CN105461625A - Benzopyridone compound, preparing method thereof and applications of the compound - Google Patents
Benzopyridone compound, preparing method thereof and applications of the compound Download PDFInfo
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- CN105461625A CN105461625A CN201510795499.4A CN201510795499A CN105461625A CN 105461625 A CN105461625 A CN 105461625A CN 201510795499 A CN201510795499 A CN 201510795499A CN 105461625 A CN105461625 A CN 105461625A
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- -1 Benzopyridone compound Chemical class 0.000 title abstract description 16
- 150000001875 compounds Chemical class 0.000 title abstract description 10
- 238000000034 method Methods 0.000 title abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 66
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000000284 extract Substances 0.000 claims abstract description 16
- 238000000746 purification Methods 0.000 claims abstract description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000000203 mixture Substances 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 235000013305 food Nutrition 0.000 claims abstract description 7
- 239000002537 cosmetic Substances 0.000 claims abstract description 6
- 239000003814 drug Substances 0.000 claims abstract description 6
- 230000002087 whitening effect Effects 0.000 claims abstract description 6
- 238000013375 chromatographic separation Methods 0.000 claims abstract description 5
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical class C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 claims description 30
- 238000002360 preparation method Methods 0.000 claims description 23
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 20
- 238000000605 extraction Methods 0.000 claims description 18
- 241000028057 Cynanchum auriculatum Species 0.000 claims description 17
- 235000006386 Polygonum aviculare Nutrition 0.000 claims description 17
- 238000010898 silica gel chromatography Methods 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- 239000012141 concentrate Substances 0.000 claims description 8
- 238000000926 separation method Methods 0.000 claims description 8
- 239000003480 eluent Substances 0.000 claims description 7
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 7
- 239000011259 mixed solution Substances 0.000 claims description 7
- 102000004316 Oxidoreductases Human genes 0.000 claims description 6
- 108090000854 Oxidoreductases Proteins 0.000 claims description 6
- 230000001681 protective effect Effects 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 claims description 6
- 206010040829 Skin discolouration Diseases 0.000 claims description 4
- 239000000287 crude extract Substances 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 3
- 238000010298 pulverizing process Methods 0.000 claims description 2
- 230000001629 suppression Effects 0.000 claims description 2
- 241001377695 Polygonum arenastrum Species 0.000 claims 2
- 102000003425 Tyrosinase Human genes 0.000 abstract description 6
- 108060008724 Tyrosinase Proteins 0.000 abstract description 6
- 230000002401 inhibitory effect Effects 0.000 abstract description 6
- 241000196324 Embryophyta Species 0.000 abstract description 3
- 238000011161 development Methods 0.000 abstract description 2
- 241001289522 Fallopia Species 0.000 abstract 2
- 229940079593 drug Drugs 0.000 abstract 1
- 244000292697 Polygonum aviculare Species 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 229960001866 silicon dioxide Drugs 0.000 description 8
- 235000008504 concentrate Nutrition 0.000 description 6
- 238000010828 elution Methods 0.000 description 6
- 239000006187 pill Substances 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical class C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000004252 FT/ICR mass spectrometry Methods 0.000 description 1
- 241000571089 Fezia pterocarpa Species 0.000 description 1
- 241000640209 Funastrum cynanchoides Species 0.000 description 1
- 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 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229920001030 Polyethylene Glycol 4000 Polymers 0.000 description 1
- 206010000496 acne Diseases 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000002034 butanolic fraction Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000000119 electrospray ionisation mass spectrum Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229930003944 flavone Natural products 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 235000011949 flavones Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000002262 irrigation Effects 0.000 description 1
- 238000003973 irrigation Methods 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 235000014666 liquid concentrate Nutrition 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 201000001441 melanoma Diseases 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 description 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 1
- 239000006191 orally-disintegrating tablet Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000002791 soaking Methods 0.000 description 1
- PODWXQQNRWNDGD-UHFFFAOYSA-L sodium thiosulfate pentahydrate Chemical compound O.O.O.O.O.[Na+].[Na+].[O-]S([S-])(=O)=O PODWXQQNRWNDGD-UHFFFAOYSA-L 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/58—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems with hetero atoms directly attached to the ring nitrogen atom
- C07D215/60—N-oxides
-
- 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
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- 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
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- 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
- A23V2200/318—Foods, ingredients or supplements having a functional effect on health having an effect on skin health and hair or coat
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Dermatology (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a benzopyridone compound, a preparing method thereof and applications of the benzopyridone compound. The structure of the benzopyridone compound is shown as a formula (I). The preparing method includes adding smashed whole plant of fallopia cynanchoides into an organic solvent, digesting, separating to obtain leach liquor, extracting the leach liquor, concentrating extract liquid to obtain an extract, and subjecting the extract to chromatographic separation for purification to obtain the benzopyridone compound. The organic solvent is one or a mixture of more selected from methanol, ethanol, n-butanol and acetone. The benzopyridone compound having a novel structure is obtained by extracting the whole plant of fallopia cynanchoides and separating. The compound is good in tyrosinase inhibiting activity, can be used for preparing tyrosinase inhibiting medicines, whitening cosmetics or whitening healthcare foods, and has a good development prospect.
Description
Technical field
The present invention relates to active components of plants field, particularly relate to a kind of benzo pyridinone compounds and its preparation method and application.
Background technology
Cynanchum auriculatum Royle ex Wight knotweed (Classification system: Fallopiacynanchoides (Hemsl.) Harald.var.cynanchoides).Perennial herb.Stem is wound around, long 1-1.5 rice, without vertical rib, close by brown pubescence and sparse grow bristle.Feel relieved shape or wide halberd shape of leaf is heart-shaped, long 5-10 centimetre, wide 3-8 centimetre, and top is gradually sharp, base portion innermost being shape, and side raw sliver circle is blunt, or anxious point, the full edge in edge, and tool echinid, dredges raw short strigose above, below close by the long pubescence of brown; The long 3-5 centimetre of petiole, close by brown pubescence and sparse long bristle; Stipular sheath film quality, deflection, top point, close stiff hair.Inflorescence is coniform, and armpit is raw or top is raw, long 10-15 centimetre, close by pubescence and sparse grow bristle; Bract is avette, long 1-1.5 millimeter, and top is gradually sharp, by bristle, and tool 2-4 flower in every bud; Perianth 5 drastic crack, light green, the wide ellipse of tapel, long 1.5-2 millimeter; Bennet is sturdy, long 2-2.5 millimeter, tool joint, upper middle part, dredges by pubescence; Stamen 8, shorter than perianth, filigree base portion is wider; Style 3, sturdy, base portion symphysis; Column cap head, close by pimple.Achene is avette, tool 3 rib, long 2-2.5 millimeter, and black is glossy, is wrapped in persitent perianth.The florescence 8-9 month, the fruit phase 9-10 month [Hou Yuantong, Shandong Normal University's Ph D dissertation 2006,290-295].
Current research shows, mainly flavones ingredient [Min-HaKim in cynanchum auriculatum Royle ex Wight knotweed F.cynanchoides and adjacent kind of Fallopiaxlipes (Hara) Holub and F.pterocarpa (Wall.exMeisn.) Holub, JinHeePark, Chong-WookPark, BiochemicalSystematicsandEcology28 (2000) 433-441].But pyridinone composition is not in the news, for this reason, the natural radioactivity pyridone composition in research cynanchum auriculatum Royle ex Wight knotweed herb, can provide new approaches for the utilization of cynanchum auriculatum Royle ex Wight knotweed herb.
Summary of the invention
The invention provides a kind of benzo pyridinone compounds, this compound is the natural active matter extracting acquisition in the herb of cynanchum auriculatum Royle ex Wight knotweed, has anti-oxidant activity.
A kind of benzo pyridinone compounds, structure is as shown in formula I:
This benzo pyridinone compounds is extract from cynanchum auriculatum Royle ex Wight knotweed first and confirm the new compound of its structure, result of study shows, this benzo pyridinone compounds has good inhibit activities to tyrosine oxidase, can the synthesis of check melanin effectively, thus there are the potentiality as skin-lightening cosmetic or whitening protective foods.
The invention provides a kind of preparation method of described benzo pyridinone compounds, comprise the following steps:
(1) adopt organic solvent that cynanchum auriculatum Royle ex Wight knotweed (Fallopiacynanchoides (Hemsl.) Harald.var.cynanchoides) herb after pulverizing is carried out to lixiviate and obtains vat liquor;
Described organic solvent is one or more mixtures in methyl alcohol, ethanol, propyl carbinol and acetone;
(2) extract the vat liquor that step (1) obtains with extraction agent, extraction liquid obtains crude extract after concentrated;
(3) chromatographic separation and purification process are carried out to the crude extract that step (2) obtains, obtain described benzo pyridinone compounds.
In step (1), described cynanchum auriculatum Royle ex Wight knotweed herb is pulverized to be placed in organic solvent and carries out lixiviate, be more conducive to the leaching of benzo pyridinone compounds.Described cynanchum auriculatum Royle ex Wight knotweed herb and the weight ratio of organic solvent are preferably 1:1-1:8.Described lixiviate can be cold soaking or circumfluence distillation.
In step (2), described extraction agent is propyl carbinol.
As preferably, in step (2), described extracting solution first concentrates, and then adds diatomite and mixes sample, then adds described extraction agent and extract.
As other preferred, in step (2), described extracting solution first concentrates, and then adds water and carries out suspendible, then adds described extraction agent and extract.
As preferably, in step (3), described chromatographic separation is purification on normal-phase silica gel column chromatography for separation, and eluent is the mixed solution of chloroform and methyl alcohol.As further preferred, in described purification on normal-phase silica gel column chromatography for separation: after loading, using chloroform/methanol mixed solution as eluent, 9:1,5:1,3:1,1:1,1:3,1:9 carry out gradient elution by volume, the cut eluted when collecting eluent volume ratio 3:1.
As preferably, in step (3), described purification process comprises: reversed-phase silica gel column chromatography is separated, high performance liquid chromatography is separated and one or more in recrystallization.By purifying, the benzo pyridinone compounds that purity is higher can be obtained.
Present invention also offers described benzo pyridinone compounds and prepare the application in tyrosine oxidase suppression medicine or melanoma medicine.This medicine for main active ingredient with benzo pyridinone compounds of the present invention, adds acceptable auxiliary material in pharmaceutics and makes, can make preparation according to the formulation preparation method that pharmaceutics is recorded.Described preparation can be injection liquid, drip liquid, powder injection, granule, tablet, electuary, powder, oral liquid, sugar coated tablet, film coated tablet, enteric coated tablet, suck agent, granule, pill, paste, sublimed preparation, sprays, pill, disintegrating agent, orally disintegrating tablet, micropill etc.
Present invention also offers the described application of benzo pyridinone compounds in skin-lightening cosmetic.These makeup for main active ingredient with benzo pyridinone compounds of the present invention, add acceptable cosmetic and make.
Present invention also offers the application of described benzo pyridinone compounds in preparation whitening protective foods.This protective foods for main active ingredient with benzo pyridinone compounds of the present invention, adds acceptable protective foods auxiliary material and makes.
The present invention's extracting and developing from cynanchum auriculatum Royle ex Wight knotweed herb obtains a kind of benzo pyridinone compounds with novel structure, and the method is easy and simple to handle, extraction yield is high, product purity is high, is applicable to large-scale production.
By external tyrosinase activity inhibition test, show that benzo pyridinone compounds provided by the invention has good tyrosinase inhibitory action, its IC
50value is 19 μMs, can be used for preparing tyrosine oxidase and suppresses medicine, skin-lightening cosmetic or whitening protective foods, have good DEVELOPMENT PROSPECT.
Accompanying drawing explanation
Fig. 1 is that the HMBC of compound in embodiment 6 is correlated with collection of illustrative plates.
Embodiment
The preparation of embodiment 1 benzo pyridinone compounds
Get 5kg cynanchum auriculatum Royle ex Wight knotweed (Fallopiacynanchoides (Hemsl.) Harald.var.cynanchoides) herb, dry, pulverize, 2 weeks are soaked with methyl alcohol (40L), 1L distilled water suspendible used by soak solution (100mL) after concentrated, aqueous suspension 1L n-butanol extraction, butanol extraction liquid obtains medicinal extract through concentrated; Mix sample with silica gel (100 orders, 100g), carry out purification on normal-phase silica gel column chromatography for separation (200-300 order, 1kg; Silicagel column size L500mm,
), carry out gradient elution with the chloroform/methanol of volume ratio 9:1,5:1,3:1,1:1,1:3,1:9 successively, each 5L; TLC detects cut, and the cut collecting wash-out ratio 3:1 merges, then uses recrystallizing methanol.
The preparation of embodiment 2 benzo pyridinone compounds
Get 5kg cynanchum auriculatum Royle ex Wight knotweed herb, dry, pulverize, use 5L alcohol reflux, extracting solution concentrates (100mL), and aqueous suspension (1L) uses 1L chloroform extraction, and chloroform layer discards.Water layer 1L n-butanol extraction; N-butanol fraction concentrates, and mixes sample, carry out purification on normal-phase silica gel column chromatography for separation (200-300 order, 1kg with silica gel (100 orders, 100g); Silicagel column size L500mm,
), carry out gradient elution with the chloroform/methanol of volume ratio 9:1,5:1,3:1,1:1,1:3,1:9 successively, each 5L; TLC detects cut, and the cut collecting wash-out ratio 3:1 merges, then uses recrystallizing methanol.
The preparation of embodiment 3 benzo pyridinone compounds
Get 5kg cynanchum auriculatum Royle ex Wight knotweed herb, pulverize, extract with 5L methanol/ethanol mixed-liquor return, extract concentrates (100mL), mixes sample with 100g diatomite, and 5L propyl carbinol heat is extracted; Carry out purification on normal-phase silica gel column chromatography for separation (200-300 order, 1kg; Silicagel column size L500mm,
), carry out gradient elution with the chloroform/methanol mixed solution of volume ratio 9:1,5:1,3:1,1:1,1:3,1:9 successively, each 5L; TLC detects cut, and the cut collecting wash-out ratio 3:1 merges, then uses acetone/normal hexane (volume ratio 1:1) recrystallization.
The preparation of embodiment 4 benzo pyridinone compounds
Get 5kg cynanchum auriculatum Royle ex Wight knotweed herb, pulverize, extract with 5L methanol/ethanol mixed-liquor return, extract concentrates (100mL), mixes sample with 100g diatomite, and 5L propyl carbinol heat is extracted; Carry out purification on normal-phase silica gel column chromatography for separation (200-300 order, 1kg; Silicagel column size L500mm,
), carry out gradient elution with the chloroform/methanol mixed solution of volume ratio 9:1,5:1,3:1,1:1,1:3,1:9 successively, each 5L; TLC detects cut, and the cut collecting wash-out ratio 3:1 merges; Cut reversed-phase silica gel column chromatography/high performance liquid chromatography is separated, and eluent is methanol/water (9:1-1:9), and the determined wavelength of high performance liquid chromatography is 254nm; Use recrystallizing methanol.
The preparation of embodiment 5 benzo pyridinone compounds
Get 5kg cynanchum auriculatum Royle ex Wight knotweed herb, pulverize, by 5L methanol/ethanol/acetone mixture refluxing extraction, extract is concentrated into without alcohol taste, uses 5L n-butanol extraction, extraction liquid concentrate, after water suspendible go up macroporous resin (size L500mm,
) except sugar; Ethanol is washed lower rear concentrated, and 100g silica gel mixed sample, carries out purification on normal-phase silica gel column chromatography for separation (200-300 order, 1kg; Silicagel column size L500mm,
), carry out gradient elution with the chloroform/methanol mixed solution of volume ratio 9:1,5:1,3:1,1:1,1:3,1:9 successively, each 5L; TLC detects cut, and the cut collecting wash-out ratio 3:1 merges; Cut reversed-phase silica gel column chromatography/high performance liquid chromatography is separated, and eluent is methanol/water (9:1-1:9), and the determined wavelength of high performance liquid chromatography is 254nm; Use recrystallizing methanol.
The Structural Identification of embodiment 6 benzo pyridinone compounds
Adopt HPLC to carry out Purity to obtained compound, the sample that purity is greater than 98% uses mass spectrum and nuclear magnetic resonance technique to carry out Structural Identification, and nucleus magnetic resonance BrukerAVANCEDRX-500NMRSectrometer measures, mark in TMS does; High resolution mass spectrum FTICRMS BrukerApexSpectrometer measures; Electrospray ionization mass spectrum ESI-MS BrukerEsquire3000
plusspectrometer measures.
According to one-dimensional NMR analytical results (see table 1) and the two-dimentional NMR analytical results (see Fig. 1) of compound, known, this material is benzo pyridinone compounds, and molecular formula is C
12h
11nO
5, structure is as follows:
The NMR data of table 1 benzo pyridinone compounds
aRecordedon125MHz.
bMultiplicitiesinferredfromDEPTandHMQCexperiments.
cRecordedon500MHz.
Embodiment 7 benzo pyridinone compounds is to tyrosinase inhibitory activity analysis
Benzo pyridinone compounds dissolve with methanol to concentration is 2.5%; Tyrosine oxidase (28nM) and compound incubation 10 minutes; Add LDOPA (0.5mM).The inhibit activities calculation formula of compound to tyrosine oxidase is as follows:
Inhibiting rate (%)=[(B – S)/B] × 100%
Wherein, B is blank absorption, and S is absorption of sample.
Known by experimental result, the IC of this compound
50=19 μMs, show that this compound is better to tyrosinase inhibitory activity.
Embodiment 8 is containing the preparation of benzo pyridinone compounds dropping pill formulation
Get 0.5g benzo pyridinone compounds to mix with 10.5g PEG-4000, heating and melting, move in dripping pill drip irrigation after material, liquid drops in 6 ~ 8 DEG C of whiterusss, oil removing, obtained dripping pill 300.
Embodiment 9 is containing the preparation of benzo pyridinone compounds lyophilized injectable powder
Get benzo pyridinone compounds 0.5g, glucose 4.5g, Sulfothiorine 0.9g and distilled water 1000ml, after said components mixes, lyophilize, packing 400, to obtain final product.
Claims (10)
1. a benzo pyridinone compounds, is characterized in that, structure is as shown in formula I:
2. a preparation method for benzo pyridinone compounds as claimed in claim 1, is characterized in that, comprise the following steps:
(1) adopt organic solvent that cynanchum auriculatum Royle ex Wight knotweed (Fallopiacynanchoides (Hemsl.) Harald.var.cynanchoides) herb after pulverizing is carried out to lixiviate and obtains vat liquor;
Described organic solvent is one or more mixtures in methyl alcohol, ethanol, propyl carbinol and acetone;
(2) extract the vat liquor that step (1) obtains with extraction agent, extraction liquid obtains crude extract after concentrated;
(3) chromatographic separation and purification process are carried out to the crude extract that step (2) obtains, obtain described benzo pyridinone compounds.
3. the preparation method of benzo pyridinone compounds according to claim 2, is characterized in that, described cynanchum auriculatum Royle ex Wight knotweed herb and the weight ratio of organic solvent are preferably 1:1-1:8.
4. preparation method according to claim 2, is characterized in that, in step (2), described extraction agent is propyl carbinol.
5. preparation method according to claim 2, is characterized in that, in step (2), described extracting solution first concentrates, and then adds diatomite and mixes sample, then adds described extraction agent and extract.
6. preparation method according to claim 2, is characterized in that, in step (2), described extracting solution first concentrates, and then adds water and carries out suspendible, then adds described extraction agent and extract.
7. preparation method according to claim 2, is characterized in that, in step (3), described chromatographic separation is purification on normal-phase silica gel column chromatography for separation, and eluent is the mixed solution of chloroform and methyl alcohol.
8. preparation method according to claim 2, is characterized in that, in step (3), described purification process comprises: reversed-phase silica gel column chromatography be separated, high performance liquid chromatography be separated and recrystallization in one or more.
9. preparation method according to claim 8, is characterized in that, the eluent that described reversed-phase silica gel column chromatography is separated is the mixed solution of first alcohol and water.
10. a benzo pyridinone compounds as claimed in claim 1 is preparing the application in tyrosine oxidase suppression medicine, skin-lightening cosmetic or whitening protective foods.
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