, 이에 한정되는 것은 아니다.In the present invention, the method for preparing ceramide may be performed at 40 to 80 ° C. for 16 to 32 hours, but is not limited thereto.
구체적으로, 상기와 같은 온도 범위는 마일드한 조건으로서, 고리형 아민 염기계열 촉매를 사용할 경우 반응 온도를 마일드 조건으로 진행하더라도 고수율의 세라마이드를 합성할 수 있는 이점이 있다.Specifically, the temperature range as described above is a mild condition, and when using a cyclic amine base-based catalyst, there is an advantage in synthesizing ceramide with a high yield even if the reaction temperature is progressed under mild conditions.
본 발명에 있어서, 화학식 1로 표시되는 세라마이드는 하기 화학식 1-1 내지 화학식 1-5로 표시되는 화합물 중 어느 하나 이상일 수 있으며, 이에 한정되는 것은 아니다.In the present invention, the ceramide represented by Chemical Formula 1 may be any one or more of the compounds represented by Chemical Formulas 1-1 to 1-5 below, but is not limited thereto.
[화학식 1-1][Formula 1-1]
[화학식 1-2][Formula 1-2]
[화학식 1-3][Formula 1-3]
[화학식 1-4][Formula 1-4]
[화학식 1-5][Formula 1-5]
구체적으로, 화학식 1-1로 표시되는 세라마이드는 N-라우로일-피토스핑고신(N-Lauroyl Phytosphingosine)이고, 화학식 1-2로 표시되는 세라마이드는 N-팔미토일-피토스핑고신(N-Palmitoyl Phytosphingosine)이며, 화학식 1-3으로 표시되는 세라마이드는 N-스테아로일-피토스핑고신 (N-Stearoyl-phytosphingosine)이고, 화학식 1-4로 표시되는 세라마이드는 N-올레일-피토스핑고신(N-Oleayl-phytosphingosine, 세라마이드 NP)이며, 화학식 1-5로 표시되는 세라마이드는 N-살리실로일-피토스핑고신(N-Salicyloyl-phytosphingosine)이다.Specifically, the ceramide represented by Formula 1-1 is N-Lauroyl Phytosphingosine, and the ceramide represented by Formula 1-2 is N-palmitoyl-phytosphingosine (N-Lauroyl Phytosphingosine). -Palmitoyl Phytosphingosine), ceramide represented by Formula 1-3 is N-Stearoyl-phytosphingosine, and ceramide represented by Formula 1-4 is N-oleyl-phytosine. It is phingosine (N-Oleayl-phytosphingosine, ceramide NP), and the ceramide represented by Formula 1-5 is N-salicyloyl-phytosphingosine.
본 발명에 있어서, 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 1 : 0.5 ~ 1.5의 중량비로 반응시킬 수 있으며, 구체적으로는 1 : 0.7 ~ 1.25의 중량비로 반응시킬 수 있고, 이에 한정되는 것은 아니다.In the present invention, phytosphingosine and the methyl ester-based compound represented by Formula 2 may be reacted in a weight ratio of 1: 0.5 to 1.5, specifically 1: 0.7 to 1.25. It is not limited.
상기 중량비 범위 내에서 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 반응시킬 경우 세척을 줄이고 고순도의 세라마이드를 수득할 수 있는 이점이 있다.When phytosphingosine and the methyl ester-based compound represented by Formula 2 are reacted within the above weight ratio range, there is an advantage in reducing washing and obtaining high-purity ceramide.
본 발명에 있어서, 고리형 아민 염기계열 촉매는 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물의 총 합을 기준으로 3.5 내지 10 중량%를 투입할 수 있으며, 구체적으로는 5 내지 8 중량%를 투입할 수 있고, 이에 한정되는 것은 아니다.In the present invention, the cyclic amine base-based catalyst may be added in an amount of 3.5 to 10% by weight based on the total sum of phytosphingosine and the methyl ester-based compound represented by Formula 2, specifically 5 to 8% by weight % can be added, but is not limited thereto.
상기 함량 범위 내에서 고리형 아민 염기계열 촉매가 3.5 중량% 미만일 경우 반응시간이 길어지고, 10 중량% 초과일 경우 반응시간은 단축되지만, 촉매의 단가가 높아 합성물의 경제성에 영향을 주게 된다.Within the above content range, when the cyclic amine base-based catalyst is less than 3.5% by weight, the reaction time is increased, and when it is greater than 10% by weight, the reaction time is shortened, but the cost of the catalyst is high, which affects the economics of the compound.
본 발명에 있어서, 상기 방법은 디클로로메탄 용매 또는 무용매 조건 하에서 반응을 수행할 수 있으며, 이에 한정되는 것은 아니다.In the present invention, the method may be carried out under dichloromethane solvent or solventless conditions, but is not limited thereto.
본 발명에 따라 합성된 세라마이드는 화장품에 적용 시 피부에 도포되어 보습력 및 탄력, 주름미백 등의 효과를 기대할 수 있을 것이다.The ceramide synthesized according to the present invention is applied to the skin when applied to cosmetics, and effects such as moisturizing power, elasticity, and wrinkle whitening can be expected.
이하, 본 발명을 실시예로서 더욱 상세하게 설명한다. 그러나 본 발명은 여러 가지 상이한 형태로 구현될 수 있으며 아래 기재된 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in more detail by way of examples. However, the present invention may be embodied in many different forms and is not limited to the examples described below.
실시예Example
[재료][ingredient]
하기 실시예 및 비교예에서 사용한 원료들은 Sigma-Aldrich Korea 및 TCI 사 등으로부터 구입한 것을 사용하였다.Raw materials used in the following Examples and Comparative Examples were purchased from Sigma-Aldrich Korea and TCI.
[1H-NMR][ 1 H-NMR]
1H-NMR은 Bruker Advance III HD 400을 사용하여 수행하였다. 1 H-NMR was performed using a Bruker Advance III HD 400.
실시예 1. N-올레일-피토스핑고신(N-Oleayl-phytosphingosine, 세라마이드 NP) 합성Example 1. Synthesis of N-Oleayl-phytosphingosine (ceramide NP)
피토스핑고신(Phytosphingosine) 20 g, 메틸 올레이트(Methyl oleate) 25 g, 1,5,7-트리아자비시클로[4,4,0]데크-5-엔 (1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD) 2.6 g를 반응기에 투입한 후 용매인 디클로로메탄(dichloromethane; DCM, 50 mL)을 투입하였다. 이후 40℃에서 24시간 동안 환류 교반한 후, 반응 종결 시 용매인 디클로로메탄을 감압하여 제거하였다. 농축된 반응 혼합물에 메탄올/물 혼합용액(9/1 (v/v), 700 mL)을 가하여 생성된 백색 침전물을 여과 및 건조하여 세라마이드의 일 예인 N-올레일-피토스핑고신(N-Oleayl-phytosphingosine, 세라마이드 NP)를 수득하였다 (30 g, 수율: 85%).Phytosphingosine 20 g, Methyl oleate 25 g, 1,5,7-triazabicyclo[4,4,0]dec-5-ene (1,5,7-Triazabicyclo[ After 2.6 g of 4.4.0]dec-5-ene; TBD) was added to the reactor, dichloromethane (DCM, 50 mL) as a solvent was added. After stirring under reflux for 24 hours at 40 ° C., dichloromethane as a solvent was removed under reduced pressure at the end of the reaction. A methanol/water mixed solution (9/1 (v/v), 700 mL) was added to the concentrated reaction mixture, and the resulting white precipitate was filtered and dried to obtain N-oleyl-phytosphingosine (N- Oleayl-phytosphingosine, ceramide NP) was obtained (30 g, yield: 85%).
1H-NMR (400 MHz, CDCl3): δ 6.51 (1H, m, -NH-), 5.36 (2H, m, -CH2-CH=CH-CH2-), 4.41 (1H, s, -CHOH-CHOH-CH-), 4.01 (1H, br, -OH), 3.88 (1H, m, -CHOH-CH-CH2-), 3.72 (1H, m, -CH2-CHOH-CHOH-), 3.61 (2H, m, -CH-CH
2-OH), 2.23 (2H, t, -CH2-CH
2-CO-), 2.02 (4H, -CH
2-CH=CH-CH
2-), 1.63 (2H, m, -CH2-CH
2-CH2-CO-), 1.50 (2H, m, -CH2-CH
2-CHOH-), 1.27 (44H, br, CH3-(CH
2)12-CH2-, CH3-(CH
2)6-CH2-CH=, =CH-CH2-(CH
2)4-CH2-), 0.89 (6H, t, CH
3-). (도 1 기재 내용 참조). 1 H-NMR (400 MHz, CDCl 3 ): δ 6.51 (1H, m, -NH-), 5.36 (2H, m, -CH 2 -CH = CH -CH 2 -), 4.41 (1H, s , -CHOH- CH OH-CH-), 4.01 (1H, br, -OH ), 3.88 (1H, m, -CHOH- CH -CH 2 -), 3.72 (1H, m, -CH 2 - C H OH-CHOH-), 3.61 (2H, m, -CH-C H 2 -OH), 2.23 (2H, t, -CH 2 -C H 2 -CO-), 2.02 (4H, -C H 2 -CH=CH-C H 2 -), 1.63 (2H, m, -CH 2 -C H 2 -CH 2 -CO-), 1.50 (2H, m, -CH 2 -C H 2 -CHOH-), 1.27 (44H, br, CH 3 -(CH 2 ) 12 -CH 2 - , CH 3 -(CH 2 ) 6 -CH 2 -CH=, =CH-CH 2 -( CH 2 ) 4 -CH 2 -), 0.89 (6H, t, C H 3 -). (See Figure 1 description).
[반응식 2][Scheme 2]
실시예 2. N-살리실로일-피토스핑고신(N-Salicyloyl-phytosphingosine) 합성Example 2. Synthesis of N-Salicyloyl-phytosphingosine
피토스핑고신(Phytosphingosine) 20 g, 메틸 살리실레이트(Methyl salicylate) 14 g, 1,5,7-트리아자비시클로[4,4,0]데크-5-엔 (1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD) 2.7 g를 반응기에 투입한 후 무용매 조건 하에서 (solvent free condition; S.F.C.) 80 ℃에서 24시간 동안 반응을 유지하였다. 이후 감압 농축하여 생성된 부산물인 메탄올을 제거하고 디클로로메탄/헥산 혼합용액(디클로로메탄: 헥산 = 3 : 5의 중량비율, 500 mL)을 가하여 생성된 백색 침전물을 여과 및 건조하여 세라마이드의 일 예인 N-살리실로일-피토스핑고신(N-Salicyloyl-phytosphingosine)을 수득하였다 (19 g, 수율: 69%).Phytosphingosine 20 g, Methyl salicylate 14 g, 1,5,7-triazabicyclo[4,4,0]dec-5-ene (1,5,7-Triazabicyclo After adding 2.7 g of [4.4.0]dec-5-ene; TBD) to the reactor, the reaction was maintained at 80 °C for 24 hours under solvent free condition (S.F.C.). Thereafter, methanol, a by-product produced by concentration under reduced pressure, was removed, and a dichloromethane/hexane mixed solution (dichloromethane: hexane = 3: 5 weight ratio, 500 mL) was added, and the resulting white precipitate was filtered and dried to obtain N, an example of ceramide. -Salicyloyl-phytosphingosine (N-Salicyloyl-phytosphingosine) was obtained (19 g, yield: 69%).
1H-NMR (400 MHz, CDCl3): δ 12.07 (1H, s, -NH-), 7.46 (2H, m, Ar), 7.01 (1H, d, Ar), 6.89 (1H, t, Ar), 4.40 (1H, s, -CHOH-CHOH-CH-), 4.10 (1H, d, -CHOH-CH-CH2-), 3.89 (1H, m, -CH2-CHOH-CHOH-), 3.74 (2H, s, -CH-CH
2-OH), 1.81 (1H, s, -CH2-CH
2-CHOH-), 1.54 (1H, s, -CH2-CH
2-CHOH-), 1.27 (24H, br, CH3-(CH
2)12-CH2-), 0.90 (3H, t, CH
3-). (도 2 기재 내용 참조). 1 H-NMR (400 MHz, CDCl 3 ): δ 12.07 (1H, s, -NH-), 7.46 (2H, m, Ar), 7.01 (1H, d, Ar), 6.89 (1H, t, Ar) , 4.40 (1H, s, -CHOH- CH OH-CH-), 4.10 (1H, d, -CHOH- CH -CH 2 -), 3.89 (1H, m, -CH 2 -CH OH-CHOH -), 3.74 (2H, s, -CH- CH 2 -OH), 1.81 (1H, s, -CH 2 -CH 2 -CHOH- ), 1.54 (1H, s, -CH 2 -CH 2 -CHOH-), 1.27 (24H, br, CH 3 -( CH 2 ) 12 -CH 2 -), 0.90 (3H, t, CH 3 - ). (See Figure 2 description).
[반응식 3][Scheme 3]
비교예comparative example
비교예 1. N-올레일-피토스핑고신(N-Oleayl-phytosphingosine, 세라마이드 NP) 합성Comparative Example 1. N-oleyl-phytosphingosine (N-Oleayl-phytosphingosine, ceramide NP) synthesis
피토스핑고신(Phytosphingosine) 20 g, 올레인산(Oleic acid) 20 g, p-톨루엔설폰산 1.2 g를 반응기에 투입하고, 유기용매인 톨루엔(Toluene, 100 mL)을 투입하였다. 이후 질소(N2) 분위기 하에서 10시간 동안 110 ℃에서 환류 교반하고 반응 종결 후 유기용매인 톨루엔을 감압하여 제거하였다. 메탄올/물 혼합용액(9/1 (v/v), 700 mL)을 가하여 생성된 백색 침전물을 여과 및 건조하여 세라마이드의 일 예인 N-올레일-피토스핑고신(N-Oleayl-phytosphingosine, 세라마이드 NP)을 수득하였다 (9 g, 수율: 24%).20 g of phytosphingosine, 20 g of oleic acid, and 1.2 g of p-toluenesulfonic acid were added to the reactor, and an organic solvent, toluene (100 mL) was added. Thereafter, the mixture was refluxed and stirred at 110° C. for 10 hours under a nitrogen (N 2 ) atmosphere, and after the reaction was completed, toluene, an organic solvent, was removed under reduced pressure. A white precipitate produced by adding methanol/water mixture solution (9/1 (v/v), 700 mL) was filtered and dried to obtain N-Oleayl-phytosphingosine, an example of ceramide. NP) was obtained (9 g, yield: 24%).
1H-NMR (400 MHz, CDCl3): δ 6.42 (1H, m, -NH-), 5.36 (2H, m, -CH2-CH=CH-CH2-), 4.16 (1H, m, -CHOH-CHOH-CH-), 3.91 (3H, br, -OH, -CHOH-CH-CH2-), 3.73 (1H, m, -CH2-CHOH-CHOH-), 3.61 (2H, m, -CH-CH
2-OH), 3.11 (1H, br, -OH), 2.24 (2H, t, -CH2-CH
2-CO-), 2.02 (4H, -CH
2-CH=CH-CH
2-), 1.64 (2H, m, -CH2-CH
2-CH2-CO-), 1.51 (2H, m, -CH2-CH
2-CHOH-), 1.27 (44H, br, CH3-(CH
2)12-CH2-, CH3-(CH
2)6-CH2-CH=, =CH-CH2-(CH
2)4-CH2-), 0.90 (6H, t, CH
3-). (도 3 기재 내용 참조). 1 H-NMR (400 MHz, CDCl 3 ): δ 6.42 (1H, m, -NH-), 5.36 (2H, m, -CH 2 -CH = CH -CH 2 -), 4.16 (1H, m , -CHOH-C H OH-CH-), 3.91 (3H, br, -O H , -CHOH-C H -CH 2 -), 3.73 (1H, m, -CH 2 -C H OH-CHOH-) , 3.61 (2H, m, -CH- CH 2 -OH), 3.11 (1H, br, -OH), 2.24 (2H , t, -CH 2 -CH 2 -CO-), 2.02 (4H, - C H 2 -CH=CH-C H 2 -), 1.64 (2H, m, -CH 2 -C H 2 -CH 2 -CO-), 1.51 (2H, m, -CH 2 -C H 2 -CHOH -), 1.27 (44H , br, CH 3 -(CH 2 ) 12 -CH 2 -, CH 3 -(CH 2 ) 6 -CH 2 -CH=, =CH-CH 2 -( CH 2 ) 4 -CH 2 -), 0.90 (6H, t, CH 3 -). (See FIG. 3 description).
비교예 2. N-살리실로일-피토스핑고신(N-Salicyloyl-phytosphingosine) 합성Comparative Example 2. Synthesis of N-Salicyloyl-phytosphingosine
피토스핑고신(Phytosphingosine) 20 g, 살리실산(Salicylic acid) 10 g, p-톨루엔설폰산(P-Toluenesulfonic acid) 1.2 g를 반응기에 투입하고 유기용매인 톨루엔(Toluene, 80 mL)을 투입하였다. 이후 질소(N2) 분위기 하에서 24시간 동안 110 ℃에서 환류 교반한 뒤 유기용매인 톨루엔을 감압 제거하였다. 디클로로메탄/헥산 혼합용액(디클로로메탄: 헥산 = 3 : 5의 중량비율, 500 mL)을 가하여 생성된 백색 침전물을 여과 및 건조하여 세라마이드의 일 예인 N-살리실로일-피토스핑고신(N-Salicyloyl-phytosphingosine)을 수득하였다 (4 g, 수율: 15% ).20 g of phytosphingosine, 10 g of salicylic acid, and 1.2 g of p-toluenesulfonic acid were added to the reactor, and an organic solvent, toluene (80 mL) was added. Thereafter, the mixture was refluxed and stirred at 110 °C for 24 hours under a nitrogen (N 2 ) atmosphere, and then toluene, an organic solvent, was removed under reduced pressure. A white precipitate produced by adding a dichloromethane/hexane mixed solution (dichloromethane:hexane = 3:5 weight ratio, 500 mL) was filtered and dried to obtain N-salicyloyl-phytosphingosine (N-salicyloyl-phytosphingosine, an example of ceramide). Salicyloyl-phytosphingosine) was obtained (4 g, yield: 15%).
1H-NMR (400 MHz, CDCl3): δ 12.05 (1H, s, -NH-), 7.46 (2H, m, Ar), 7.01 (1H, d, Ar), 6.89 (1H, t, Ar), 4.40 (1H, s, -CHOH-CHOH-CH-), 4.10 (1H, m, -CHOH-CH-CH2-), 3.89 (1H, m, -CH2-CHOH-CHOH-), 3.74 (2H, s, -CH-CH
2-OH), 2.42 (4H, br, -OH), 1.81 (1H, s, -CH2-CH
2-CHOH-), 1.54 (1H, s, -CH2-CH
2-CHOH-), 1.27 (24H, br, CH3-(CH
2)12-CH2-), 0.90 (3H, t, CH
3-). (도 4 기재 내용 참조). 1 H-NMR (400 MHz, CDCl 3 ): δ 12.05 (1H, s, -NH-), 7.46 (2H, m, Ar), 7.01 (1H, d, Ar), 6.89 (1H, t, Ar) , 4.40 (1H, s, -CHOH- CH OH-CH-), 4.10 (1H, m, -CHOH- CH -CH 2 -), 3.89 (1H, m, -CH 2 -CH OH-CHOH -), 3.74 (2H, s, -CH- CH 2 -OH), 2.42 (4H, br, -OH), 1.81 (1H, s, -CH 2 -CH 2 -CHOH-), 1.54 (1H , s, -CH 2 -CH 2 -CHOH-), 1.27 (24H, br, CH 3 -(CH 2 ) 12 -CH 2 -), 0.90 (3H, t, CH 3 -). (See FIG. 4 description).
천연 세라마이드를 합성 시 고리형 아민 염기계열 촉매인 1,5,7-트리아자비시클로[4,4,0]데크-5-엔 (1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD)를 사용함으로써 종래 합성 방법(비교예 1 및 2)에 의해 합성된 세라마이드 대비 마일드한 조건에서 높은 수율로 세라마이드를 얻을 수 있음을 확인할 수 있다.When synthesizing natural ceramide, 1,5,7-triazabicyclo[4,4,0]dec-5-ene (1,5,7-Triazabicyclo[4.4.0]dec-5- ene; TBD), it can be confirmed that ceramide can be obtained in a high yield under mild conditions compared to ceramides synthesized by conventional synthesis methods (Comparative Examples 1 and 2).
Claims (9)
- 고리형 아민 염기계열 촉매 존재 하에 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 반응시켜 화학식 1로 표시되는 세라마이드를 제조하는 방법:Method for preparing ceramide represented by Chemical Formula 1 by reacting phytosphingosine with a methyl ester-based compound represented by Chemical Formula 2 in the presence of a cyclic amine base-based catalyst:[화학식 1][Formula 1][화학식 2][Formula 2]상기 화학식 1 및 2에서,In Formulas 1 and 2,R은 치환 또는 비치환된 C8 내지 C25 알킬, 치환 또는 비치환된 C8 내지 C25 알케닐, 치환 또는 비치환된 C8 내지 C25 알키닐, 치환 또는 비치환된 C6 내지 C12 아릴, 또는 치환 또는 비치환된 C6 내지 C12 헤테로아릴임.R is a substituted or unsubstituted C 8 to C 25 alkyl, a substituted or unsubstituted C 8 to C 25 alkenyl, a substituted or unsubstituted C 8 to C 25 alkynyl, a substituted or unsubstituted C 6 to C 12 aryl, or substituted or unsubstituted C 6 to C 12 heteroaryl.
- 제1항에 있어서,According to claim 1,고리형 아민 염기계열 촉매는 1,8-디아자비시클로[5,4,0]운데크-7-엔{1,8-Diazabicyclo[5,4,0]undec-7-ene; DBU}, 1,5-디아자비시클로[4,3,0]논-5-엔{1,5-Diazabicyclo[4,3,0]non-5-ene; DBN}, 1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD} 및 7-메틸-1,5,7-트리아자비시클로[4,4,0]데크-5-엔{1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD}로 이루어진 군에서 선택된 어느 하나 이상인 것을 특징으로 하는 방법.Cyclic amine base-based catalysts include 1,8-diazabicyclo[5,4,0]undec-7-ene; DBU}, 1,5-Diazabicyclo[4,3,0]non-5-ene; DBN}, 1,5,7-Triazabicyclo[4,4,0]dec-5-ene {1,5,7-Triazabicyclo[4.4.0]dec-5-ene; TBD} and 7-methyl-1,5,7-triazabicyclo[4,4,0]dec-5-ene {1,5,7-Triazabicyclo[4.4.0]dec-5-ene; MTBD} method characterized in that any one or more selected from the group consisting of.
- 제1항에 있어서,According to claim 1,상기 화학식 1 및 2에서,In Formulas 1 and 2,R은 치환 또는 비치환된 C8 내지 C25 알킬, 치환 또는 비치환된 C8 내지 C25 알케닐 또는 치환 또는 비치환된 C6 내지 C12 아릴 중 어느 하나인 것을 특징으로 하는 방법.Wherein R is any one of substituted or unsubstituted C 8 to C 25 alkyl, substituted or unsubstituted C 8 to C 25 alkenyl, or substituted or unsubstituted C 6 to C 12 aryl.
- 제1항에 있어서,According to claim 1,상기 화학식 1 및 2에서,In Formulas 1 and 2,R은 치환 또는 비치환된 C8 내지 C17 알킬, 치환 또는 비치환된 C8 내지 C17 알케닐 또는 치환 또는 비치환된 C6 내지 C8 아릴 중 어느 하나인 것을 특징으로 하는 방법.Wherein R is any one of substituted or unsubstituted C 8 to C 17 alkyl, substituted or unsubstituted C 8 to C 17 alkenyl, or substituted or unsubstituted C 6 to C 8 aryl.
- 제1항에 있어서,According to claim 1,상기 화학식 2로 표시되는 메틸 에스터계 화합물은, 하기 화학식 2-1 내지 화학식 2-5로 표시되는 화합물 중 어느 하나 이상인 것을 특징으로 하는 방법:A method characterized in that the methyl ester-based compound represented by Formula 2 is at least one of the compounds represented by Formulas 2-1 to 2-5 below:[화학식 2-1][Formula 2-1][화학식 2-2][Formula 2-2][화학식 2-3][Formula 2-3][화학식 2-4][Formula 2-4][화학식 2-5][Formula 2-5]
- 제1항에 있어서,According to claim 1,40 내지 80℃에서 16 내지 32시간 동안 수행되는 것인 방법.The method is carried out at 40 to 80 ℃ for 16 to 32 hours.
- 제1항에 있어서,According to claim 1,화학식 1로 표시되는 세라마이드는 하기 화학식 1-1 내지 화학식 1-5로 표시되는 화합물 중 어느 하나 이상인 것을 특징으로 하는 방법:A method characterized in that the ceramide represented by Formula 1 is any one or more of the compounds represented by Formulas 1-1 to 1-5 below:[화학식 1-1][Formula 1-1][화학식 1-2][Formula 1-2][화학식 1-3][Formula 1-3][화학식 1-4][Formula 1-4][화학식 1-5][Formula 1-5]
- 제1항에 있어서,According to claim 1,피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물을 1 : 0.5 ~ 1.5의 중량비로 반응시키는 것을 특징으로 하는 방법.A method characterized by reacting phytosphingosine with a methyl ester-based compound represented by Formula 2 at a weight ratio of 1:0.5 to 1.5.
- 제1항에 있어서,According to claim 1,고리형 아민 염기계열 촉매는 피토스핑고신과 화학식 2로 표시되는 메틸 에스터계 화합물의 총 합을 기준으로 3.5 내지 10 중량%를 투입하는 것을 특징으로 하는 방법.The cyclic amine base-based catalyst is characterized in that 3.5 to 10% by weight is added based on the total sum of phytosphingosine and the methyl ester-based compound represented by Formula 2.
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