CN108503653A - It a kind of naphthoquinone compound and its prepares and the application in preparing hypoglycemic product - Google Patents
It a kind of naphthoquinone compound and its prepares and the application in preparing hypoglycemic product Download PDFInfo
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- CN108503653A CN108503653A CN201810359024.4A CN201810359024A CN108503653A CN 108503653 A CN108503653 A CN 108503653A CN 201810359024 A CN201810359024 A CN 201810359024A CN 108503653 A CN108503653 A CN 108503653A
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- Prior art keywords
- naphthoquinone compound
- fraction
- petroleum ether
- silica gel
- water chestnut
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- 229930192627 Naphthoquinone Natural products 0.000 title claims abstract description 32
- -1 naphthoquinone compound Chemical class 0.000 title claims abstract description 32
- 230000002218 hypoglycaemic effect Effects 0.000 title claims abstract description 19
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 38
- 235000003283 Pachira macrocarpa Nutrition 0.000 claims abstract description 30
- 235000014364 Trapa natans Nutrition 0.000 claims abstract description 30
- 235000009165 saligot Nutrition 0.000 claims abstract description 30
- 241001083492 Trapa Species 0.000 claims abstract description 28
- 238000010898 silica gel chromatography Methods 0.000 claims abstract description 15
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims abstract description 11
- 238000004821 distillation Methods 0.000 claims abstract description 10
- 239000000126 substance Substances 0.000 claims abstract description 7
- 239000000499 gel Substances 0.000 claims abstract description 6
- 239000007791 liquid phase Substances 0.000 claims abstract description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 239000003208 petroleum Substances 0.000 claims description 34
- 238000010828 elution Methods 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 claims description 15
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 13
- 238000000034 method Methods 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 13
- 241001276404 Arius Species 0.000 claims description 11
- 229940079593 drug Drugs 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 239000000047 product Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 6
- 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 claims description 5
- 239000012071 phase Substances 0.000 claims description 5
- 239000006228 supernatant Substances 0.000 claims description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 4
- 235000013305 food Nutrition 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 208000013016 Hypoglycemia Diseases 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 238000013270 controlled release Methods 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000008187 granular material Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 19
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 abstract description 5
- 229960002632 acarbose Drugs 0.000 abstract description 5
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 abstract description 5
- 241000196324 Embryophyta Species 0.000 abstract description 4
- 239000013641 positive control Substances 0.000 abstract description 4
- 238000011161 development Methods 0.000 abstract description 3
- 230000009977 dual effect Effects 0.000 abstract description 3
- 239000000463 material Substances 0.000 abstract description 3
- 239000003472 antidiabetic agent Substances 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- 229920005654 Sephadex Polymers 0.000 abstract 1
- 239000012507 Sephadex™ Substances 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 description 21
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 15
- 102000004190 Enzymes Human genes 0.000 description 9
- 108090000790 Enzymes Proteins 0.000 description 9
- 235000019441 ethanol Nutrition 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- 108010028144 alpha-Glucosidases Proteins 0.000 description 8
- 239000007853 buffer solution Substances 0.000 description 7
- 230000005764 inhibitory process Effects 0.000 description 7
- 238000000926 separation method Methods 0.000 description 6
- 102100024295 Maltase-glucoamylase Human genes 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 4
- 206010013786 Dry skin Diseases 0.000 description 3
- 102000016679 alpha-Glucosidases Human genes 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 239000002398 materia medica Substances 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- BTJIUGUIPKRLHP-UHFFFAOYSA-N 4-nitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1 BTJIUGUIPKRLHP-UHFFFAOYSA-N 0.000 description 2
- 241001614291 Anoplistes Species 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 241000202829 Eleocharis Species 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 240000001085 Trapa natans Species 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000000378 dietary effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000003919 heteronuclear multiple bond coherence Methods 0.000 description 2
- 150000002791 naphthoquinones Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- KNMBMVIRNMTOOU-UHFFFAOYSA-N 2-(1,3-benzodioxol-5-yl)-3,7-dihydroxy-5,6-dimethoxychromen-4-one Chemical compound C1=C2OCOC2=CC(C=2OC3=CC(O)=C(C(=C3C(=O)C=2O)OC)OC)=C1 KNMBMVIRNMTOOU-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 241001269238 Data 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
- 206010062717 Increased upper airway secretion Diseases 0.000 description 1
- 229910002570 KH2PO4-Na2HPO4 Inorganic materials 0.000 description 1
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 241000287420 Pyrus x nivalis Species 0.000 description 1
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 244000269722 Thea sinensis Species 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer 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
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000005100 correlation spectroscopy Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 125000000597 dioxinyl group Chemical group 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 201000006549 dyspepsia Diseases 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000011389 fruit/vegetable juice Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000013402 health food Nutrition 0.000 description 1
- 238000002114 high-resolution electrospray ionisation mass spectrometry Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 229940124531 pharmaceutical excipient Drugs 0.000 description 1
- 208000026435 phlegm Diseases 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000035922 thirst Effects 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011716 vitamin B2 Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 239000000341 volatile oil Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- General Chemical & Material Sciences (AREA)
- Polymers & Plastics (AREA)
- Nutrition Science (AREA)
- Mycology (AREA)
- Emergency Medicine (AREA)
- Botany (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicines Containing Plant Substances (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
The invention belongs to field of natural medicinal chemistry, and in particular to a kind of naphthoquinone compound and its prepare and the application in preparing hypoglycemic product.For the chemical structural formula of the naphthoquinone compound as shown in formula I, circumfluence distillation after the present invention crushes water chestnut obtains water chestnut total extract；Then it is extracted successively with hexamethylene, ethyl acetate, extract obtains naphthoquinone compound after silica gel column chromatography, 20 gel columns of Sephadex LH, 40 columns of Toyopearl HW, half prepare liquid phase C18 column separating purifications.The naphthoquinone compound structure novel has preferable hypoglycemic activity, and hypoglycemic activity is higher than positive control acarbose, this has established important material base for the hypoglycemic drug that development efficacy is notable from medical and edible dual purpose plant from now on and toxic side effect is small.
Description
Technical field
The invention belongs to field of natural medicinal chemistry, and in particular to a kind of naphthoquinone compound and its prepare and drop preparing
Application in blood glucose product.
Background technology
Water chestnut (Heleocharis dulcis), is commonly called as horseshoe, Di Li, is the perennial shallow water draft of Cyperaceae Eleocharis
Plant.It is as a kind of food of dietotherapeutic, and fine and tender taste, juice multi-flavor sweet tea is fresh and crisp, just have from ancient times " underground pyrus nivalis " it
Good reputation, it is very popular.In every 100g water chestnut fresh goods, moisture content 68g, carbohydrate 21.8g, protein 1.5g, fat
Fat 0.1g, crude fibre 0.5g, calcium 5mg, phosphorus 68mg, iron 0.5mg, carrotene 0.01mg, vitamin B B10.04mg, vitamin B2
0.02mg, vitamin C 3mg, niacin 0.4mg etc..《Compendium of Materia Medica》Water chestnut energy fall fire is recorded, tonifying lung cool liver eliminates indigestion and phlegm.
According to《Dietetic materia medica》With《Compendium of Materia Medica》It records, water chestnut can only quench one's thirst, property cold Yin Qigan, clearing heat and promoting fluid, hinder in pyreticosis Tianjin
It can be used when polydipsia.Modern pharmacological studies have shown that water chestnut has antibacterial, anticancer and the pharmacological actions such as anti-oxidant.
The chemical constitution study of water chestnut show water chestnut contain polysaccharide, polyphenol, flavonoids, sterol, volatile oil etc. chemistry at
Point.Currently, the function research to water chestnut mixed extract is more, and it is less to the report of one-component, it is extracted from water chestnut
It detaches, extract in object, being purified into a kind of single-activity component, developing water chestnut series function health food and its drug, answer
It is very wide with foreground.
Invention content
For overcome the deficiencies in the prior art and disadvantage, the primary purpose of the present invention is that providing a kind of naphthoquinones class chemical combination
Object, the compound are isolated from water chestnut for the first time.
Another object of the present invention is to provide the preparation methods of above-mentioned naphthoquinone compound.
It is still another object of the present invention to provide application of the above-mentioned naphthoquinone compound in preparing hypoglycemic product.
The purpose of the invention is achieved by the following technical solution：
A kind of naphthoquinone compound is named as 6,11- dimethoxy -15,16- dimethyl furan-Nai Bing dioxines -1,2,
14- triketones, molecular formula C18H14O8, chemical structural formula is as shown in formula I：
The preparation method of the naphthoquinone compound, comprises the following steps：
(1) dry water chestnut is crushed, is placed in ethanol solution and impregnates；Then circumfluence distillation, extracting solution merges and mistake
Filter, filtrate low temperature drying to no alcohol taste obtain water chestnut total extract；
(2) water chestnut total extract is suspended in water, carries out pinching molten (i.e. fully dissolving), stands, filtering obtains supernatant
Liquid；Then it is extracted successively with hexamethylene, ethyl acetate, it is dry, respectively obtain hexamethylene extract and ethyl acetate extraction
Object；
(3) acetic acid ethyl ester extract made from step (2) is dissolved with solvent, silica gel column chromatography is carried out, using petroleum ether-
Ethyl acetate elution system carries out gradient elution, and it is 8 to collect petroleum ether-ethyl acetate volume ratio:1 fraction；
(4) fraction that step (3) is collected is subjected to silica gel column chromatography again, is carried out using petroleum ether-acetone elution system
Gradient elution, it is 9 to collect petroleum ether-acetone volume ratio:1 Arius part；
(5) Arius part that step (4) is collected is dissolved with methanol, upper Sephadex LH-20 gel columns use volume fraction
It is eluted for 95% methanol, obtains time fraction；The secondary fraction is gone up into Toyopearl HW-40 columns again, is with volume fraction
95% acetonitrile elution, obtains small fraction；
(6) the small fraction upper half for obtaining step (5) prepares liquid phase C18 columns, is isolated and purified, obtains naphthoquinones class chemical combination
Object；
Crushing described in step (1) is preferably crushed to 0.5~1.0 centimetre；
The volume fraction of ethanol solution described in step (1) is preferably 90~95%；
The time of immersion described in step (1) is preferably 12~18h；
The condition of circumfluence distillation described in step (1) is preferably circumfluence distillation 3 times, every time 2~3h；
The temperature of low temperature drying described in step (1) is preferably 50~55 DEG C；
The volume ratio of water chestnut total extract and water described in step (2) is preferably 1:1；
The time of standing described in step (2) is preferably 20~for 24 hours；
Solvent described in step (3) is preferably petroleum ether；
Silica gel column chromatography described in step (3) is preferably wet method upper prop, and silica gel is preferably 100~200 mesh；
Gradient elution described in step (3) is preferably 12 according to petroleum ether-ethyl acetate volume ratio:1、8:1、4:1
Carry out gradient elution；
Silica gel column chromatography described in step (4) is preferably wet method upper prop, and silica gel is preferably 200~300 mesh；
Gradient elution described in step (4) is preferably 15 according to petroleum ether-acetone volume ratio:1、9:1、5:1 carries out
Gradient elution；
The condition isolated and purified described in step (6) is preferably mobile phase：The methanol that volume fraction is 90~95% is molten
Liquid, absorbing wavelength 210nm；
Application of the naphthoquinone compound in preparing hypoglycemic product；
The hypoglycemic product is preferably hypoglycemia healthcare food or drug；
Naphthoquinone compound containing therapeutically effective amount in the drug, surplus are pharmaceutic adjuvant or other compatible medicines
Object；
The pharmaceutic adjuvant refers to conventional pharmaceutical excipient, as solvent, disintegrant, corrigent, preservative, colorant and
Adhesive etc.；
Other compatible drugs, refer to using the naphthoquinone compound of effective dose as medicine material, then compatibility
Other natural drugs or chemicals；
The drug includes various clinical pharmaceutical dosage form, such as tablet, injection, liposome nano granule, controlled release agent；
The present invention has the following advantages and effects with respect to the prior art：
(1) present invention chooses medical and edible dual purpose plant --- and water chestnut is full of nutrition as research object, on history tree
It is mostly on the books, there is good medicinal dietary function, there is potential Development volue.
(2) naphthoquinone compound structure novel provided by the invention has preferable hypoglycemic activity, this is from now on from medicine
The hypoglycemic drug that development efficacy is notable in food dual purpose plant and toxic side effect is small has established important material base.
(3) so far, the preparation method of naphthoquinone compound provided by the invention and inhibition alpha-glucosidase activity
Relevant references or patent report are there are no, is had creative well.
Description of the drawings
Fig. 1 is the preparation flow figure of naphthoquinone compound in embodiment 1.
Fig. 2 is the coupling correlation figure of naphthoquinone compound.
Specific implementation mode
Present invention will now be described in further detail with reference to the embodiments and the accompanying drawings, but embodiments of the present invention are unlimited
In this.
Embodiment 1
(1) dry water chestnut (10.0 kilograms) is ground into fritter (0.8 centimetre), is placed in the ethyl alcohol that volume fraction is 92%
After impregnating 16h in solution, circumfluence distillation is carried out 3 times, each 3h, extracting solution merges and filters, (53 DEG C) dryings of filtrate low temperature
To no alcohol taste, water chestnut total extract (1.05 kilograms) is obtained；
(2) water chestnut total extract is suspended in water (V/V=1:1) it, carries out pinching molten (i.e. fully dissolving), stand for 24 hours, mistake
Filter, obtains supernatant；It is extracted successively with hexamethylene, ethyl acetate, n-butanol, solvent evaporated, respectively obtains hexamethylene extraction
Take object (46.5 grams), acetic acid ethyl ester extract (126.2 grams) and n-butyl alcohol extract (258.6 grams)；
(3) extract made from step (2) is carried out inhibiting alpha-glucosidase activity screening experiment (detailed in Example 4
Screening active ingredients part), the results showed that acetic acid ethyl ester extract (active site), which has, significantly inhibits alpha-glucosidase activity；
(4) by acetic acid ethyl ester extract petroleum ether dissolution made from step (2), carry out silica gel column chromatography (wet method upper prop,
100~200 mesh)；Using petroleum ether-ethyl acetate elution system according to petroleum ether-ethyl acetate volume ratio 12:1→8:1→4:
1 carries out gradient elution, respectively obtains 3 fractions such as A (20.5 grams), B (62.8 grams), C (27.5 grams)；
(5) using the method for activity tracking separation, B fractions (the petroleum ether-ethyl acetate volume ratio that step (4) is obtained
It is 8:1 fraction afforded) silica gel column chromatography (wet method upper prop, 200~300 mesh) is carried out again, it is washed using petroleum ether-acetone
De- system is according to petroleum ether-acetone volume ratio 15:1→9:1→5:1 carries out gradient elution, obtains B-1 (11.4 grams), B-2
3 Arius parts such as (30.6 grams), B-3 (15.2 grams)；
(6) (petroleum ether-acetone volume ratio is 9 to the Arius part B-2 obtained step (5):1 Arius part afforded) it uses
Methanol dissolves, upper Sephadex LH-20 gel columns, and the methanol for being 95% with volume fraction elutes, and obtains time fraction B-2-1
(26.4 grams)；By the secondary fraction, upper Toyopearl HW-40 columns, the acetonitrile for being 95% with volume fraction are eluted, are obtained small again
Fraction B-2-1-1 (18.5 grams)；
(7) the small fraction upper half for obtaining step (6) prepares liquid phase C18 columns, is isolated and purified (mobile phase：Volume point
Number is 90~95% methanol, absorbing wavelength：210nm), by separation, purifying repeatedly, monomeric compound I is finally obtained
(10.05 milligrams) (preparation flow is shown in Fig. 1).
Gained monomeric compound I of the invention is light yellow solid (methanol), HR-ESI-MS m/z 381.2314 [M+Na]+
It is C to prompt its molecular composition18H14O8(calcd.for C18H14O8Na, 381.2342).UV (MeOH) λ of chemical compounds Imax:
215,255,415nm；IRνmax:3429.2,2923.5,1731.5,1618.7,1358.3,1125.1cm-1；Monomeric compound I
's1H NMR(CD3COCD3, 400MHz) and13C NMR(CD3COCD3, 100MHz) and data are shown in Table 1.Comprehensively utilize Modern spectroscopy skill
Art and bibliography, and the HMBC of binding compounds I,1H-1The coupling such as H COSY is related (Fig. 2), final to determine monomeric compound I
For a new naphthoquinone compound (formula I).
1 monomeric compound I of table1H NMR、13C NMR and HMBC related datas
Embodiment 2
(1) dry water chestnut is ground into fritter (0.5 centimetre), is placed in the ethanol solution that volume fraction is 95% and impregnates
After 18h, circumfluence distillation is carried out 3 times, each 2h, extracting solution merges and filters, and (55 DEG C) dryings of filtrate low temperature are obtained to no alcohol taste
To water chestnut total extract；
(2) water chestnut total extract is suspended in water (V/V=1:1) it, carries out pinching molten (i.e. fully dissolving), stands 22h, mistake
Filter, obtains supernatant；It is extracted successively with hexamethylene, ethyl acetate, n-butanol, solvent evaporated, respectively obtains hexamethylene extraction
Take object, acetic acid ethyl ester extract and n-butyl alcohol extract；
(3) by acetic acid ethyl ester extract petroleum ether dissolution made from step (2), carry out silica gel column chromatography (wet method upper prop,
100~200 mesh)；Using petroleum ether-ethyl acetate elution system according to petroleum ether-ethyl acetate volume ratio 12:1→8:1→4:
1 carries out gradient elution, respectively obtains 3 fractions such as A, B, C；
(4) using the method for activity tracking separation, B fractions (the petroleum ether-ethyl acetate volume ratio that step (3) is obtained
It is 8:1 fraction afforded) silica gel column chromatography (wet method upper prop, 200~300 mesh) is carried out again, it is washed using petroleum ether-acetone
De- system is according to petroleum ether-acetone volume ratio 15:1→9:1→5:1 carries out gradient elution, obtains 3 Asias such as B-1, B-2, B-3
Fraction；
(5) (petroleum ether-acetone volume ratio is 9 to the Arius part B-2 obtained step (5):1 Arius part afforded) it uses
Methanol dissolves, upper Sephadex LH-20 gel columns, and the methanol for being 95% with volume fraction elutes, and obtains time fraction B-2-1；It will
Upper Toyopearl HW-40 columns, the acetonitrile for being 95% with volume fraction elute the secondary fraction again, obtain small fraction B-2-1-1；
(6) the small fraction upper half for obtaining step (5) prepares liquid phase C18 columns, is isolated and purified (mobile phase：Volume point
Number is 90~95% methanol, absorbing wavelength：210nm), by separation, purifying repeatedly, monomeric compound I is finally obtained.
Embodiment 3
(1) dry water chestnut is ground into fritter (1.0 centimetres), is placed in the ethanol solution that volume fraction is 90% and impregnates
After 12h, circumfluence distillation is carried out 3 times, each 2.5h, extracting solution merges and filters, (50 DEG C) dryings of filtrate low temperature to no alcohol taste,
Obtain water chestnut total extract；
(2) water chestnut total extract is suspended in water (V/V=1:1) it, carries out pinching molten (i.e. fully dissolving), stands 20h, mistake
Filter, obtains supernatant；It is extracted successively with hexamethylene, ethyl acetate, n-butanol, solvent evaporated, respectively obtains hexamethylene extraction
Take object, acetic acid ethyl ester extract and n-butyl alcohol extract；
(3) by acetic acid ethyl ester extract petroleum ether dissolution made from step (2), carry out silica gel column chromatography (wet method upper prop,
100~200 mesh)；Using petroleum ether-ethyl acetate elution system according to petroleum ether-ethyl acetate volume ratio 12:1→8:1→4:
1 carries out gradient elution, respectively obtains 3 fractions such as A, B, C；
(4) using the method for activity tracking separation, B fractions (the petroleum ether-ethyl acetate volume ratio that step (3) is obtained
It is 8:1 fraction afforded) silica gel column chromatography (wet method upper prop, 200~300 mesh) is carried out again, it is washed using petroleum ether-acetone
De- system is according to petroleum ether-acetone volume ratio 15:1→9:1→5:1 carries out gradient elution, obtains 3 Asias such as B-1, B-2, B-3
Fraction；
(5) (petroleum ether-acetone volume ratio is 9 to the Arius part B-2 obtained step (5):1 Arius part afforded) it uses
Methanol dissolves, upper Sephadex LH-20 gel columns, and the methanol for being 95% with volume fraction elutes, and obtains time fraction B-2-1；It will
Upper Toyopearl HW-40 columns, the acetonitrile for being 95% with volume fraction elute the secondary fraction again, obtain small fraction B-2-1-1；
(6) the small fraction upper half for obtaining step (5) prepares liquid phase C18 columns, is isolated and purified (mobile phase：Volume point
Number is 90~95% methanol, absorbing wavelength：210nm), by separation, purifying repeatedly, monomeric compound I is finally obtained.
The hypoglycemic activity of 4 monomeric compound I of embodiment
(1) experimental method
(1) alpha-glucosidase activity measures
10 μ L of a concentration of 1U/mL alpha-glucosidases (being configured with buffer solution) are added in 100 μ L buffer solutions, 37 DEG C of cultivations
10min adds a concentration of 0.01mol/L p-nitrophenyl-β-D- glucopyranosides (PNPG) 90 μ L, 37 DEG C of cultivation 10min,
It is measured and is absorbed in wavelength 405nm with microplate reader.Wherein enzyme activity unit defines：At 37 DEG C, under the conditions of pH=6.8, water in 1min
Solve the enzyme amount needed for PNPG 1 μm of ol paranitrophenol (PNP) of release.
(2) alpha-glucosidase activity is inhibited to measure
A concentration of 1U/mL alpha-glucosidases of 10 μ L (being configured with buffer solution) are added in the sample of various concentration, are added
50 μ L buffer solutions, 37 DEG C of cultivation 10min；Add a concentration of 0.01mol/L PNPG 90 μ L, 37 DEG C of cultivation 10min, with enzyme mark
Instrument is measured in wavelength 405nm to be absorbed.Inhibitor unit of activity is defined as：It reduces under the same conditions needed for 1 enzyme activity unit
Inhibition dosage.
(3) positive control
A concentration of 1U/mL alpha-glucosidases of 10 μ L (using buffer) are added in acarbose, add 50 μ L
Buffer solution, 37 DEG C of cultivation 10min；Add 0.01mol/L PNPG 90 μ L, 37 DEG C of cultivation 10min, in wavelength 405nm measurement
It absorbs.
(4) blank control
50 μ L buffer solutions are added in sample solvent, 37 DEG C of cultivation 10min add a concentration of 0.01mol/L90 μ L
PNPG, 37 DEG C of cultivation 10min, measures in wavelength 405nm and absorbs.
(5) buffer solution：0.067mol/L KH2PO4-Na2HPO4, pH 6.8；
The calculating of inhibiting rate：(AEnzyme-ABlank-ASuppression)100/(AEnzyme-ABlank)。
(2) first test result
Monomeric compound I (formula I) is subjected to alpha-glucosaccharase enzyme inhibition activity screening, using acarbose as positive control.
Using 400 μm of ol of constant density (each sample is parallel to be surveyed three times, is averaged), tested as stated above, with inhibiting rate
Think active in 50% or more person.Experimental result (is shown in Table 2).
2 monomeric compound I of table is to alpha-glucosaccharase enzyme inhibition activity the selection result
| Compound | Inhibiting rate (%) |
| Chemical compounds I | 86.7 |
| Acarbose | 50 |
(3) IC50Test result
Monomeric compound I with alpha-glucosaccharase enzyme inhibition activity after primary dcreening operation is further tested, in inhibiting effect
Various concentration is chosen in concentration range, alpha-glucosaccharase enzyme inhibition activity test is carried out to compound monomer I respectively, takes it average
Value, calculates IC50Value.As a result (3 are shown in Table).
3 monomeric compound I of table inhibits the IC of alpha-glucosaccharase enzyme inhibition activity50Value
| Compound | IC50(μM) |
| Chemical compounds I | 20.8±5.7 |
| Acarbose | 38.6±8.9 |
It these results suggest that monomeric compound I has hypoglycemic activity, and hypoglycemic activity is higher than positive control A Kabo
Sugar.
The above embodiment is a preferred embodiment of the present invention, but embodiments of the present invention are not by above-described embodiment
Limitation, it is other it is any without departing from the spirit and principles of the present invention made by changes, modifications, substitutions, combinations, simplifications,
Equivalent substitute mode is should be, is included within the scope of the present invention.
Claims (10)
1. a kind of naphthoquinone compound, it is characterised in that its chemical structural formula is as shown in formula I：
2. the preparation method of naphthoquinone compound described in claim 1, it is characterised in that comprise the following steps：
(1) dry water chestnut is crushed, is placed in ethanol solution and impregnates；Then circumfluence distillation, extracting solution merge and filter, filter
Liquid low temperature drying obtains water chestnut total extract to no alcohol taste；
(2) water chestnut total extract is suspended in water, pinch molten, standing, filtering obtains supernatant；Then hexamethylene is used successively
Alkane, ethyl acetate are extracted, dry, respectively obtain hexamethylene extract and acetic acid ethyl ester extract；
(3) acetic acid ethyl ester extract made from step (2) is dissolved with solvent, silica gel column chromatography is carried out, using petroleum ether-acetic acid
Ethyl ester elution system carries out gradient elution, and it is 8 to collect petroleum ether-ethyl acetate volume ratio:1 fraction；
(4) fraction that step (3) is collected is subjected to silica gel column chromatography again, gradient is carried out using petroleum ether-acetone elution system
Elution, it is 9 to collect petroleum ether-acetone volume ratio:1 Arius part；
(5) Arius part that step (4) is collected is dissolved with methanol, upper Sephadex LH-20 gel columns are with volume fraction
95% methanol elution, obtains time fraction；The secondary fraction is gone up into Toyopearl HW-40 columns again, is 95% with volume fraction
Acetonitrile elution, obtain small fraction；
(6) the small fraction upper half for obtaining step (5) prepares liquid phase C18 columns, is isolated and purified, obtains naphthoquinone compound.
3. the preparation method of naphthoquinone compound according to claim 2, it is characterised in that：
The condition of circumfluence distillation described in step (1) is circumfluence distillation 3 times, every time 2~3h.
4. the preparation method of naphthoquinone compound according to claim 2, it is characterised in that：
Silica gel column chromatography described in step (3) is wet method upper prop, and silica gel is 100~200 mesh；
It is 12 that gradient elution described in step (3), which is according to petroleum ether-ethyl acetate volume ratio,:1、8:1、4:1 carries out gradient
Elution.
5. the preparation method of naphthoquinone compound according to claim 2, it is characterised in that：
Silica gel column chromatography described in step (4) is wet method upper prop, and silica gel is 200~300 mesh；
It is 15 that gradient elution described in step (4), which is according to petroleum ether-acetone volume ratio,:1、9:1、5:1 carries out gradient elution.
6. the preparation method of naphthoquinone compound according to claim 2, it is characterised in that：
The condition isolated and purified described in step (6) is mobile phase：The methanol solution that volume fraction is 90~95% absorbs wave
Long 210nm.
7. application of the naphthoquinone compound described in claim 1 in preparing hypoglycemic product.
8. application of the naphthoquinone compound according to claim 7 in preparing hypoglycemic product, it is characterised in that：
The hypoglycemic product is hypoglycemia healthcare food or drug.
9. application of the naphthoquinone compound according to claim 8 in preparing hypoglycemic product, it is characterised in that：
Naphthoquinone compound containing therapeutically effective amount in the drug, surplus are pharmaceutic adjuvant or other compatible medicines
Object.
10. application of the naphthoquinone compound according to claim 8 in preparing hypoglycemic product, it is characterised in that：
The pharmaceutical dosage form of the drug is tablet, injection, liposome nano granule or controlled release agent.
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| 赵广河等: "荸荠活性成分与功能作用研究进展", 《食品研究与开发》 * |
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