KR20140144592A - Novel triterpenoids from acanthopanax sessiliflorus and an anti-inflammatory composition containing it - Google Patents
Novel triterpenoids from acanthopanax sessiliflorus and an anti-inflammatory composition containing it Download PDFInfo
- Publication number
- KR20140144592A KR20140144592A KR1020130066746A KR20130066746A KR20140144592A KR 20140144592 A KR20140144592 A KR 20140144592A KR 1020130066746 A KR1020130066746 A KR 1020130066746A KR 20130066746 A KR20130066746 A KR 20130066746A KR 20140144592 A KR20140144592 A KR 20140144592A
- Authority
- KR
- South Korea
- Prior art keywords
- carbon atoms
- alkyl
- compound
- less carbon
- composition
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 52
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 31
- 235000017615 Acanthopanax sessiliflorus Nutrition 0.000 title abstract description 4
- 241001505454 Eleutherococcus sessiliflorus Species 0.000 title abstract 3
- 150000003648 triterpenes Chemical class 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 66
- -1 triterpenoid compound Chemical class 0.000 claims abstract description 25
- 235000013305 food Nutrition 0.000 claims abstract description 18
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 14
- 239000002537 cosmetic Substances 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims description 73
- 125000000217 alkyl group Chemical group 0.000 claims description 54
- 125000005640 glucopyranosyl group Chemical group 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 20
- 239000000284 extract Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 7
- 235000013628 Lantana involucrata Nutrition 0.000 claims description 6
- 235000006677 Monarda citriodora ssp. austromontana Nutrition 0.000 claims description 6
- 240000007673 Origanum vulgare Species 0.000 claims description 6
- 241000195493 Cryptophyta Species 0.000 claims 1
- 230000000895 acaricidal effect Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 5
- 238000004440 column chromatography Methods 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 24
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 21
- 239000000843 powder Substances 0.000 description 15
- 238000004809 thin layer chromatography Methods 0.000 description 15
- 229910052799 carbon Inorganic materials 0.000 description 14
- 238000002000 high resolution fast-atom bombardment mass spectrometry Methods 0.000 description 13
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- GKRMBTQHEPCVKU-UHFFFAOYSA-N 28-dioic acid Natural products OC1C(O)C(OC2C(C(O)C(O)CO2)O)C(C)OC1OC1C(O)C(O)COC1OC(=O)C1(CCC2(C)C3(C)CCC4C5(C)C(O)=O)CCC(C)(C)CC1C2=CCC3C4(C)CC(O)C5OC1OC(CO)C(O)C(O)C1OC1OC(CO)C(O)C(O)C1O GKRMBTQHEPCVKU-UHFFFAOYSA-N 0.000 description 11
- 239000000741 silica gel Substances 0.000 description 11
- 229910002027 silica gel Inorganic materials 0.000 description 11
- 229960001866 silicon dioxide Drugs 0.000 description 11
- 238000005481 NMR spectroscopy Methods 0.000 description 10
- 229940126214 compound 3 Drugs 0.000 description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
- 206010057190 Respiratory tract infections Diseases 0.000 description 9
- 229940125898 compound 5 Drugs 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 230000002265 prevention Effects 0.000 description 8
- WUKWITHWXAAZEY-UHFFFAOYSA-L calcium difluoride Chemical compound [F-].[F-].[Ca+2] WUKWITHWXAAZEY-UHFFFAOYSA-L 0.000 description 7
- 229910001634 calcium fluoride Inorganic materials 0.000 description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 7
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 6
- 150000001793 charged compounds Chemical class 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 238000001052 heteronuclear multiple bond coherence spectrum Methods 0.000 description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 6
- 230000006872 improvement Effects 0.000 description 6
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 6
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 6
- GLRHOGWDMAVPRF-PEBBSWCFSA-N 3-[(3s,4s,5r,8r,9r,10r,13s,14r,15r)-4,9,10-trimethyl-3,15-bis(prop-1-en-2-yl)-13-[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxycarbonyl-2,3,5,6,7,8,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthren-4-yl]propanoic acid Chemical compound O=C([C@]12CC[C@H]([C@@H]1[C@@H]1[C@@]([C@@]3(CC[C@H]([C@](C)(CCC(O)=O)[C@H]3CC1)C(C)=C)C)(C)CC2)C(=C)C)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O GLRHOGWDMAVPRF-PEBBSWCFSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 239000006071 cream Substances 0.000 description 5
- 230000036541 health Effects 0.000 description 5
- 208000027866 inflammatory disease Diseases 0.000 description 5
- 230000007774 longterm Effects 0.000 description 5
- 210000002540 macrophage Anatomy 0.000 description 5
- NLQYJKRUOHDYPF-FZJIDXKTSA-N (3s,4s,5r,8r,9r,10r,13s,14r,15r,17s)-17-hydroxy-4-(3-methoxy-3-oxopropyl)-4,9,10-trimethyl-3,15-bis(prop-1-en-2-yl)-2,3,5,6,7,8,11,12,14,15,16,17-dodecahydro-1h-cyclopenta[a]phenanthrene-13-carboxylic acid Chemical compound C1C[C@@]2(C)[C@]3(C)CC[C@@H](C(C)=C)[C@@](CCC(=O)OC)(C)[C@H]3CC[C@@H]2[C@H]2[C@H](C(C)=C)C[C@H](O)[C@@]21C(O)=O NLQYJKRUOHDYPF-FZJIDXKTSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 4
- SIHHLZPXQLFPMC-UHFFFAOYSA-N chloroform;methanol;hydrate Chemical compound O.OC.ClC(Cl)Cl SIHHLZPXQLFPMC-UHFFFAOYSA-N 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
- 230000004054 inflammatory process Effects 0.000 description 4
- 150000002772 monosaccharides Chemical group 0.000 description 4
- 229930014626 natural product Natural products 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 3
- 244000167222 Acanthopanax sessiliflorus Species 0.000 description 3
- 206010003645 Atopy Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000005903 acid hydrolysis reaction Methods 0.000 description 3
- 235000013361 beverage Nutrition 0.000 description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 229930182470 glycoside Natural products 0.000 description 3
- 150000002338 glycosides Chemical class 0.000 description 3
- 230000002757 inflammatory effect Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 3
- 206010039073 rheumatoid arthritis Diseases 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 2
- XILIYVSXLSWUAI-UHFFFAOYSA-N 2-(diethylamino)ethyl n'-phenylcarbamimidothioate;dihydrobromide Chemical compound Br.Br.CCN(CC)CCSC(N)=NC1=CC=CC=C1 XILIYVSXLSWUAI-UHFFFAOYSA-N 0.000 description 2
- 208000002874 Acne Vulgaris Diseases 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 102000004127 Cytokines Human genes 0.000 description 2
- 108090000695 Cytokines Proteins 0.000 description 2
- 201000004624 Dermatitis Diseases 0.000 description 2
- 239000004606 Fillers/Extenders Substances 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- 102100029438 Nitric oxide synthase, inducible Human genes 0.000 description 2
- 101710089543 Nitric oxide synthase, inducible Proteins 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010040070 Septic Shock Diseases 0.000 description 2
- 206010040880 Skin irritation Diseases 0.000 description 2
- 208000000491 Tendinopathy Diseases 0.000 description 2
- 206010043255 Tendonitis Diseases 0.000 description 2
- GMWCFIADDGQIDG-KTJYCLMOSA-N acanthosessiligenin ii Chemical compound C1C[C@@]2(C)[C@]3(C)CC[C@H]4C(C)(C)O[C@H](CC(=O)OC)[C@]4(C)[C@H]3[C@H](O)C[C@@H]2[C@H]2[C@H](C(C)=C)CC[C@@]21C(O)=O GMWCFIADDGQIDG-KTJYCLMOSA-N 0.000 description 2
- 206010000496 acne Diseases 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 208000009956 adenocarcinoma Diseases 0.000 description 2
- HAMNKKUPIHEESI-UHFFFAOYSA-N aminoguanidine Chemical compound NNC(N)=N HAMNKKUPIHEESI-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000030833 cell death Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 231100000263 cytotoxicity test Toxicity 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 238000010828 elution Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 235000013376 functional food Nutrition 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 125000002791 glucosyl group Chemical group C1([C@H](O)[C@@H](O)[C@H](O)[C@H](O1)CO)* 0.000 description 2
- 239000007902 hard capsule Substances 0.000 description 2
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 2
- 208000013403 hyperactivity Diseases 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- XELZGAJCZANUQH-UHFFFAOYSA-N methyl 1-acetylthieno[3,2-c]pyrazole-5-carboxylate Chemical compound CC(=O)N1N=CC2=C1C=C(C(=O)OC)S2 XELZGAJCZANUQH-UHFFFAOYSA-N 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 235000016709 nutrition Nutrition 0.000 description 2
- 239000000419 plant extract Substances 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000036303 septic shock Effects 0.000 description 2
- 230000036556 skin irritation Effects 0.000 description 2
- 231100000475 skin irritation Toxicity 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 201000004415 tendinitis Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- XYHAYMZPPJMGBL-DWLKFTGOSA-N (+)-divaroside Chemical compound C([C@H]1O[C@H]([C@@H]([C@@H](O)[C@@H]1O)O)OC(=O)[C@]12CC[C@H]([C@@H]1[C@@H]1[C@@]([C@]3(C)CC[C@H]([C@]4(C)[C@H](O)CC(=O)O[C@@H]([C@@H]34)C1)C(C)=C)(C)CC2)C(=C)C)O[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O XYHAYMZPPJMGBL-DWLKFTGOSA-N 0.000 description 1
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 1
- XBZYWSMVVKYHQN-MYPRUECHSA-N (4as,6as,6br,8ar,9r,10s,12ar,12br,14bs)-10-hydroxy-2,2,6a,6b,9,12a-hexamethyl-9-[(sulfooxy)methyl]-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,13,14b-icosahydropicene-4a-carboxylic acid Chemical compound C1C[C@H](O)[C@@](C)(COS(O)(=O)=O)[C@@H]2CC[C@@]3(C)[C@]4(C)CC[C@@]5(C(O)=O)CCC(C)(C)C[C@H]5C4=CC[C@@H]3[C@]21C XBZYWSMVVKYHQN-MYPRUECHSA-N 0.000 description 1
- UNILWMWFPHPYOR-KXEYIPSPSA-M 1-[6-[2-[3-[3-[3-[2-[2-[3-[[2-[2-[[(2r)-1-[[2-[[(2r)-1-[3-[2-[2-[3-[[2-(2-amino-2-oxoethoxy)acetyl]amino]propoxy]ethoxy]ethoxy]propylamino]-3-hydroxy-1-oxopropan-2-yl]amino]-2-oxoethyl]amino]-3-[(2r)-2,3-di(hexadecanoyloxy)propyl]sulfanyl-1-oxopropan-2-yl Chemical compound O=C1C(SCCC(=O)NCCCOCCOCCOCCCNC(=O)COCC(=O)N[C@@H](CSC[C@@H](COC(=O)CCCCCCCCCCCCCCC)OC(=O)CCCCCCCCCCCCCCC)C(=O)NCC(=O)N[C@H](CO)C(=O)NCCCOCCOCCOCCCNC(=O)COCC(N)=O)CC(=O)N1CCNC(=O)CCCCCN\1C2=CC=C(S([O-])(=O)=O)C=C2CC/1=C/C=C/C=C/C1=[N+](CC)C2=CC=C(S([O-])(=O)=O)C=C2C1 UNILWMWFPHPYOR-KXEYIPSPSA-M 0.000 description 1
- JVLBOZIUMGNKQW-UHFFFAOYSA-N 1-hydroxy-3,4-seco-4(23),20(29)-lupadien-3,11-olid-28-oic acid 28-O-alpha-L-rhamnopyranosyl-(1->4)-O-beta-D-glucopyranosyl-(1->6)-O-beta-D-glucopyranoside Natural products OC1C(O)C(O)C(C)OC1OC1C(CO)OC(OCC2C(C(O)C(O)C(OC(=O)C34C(C(CC3)C(C)=C)C3C(C5(C)CCC(C6(C)C(O)CC(=O)OC(C56)C3)C(C)=C)(C)CC4)O2)O)C(O)C1O JVLBOZIUMGNKQW-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- HAEQAUJYNHQVHV-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-phenylbenzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NC2=CC=CC=C2)C=CC=1 HAEQAUJYNHQVHV-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 241000208340 Araliaceae Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241001164374 Calyx Species 0.000 description 1
- WIDAUXGFFXJZKU-HVLVMTFESA-N Chiisanoside Natural products C[C@@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)[C@H](OC[C@H]3O[C@@H](OC(=O)[C@]45CC[C@H]([C@@H]4[C@H]6C[C@H]7OC(=O)C[C@@H](O)[C@@H]8[C@@H](CC[C@](C)([C@H]78)[C@]6(C)CC5)C(=C)C)C(=C)C)[C@H](O)[C@@H](O)[C@@H]3O)O[C@@H]2CO)[C@H](O)[C@H](O)[C@H]1O WIDAUXGFFXJZKU-HVLVMTFESA-N 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 235000011511 Diospyros Nutrition 0.000 description 1
- 244000236655 Diospyros kaki Species 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 1
- 208000007882 Gastritis Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- MCYHPZGUONZRGO-VKHMYHEASA-N L-cysteine methyl ester hydrochloride Natural products COC(=O)[C@@H](N)CS MCYHPZGUONZRGO-VKHMYHEASA-N 0.000 description 1
- WHOHXJZQBJXAKL-DFWYDOINSA-N Mecysteine hydrochloride Chemical compound Cl.COC(=O)[C@@H](N)CS WHOHXJZQBJXAKL-DFWYDOINSA-N 0.000 description 1
- 102000013967 Monokines Human genes 0.000 description 1
- 108010050619 Monokines Proteins 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- MSPCIZMDDUQPGJ-UHFFFAOYSA-N N-methyl-N-(trimethylsilyl)trifluoroacetamide Chemical compound C[Si](C)(C)N(C)C(=O)C(F)(F)F MSPCIZMDDUQPGJ-UHFFFAOYSA-N 0.000 description 1
- 235000017879 Nasturtium officinale Nutrition 0.000 description 1
- 240000005407 Nasturtium officinale Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 229930012538 Paclitaxel Natural products 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 239000004902 Softening Agent Substances 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 235000013334 alcoholic beverage Nutrition 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- 201000006662 cervical adenocarcinoma Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- JVLBOZIUMGNKQW-JBPVHNHLSA-N chiisanoside Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](CO)O[C@@H](OC[C@@H]2[C@H]([C@H](O)[C@@H](O)[C@H](OC(=O)[C@@]34[C@H]([C@@H](CC3)C(C)=C)[C@@H]3[C@@]([C@]5(C)CC[C@H]([C@]6(C)[C@H](O)CC(=O)O[C@@H]([C@@H]56)C3)C(C)=C)(C)CC4)O2)O)[C@H](O)[C@H]1O JVLBOZIUMGNKQW-JBPVHNHLSA-N 0.000 description 1
- SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 1
- 235000019219 chocolate Nutrition 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 206010009887 colitis Diseases 0.000 description 1
- 201000010897 colon adenocarcinoma Diseases 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 229940125797 compound 12 Drugs 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 238000001212 derivatisation Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 235000011869 dried fruits Nutrition 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 239000000469 ethanolic extract Substances 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000012041 food component Nutrition 0.000 description 1
- 239000005417 food ingredient Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000002196 fr. b Anatomy 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 230000013595 glycosylation Effects 0.000 description 1
- 238000006206 glycosylation reaction Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002373 hemiacetals Chemical group 0.000 description 1
- 208000014617 hemorrhoid Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 206010073071 hepatocellular carcinoma Diseases 0.000 description 1
- 238000005570 heteronuclear single quantum coherence Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 235000015243 ice cream Nutrition 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- DEXFQQWSJHKUIA-UHFFFAOYSA-N isochiisanoside Natural products OC1C(O)C(O)C(C)OC1OC1C(CO)OC(OCC2C(C(O)C(O)C(OC(=O)C34C(C(CC3)C(C)=C)C3C(C5(C)CCC6C(C)(C)OC(CC(O)=O)C6(C)C5C(O)C3)(C)CC4)O2)O)C(O)C1O DEXFQQWSJHKUIA-UHFFFAOYSA-N 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 206010025135 lupus erythematosus Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 235000013372 meat Nutrition 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical group C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical group C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 1
- 230000000116 mitigating effect Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 210000002864 mononuclear phagocyte Anatomy 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 235000012149 noodles Nutrition 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 238000012585 nuclear overhauser effect spectroscopy experiment Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000003715 nutritional status Nutrition 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000004783 oxidative metabolism Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 229960001592 paclitaxel Drugs 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 201000001245 periodontitis Diseases 0.000 description 1
- 235000013550 pizza Nutrition 0.000 description 1
- 230000010287 polarization Effects 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000012925 reference material Substances 0.000 description 1
- 235000021067 refined food Nutrition 0.000 description 1
- 230000000246 remedial effect Effects 0.000 description 1
- 201000003068 rheumatic fever Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 238000011012 sanitization Methods 0.000 description 1
- 235000013580 sausages Nutrition 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000009759 skin aging Effects 0.000 description 1
- 235000011888 snacks Nutrition 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 238000012916 structural analysis Methods 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 208000037816 tissue injury Diseases 0.000 description 1
- 206010044008 tonsillitis Diseases 0.000 description 1
- 229940124594 traditional oriental medicine Drugs 0.000 description 1
- 238000002495 two-dimensional nuclear magnetic resonance spectrum Methods 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
- A61K36/254—Acanthopanax or Eleutherococcus
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/105—Plant extracts, their artificial duplicates or their derivatives
- A23L33/11—Plant sterols or derivatives thereof, e.g. phytosterols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Natural Medicines & Medicinal Plants (AREA)
- Botany (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Mycology (AREA)
- Pharmacology & Pharmacy (AREA)
- Microbiology (AREA)
- Medicinal Chemistry (AREA)
- Medical Informatics (AREA)
- Biotechnology (AREA)
- Alternative & Traditional Medicine (AREA)
- Birds (AREA)
- Nutrition Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Medicines Containing Plant Substances (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
본 발명은 오갈피 유래 신규 트리터페노이드 화합물들 및 이를 포함하는 항염증 조성물에 대한 것이다.The present invention relates to novel triterpenoid compounds derived from anthracnose and an antiinflammatory composition comprising the same.
오갈피(아칸토파낙스 세실리플로러스, Acanthopanax sessiliflorus)(Rupr. et Maxim)는 두릅나무과(Araliaceae)에 속하며, 한국, 중국 및 일본에 넓게 분포한다. 오갈피 종은 전통 한의학에서 류머티스 관절염, 당뇨, 암, 고혈압 및 뇌혈관질환의 치료에 널리 사용되었다(한국공개특허 10-1168379호). 그러나 대부분의 오갈피 연구는 오갈피종의 잎, 줄기 및 뿌리에 주로 중점을 두었으며, 그 열매를 다룬 연구는 매우 적다.
Acanthopanax cecilis , acanthopanax sessiliflorus (Rupr. et Maxim) belongs to Araliaceae and is widely distributed in Korea, China and Japan. Ogallippi has been widely used in traditional oriental medicine for the treatment of rheumatoid arthritis, diabetes, cancer, hypertension and cerebrovascular disease (Korean Patent Laid-Open No. 10-1168379). However, most of the Ogalli studies have focused primarily on the leaves, stems and roots of the Ogallippi species, and very few studies have examined the fruit.
염증은 단핵구(monocytes) 및/또는 대식세포(macrophages)의 활성이 수반되는 과정이다. 대식세포의 활성화는 사이토카인, 산화질소(NO) 또는 프로스타글라딘 등과 같은 많은 염증성 매개체들을 방출시킨다. NO의 과활성화는 조직 상처, 패혈 쇼크, 신경 손상, 세포사 및 괴사(Wang L, Son HJ, Xu ML, Hu JH, Wang MH. Anti-inflammatory and anticancer properties of dichloromethane and butanol fractions from the stem bark of Broussonetia papyrifera. J Korean Soc Appl Biol Chem 2010; 53(3): 297-303)를 포함하는 다양한 해로운 반응을 야기한다. 따라서, iNOS 발현을 막음으로써, NO 생산을 억제하는 것은 다양한 염증성 질환의 치료를 위한 유용한 전략이다. LPS는 다양한 세포 타입에서 iNOS 및 COX-2와 같은 사이토카인, 염증전 독소의 생산을 촉발시키는, 그람-음성 박테리아의 외막의 한 부분이다(Kim HJ, Park TS, Jung MS, Son JH. Study on the anti-oxidant and anti-inflammatory activities of sarcocarp and calyx of persimmon. J Appl Biol Chem 2011; 54(2): 71-78). 단핵 포식세포(mononuclear phagocytes)들이 박테리아 LPS에 노출되는 것은, 시험 세팅에서 염증전 자극으로 LPS가 널리 사용되는 것과 같이, 포식작용, 산화성 대사의 증가, 및 모노카인(monokines)들의 합성 및 분비를 포함하는 다양한 세포 활성을 촉진하는 것으로 알려져 있다.
Inflammation is a process involving the activation of monocytes and / or macrophages. Activation of macrophages releases many inflammatory mediators such as cytokines, nitric oxide (NO) or prostaglandins. NO and hyperactivity are associated with tissue injury, septic shock, nerve injury, cell death and necrosis (Wang L, Son HJ, Xu ML, Hu JH, Wang MH, papyrifera. J Korean Soc Appl Biol Chem 2010; 53 (3): 297-303). Thus, inhibiting NO production by inhibiting iNOS expression is a useful strategy for the treatment of a variety of inflammatory diseases. LPS is part of the outer membrane of gram-negative bacteria, which triggers the production of cytokines, inflammatory precursors, such as iNOS and COX-2, in a variety of cell types (Kim HJ, Park TS, Jung MS, the anti-oxidant and anti-inflammatory activities of sarcocarp and calyx of persimmon. J Appl Biol Chem 2011; 54 (2): 71-78). The exposure of mononuclear phagocytes to bacterial LPS involves predation, increased oxidative metabolism, and the synthesis and secretion of monokines, as LPS is widely used as a pre-inflammatory stimulus in test settings. Lt; RTI ID = 0.0 > cell < / RTI >
본 발명자들은 오갈피 열매를 연구하던 중, 이로부터 분리된 특정 화합물들이 항염증 활성을 갖는 것을 확인하고 본 발명을 완성하였다.
The inventors of the present invention have confirmed that certain compounds isolated therefrom have anti-inflammatory activity while studying acanthopanoptera, and completed the present invention.
본 발명의 목적은 항염증 조성물을 제공하는 것이다.It is an object of the present invention to provide an anti-inflammatory composition.
상기 목적을 달성하기 위하여 본 발명은 오갈피로부터 분리한 신규 화합물 및 이를 포함하는 항염증 조성물을 제공한다. In order to accomplish the above object, the present invention provides a novel compound isolated from the ogal and an anti-inflammatory composition containing the same.
본 발명의 화합물 및 조성물은 항염증 효과가 있다.The compounds and compositions of the present invention have anti-inflammatory effects.
도 1은 화합물 1 및 화합물 3의 1H-1H COSY, HMBC 및 NOESY 상호관련성을 나타낸다.Figure 1 shows the 1H-1H COZY, HMBC and NOESY correlations of
본 발명은 항염증 활성을 갖는, 하기 화학식 1 내지 3으로 표시되는 화합물 중 어느 하나의 화합물에 대한 것이다:
The present invention is directed to any one of compounds represented by the following formulas (1) to (3) having anti-inflammatory activity:
<화학식 1>≪ Formula 1 >
이때,At this time,
R1은 H 또는 탄소 수 5 이하의 알킬이고,R < 1 > is H or alkyl having up to 5 carbon atoms,
R2는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R2 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R3는 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
R3 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
<화학식 2>(2)
이때,At this time,
R4는 H 또는 탄소 수 5 이하의 알킬이고,R4 is H or alkyl having up to 5 carbon atoms,
R5는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R5 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R6은 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R6 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R7은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
R7 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
<화학식 3>(3)
이때,At this time,
R8은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
R8 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
또한 본 발명은 하기 화학식 1 내지 3으로 표시되는 화합물 중 어느 하나를 포함하는 것을 특징으로 하는 항염증 조성물에 대한 것이다:
The present invention also relates to an anti-inflammatory composition comprising any one of the compounds represented by the following formulas (1) to (3):
<화학식 1>≪ Formula 1 >
이때,At this time,
R1은 H 또는 탄소 수 5 이하의 알킬이고,R < 1 > is H or alkyl having up to 5 carbon atoms,
R2는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R2 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R3는 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
R3 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
<화학식 2>(2)
이때,At this time,
R4는 H 또는 탄소 수 5 이하의 알킬이고,R4 is H or alkyl having up to 5 carbon atoms,
R5는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R5 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R6은 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R6 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R7은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
R7 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
<화학식 3>(3)
이때,At this time,
R8은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
R8 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
본 발명은 또한 오갈피 추출물을 포함하는 항염증 조성물에 대한 것이다.
The present invention is also directed to an anti-inflammatory composition comprising an extract of augury.
이하, 본 발명을 자세히 설명한다.
Hereinafter, the present invention will be described in detail.
화학식 1의 화합물The compound of formula (1)
본 발명은 화학식 1의 화합물에 대한 것이다. 또한 본 발명은 화학식 1의 화합물을 포함하는 항염증 조성물에 대한 것이다. 또한 본 발명은 오갈피 추출물을 포함하는 항염증 조성물에 대한 것으로, 상기 오갈피 추출물은 화학식 1의 화합물을 포함할 수 있다. 상기 화합물은 천연물, 바람직하게는 오갈피로부터 추출될 수 있으며, 합성될 수도 있다.
The present invention is directed to compounds of formula (I). The present invention also relates to an anti-inflammatory composition comprising a compound of formula (I). The present invention also relates to an anti-inflammatory composition comprising an extract from a plant extract, which may comprise a compound of formula (I). The compound can be extracted from a natural product, preferably an oregano, and synthesized.
<화학식 1>≪ Formula 1 >
이때,At this time,
R1은 H 또는 탄소 수 5 이하의 알킬이고,R < 1 > is H or alkyl having up to 5 carbon atoms,
R2는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R2 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R3는 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
R3 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
이때, 상기 탄소 수 5 이의의 알킬은 직쇄 또는 측쇄 사슬인 C1-5알킬이며, 바람직하게는 C1-3알킬이다. 상기 탄소 수 5 이하의 알콕시는 메톡시, 에톡시, 프로톡시, 부톡시, 펜톡시 등이다. 상기 글루코피라노실은 베타-D-글루코피라노실인 것이 바람직하다. 상기 화합물은 천연물, 바람직하게는 오갈피로부터 추출될 수 있으며, 합성될 수도 있다.The alkyl of 5 carbon atoms is C1-5 alkyl, preferably C1-3 alkyl, which is a linear or branched chain. The alkoxy having 5 or less carbon atoms is methoxy, ethoxy, propoxy, butoxy, pentoxy, and the like. The glucopyranosyl is preferably beta-D-glucopyranosyl. The compound can be extracted from a natural product, preferably an oregano, and synthesized.
바람직하게는 , R1은 CH3, R2는 OH, R3는 H(화합물 1)이거나, 또는 R1은 H, R2는 H, R3는 베타-D-글루코피라노실(화합물 2)이다.
Preferably, R1 is CH3, R2 is OH, R3 is H (compound 1), or R1 is H, R2 is H and R3 is beta-D-glucopyranosyl (compound 2).
화학식 2의 화합물The compound of formula 2
본 발명은 화학식 2의 화합물에 대한 것이다. 또한 본 발명은 화학식 2의 화합물을 포함하는 항염증 조성물에 대한 것이다. 또한 본 발명은 오갈피 추출물을 포함하는 항염증 조성물에 대한 것으로, 상기 오갈피 추출물은 화학식 2의 화합물을 포함할 수 있다. 상기 화합물은 천연물, 바람직하게는 오갈피로부터 추출될 수 있으며, 합성될 수도 있다.
The present invention relates to compounds of formula (2). The present invention also relates to an anti-inflammatory composition comprising a compound of formula (2). In addition, the present invention relates to an anti-inflammatory composition comprising an extract from a plant extract, which may comprise a compound of the general formula (2). The compound can be extracted from a natural product, preferably an oregano, and synthesized.
<화학식 2>(2)
이때,At this time,
R4는 H 또는 탄소 수 5 이하의 알킬이고,R4 is H or alkyl having up to 5 carbon atoms,
R5는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R5 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R6은 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,R6 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R7은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
R7 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
이때, 상기 탄소 수 5 이의의 알킬은 직쇄 또는 측쇄 사슬인 C1-5알킬이며, 바람직하게는 C1-3알킬이다. 상기 탄소 수 5 이하의 알콕시는 메톡시, 에톡시, 프로톡시, 부톡시, 펜톡시 등이다. 상기 글루코피라노실은 베타-D-글루코피라노실인 것이 바람직하다. The alkyl of 5 carbon atoms is C1-5 alkyl, preferably C1-3 alkyl, which is a linear or branched chain. The alkoxy having 5 or less carbon atoms is methoxy, ethoxy, propoxy, butoxy, pentoxy, and the like. The glucopyranosyl is preferably beta-D-glucopyranosyl.
바람직하게는 R4는 CH3, R5는 OH, R6은 H, R7은 H이거나(화합물 3), R4는 CH3, R5는 OH, R6은 H, R7은 베타-D-글루코피라노실이거나(화합물 4), R4는 CH3, R5는 OH, R6은 OH, R7은 베타-D-글루코피라노실(화합물 5)이거나, R4는 H, R5는 H, R6은 OH, R7은 베타-D-글루코피라노실(화합물 6)이다.
Preferably, R4 is CH3, R5 is OH, R6 is H, R7 is H (compound 3), R4 is CH3, R5 is OH, R6 is H and R7 is beta-D-glucopyranosyl (compound 4) , R4 is CH3, R5 is OH, R6 is OH and R7 is beta-D-glucopyranosyl (Compound 5), or R4 is H, R5 is H, R6 is OH and R7 is beta-D-glucopyranosyl Compound 6).
화학식 3의 화합물The compound of
본 발명은 화학식 3의 화합물에 대한 것이다. 또한 본 발명은 화학식 3의 화합물을 포함하는 항염증 조성물에 대한 것이다. 또한 본 발명은 오갈피 추출물을 포함하는 항염증 조성물에 대한 것으로, 상기 오갈피 추출물은 화학식 3의 화합물을 포함할 수 있다. 상기 화합물은 천연물, 바람직하게는 오갈피로부터 추출될 수 있으며, 합성될 수도 있다.
The present invention relates to compounds of formula (3). The present invention also relates to an anti-inflammatory composition comprising a compound of formula (3). The present invention also relates to an anti-inflammatory composition comprising an extract of Ocgal, wherein the Ogalli extract may comprise a compound of formula (3). The compound can be extracted from a natural product, preferably an oregano, and synthesized.
<화학식 3>(3)
이때,At this time,
R8은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
R8 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
이때, 상기 탄소 수 5 이의의 알킬은 직쇄 또는 측쇄 사슬인 C1-5알킬이며, 바람직하게는 C1-3알킬이다. The alkyl of 5 carbon atoms is C1-5 alkyl, preferably C1-3 alkyl, which is a linear or branched chain.
바람직하게는 R8은 베타-D-글루코피라노실이다(화합물 7).
Preferably R8 is beta-D-glucopyranosyl (Compound 7).
오갈피 추출물Acaricus extract
본 발명의 오갈피 추출물은 오갈피의 뿌리, 줄기, 잎, 열매 등을 물 또는 탄소 수 3 이하의 저가 알코올로 추출한 추출물이다. 상기 저가 알코올은 바람직하게는 에탄올이다.
The extract of the present invention is an extract obtained by extracting roots, stems, leaves, fruits and the like of watercress with water or a low-alcohol having 3 or less carbon atoms. The lower alcohol is preferably ethanol.
항염증 조성물Antiinflammatory composition
본 발명의 항염증 조성물은 산화질소(NO)의 생산을 저해하고, NO의 과활성을 억제하여, 염증의 진행을 억제한다. 이로써 본 발명의 항염증 조성물은 조직 상처, 패혈 쇼크, 신경 손상, 세포사 및 괴사 등을 예방하게 된다.The anti-inflammatory composition of the present invention inhibits the production of nitric oxide (NO), inhibits the hyperactivity of NO, and inhibits the progress of inflammation. As a result, the anti-inflammatory composition of the present invention prevents tissue wounds, septic shock, nerve damage, cell death and necrosis.
본 발명의 항염증 조성물은 염증성 질환의 예방 및 치료용 약학적 조성물, 염증성 질환의 예방 및 개선용 식품 조성물 또는 화장료 조성물일 수 있다.
The anti-inflammatory composition of the present invention may be a pharmaceutical composition for the prevention and treatment of inflammatory diseases, a food composition or a cosmetic composition for the prevention and improvement of inflammatory diseases.
약학적 조성물Pharmaceutical composition
본 발명의 항염증 조성물은 염증성 질환의 예방 및 치료용 약학적 조성물일 수 있다. 상기 염증성 질환은 피부염, 알레르기, 아토피, 천식, 결막염, 치주염, 비염, 중이염, 인후염, 편도염, 폐렴, 위궤양, 위염, 크론병, 대장염, 치질, 통풍, 강직성 척추염, 류마티스 열, 루푸스, 섬유근통 (fibromyalgia), 건선관절염, 골관절염, 류마티스 관절염, 견관절주위염, 건염, 건초염, 건주위염, 근육염, 간염, 방광염, 신장염, 쇼그렌 증후군(sjogren's syndrome), 다발성 경화증, 및 급성 및 만성 염증 질환으로 이루어지는 군으로부터 선택되는 어느 하나일 수 있다. 또한 본 발명의 약학적 조성물은 염증 완화, 피부자극 완화, 피부 진정, 아토피의 예방 및 개선, 여드름의 예방 및 치료용일 수 있다.
The anti-inflammatory composition of the present invention may be a pharmaceutical composition for the prevention and treatment of inflammatory diseases. The inflammatory disease may be selected from the group consisting of dermatitis, allergy, atopy, asthma, conjunctivitis, periodontitis, rhinitis, otitis, sore throat, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, ankylosing spondylitis, rheumatic fever, lupus, fibromyalgia ), Rheumatoid arthritis, osteoarthritis, rheumatoid arthritis, periarthritis, tendinitis, hay fever, tendinitis, myositis, hepatitis, cystitis, nephritis, sjogren's syndrome, multiple sclerosis and acute and chronic inflammatory diseases It can be either. In addition, the pharmaceutical composition of the present invention can be used for inflammation relief, skin irritation mitigation, skin soothing, prevention and improvement of atopy, and prevention and treatment of acne.
본 발명의 약학적 조성물은 조성물 100 중량부에 대하여 본 발명의 상기 화합물, 오갈피 추출물 또는 이드릉ㄹ 포함하는 항염증 조성물을 0.01 내지 99.99 중량부 포함할 수 있으며, 바람직하게는 60 내지 98 중량부 포함할 수 있다. 더욱 바람직하게는 본 발명의 약학적 조성물은 조성물 100 중량부에 대하여 본 발명의 화합물을 90 내지 95 중량부 포함할 수 있다. 그러나 이는 투약자의 필요에 따라 증감할 수 있으며, 식생활, 영양 상태, 병의 진행 정도, 염증의 정도 등 상황에 따라 적절히 증감할 수 있다. 또한 본 발명의 약학적 조성물은 본 발명의 화합물을 약학적으로 허용되는 담체와 함께 적합한 형태로 제형화 될 수 있다. ‘약학적으로 허용되는’이란 생리학적으로 허용되고 인간에게 투여될 때, 통상적으로 위장장애, 현기증 등과 같은 알레르기 반응 또는 이와 유사한 반응을 일으키지 않는 조성물을 말한다.
The pharmaceutical composition of the present invention may contain 0.01 to 99.99 parts by weight, preferably 60 to 98 parts by weight, of the compound of the present invention, an anti-inflammatory agent extract or an anti-inflammatory composition containing the anti-inflammatory agent, can do. More preferably, the pharmaceutical composition of the present invention may contain 90 to 95 parts by weight of the compound of the present invention per 100 parts by weight of the composition. However, this can be increased or decreased according to the need of the medicinal person, and it can be appropriately increased or decreased according to the situation such as the diet, nutritional status, disease progression, degree of inflammation. In addition, the pharmaceutical composition of the present invention may be formulated into a suitable form together with a pharmaceutically acceptable carrier. &Quot; Pharmaceutically acceptable " refers to compositions which are physiologically acceptable and which, when administered to humans, do not normally cause allergic reactions such as gastrointestinal disorders, dizziness, or the like.
본 발명의 약학적 조성물은 경구 또는 비경구로 투여가 가능하며 일반적인 의약품 제제의 형태로 사용될 수 있다. 바람직한 약제학적 제제는 정제, 경질 또는 연질 캅셀제, 액제, 현탁제 등과 같은 경구투여용 제제가 있으며 이들 약제학적 제제는 약제학적으로 허용 가능한 통상의 담체, 예를 들어 경구투여용 제제의 경우에는 부형제, 결합제, 붕해제, 활택제, 가용화제, 현탁화제, 보존제 또는 증량제 등을 사용하여 조제할 수 있다.
The pharmaceutical composition of the present invention can be administered orally or parenterally and can be used in the form of a general pharmaceutical preparation. The preferred pharmaceutical preparations are those for oral administration such as tablets, hard or soft capsules, liquids, suspensions, etc. These pharmaceutical preparations can be prepared into conventional pharmaceutically acceptable carriers, for example, excipients such as excipients, Binders, disintegrators, lubricants, solubilizers, suspending agents, preservatives or extenders.
본 발명의 약학적 조성물의 투여 용량은, 환자의 상태, 연령, 성별 및 합병증 등의 다양한 요인에 따라 전문가에 의해 결정될 수 있지만 일반적으로는 성인 1kg 당 0.1㎎ 내지 10g, 바람직하게는 10 mg 내지 5g의 용량으로 투여될 수 있다. 또, 단위 제형당 상기 약학적 조성물의 1일 용량 또는 이의 1/2, 1/3 또는 1/4의 용량이 함유되도록 하며, 하루 1 내지 6 회 투여될 수 있다. 그러나 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 양은 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로도 사용될 수 있다.
The dosage of the pharmaceutical composition of the present invention may be determined by a specialist depending on various factors such as the condition of the patient, age, sex, and complications, but is generally from 0.1 mg to 10 g, preferably from 10 mg to 5 g ≪ / RTI > Also, the daily dosage of the pharmaceutical composition per unit dosage form, or a half, 1/3 or 1/4 dose thereof, may be contained, and may be administered 1 to 6 times per day. However, in the case of long-term intake for the purpose of health and hygiene or for the purpose of controlling health, the amount may be less than the above range, and the active ingredient may be used in an amount of more than the above range since there is no problem in terms of safety.
식품 조성물Food composition
본 발명의 식품은 건강보조식품, 건강기능식품, 기능성 식품 등이 될 수 있으나 이에 제한되는 것은 아니며, 천연식품, 가공식품, 환자식품, 일반적인 식자재 등에 본 발명의 화합물을 첨가하는 것도 포함된다.
The food of the present invention may be a health supplement food, a health functional food, a functional food, and the like, but is not limited thereto and includes the addition of the compound of the present invention to natural foods, processed foods, patient foods, and general food ingredients.
본 발명의 식품 조성물은, 상기 본 발명의 화합물 또는 이를 포함하는 항염증 조성물을 그대로 첨가하거나 다른 식품 또는 식품 조성물과 함께 사용될 수 있으며, 통상적인 방법에 따라 적절하게 사용될 수 있다. 유효 성분의 혼합양은 그의 사용 목적(예방, 개선 또는 치료적 처치)에 따라 적합하게 결정될 수 있다. 일반적으로, 본 발명의 항염증 조성물 또는 화합물 또는 오갈피 추출물은, 식품 또는 음료의 제조 시에 식품 또는 음료의 원료 100 중량부에 대하여 0.1 내지 70 중량부, 바람직하게는 2 내지 50 중량부 첨가될 수 있다. 상기 화합물의 유효용량은 상기 약학적 조성물의 유효용량에 준해서 사용할 수 있으나, 건강 및 위생을 목적으로 하거나 또는 건강 조절을 목적으로 하는 장기간의 섭취의 경우에는 상기 범위 이하일 수 있으며, 유효성분은 안전성 면에서 아무런 문제가 없기 때문에 상기 범위 이상의 양으로도 사용될 수 있다.
The food composition of the present invention can be used as it is or in combination with other food or food compositions, and can be suitably used according to conventional methods. The amount of the active ingredient to be mixed can be suitably determined according to its intended use (prevention, improvement, or therapeutic treatment). In general, the anti-inflammatory composition or the compound or the extract of Ocarki of the present invention may be added in an amount of 0.1 to 70 parts by weight, preferably 2 to 50 parts by weight, relative to 100 parts by weight of the raw material of the food or beverage in the production of food or beverage have. The effective dose of the compound may be used in accordance with the effective dose of the pharmaceutical composition, but may be less than the above range for health and hygiene purposes or long-term intake for health control purposes, It can be used in an amount exceeding the range described above.
상기 식품의 종류에는 특별한 제한은 없다. 상기 식품 조성물은 정제, 경질 또는 연질 캅셀제, 액제, 현탁제 등과 같은 경구투여용 제제의 형태로 이용될 수 있으며, 이들 제제는 허용 가능한 통상의 담체, 예를 들어 경구투여용 제제의 경우에는 부형제, 결합제, 붕해제, 활택제, 가용화제, 현탁화제, 보존제 또는 증량제 등을 사용하여 조제할 수 있다.
There is no particular limitation on the kind of the food. The food composition may be used in the form of tablets, hard or soft capsules, liquids, suspensions, and the like, which may contain conventional excipients, such as excipients in the case of oral preparations, Binders, disintegrators, lubricants, solubilizers, suspending agents, preservatives or extenders.
상기 화합물 또는 본 발명의 항염증 조성물을 첨가할 수 있는 식품의 예로는 육류, 소세지, 빵, 쵸코렛, 캔디류, 스넥류, 과자류, 피자, 라면, 기타 면류, 껌류, 아이스크림류를 포함한 낙농제품, 각종 스프, 음료수, 차, 드링크제, 알콜 음료 및 비타민 복합제, 기타 영양제 등을 들 수 있으나 이들 종류의 식품으로 제한되는 것은 아니다.
Examples of the food to which the compound or the antiinflammatory composition of the present invention can be added include meat, sausage, bread, chocolate, candy, snack, confectionery, pizza, ramen, other noodles, gums, dairy products including ice cream, , Beverages, tea, drinks, alcoholic beverages and vitamin complexes, and other nutrients, but are not limited to these kinds of foods.
화장료Cosmetics 조성물 Composition
본 발명의 항염증 조성물은 화장료 조성물일 수 있다. 본 발명의 화장료 조성물은 피부 염증 예방 및 완화, 피부자극 완화, 피부 진정, 주름 개선 및 완화, 피부 노화 저해, 여드름의 예방 및 개선, 아토피의 예방 및 개선 효능을 갖는다.
The anti-inflammatory composition of the present invention may be a cosmetic composition. The cosmetic composition of the present invention has preventive and remedial effects on skin inflammation, alleviation of skin irritation, skin soothing, wrinkle improvement and alleviation, inhibition of skin aging, prevention and improvement of acne, prevention and improvement of atopy.
본 발명의 화장료 조성물은, 당업계의 통상적으로 제조되는 어떠한 제형에도 제조될 수 있으며 용액, 현탁액, 유탁액, 페이스트, 젤, 크림, 로션, 파우더, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션 및 스프레이 등으로 제형화될 수 있으나, 이에 제한되는 것은 아니다. 또한 본 발명의 화장료 조성물은 유연화장수, 영양화장수, 영양크림, 마사지크림, 에센스, 아이크림, 클렌징크림, 클렌징폼, 클렌징워터, 팩, 스프레이 또는 파우더 제형으로 제조될 수도 있다.
The cosmetic composition of the present invention may be prepared in any formulations conventionally produced in the art and may be formulated into a solution, suspension, emulsion, paste, gel, cream, lotion, powder, soap, surfactant- containing cleansing oil, powder foundation , An emulsion foundation, a wax foundation and a spray, but is not limited thereto. The cosmetic composition of the present invention may also be formulated as a softening agent, a nutritional lotion, a nutritional cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder.
본 발명의 이점 및 특징, 그리고 그것들을 달성하는 방법은 첨부되는 도면과 함께 상세하게 후술되어 있는 실시예들을 참조하면 명확해질 것이다. 그러나, 본 발명은 이하에서 개시되는 실시예들에 한정되는 것이 아니라 서로 다른 다양한 형태로 구현될 것이며, 단지 본 실시예들은 본 발명의 개시가 완전하도록 하며, 본 발명이 속하는 기술분야에서 통상의 지식을 가진 자에게 발명의 범주를 완전하게 알려주기 위해 제공되는 것이며, 본 발명은 청구항의 범주에 의해 정의될 뿐이다.
BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention, and the manner of achieving them, will be apparent from and elucidated with reference to the embodiments described hereinafter in conjunction with the accompanying drawings. It should be understood, however, that the invention is not limited to the disclosed embodiments, but is capable of many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, To fully disclose the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims.
<재료 및 방법>≪ Materials and methods >
식물plant
오갈피(A. sessilif lorus) 열매들은 2009년 8월 정선 농업센터, 정선, 대한민국으로부터 수득하였으며, 한국 전주 우석대학교 약학대학 김대균 교수에 의하여 확인받았다.
A. sessilif lorus were obtained from Jeongseon Agricultural Center, Jeongseon, Korea in August 2009 and confirmed by Prof. Dae-Gyun Kim of the College of Pharmacy, Woosuk University in Jeonju, Korea.
전반적인 실험 공정Overall experimental process
현미경으로 Fisher-John’s 녹는점 장치(melting point apparatus)를 이용하여 녹는점을 수득하였다. 편광은 JASCO P-1010 디지털 편광계로 측정하였다. H, 13C, 및 2D NMR 스펙트럼들은 Varian Unity INOVA AS 400 FT-NMR 인스트루먼트 상에 기록되었으며, 화학적 이동들은 내부표준으로서 테트라메틸실란(tetramethylsilane) (TMS)에 기초하여 δ (ppm)로 제공하였다. IR 스펙트럼은 Perkin-Elmer Spectrum One FT-IR 스펙트로미터로 수행하였다. HRFABMS는 JEOL JMS-700 매스 스펙트로미터를 이용하여 수득하였다. 온-칼럼(on-column) 연료 주입 장치(injection system) 및 이온화식 감지기(ionization detector (FID)를 갖춘 Shimadzu 가스 크로마토그래프(GC-14B)를 사용하였다. 실리카겔 60(Merck, 230-400 메쉬), LiChroprep RP-18 (Merck, 40-63 μm), 및 Sephadex LH-20 (Amersham Biosciences)를 칼럼 크로마토그래피(CC)에 사용하였다. 전코팅(precoat)된 겔 플레이트(Merck, Kieselgel 60 F254, 0.25 mm) 및 전코팅된 RP-18 F254s 플레이트(Merck)들을 분석 박막 크로마토그래피(analytical thin-layer chromatography)에 사용하였다. 스팟들은 10% 수성 H2SO4 용액을 분무하고 그 후 가열하여 가시화되었다.
Using a microscope, a melting point was obtained using a Fisher-John's melting point apparatus. Polarization was measured with a JASCO P-1010 digital polarimeter. H, 13 C, and 2D NMR spectra were recorded on a Varian Unity INOVA AS 400 FT-NMR instrument and chemical shifts were provided in delta (ppm) based on tetramethylsilane (TMS) as an internal standard. IR spectra were performed on a Perkin-Elmer Spectrum One FT-IR spectrometer. HRFABMS was obtained using a JEOL JMS-700 mass spectrometer. A Shimadzu gas chromatograph (GC-14B) equipped with an on-column fuel injection system and an ionization detector (FID) was used. Silica gel 60 (Merck, 230-400 mesh) , LiChroprep RP-18 (Merck, 40-63 μm), and Sephadex LH-20 (Amersham Biosciences) were used for column chromatography (CC). Precoated gel plates (Merck, Kieselgel 60 F254, 0.25 mm) and precoated RP-18 F254s plates (Merck) were used for analytical thin-layer chromatography. Spots were visualized by spraying with a 10% aqueous H2SO4 solution and then heating.
<실험예 1><Experimental Example 1>
오갈피(A. sessilif lorus)의 기건 과일들(10 kg)을 분말화하고 실온에서 수성 70% EtOH 36 L로 24시간 동안 3회 추출하였다. 진공 속에서 농축한 후, 상기 에탄올 추출물(2012 g)을 H2O (3 L)에서 현탁시키고, 그 후 EtOAc (3 L × 3) 및 n-BuOH (3 L)으로 연속하여 분배하고(partition), 그 후 농축하여, EtOAc (E, 118 g), n-BuOH (B, 284 g), 및 물 (1610 g) 분획들을 제공하였다. 분획 E (100 g)를 CHCl3-MeOH (각각 15:1 → 10:1 → 5:1 → 3:1 → 1:1, 2.8 L)의 구배(gradient)를 이용하여 실리카 겔 CC(15 × 21 cm)에 가하여, 14개 분획을 수득하였다(E1 내지 E14). 분획 E3 [36.3 g, 용출 부피/총 부피 (Ve/ Vt) 0.15-0.33]는 실리카겔 CC [6 × 16 cm, CHCl3-EtOAc (7:1, 5.5 L)]에 가하여, 5개의 소분획(subfraction)들을 수득하였다(E3-1 내지 E3-5). 소분획 E3-3 (1.80 g, Ve/Vt 0.34-0.53)의 CC [silicagel (3.5 × 16 cm), n-hexane-EtOAc (1:1, 3 L)]는 19개 소분획들을 제공하였다(E3-3-1 내지 E3-3-19). 소분획 E3-3-7 (184 mg, Ve/Vt 0.30-0.41)는 CC[RP-18 (3.5 × 5.5 cm), acetone-H2O (3:2, 1.6 L)]에 의하여 분리되어 화합물 3[19.7 mg, Ve/Vt 0.46-0.65, TLC (RP-18 F254s) Rf 0.55, acetone-H2O (4:1)] 및 화합물 9 [12.2 mg, Ve/Vt 0.87-0.92, TLC (RP-18 F254s) Rf 0.25, acetone-H2O (4:1)]을 제공하였다. 소분획 E3-3-9 (95 mg,Ve/Vt 0.49-0.53)은 [RP-18 (3.5 × 6.5 cm),아세톤-메탄올-H2O (1:1:4, 0.8 L)] 크로마토그래피를 하여 화합물 8[38.9 mg,Ve/Vt 0.52-0.76, TLC (RP-18 F254s) Rf 0.40, 아세톤-메탄올-H2O (1:1:1)]를 제공하였다. 분획 E8 (8.98 g, Ve/Vt 0.59-0.67)은 실리카겔 CC [4 × 12 cm, CHCl3-MeOH-H2O (16:3:1 → 13:3:1, each 3.7 L)]를 이용하여 분획하고, 9개의 소분획을 제공하였다(E8-1 내지 E8-9). 소분획 E8-4 (1.85 g, Ve/Vt 0.45-0.58)을 CC [RP-18 (3.5 × 6.5 cm), MeOH-H2O (3:1, 1.2 L)]를 이용하여 정제하고, 화합물 2[93 mg, Ve/Vt 0.84-0.98, TLC (RP-18 F254s) Rf 0.40, 메탄올-H2O (5:1)]를 제공하였다. 소분획 E8-5 (1.22 g, Ve/Vt 0.59-0.68)를 Sephadex LH 20 CC [3 × 50 cm, MeOH-H2O (4:1, 1.8 L)]를 이용하여 분획하여 5개의 소분획 (E8-5-1 to E8-5-5)을 수득하였다. CC [RP-18 (3 × 6 cm), MeOH-H2O (1:1, 0.6 L)]를 이용한 소분획 E8-5-1 (280 mg, Ve/Vt 0.01-0.25)의 정제로 화합물 10[35 mg, Ve/Vt 0.77-0.85, TLC (RP-18 F254s) Rf 0.40, MeOH-H2O (2:1)]을 얻었다. 분획 E9 (5.80 g, Ve/Vt 0.68-0.72)를 실리카 겔 CC [5 × 18 cm, CHCl3-EtOH-H2O (16:3:1 → 13:3:1 → 10:3:1, each 3.2 L)]을 이용하여 분획하고, 4개의 소분획들을 수득하였다(E9-1 내지 E9- 4). 소분획 E9-1 (1.25 g, Ve/Vt 0.01-0.30)을 용리제로서 RP- 18 (3 × 6 cm) CC using MeOH-H2O (3:1, 1.5 L)로 분리하고, 나아가 RP-18 CC (2.5 × 5 cm)로 정제하고 MeOH-H2O (2:1)로 용출시키고, 화합물 4[23 mg, Ve/Vt 0.54-0.61, TLC (RP-18 F254s) Rf 0.30, MeOH-H2O (3:1)]를 수득하였다. 소분획 E9-2 (2.45 g, Ve/Vt 0.31-0.68)를 RP-18 (5 × 5.5 cm)으로 크로마토그래피하고, 메탄올-H2O (1:1 → 2:1, 각각 1.8 L)로 용출시키고, 11개 소분획들을 제공하였다(E9-2-1 to E-9-2-11). 소분획 E9-2-7 (140 mg, Ve/Vt 0.66-0.78)을 실리카 겔(3 × 15 cm)로 정제하고 CHCl3-메탄올 (3:1, 0.8 L)로 용출시켜, 화합물 1 [21 mg, Ve/Vt 0.22-0.32, TLC (실리카 겔 F254) Rf 0.55, CHCl3-메탄올-H2O (13:3:1)]을 제공하였다. 분획 E10 (6.75 g, Ve/Vt 0.72-0.78)은 실리카 겔 CC [7 × 15 cm, CHCl3-MeOH-H2O (17:3:1 → 15:3:1 → 13:3:1, each 3.2 L)]을 이용하여 분별하였으며(fractionate), 10개 소분획들을 제공하였다(E10-1 to E10-10). 소분획 E10-6 (624 mg, Ve/Vt 0.75-0.82)은 RP-18 (3.5 × 9 cm) CC 에 의하여 분리되었으며, 메탄올-H2O (2:3, 1.7 L)로 용출시키고, 화합물 6[8 mg, Ve/Vt 0.78-0.81, TLC (RP-18 F254s) Rf 0.50, 메탄올-H2O (3:1)]을 수득하였다. 소분획 E10-4 (1.64 g, Ve/Vt 0.35-0.60)은 RP-18 column (4.5 × 10 cm)로 크로마토그래피하고, 메탄올-H2O (1:1.5, 2 L)로 용출시키고, 나아가 RP-18 (2.5 × 7 cm) CC [E10-4-14 (34 mg, Ve/Vt 0.76-0.81)]에 의하여 정제하고, 용리제로 메탄올-H2O (2:1, 0.4 L)을 사용하여, 화합물 5[10 mg, Ve/Vt 0.50-1.00, TLC (RP-18 F254s) Rf 0.30, MeOH-H2O (2:1)]를 제공하였다. 분획 E12 (10.56 g, Ve/ Vt 0.84-0.91)은 실리카 겔 CC [CHCl3-EtOH-H2O, 17:3:1 → 12:3:1 → 9:3:1 (각각 3.5 L)]을 이용하여 분별하였으며, 25개 소분획들을 제공하였다(E12-1 내지 E12-25). 소분획 E12-6 (559 mg, Ve/Vt 0.23-0.28)를 RP-18 CC [3.5 × 4.5 cm, MeOH-H2O (1:3 → 1:2 → 1:1, each 0.8 L)]에 가하여 18개 분획들(E12-6-1 to E12-6-18)을 제공하였으며, 나아가 RP-18 CC [E12-6-12 (115 mg, Ve/Vt 0.54-0.70)]로 정제하고, 용리제로서 EtOH-MeOH-H2O (1:1:3, 2.4 L)를 이용하여, 화합물 7[12 mg, Ve/Vt 0.50-0.60, TLC (RP-18 F254s) Rf 0.60, EtOH-MeOH-H2O (1:1:1)]을 수득하였다.
Dried fruits of A. sessilif lorus (10 kg) were powdered and extracted 3 times with 36 L of aqueous 70% EtOH at room temperature for 24 hours. After concentrating in vacuo, the ethanol extract (2012 g) was suspended in H 2 O (3 L), then partitioned successively with EtOAc (3 L × 3) and n-BuOH (3 L) It was then concentrated to give EtOAc (E, 118 g), n-BuOH (B, 284 g), and water (1610 g) fractions. Fraction E (100 g) was purified by column chromatography on silica gel CC (15 x 21 < RTI ID = 0.0 > (5 x < / RTI > cm) to obtain 14 fractions (E1 to E14). Fraction E3 [36.3 g, elution volume / total volume (Ve / Vt) 0.15-0.33] was added to silica gel CC [6 x 16 cm, CHCl3-EtOAc (7: 1, 5.5 L) ) (E3-1 to E3-5). CC [silicagel (3.5 x 16 cm), n-hexane-EtOAc (1: 1, 3 L)] of small fraction E3-3 (1.80 g, Ve / Vt 0.34-0.53) provided 19 small fractions E3-3-1 to E3-3-19). The small fraction E3-3-7 (184 mg, Ve / Vt 0.30-0.41) was isolated by CC [RP-18 (3.5 x 5.5 cm), acetone- (RP-18 F254s) Rf 0.55, acetone-H2O (4: 1)] and Compound 9 [12.2 mg, Ve / Vt 0.87-0.92, TLC Rf 0.25, acetone-H2O (4: 1)]. The small fraction E3-3-9 (95 mg, Ve / Vt 0.49-0.53) was chromatographed [RP-18 (3.5 x 6.5 cm), acetone-methanol-H2O (1: 1: 4, 0.8 L) Compound 8 [38.9 mg, Ve / Vt 0.52-0.76, TLC (RP-18 F254s) Rf 0.40, acetone-methanol-H2O (1: 1: 1)]. Fraction E8 (8.98 g, Ve / Vt 0.59-0.67) was fractionated using silica gel CC [4 x 12 cm, CHCl3-MeOH-H2O (16: 3: 1 to 13: 3: 1, each 3.7 L)] , And nine small fractions (E8-1 to E8-9). The minor fraction E8-4 (1.85 g, Ve / Vt 0.45-0.58) was purified using CC [RP-18 (3.5 x 6.5 cm), MeOH-H2O (3: 1, 1.2 L) 93 mg, Ve / Vt 0.84-0.98, TLC (RP-18 F254s) Rf 0.40, methanol-H2O (5: 1)]. The small fraction E8-5 (1.22 g, Ve / Vt 0.59-0.68) was fractionated using Sephadex LH 20 CC (3 x 50 cm, MeOH-H2O (4: 1, 1.8 L) -5-1 to E8-5-5). Purification of a small fraction E8-5-1 (280 mg, Ve / Vt 0.01-0.25) using CC [RP-18 (3 x 6 cm), MeOH-H2O (1: 35 mg, Ve / Vt 0.77-0.85, TLC (RP-18 F254s) Rf 0.40, MeOH-H2O (2: 1)]. Fraction E9 (5.80 g, Ve / Vt 0.68-0.72) was purified by column chromatography on silica gel CC [5 x 18 cm, CHCl 3-EtOH-H 2 O (16: 3: 1 -> 13: 3: 1 -> 10: )], And four small fractions were obtained (E9-1 to E9-4). The small fraction E9-1 (1.25 g, Ve / Vt 0.01-0.30) was separated into MeOH-H2O (3: 1, 1.5 L) using RP-18 (3 x 6 cm) CC as eluent, Purified with CC (2.5 x 5 cm), eluted with MeOH-H2O (2: 1) and compound 4 [23 mg, Ve / Vt 0.54-0.61, TLC (RP-18 F254s) Rf 0.30, MeOH- : 1)]. The small fraction E9-2 (2.45 g, Ve / Vt 0.31-0.68) was chromatographed with RP-18 (5 x 5.5 cm) and eluted with methanol-H2O (1: 1 -> 2: 1, 1.8 L each) , And 11 small fractions were provided (E9-2-1 to E-9-2-11). The small fraction E9-2-7 (140 mg, Ve / Vt 0.66-0.78) was purified by silica gel (3 x 15 cm) and eluted with CHCl3-methanol (3: 1, 0.8 L) to give 21 mg , Ve / Vt 0.22-0.32, TLC (silica gel F254) Rf 0.55, CHCl3-methanol-H2O (13: 3: 1)]. Fraction E10 (6.75 g, Ve / Vt 0.72-0.78) was purified on silica gel CC [7 x 15 cm, CHCl3-MeOH-H2O (17: 3: 1 -> 15: 3: 1 -> 13: ) And fractionated to provide 10 small fractions (E10-1 to E10-10). The small fraction E10-6 (624 mg, Ve / Vt 0.75-0.82) was isolated by RP-18 (3.5 x 9 cm) CC and eluted with methanol-H2O (2: 3, 1.7 L) 8 mg, Ve / Vt 0.78-0.81, TLC (RP-18 F254s) Rf 0.50, methanol-H2O (3: 1)]. The small fraction E10-4 (1.64 g, Ve / Vt 0.35-0.60) was chromatographed on a RP-18 column (4.5 x 10 cm), eluted with methanol-H2O (1: 1.5, 2 L) (2.5 x 7 cm) CC [E10-4-14 (34 mg, Ve / Vt 0.76-0.81)] and using methanol-H2O (2: 1, 0.4 L) [10 mg, Ve / Vt 0.50-1.00, TLC (RP-18 F254s) Rf 0.30, MeOH-H2O (2: 1)]. Fraction E12 (10.56 g, Ve / Vt 0.84-0.91) was eluted with silica gel CC [CHCl3-EtOH-H2O, 17: 3: 1 to 12: 3: 1 to 9: 3: 1 (3.5 L each) And 25 small fractions were provided (E12-1 to E12-25). The small fraction E12-6 (559 mg, Ve / Vt 0.23-0.28) was added to RP-18 CC [3.5 x 4.5 cm, MeOH-H2O (1: 3 1: 2 1: 1, each 0.8 L) Eighteen fractions (E12-6-1 to E12-6-18) were further purified and further purified with RP-18 CC [E12-6-12 (115 mg, Ve / Vt 0.54-0.70) (RP-18 F254s) Rf 0.60, EtOH-MeOH-H2O (1, : 1: 1)].
분획 B를 고다공성 폴리머 Diaion HP-20 (12 × 45 cm)로 제조된 칼럼으로 크로마토그래피를 하고, 연속적으로 H2O 및 메탄올로 용리시켜, 2개의 분획을 제공하였다(B1 및 B2). 분획 B2 (73.40 g)를 CHCl3-메탄올-H2O [7:3:1 (8 L) → 65:35:10 (12 L)]의 구배를 이용하여 실리카 겔 (12 × 15 cm) CC에 가하고, 11개 분획들을 생산하였다(B2-1 내지 B2-11). 분획 B2-4 (3.50 g, Ve/Vt 0.31-0.36)을 메탄올-H2O [1.5:1 (3.2 L) → 2:1 (2.8 L) → 4:1 (3.6 L)]로 RP-18 (5 × 7 cm) CC 용리하여 6개의 소분획들 (B2-4-1 내지 B2-4-6)을 제공하였다. 소분획 B2-4-1 (913 mg, Ve/Vt 0.01-0.34)을 RP-18 (4 × 7.5 cm) CC로 정제하고, 메탄올-H2O (3:2, 2.2 L)로 용리하여, 화합물 12[250 mg, Ve/Vt 0.34-0.56, TLC (RP-18 F254s) Rf 0.60, 메탄올-H2O (2:1)] 및 화합물 11[35 mg, Ve/Vt 0.87-0.92, TLC (RP-18 F254s) Rf 0.25, 메탄올-H2O (2:1)]를 제공하였다. 분획 B2-7 (4.95 g, Ve/Vt 0.45-0.52)을 RP-18 (4 × 9 cm)로 크로마토그래피하고, 메탄올-H2O (1:1, 4 L)로 용리시키고, 10개 소분획들을 제공하였다(B2-7-1 내지 B2-7-15). 분획 B2-7-4 (1.05 g, Ve/Vt 0.25-0.51)을 RP-18 (4 × 7.5 cm) CC로 분리하고, 메탄올-H2O (1:1, 1.8 L)로 용리시키고, 화합물 13 [350 mg, Ve/Vt 0.32-0.60, TLC (RP-18 F254s) Rf 0.55, MeOH-H2O (2:1)]를 수득하였다.
Fraction B was chromatographed with a column made of high porosity polymer Diaion HP-20 (12 x 45 cm) and successively eluted with H2O and methanol to give two fractions (B1 and B2). Fraction B2 (73.40 g) was added to silica gel (12 x 15 cm) CC using a gradient of CHCl3-methanol-H2O [7: 3: 1 (8 L) to 65:35:10 (12 L) 11 fractions were produced (B2-1 to B2-11). The fraction B2-4 (3.50 g, Ve / Vt 0.31-0.36) was dissolved in RP-18 (5 mL) with methanol-H2O [1.5: 1 (3.2 L) -> 2: 1 (2.8 L) -> × 7 cm) CC elution to provide six small fractions (B2-4-1 to B2-4-6). The small fraction B2-4-1 (913 mg, Ve / Vt 0.01-0.34) was purified by RP-18 (4 x 7.5 cm) CC and eluted with methanol-H2O (3: 2, 2.2 L) (RP-18 F254s) Rf 0.60, methanol-H2O (2: 1)] and compound 11 [35 mg, Ve / Vt 0.87-0.92, TLC ) Rf 0.25, methanol-H2O (2: 1)]. The fractions B2-7 (4.95 g, Ve / Vt 0.45-0.52) were chromatographed with RP-18 (4 x 9 cm), eluted with methanol-H2O (1: 1, 4 L) and 10 small fractions (B2-7-1 to B2-7-15). The fraction B2-7-4 (1.05 g, Ve / Vt 0.25-0.51) was separated into RP-18 (4 x 7.5 cm) CC and eluted with methanol-H2O (1: 1, 1.8 L) 350 mg, Ve / Vt 0.32-0.60, TLC (RP-18 F254s) Rf 0.55, MeOH-H2O (2: 1)].
<실험예 2> 구조 분석<Experimental Example 2> Structural analysis
화합물 1-7은 FT-IR 스펙트럼에서 3462 내지 3342, 1746 내지 1710, 및 1665 내지 1640 cm-1에서 밴드를 보였는데, 이는 하이드록시 그룹, 카보닐 그룹 및 이중 결합 흡수의 존재를 제시한다. 이들 중 화합물 1은 흰색 무정형 분말로 수득되었다. 분자식은 네거티브 HRFABMS에서, 유사분자 이온 피크(pseudomolecular ion peak) [M - H]- at m/z 499.3401 (calcd for C31H47O5, 499.3423)로부터 C31H48O5로 결정되었다. 1H NMR 스펙트럼(표 1)에서, sp2 탄소에 위치한 두 개의 알릴 메틸 양성자들[δH 1.72 (H-24) 및 2.03 (H-29)]의 2 개 신호 및 δH 5.07 (J =2.0 Hz, H-23a), 4.83 (J = 2.0 Hz, H-23b), 4.90 (brs), 및 4.79 (brs)의 4개의 올레핀 메틴(olefinic methane) 양성자들이 관찰되는데, 이들의 화학적 쉬프트 및 작은 결합 상수(small coupling constant)(또는 넓은 하나(singlet))들은 2 개의 엑소메틸렌(exomethylen) 단위의 전형적인 것으로, 2 개의 이소프로페닐 모이어티의 존재를 확인해준다. 또한 3개의 3차 메틸 양성자들[δH 1.21 (H-26), 1.12 (H-25), 0.80 (H-27)], 하나의 산소화된 메틴(methane) 양성자[δH 4.80 (brd, J = 4.4 Hz, H-22)], 및 메톡시 양성자(δH 3.65)에 대한 신호들이 관찰되었다. DEPT 실험에 의하여 뒷받침되는 1의 13C NMR 스펙트럼(표 2)는 2개의 카보닐 카본들[δC 174.2 (C-3) 및 178.8 (C-28)], 2 개의 올레핀 4차 탄소들[δC 151.7 (C-20), 147.9 (C-4)], 2 개의 엑소메틸렌 탄소들[δC 113.7 (C-23), 110.4 (C-30)], 산소화된 메틴 탄소[δC 75.6 (C-22)], 메톡시 탄소(δC 51.5), 5개의 메틸 탄소들[(δC 23.6 (C-24), 20.5 (C-25), 19.5 (C-29), 16.5 (C-26), 15.0 (C-27)], 및 18개의 다른 탄소 신호들을 포함하는 31개 탄소들의 존재를 가리킨다. 1H-1H COSY 스펙트럼의 몇몇의 크로스-피크들은 양성자 신호들 간의 핵심적인 관련성을 확인해준다. HMBC 스펙트럼은 H-23a, H-23b/C-5; H-2a, H-2b/C-3; and H-1a/C-3 간의 결정적인 장거리 상관성(longrange correlation)을 보여준다(도 1). 1의 HSQC 및 DEPT 135 스펙트럼의 추가적인 분석에서, 양성자의 배치 및 탄소 NMR 신호(표 1 및 2)는 분명히 확인되었다. 그러므로, 1은 3,4-세코루판-타입 트리터페노이드(3,4-secolupane-type triterpenoid)로 부여되었다. 추가로, 메톡시 양성자들(δH 3.65) 및 C-3 카보닐 탄소(δC 174.2)의 신호들 간의 장거리 상관성 역시 분명하였다. H-22 및 H-21 간의 결합 상수는 4.4 Hz였는데, 이는 OH-22이 α-지향(oriented)이라는 것을 가리킨다. 그러므로 화합물 1의 구조는 22α-하이드록시-3,4-세코-루파-4(23), 20(30)-디엔-3,28-디오익 액시드 3-메틸 에스터(22α-hydroxy-3,4-seco-lupa-4(23), 20(30)-diene-3,28-dioic acid 3-methyl ester)로 결정되었으며, 이는 전에 보고되지 않은 것으로, 이 화합물은 아칸토세실리게닌 Ⅰ(acanthosessiligenin Ⅰ)으로 명명하였다.
Compound 1-7 showed bands at 3462 to 3342, 1746 to 1710, and 1665 to 1640 cm -1 in the FT-IR spectrum, suggesting the presence of hydroxy groups, carbonyl groups and double bond absorption. Among them,
화합물 2는 흰색 분말로 분리되었으며, 그 분자식은 양성 HRFABMS의 유사분자 이온 피크 [M + H]+ at m/z 633.3637 (calcd for C36H57O9, 633.4002)로부터 C36H56O9로 확정되었다. 추가적인 당 모이어티를 위한 양성자 및 탄소 공명 및 각각 C-3 및 C-22 위치의 메톡시 그룹과 산소화된 메틴 모이어티의 부족은 예외로 하고, 그것의 1H 및 13C NMR 스펙트럼(표 1 및 2)는 1의 그것들과 유사하다. 1 및 22α-하이드록시치사노사이드(hydroxychiisanoside)(14)와 비교할 때, C-17 (δC 56.6) 이동된 6.3 ppm 업필드(upfield)에 대한 4차 탄소 신호는 2의 C-22가 메틸렌 그룹이라는 것을 제시한다. 단당류 단위로서, δH 6.32 (d, J = 8.0 Hz)에서의 아노머 양성자 신호 및 δC 95.5 (C-1′)에서의 탄소 신호는, δC 79.3 (C-5′), 78.4 (C-3′), 74.1 (C-2′), 71.0 (C-4′), 및 62.2 (C-6′)의 산소화된 메틴 및 메틸렌 탄소 신호들과 함께, β-글루코피라노실(glucopyranosyl) 그룹의 존재를 제안한다. 글루코피라노실 단위(C-1′) 및 아글리콘의 C-28 간 연결성은 아노머 탄소 신호(δC 95.5)의 화학적 이동과 함께 HMBC 스펙트럼의 δH 6.32 (H-1′) 및 δC 174.8 (C-28) 간 크로스-피크의 존재에 의하여 확인되었다. 그러므로 2 (아칸토세실리오사이드(acanthosessilioside) A)의 구조는 3,4-세코-루파-4(23),20(30)-디엔-3,28-디오익 액시드 28-O-β-D-글루코피라노사이드(3,4-seco-lupa-4(23),20(30)-diene-3,28-dioic acid 28-O-β-D-glucopyranoside)로 결정되었다.
Compound 2 was isolated as a white powder and its molecular formula was confirmed as C36H56O9 from the similar molecular ion peak [M + H] + at m / z 633.3637 (calcd for C36H57O9, 633.4002) of positive HRFABMS. The 1H and 13C NMR spectra (Tables 1 and 2), with the exception of proton and carbon resonance for additional sugar moieties and the lack of oxygenated methine moieties with methoxy groups at C-3 and C-22 positions respectively, Are similar to those of 1. The fourth carbon signal for the 6.3 ppm upfield shifted to C-17 (delta C 56.6) compared to the hydroxychiisanoside (14) of the C-22 of 1 and 22 alpha -hydroxychisanoside . The anomeric proton signal at δH 6.32 (d, J = 8.0 Hz) and the carbon signal at δC 95.5 (C-1 ') as monosaccharide units were δC 79.3 (C-5'), 78.4 ), 74.1 (C-2 '), 71.0 (C-4'), and 62.2 (C-6 ') in the presence of .beta.-glucopyranosyl groups I suggest. The connectivity between the glucopyranosyl unit (C-1 ') and the C-28 of the aglycons is shown by the chemical shifts of the anomeric carbon signal (delta C 95.5) and the delta H 6.32 (H-1') and delta C 174.8 (C- 28) cross-peak. Therefore, the structure of 2 (acanthosessilioside A) is 3,4-seco-rupa- 4 (23), 20 (30) -diene-3,28-dioic acid 28- D-glucopyranoside was determined to be 3,4-seco-lupa-4 (23), 20 (30) -diene-3,28-dioic acid 28-O- beta -D-glucopyranoside.
화합물 3은 흰색, 바늘-같은 결정으로 분리되었다. C31H49O6 (calcd for C31H49O6, 517.3529) 유사분자 이온에 부합하게, 화합물 3의 양성 HRFABMS은 m/z 517.3307에서 [M + H]+ 이온 피크를 보였다. 1H and 13C NMR 스펙트럼(표 1 및 2)은 5개의 4차 메틸 그룹들(δH 1.37, 1.29, 1.09, 1.05, 0.91), 하나의 알릴 메틸 그룹(δH 1.69), 이소프로페닐 모이어티에 의한 하나의 엑소메틸렌 그룹(δH 4.77, 4.61), 2개의 사놋화된 메틴 그룹들 [δH 4.72 (dd, J = 2.4, 11.6 Hz, H-1), δC 86.6 (C-1); δH 4.00 (ddd, J = 6.2, 10.8, 11.6 Hz, H-11), δC 67.2 (C-11)], 하나의 메톡시 그룹(δH 3.61, δC 51.1), 및 두 개의 카보닐 그룹들[δC 173.5 (C-3), 179.0 (C-28)]의 신호들을 보인다. 이전에 보고된 화합물인 이소치사노사이드 (isochiisanoside)와 비교할 때, 화합물 3은 C-28 위치에 당 모이어티가 부족하며, 추가적인 메톡시 그룹을 갖는 것으로 발견되었다. 화합물 3의 산소화된 메틴 양성자(H-11)는 δH 4.00 (ddd, J11,12eq = 6.2 Hz, J11,12ax = 11.6 Hz, J9,11 = 10.8 Hz)에 나타났으며, H-9 [δH 1.78 (d, J = 10.8 Hz)]와 결합(couple)되었다. 이 데이터들은 H-9 and H-11 간의 2축 배치(diaxial arrangement) 및 C-11에서의 하이드록시 그룹의 확인을 가리킨다. 게다가 화학식 3의 입체 구조는 NOESY 실험에 의하여 확인되었는데(도 1), 이는 H-11 및 H3-25, H3-26와 함께 H-1 및 H3-24, H3-25 간의 상관성을 보여준다. 이들 NOE 상관성들은 C-1의 산소가 β-지향성이며, C-11의 하이드록시가 α-구성(configured)라는 것을 가리킨다. 또한 HMBC 스펙트럼의 메톡시 양성자 신호(δH 3.61) 및 C-3의 카보닐 탄소(δC 173.5) 간의 장거리 상관성은 메톡시 그룹이 C-3에 붙는다는 것을 드러낸다. 따라서 화학식 3(아칸토세실리게닌 Ⅱ(acanthosessiligenin Ⅱ))는 (1R)-1,4-epoxy-11α-hydroxy-3,4-seco-lup-20(30)-ene-3,28-dioic acid 3-methyl ester((1R)-1,4-epoxy-11α-hydroxy-3,4-seco-lup-20(30)-ene-3,28-dioic acid 3-methyl ester)로 결정되었다.
흰색 분말인 화합물 4는 양성 HRFABMS에서 m/z 679.4003에서 유사분자 이온 피크 [M + H]+를 보였으며, 이는 화학식 3의 것보다 162 질량 단위(mass unit) 더 크고 C37H59O11 (calcd for C37H59O11, 679.4057)의 유사분자식과 일치하였다. 1H and 13C NMR 스펙트럼의 비교는 그것들이 추가적인 β-글루코피라노실 그룹에 대한 양성자 및 탄소 공명이 존재한다는 점을 제외하고, 화합물 3의 그것과 매우 유사하다(표 1 및 2). 이러한 발견은, 화합물 4의 산 가수분해에 의하여 화합물 3 및 D-글루코스 [TLC, Rf 0.40 (silica gel F254), CHCl3-MeOH-H2O (65:35:10)]의 그것과 같이, 동일한 아글리콘[TLC, Rf 0.55 (RP-18 F254s), acetone-H2O (4:1)]이 얻어진다는 것에 의하여 확인되었다. 글루코스 모이어티는 화학식 3(δC 174.8 in 4 vs δC 179.0 in 3)의 그것에 대하여 C-28의 13C NMR 공명의 글리코실화 효과의 관찰에 의하여, 또한 HMBC 스펙트럼에서 관찰된 C-28(δC 174.8)과 함께 H-1′ (δH 6.39, d, J = 8.0 Hz) 장거리 상관성으로부터 C-28에 부착된 것으로 결정되었다. 그러므로 화합물 4(아칸토세실리오사이드 B)의 구조는 (1R)-1,4-에폭시-11α-하이드록시-3,4-세코-룹-20(30)-엔-3,28-디오익 액시드 3-메틸에스터 28-O-β-D-글루코피라노사이드((1R)-1,4-epoxy-11α-hydroxy-3,4-seco-lup-20(30)-ene-3,28-dioic acid 3-methyl ester 28-O-β-D-glucopyranoside)로 결정되었다.
Compound 4 as a white powder showed a similar molecular ion peak [M + H] + at m / z 679.4003 in positive HRFABMS, which is 162 mass units larger than that of
화합물 5는 흰색 분말로 분리되었으며, 그것의 분자식은 양성 HRFABMS의 m/z 695.3936 (calcd for C37H59O12, 695.4006)에서 유사분자 이온 [M + H]+로부터 C37H58O12로 확정되었다. 화합물 5의 1H and 13C NMR 스펙트럼(표 1 및 2)은 화합물 4의 C-22로 인한 메틸렌 신호가 화합물 5에서는 산소화된 메틴(δH 4.77 and δC 74.8)의 그것들로 대체되었다는 점을 제외하면, 화학식 4의 그것과 유사하였다. 화합물 5의 분자량은 화합물 4보다 큰 16 Da였으며, 이는 추가적인 하이드록시 그룹의 존재를 가리킨다. 화합물 5에서, C-17 (δC 63.0) 및 C-21 (δC 41.9)의 탄소 신호의 화학적 이동들은 각각 6.0 및 11.4 ppm으로 다운필드로 이동되고, C-18 (δC 44.1)의 그것은 화합물 4 및 이소치사노사이드와 비교할 때, 5.5 ppm로 업필드로 이동하였는데, 이는 C-22가 수산화(hydroxylated)되어 있다는 것을 제안한다. 이 결론은 H-22 (δH 4.77)의 양성자 신호 및 C-18 (δC 44.1), C-19 (δC 47.5), and C-28 (δC 174.7)의 탄소 신호들간의 장거리 상관성을 보여주는 HMBC 스펙트럼에 의하여 뒷받침되었다. H-22 and H-21간의 결합 상수는 5.2 Hz였고, 이는 OH-22가 α-지향성이라는 것을 가리킨다. 따라서, 화합물 5(아칸토세실리오사이드 C)의 구조는 (1R)-1,4-에폭시-11α,22α-디하이드록시-3,4-세코-룹-20(30)-엔-3,28-디오익 액시드 3-메틸 에스터 28-O-β-D-글루코피라노사이드((1R)-1,4-epoxy-11α,22α-dihydroxy-3,4-seco-lup-20(30)-ene-3,28-dioic acid 3-methyl ester 28-O-β-D-glucopyranoside)로 결정되었다.
Compound 5 was isolated as a white powder and its molecular formula was determined from the similar molecular ion [M + H] + to C37H58O12 at m / z 695.3936 (calcd for C37H59O12, 695.4006) of positive HRFABMS. The 1H and 13C NMR spectra (Tables 1 and 2) of Compound 5 showed that the methylene signal due to C-22 of Compound 4 was replaced with those of oxygenated methine (? H 4.77 and? C 74.8) 4. The molecular weight of compound 5 was 16 Da, which is greater than that of compound 4, indicating the presence of an additional hydroxy group. In compound 5, the chemical shifts of the carbon signals of C-17 (delta C 63.0) and C-21 (delta C 41.9) were shifted downfield to 6.0 and 11.4 ppm, respectively, and that of C-18 (delta C 44.1) Compared to isoschisanoside, it moved to the upfield at 5.5 ppm suggesting that C-22 is hydroxylated. This conclusion is based on the HMBC spectrum showing the long-term correlation between the protons of H-22 (δH 4.77) and the carbon signals of C-18 (δC 44.1), C-19 (δC 47.5), and C-28 Respectively. The binding constant between H-22 and H-21 was 5.2 Hz, indicating that OH-22 is α-oriented. Therefore, the structure of compound 5 (acanthocyllioside C) is (1R) -1,4-epoxy-11α, 22α-dihydroxy-3,4- 28-dioic acid 3-methyl ester 28-O-? -D-glucopyranoside ((1R) -1,4-epoxy-11 ?, 22? -Dihydroxy-3,4-seco-lup- ) -ene-3,28-dioic acid 3-methyl ester 28-O- beta -D-glucopyranoside.
화합물 6은 흰색 분말로 분리되었으며, 그 분자식은 양성 HRFABMS에서 유사분자 이온 피크 [M + H]+ at m/z 665.3994 (calcd for C36H57O11, 665.3901)로부터 C36H56O11로 확정되었다. 화합물 6의 산소화된 메틴 그룹의 양성자 및 탄소 공명이 확인되었다(δH 4.77, brd, J = 4.4 Hz and δC 74.9). 또한 HMBC에서 H-22의 양성자 신호 및 C-18 (δC 44.2), C-19 (δC 47.6), 및 C-28 (δC 174.8)의 탄소 신호들 간의 연관성으로부터 하이드록시 그룹은 C22에 위치할 수 있었다. J값과 H-22의 배치는 다른 보고된 데이터들 및 화합물 5의 그것들과 잘 일치하였다. 또한 화합물 6의 분자량은 16 Da로 이는 추가적인 하이드록시 그룹의 존재를 가리켰다. C-28의 13C NMR 공명의, 글리코사이드화(glycosidation)-유도된 이동으로부터(δC 178.8 in 6 vs δC 174.8 in 7), 그리고 HMBC 스펙트럼에서 관찰된 H-1′ (δH 6.47, d, J = 8.0 Hz)과 C-28 (δC 174.8)의 장거리 연관성으로부터, 글루코스 모이어티는 글리코사이드 결합(linkage)을 통하여 C-28에 부착된 것으로 추정되었다. 그러므로 화합물 6(아칸토세실리오사이드 E)의 구조는 (1R)-1,4-에폭시-22α-하이드록시-3,4-세코-룹-20(30)-엔-3,28-디오익 액시드 28-O-β-D-글루코피라노사이드((1R)-1,4-epoxy-22α-hydroxy-3,4-seco-lup-20(30)-ene-3,28-dioic acid 28-O-β-D-glucopyranoside)로 결정되었다.
Compound 6 was isolated as a white powder and its molecular formula was determined from the similar molecular ion peak [M + H] + at m / z 665.3994 (calcd for C36H57O11, 665.3901) to C36H56O11 in positive HRFABMS. The proton and carbon resonance of the oxygenated methine group of compound 6 was confirmed (δH 4.77, brd, J = 4.4 Hz and δC 74.9). From the association between the protons signal of H-22 and the carbon signals of C-18 (δC 44.2), C-19 (δC 47.6), and C-28 (δC 174.8) in HMBC, the hydroxy group can be located at C22 there was. The J values and the placement of H-22 were in good agreement with those of the other reported data and compound 5. The molecular weight of Compound 6 was also 16 Da, indicating the presence of an additional hydroxy group. (隆 H 6.47, d, J = < / RTI > observed in the HMBC spectrum), from the glycosidation- 8.0 Hz) and C-28 (δC 174.8), it was assumed that the glucose moiety was attached to C-28 via a glycoside linkage. Therefore, the structure of Compound 6 (acanthocyllioside E) is (1R) -1,4-epoxy-22? -Hydroxy-3,4-secocol-20 (30) (30) -ene-3,28-dioic acid (1R) -1,4-epoxy-22? -Hydroxy-3,4-seco-lup- 28-O- [beta] -D-glucopyranoside).
화합물 7은 흰색 분말로 분리되었으며, 그 분자식은 양성 HRFABMS의 유사분자 이온 피크 [M + H]+ at m/z 663.3753 (calcd for C36H55O11, 663.3744)로부터 C36H54O11로 확정되었다. 화합물 7의 1H 및 13C NMR 스펙트럼(표 1 및 2)은 22α-하이드록시치사노게닌(22α-hydroxychiisanogenin) (화학식 8)의 모노글리코사이드로 제안되었다. 당 모이어티는 δH 6.44 (d, J = 8.0 Hz)의 헤미아세탈 양성자 신호 및 헤미아세탈 탄소 신호, 4개의 산소화된 메틴 탄소 신호들 및 하나의 산소화된 메틸렌 탄소 신호로부터 β-글루코피라노사이드로 결정되었다(표 2). δC 95.5에서의 신호는 화합물 7이 에스터 결합(bond)을 통해 28-O-글리코사이드 결합(linkage)을 갖는 것을 제안하였는데, 이는 HMBC 스펙트럼에서 관찰된 H-1′ with C-28 (δC 174.8)의 장거리 연관성으로부터 확인되었다. 그러므로, 화합물 7(아칸토세실리오사이드 F)의 구조는 (1R)-1α,11α,22α-트리하이드록시-3,4-세코-루파-4(23),20(30)-디엔-3,28-디오익 액시드 3,11-락톤 28-O-β-D-글루코피라노사이드((1R)-1α,11α,22α-trihydroxy-3,4-seco-lupa-4(23),20(30)-diene-3,28-dioic acid 3,11-lactone 28-O-β-D-glucopyranoside)로 결정되었다.
Compound 7 was isolated as a white powder and its molecular formula was confirmed as C36H54O11 from the similar molecular ion peak [M + H] + at m / z 663.3753 (calcd for C36H55O11, 663.3744) of positive HRFABMS. The 1H and 13C NMR spectra of compounds 7 (Tables 1 and 2) were proposed as monoglycosides of 22? -Hydroxychisanogenin (formula 8). The sugar moiety is determined from the hemiacetal proton signal and the hemiacetal carbon signal of? H 6.44 (d, J = 8.0 Hz), the four oxygenated methine carbon signals and one oxygenated methylene carbon signal as? -Glucopyranoside (Table 2). The signal at δC 95.5 suggested that compound 7 had a 28-O-glycoside linkage through an ester bond, which is the H-1 'with C-28 (δC 174.8) observed in the HMBC spectrum, The long-range associations of Therefore, the structure of Compound 7 (alkantocyllioside F) is (1R) -1 ?, 11 ?, 22? -Trihydroxy-3,4-seco- , 28-
각각의 글리코사이드(2, 4-8)의 수성산(aqueous acid) 가수분해 후 수득된 단당류는 진짜 샘플로 TLC 비교에 의하여 글루코스로서 확인되었다[TLC, Rf 0.40 (silica gel F254), CHCl3-MeOH-H2O (65:35:10)]. 절대 배열은 각각의 화합물의 가수분해에 의하여 얻어진 단당류의 키랄 유도체의 GC분석에 기초하여 D로 결정되었다(실험 섹션 참조). 이들 글리코사이드들의 1H NMR 스펙트럼의 아노머 양성자 신호들의 상대적으로 큰 결합 상수 (J = 8.0 Hz)(표 1)은 각각의 경우들에서 글루코피라노실 모이어티의 β-배치를 제안하였다.
The monosaccharide obtained after aqueous acid hydrolysis of each glycoside (2-4-8) was identified as a glucose by comparison of TLC with a real sample [TLC, Rf 0.40 (silica gel F254), CHCl3-MeOH -H2O (65:35:10). The absolute sequence was determined as D based on GC analysis of the chiral derivative of the monosaccharide obtained by hydrolysis of each compound (see experimental section). The relatively large binding constants (J = 8.0 Hz) of the anomeric proton signals of the 1 H NMR spectra of these glycosides (Table 1) suggested in each case the β-configuration of the glucopyranosyl moiety.
상기 분석 결과를 요약하면 하기와 같다.The results of the above analysis can be summarized as follows.
아칸토세실리게닌(Acanthosessiligenin) I (화합물 1): 흰색, 무정형 분말; mp 230-232 ℃; [α]20 D -24.1 (c 0.5, MeOH); IR (CaF2 window) νmax 3360, 1732, 1648 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 음성 HRFABMS m/z 499.3401 [M - H]- (calcd for C31H47O5, 499.3423)(화학식 1, R1은 CH3, R2는 OH, R3는 H).Acanthosessiligenin I (Compound 1): white, amorphous powder; mp 230-232 [deg.] C; [[alpha]] D -24.1 (c 0.5, MeOH); IR (CaF2 window)? Max 3360, 1732, 1648 cm -1 ; 1H and < 13 > C NMR data, see Tables 1 and 2; Negative HRFABMS m / z 499.3401 [M - H] - (calcd for C31H47O5, 499.3423) (
아칸토세실리오사이드(Acanthosessilioside) A (화합물 2): 흰색 분말; mp 242-243 ℃; [α]20 D -70.5 (c 0.5, MeOH); IR (CaF2 window) νmax 3345, 1744, 1640 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 양성 HRFABMS m/z 633.3956 [M + H]+ (calcd for C36H57O9, 633.4002)(화학식 1, R1은 H, R2는 H, R3는 베타-D-글루코피라노실).Acanthosessilioside A (Compound 2): white powder; mp 242-243 [deg.] C; [?] 20 D -70.5 (c 0.5, MeOH); IR (CaF2 window)? Max 3345, 1744, 1640 cm-1; 1H and < 13 > C NMR data, see Tables 1 and 2; Positive HRFABMS m / z 633.3956 [M + H] + (calcd for C36H57O9, 633.4002) wherein R1 is H, R2 is H and R3 is beta-D-glucopyranosyl.
아칸토세실리게닌 II (화합물 3): 흰색 바늘; mp 236-237 ℃; [α]20D-18.2 (c 0.7, MeOH); IR (CaF2 window) νmax 3350, 1740, 16548 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 양성 HRFABMS m/z 517.3307 [M + H]+ (calcd for C31H49O6, 517.3529) (화학식 2, R4는 CH3, R5는 OH, R6은 H, R7은 H).Acanthocystiligenin II (Compound 3): white needles; mp 236-237 [deg.] C; [?] 20D-18.2 (c 0.7, MeOH); IR (CaF2 window)? Max 3350, 1740, 16548 cm-1; 1H and < 13 > C NMR data, see Tables 1 and 2; (2), R4 is CH3, R5 is OH, R6 is H, R7 is H). ≪ / RTI >
아칸토세실리오사이드 B (화합물 4): 흰색 분말; mp 248-250 ℃; [α]20 D +34.6 (c 0.5, MeOH); IR (CaF2 window) νmax 3342, 1746, 1648 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 양성 HRFABMS m/z 679.4003 [M + H]+ (calcd for C37H59O11, 679.4057) (화학식 2, R4는 CH3, R5는 OH, R6은 H, R7은 베타-D-글루코피라노실).Acanthocesylioside B (Compound 4): white powder; mp 248-250 C; [?] 20 D +34.6 (c 0.5, MeOH); IR (CaF2 window)? Max 3342, 1746, 1648 cm-1; 1H and < 13 > C NMR data, see Tables 1 and 2; R4 is CH3, R5 is OH, R6 is H, and R7 is beta-D-glucopyranosyl). ≪ / RTI >
아칸토세실리오사이드 C (화합물 5): 흰색 분말; mp 252-253 ℃; [α]20 D +66.8 (c 0.5, MeOH); IR (CaF2 window) νmax 3351, 1741, 1651 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 양성 HRFABMS m/z 695.4006 [M + H]+ (calcd for C37H59O12, 695.4006)(화학식 2, R4는 CH3, R5는 OH, R6은 OH, R7은 베타-D-글루코피라노실).Acanthocosyl Rioide C (Compound 5): white powder; mp 252-253 [deg.] C; [?] 20 D +66.8 (c 0.5, MeOH); IR (CaF2 window)? Max 3351, 1741, 1651 cm @ -1; 1H and < 13 > C NMR data, see Tables 1 and 2; Positive HRFABMS m / z 695.4006 [M + H] + (calcd for C37H59O12, 695.4006) (Formula 2, R4 is CH3, R5 is OH, R6 is OH and R7 is beta-D-glucopyranosyl).
아칸토세실리오사이드 E (화합물 6): 흰색 분말; mp 255-256 ℃; [α]20 D -45.2 (c 0.5, MeOH); IR (CaF2 window) νmax 3420, 1714, 1645 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 양성 HRFABMS m/z 665.3892 [M + H]+ (calcd for C36H57O11, 665.3901)(화학식 2, R4는 H, R5는 H, R6은 OH, R7은 베타-D-글루코피라노실).Acanthocesylioside E (Compound 6): white powder; mp 255-256 [deg.] C; [?] 20 D -45.2 (c 0.5, MeOH); IR (CaF2 window) .nu.max 3420, 1714, 1645 cm @ -1; 1H and < 13 > C NMR data, see Tables 1 and 2; Positive HRFABMS m / z 665.3892 [M + H] + (calcd for C36H57O11, 665.3901) (Formula 2, R4 is H, R5 is H, R6 is OH and R7 is beta-D-glucopyranosyl).
아칸토세실리오사이드 F (화합물 7): 흰색 분말; mp 259-260 ℃; [α]20 D +19.2 (c 0.5, MeOH); IR (CaF2 window) νmax 3380, 1740, 1655 cm-1; 1H 및 13C NMR 데이터, 표 1 및 2 참조; 양성 HRFABMS m/z 663.3753 [M + H]+ (calcd for C36H55O11, 663.3744)(화학식 3, R8은 베타-D-글루코피라노실).
Acanthocesylioside F (Compound 7): white powder; mp 259-260 [deg.] C; [?] 20D +19.2 (c 0.5, MeOH); IR (CaF2 window) vmax 3380, 1740, 1655 cm < -1 >; 1H and < 13 > C NMR data, see Tables 1 and 2; Positive HRFABMS m / z 663.3753 [M + H] + (calcd for C36H55O11, 663.3744) (
NMR 및 MS 데이터들을 보고된 값들과 비교하여, 22α- 하이드록시치사노세닌(22α- hydroxychiisanogenin)(화합물 8), 3,4-세코-루판-20(30)-엔-3,28-디올릭 액시드(3,4-seco-lupan-20(30)-ene-3,28-dioic acid)(화합물 9), (1R)-1,4-에폭시-11α,22α-하이드록시-3,4-세코루판-20(30)-엔-3,28-디오익 액시드((1R)-1,4-epoxy-11α,22α-hydroxy-3,4-secolupan-20(30)-ene-3,28-dioic acid)(화합물 10), (+)-디바로사이드((+)-divaroside)(화합물 11), 치사노사이드(chiisanoside)(화합물 12), 및 22α-하이드록시치사노사이드(22α-hydroxychiisanoside)(화합물 13)인 공지의 화합물들을 확인하였다.
NMR and MS data were compared to the reported values to determine that 22 alpha -hydroxychisanogenin (Compound 8), 3,4-seco-lupan-20 (30) -en-3,28- (30) -ene-3,28-dioic acid (Compound 9), (1R) -1,4-epoxy-11 ?, 22? -Hydroxy-3,4 (3R) -1,4-epoxy-11α, 22α-hydroxy-3,4-secolupan-20 (30) -ene-3 , 28-dioic acid (Compound 10), (+) - divaroside (Compound 11), chiisanoside (Compound 12), and 22? -Hydroxycanoside 22a-hydroxychiisanoside (Compound 13).
<실험예 3> 화합물 2 및 4-7의 산 가수분해 및 단당류 성분들의 절대 배열의 결정Experimental Example 3 Acid hydrolysis of compounds 2 and 4-7 and determination of absolute arrangement of monosaccharide components
각각의 화합물(5mg)을 80 ℃에서 6시간 동안 H2O에서 2 mL의 2 N HCl로 가수분해하고, H2O 내 2 N NaOH 2 mL로 중화시킨 후, CHCl3로 추출하였다. 수성층을 진공 하 농축시켜 당 분획의 잔여물을 제공하였다. 상기 잔여물을 피리딘(100 μL) 내 용해시키고, 그 후 0.1 M L 시스테인 (L cysteine) 메틸 에스터 하이드로클로라이드(150 μL)를 첨가하였다. 60 ℃에서 90분간 반응시킨 후, 반응 혼합물을 진공 건조하였다. 유도체화를 위하여 100 μL의 N-메틸-N-(트리메틸실릴) 트리플루오로아세트아마이드(N-methyl-N-(trimethylsilyl) trifluoroacetamide)를 첨가하고, 혼합물을 37 ℃에서 30 분간 배양하였다. 그 후 혼합물을 하기 조건 하 GC 분석하였다: 모세관, DB-5 (30 m × 0.32 mm × 0.25 μm); 탐지기(detector), FID; 탐지기 온도, 280 ℃; 주입기(injector) 온도, 250 ℃; 캐리어(carrier), N2 gas (20.4 mL/min); 오븐 온도, 5 ℃/분의 비율로 170-250 ℃, 각각의 샘플은 1 μL를 주입 포트(스플릿 없는(splitless) 모드) 내로 직접 주입함. 다당류 유도체의 보유(retention) 시간을 표준 샘플(D-글루코스, Sigma)와 비교함으로써, 화합물 2 및 4-7 내 다당류의 다당류을 D-글루코스로 확인하였다(tR 12.67 분).
Each compound (5 mg) was hydrolyzed with 2 mL of 2 N HCl in H2O at 80 < 0 > C for 6 hours, neutralized with 2 mL of 2 N NaOH in H2O, and extracted with CHCl3. The aqueous layer was concentrated in vacuo to give a residue of the sugar fraction. The residue was dissolved in pyridine (100 [mu] L), then 0.1 mL cysteine methyl ester hydrochloride (150 [mu] L) was added. After reaction at 60 ° C for 90 minutes, the reaction mixture was vacuum dried. 100 μL of N-methyl-N- (trimethylsilyl) trifluoroacetamide was added for derivatization and the mixture was incubated at 37 ° C. for 30 minutes. The mixture was then analyzed by GC under the following conditions: capillary, DB-5 (30 m × 0.32 mm × 0.25 μm); Detector, FID; Detector temperature, 280 ℃; Injector temperature, 250 ° C; Carrier, N2 gas (20.4 mL / min); Oven temperature, 170-250 ° C at a rate of 5 ° C / min, 1 μL of each sample is injected directly into the injection port (splitless mode). The polysaccharide polysaccharide in compounds 2 and 4-7 was identified as D-glucose (tR 12.67 min) by comparing the retention time of the polysaccharide derivative with a standard sample (D-glucose, Sigma).
<실험예 4> 세포독성 시험<Experimental Example 4> Cytotoxicity test
인간 결장 선암(colon adenocarcinoma)(HCT-116), 인간 유방 선암(breast adenocarcinoma) (MCF-7), 인간 유방 선암(breast adenocarcinoma) (SK-BR-3), 인간 난소 선암(ovarian adenocarcinoma) (SK-OV-3), 인간 자궁경부선암(cervix adenocarcinoma) (HeLa), 인간 간암(hepatoma)(HepG2) 및 인간 흑색종(melanoma) (SKMEL- 5)에 대하여 세포 배양 및 세포독성 시험을 MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide, Sigma-Aldrich]를 이용하여 수행하였다. 사용한 참고 물질은 파클리탁셀(paclitaxel)로, 이는 HCT-116, MCF-7, SK-BR-3, SK-OV-3, 및 SK-MEL-5 세포주들 각각에 대하여 0.05, 0.90, 0.11, 0.40, 및 0.15 uM의 IC50 값들을 보였다.
Human colon adenocarcinoma (SK-BR-3), human adenocarcinoma (SK-BR-3), human adenocarcinoma Cell cultures and cytotoxicity tests were performed on MTT [3, 4, 5, 6, 7, and 8] for human cervix adenocarcinoma (HeLa), human hepatoma (HepG2), and human melanoma - (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide, Sigma-Aldrich]. The reference material used was paclitaxel, which was treated with 0.05, 0.90, 0.11, 0.40, 0.10, 0.10, 0.05, 0.10, And IC50 values of 0.15 uM.
시험 결과, 화합물 1-13은 모두 불활성으로 나타났다(IC50 값들 <10 μM).
As a result of the test, the compounds 1-13 were all inactivated (IC50 values <10 μM).
<실험예 5> NO 생산 및 세포 생존능 측정<Experimental Example 5> Measurement of NO production and cell viability
이 조사는 전술한 바와 같이 기재된다. 즉, RAW 264.7 대식세포를 수득하고 NO 생산을 측정하기 위하여 96-웰 플레이트에 접종사였다(1 × 104 세포/웰). 상기 플레이트를 다양한 농도의 샘플들로 30분간 전처리하고 LPS(1 μg/mL)로 24시간 간 배양하였다. NO의 양은 Griess 시약을 이용하여, 배양된 RAW264.7 대식세포 현탁액 내 아질산염(nitrite) 농도에 의하여 결정되었다. 세포 생존력은 MTT 환원에 의하여 평가되었으며, LPS만 처리한 그룹에 대한 퍼센트(%)로 나타내었다. 널리 알려진 NOS 억제제인 아미노구아니딘(Aminoguanidine) (Sigma)를 양성 대조군으로 하여 시험하였다.
This investigation is described as described above. That is, RAW 264.7 macrophages were obtained and inoculated on 96-well plates (1 x 104 cells / well) to measure NO production. The plate was pretreated with various concentrations of samples for 30 minutes and incubated with LPS (1 μg / mL) for 24 hours. The amount of NO was determined by nitrite concentration in cultured RAW 264.7 macrophage suspension using Griess reagent. Cell viability was assessed by MTT reduction and expressed as a percentage (%) of the group treated with LPS alone. Aminoguanidine (Sigma), a well-known NOS inhibitor, was tested as a positive control.
그 결과, 화합물 5-13은 RAW 264.7 대식세포들에서 LPS-유도된 NO 생산에 대하여 불활성이었다(IC50 > 50 μM). 그 외 화합물 1-4는 우수한 NO 생산 억제능을 보였다. c양성 대조군. 결과들은 3개의 독립된 실험들의 평균이며, 데이터들은 평균 ± 표준편차로 나타내었다(표 3).
As a result, compounds 5-13 were inactive for LPS-induced NO production in RAW 264.7 macrophages (IC50 > 50 [mu] M). Other compounds 1-4 showed excellent NO production inhibiting ability. c Positive control. Results are the mean of three independent experiments, and the data are expressed as mean ± standard deviation (Table 3).
Claims (9)
<화학식 1>
이때,
R1은 H 또는 탄소 수 5 이하의 알킬이고,
R2는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R3는 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
<화학식 2>
이때,
R4는 H 또는 탄소 수 5 이하의 알킬이고,
R5는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R6은 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R7은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
<화학식 3>
이때,
R8은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
A compound having any one of the following formulas (1) to (3), which has anti-inflammatory activity:
≪ Formula 1 >
At this time,
R < 1 > is H or alkyl having up to 5 carbon atoms,
R2 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R3 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
(2)
At this time,
R4 is H or alkyl having up to 5 carbon atoms,
R5 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R6 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R7 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
(3)
At this time,
R8 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
오갈피로부터 추출되는 것을 특징으로 하는 화합물.
The method according to claim 1,
≪ / RTI > is extracted from the algae.
An anti-inflammatory composition comprising an acaricidal extract.
약학적 조성물, 식품 조성물 또는 화장료 조성물인 것을 특징으로 하는 항염증 조성물.
The method of claim 3,
Wherein the composition is a pharmaceutical composition, a food composition or a cosmetic composition.
하기 화학식 1 내지 3으로 표시되는 화합물 중 어느 하나를 포함하는 것을 특징으로 하는 항염증 조성물:
<화학식 1>
이때,
R1은 H 또는 탄소 수 5 이하의 알킬이고,
R2는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R3는 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
<화학식 2>
이때,
R4는 H 또는 탄소 수 5 이하의 알킬이고,
R5는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R6은 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R7은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
<화학식 3>
이때,
R8은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
The method of claim 3,
An antiinflammatory composition comprising any one of compounds represented by the following formulas (1) to (3):
≪ Formula 1 >
At this time,
R < 1 > is H or alkyl having up to 5 carbon atoms,
R2 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R3 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
(2)
At this time,
R4 is H or alkyl having up to 5 carbon atoms,
R5 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R6 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R7 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
(3)
At this time,
R8 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
상기 오갈피 추출물은 오갈피를 물 또는 탄소 수 3 이하의 저가 알코올로 추출한 추출물인 것을 특징으로 하는 항염증 조성물.
The method of claim 3,
Wherein the extract is an extract obtained by extracting an oregano with water or a low-alcohol having 3 or less carbon atoms.
<화학식 1>
이때,
R1은 H 또는 탄소 수 5 이하의 알킬이고,
R2는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R3는 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
<화학식 2>
이때,
R4는 H 또는 탄소 수 5 이하의 알킬이고,
R5는 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R6은 H, OH, 탄소 수 5 이하의 알콕시 또는 탄소 수 5 이하의 알킬이고,
R7은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실이고,
<화학식 3>
이때,
R8은 H, 탄소 수 5 이하의 알킬 또는 글루코피라노실임.
An anti-inflammatory composition comprising any one of compounds represented by the following formulas (1) to (3):
≪ Formula 1 >
At this time,
R < 1 > is H or alkyl having up to 5 carbon atoms,
R2 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R3 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
(2)
At this time,
R4 is H or alkyl having up to 5 carbon atoms,
R5 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R6 is H, OH, alkoxy having 5 or less carbon atoms, or alkyl having 5 or less carbon atoms,
R7 is H, alkyl having 5 or less carbon atoms or glucopyranosyl,
(3)
At this time,
R8 is H, alkyl having up to 5 carbon atoms, or glucopyranosyl.
약학적 조성물, 식품 조성물 또는 화장료 조성물인 것을 특징으로 하는 항염증 조성물.
8. The method of claim 7,
Wherein the composition is a pharmaceutical composition, a food composition or a cosmetic composition.
상기 화합물은 오갈피로부터 추출되는 것을 특징으로 하는 항염증 조성물.
8. The method of claim 7,
Wherein said compound is extracted from an oregano.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20130066746A KR101509225B1 (en) | 2013-06-11 | 2013-06-11 | Novel triterpenoids from acanthopanax sessiliflorus and an anti-inflammatory composition containing it |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20130066746A KR101509225B1 (en) | 2013-06-11 | 2013-06-11 | Novel triterpenoids from acanthopanax sessiliflorus and an anti-inflammatory composition containing it |
Publications (2)
Publication Number | Publication Date |
---|---|
KR20140144592A true KR20140144592A (en) | 2014-12-19 |
KR101509225B1 KR101509225B1 (en) | 2015-04-10 |
Family
ID=52674798
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
KR20130066746A KR101509225B1 (en) | 2013-06-11 | 2013-06-11 | Novel triterpenoids from acanthopanax sessiliflorus and an anti-inflammatory composition containing it |
Country Status (1)
Country | Link |
---|---|
KR (1) | KR101509225B1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019240508A1 (en) * | 2018-06-14 | 2019-12-19 | 대한민국(농촌진흥청장) | Novel compound isolated from acanthopanax sp. fruit extract, and pharmaceutical composition for preventing and treating hypertension, containing same |
-
2013
- 2013-06-11 KR KR20130066746A patent/KR101509225B1/en active IP Right Grant
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2019240508A1 (en) * | 2018-06-14 | 2019-12-19 | 대한민국(농촌진흥청장) | Novel compound isolated from acanthopanax sp. fruit extract, and pharmaceutical composition for preventing and treating hypertension, containing same |
KR20190141445A (en) * | 2018-06-14 | 2019-12-24 | 대한민국(농촌진흥청장) | Novel compounds isolated from extract of Acanthopanax sp. fruit and pharmaceutical composition for preventing and treating hypertension including thereof |
Also Published As
Publication number | Publication date |
---|---|
KR101509225B1 (en) | 2015-04-10 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
Huang et al. | Triterpenoid saponins from the fruits and galls of Sapindus mukorossi | |
Tapondjou et al. | In vivo anti-inflammatory effect of a new steroidal saponin, mannioside A, and its derivatives isolated from Dracaena mannii | |
Grabowska et al. | Two new triterpenoid saponins from the leaves of Impatiens parviflora DC. and their cytotoxic activity | |
Sharma et al. | Novel chemical constituents with anti-inflammatory activity from the leaves of Sesbania aculeata | |
Kamdem et al. | Pentacyclic triterpenoids, phytosteroids and fatty acid isolated from the stem-bark of Cola lateritia K. Schum.(Sterculiaceae) of Cameroon origin; evaluation of their antibacterial activity | |
Zhang et al. | Triterpene saponins with neuroprotective effects from the leaves of Diospyros kaki Thunb | |
KR101625474B1 (en) | Manufacturing method for mass-production of ginsenoside Rh4 | |
Huang et al. | Triterpenoidal saponins from Hydrocotyle sibthorpioides | |
Ramos et al. | Immunosuppressive diacetylenes, ceramides and cerebrosides from Hydrocotyle leucocephala | |
KR101509225B1 (en) | Novel triterpenoids from acanthopanax sessiliflorus and an anti-inflammatory composition containing it | |
Liaw et al. | Cucurbitane-type triterpenoids from the vines of Momordica charantia and their anti-inflammatory, cytotoxic, and antidiabetic activity | |
CN105820208A (en) | Novel withanolide compound and preparation method and medical application thereof | |
JP6923100B1 (en) | New isoflavone compound | |
KR101220782B1 (en) | Novel Triterpenoid and Use Thereof | |
KR101780939B1 (en) | Method for Seperation of Compound Derived from Ginseng and Composition for anti-inflammatory Using the same | |
TWI612963B (en) | Cordyceps militaris extract for anti-inflammation and anti-proliferation against human liver cancer cell lines, and its preparation method | |
KR101548605B1 (en) | Compositions comprising fractions of Panax ginseng or ginsenosides isolated therefrom for prevention or treatment of disease through activation of sirtuins | |
KR101522584B1 (en) | External skin preparation comprising ginsenoside Rh6 | |
KR101556773B1 (en) | Anti-inflammatory composition containing diterpenes from the roots of oriza sativa l. | |
KR102655940B1 (en) | Novel ginsenoside, and anti-imflammantory composition comprising the same | |
KR102211799B1 (en) | Compound extracspted from the root of Camellia japonica and antioxidant composition comprising the same | |
Liao et al. | Norcucurbitane triterpenoids from the fruits of Momordica charantia var. abbreviata | |
Siddiqui et al. | A novel acyclic diterpenic alcohol isolated from antioxidant active ethanol extract of leaves of centaurothamnus maximus grown in Saudi Arabia | |
KR20140125937A (en) | Skim brightening composition containing triterpenoid compound or rubus coreanus mig. containing it | |
CN101222930B (en) | A composition comprising an extract of tiarell polyphylla and tiarellic acid isolated therefrom having antiinflammatory, antiallergic and antiasthmatic activity |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A201 | Request for examination | ||
E902 | Notification of reason for refusal | ||
E701 | Decision to grant or registration of patent right | ||
FPAY | Annual fee payment |
Payment date: 20171220 Year of fee payment: 4 |
|
FPAY | Annual fee payment |
Payment date: 20200128 Year of fee payment: 6 |