CN106946883A - Alkaloid compound and preparation method with the type skeleton of dimeric piperidine I and II in its root of arna - Google Patents
Alkaloid compound and preparation method with the type skeleton of dimeric piperidine I and II in its root of arna Download PDFInfo
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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Abstract
The present invention relates to the alkaloid compound and preparation method in a kind of arna its root with the type skeleton of dimeric piperidine I and II, with the type skeleton of dimeric piperidine class I（Ⅰ）Alkaloid compound 1 be：The methyl 2,6,7,8,8a of 2,2,4,5,7,7,8a seven, 9 hexahydros 3HCyclopenta [1,2b:3,4‑c'] double ketone of pyridine 3；With the type skeleton of dimeric piperidine class II（Ⅱ）Alkaloid compound 2 be：3a1The methyl 2,3a of hydroxyl 2,2,5,7,7,10,10 71, 7,8,10,11 hexahydros 9HPyrido [4', 3':3,4] cyclopenta [1,2,3de] quinoline 4 (6H) ketone；Extracted using the mixed solvent of acetone/methanol, total alkali is obtained by the heavy legal system of sour molten alkali, ethyl acetate extract is obtained by solvent distribution method, RP chromatography isolated alkaloid compound 1 and compound 2 with the type skeleton of dimeric piperidine I and II is recycled.
Description
Technical field
The present invention relates to the alkaloid compound and system in a kind of arna its root with the type of dimeric piperidine class I and II type skeleton
Preparation Method.
Background technology
Its root of arna is the drying of composite family (Asteraceae) plant Rome Dalmatian chrysanthemum (Anacyclus pyrethrum)
Root.《Note doctor's allusion quotation》Middle title Acker Er Kaierha,《Visit according to medicine book》In also known as Europe all Li Kai close, than close Tai Er mix storehouse according to.Point
North African, south of europe, India are distributed in, the Xinjiang region of China is also distributed；The medication in India and Xinjiang of China tie up my medicine
Extensively.The main morphological features of its root of arna are：Basal leaf rosette-stape, leaf division, sliver is in Long Circle, cauline leaf alternate；Head
Inflorescence, there is long stalk, basidixed, involucre length of a film oval or blunt circle, has sparse pubescence；Ligule floral white or back side band purple；Root is thick
Strong, cylindrical or long turbination, supporting root is few, and matter is harder, and outside is in burgundy or brownish black；Gas fragrance and it is special, it is micro- to have
Excitement；That tastes has picotement.Its root of arna is embodied in：《Chinese book on Chinese herbal medicine》、《Uygur medicine will》、《People's Republic of China's health
Portion's drug standards Uygur medicine fascicle》、《Uygur's medicinal material standard》.《Chinese book on Chinese herbal medicine》Described in function with curing mainly：It is raw dry
Heat, opens retardance, establishing-Yang of warming up, wind-expelling pain-stopping, nourishing nerve；Cure mainly raw property disease and lymphatic temperament disease, such as facial paralysis,
Paralysis, it is of flaccid muscles, benumb, vibration, hysteria, tongue weight, sexual hypoesthesia, many productive coughs are coughed, neurasthenia etc..《Note doctor's allusion quotation》Described in
Do not go out for treating sweat, joint relaxation, muscle flesh is twitched, cold toothache, tooth mobility.《Visit according to medicine book》In also record and be used for
Treatment paralysis, epilepsy (takes appropriate pellitory root, be often placed into buccal in oral cavity).
Modern pharmacology research shows that its root extract of arna has extensive bioactivity such as：The chloroform portion of its root of arna
The epileptic attack of the enough notable delay model mouse of potential energy, improves Seizure Threshold.Its 50% methanolic extract can be effectively reduced
Oxidativestress damage and cognitive impairment that model mouse epileptic attack triggers, reduce model mouse amnesia level.Ethanol extract
It can be effectively increased the body weight of male Wistar rats, sperm count, sperm motility and survival rate, and increase testosterone in serum,
Promote the concentration of yellow hormone and follicle-stimulating hormone (FSH).Ethanol extract also has Alpha amylase inhibitory activity；Arna its root fat
Acid has inhibitory action to PTP1B.And ligroin extraction feeding Wistar rats can effectively strengthen the immunity of rat.This
Outside, its root aerial parts volatile oil composition of arna tool suppresses Candida albicans and staphylococcus aureus activity.
The chemical constitution study report of its root of arna is less, is concentrated mainly on N- alkylamide Alkaloids.At present
Isolated N- alkylamides Alkaloid 14, the N- alkylamides Alkaloid 6 identified by LC-MS/MS.
The sufficient Analyze ＆ separate that the present invention is carried out to the alkaloid component of arna its root is studied, and is therefrom obtained brand-new
The type skeleton (I) of dimeric piperidine class I and II type skeleton (II) and the corresponding alkaloid compound 1 and 2 of each framework types difference.
The content of the invention
Present invention aims at there is provided the alkaloid chemical combination in a kind of arna its root with the type skeleton of dimeric piperidine I and II
Thing and preparation method, the compound 1 is：Methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentadiene of 2,2,4,5,7,7,8a- seven
And [1,2-b:3,4-c'] double pyridine -3- ketone；Compound 2 is：3a1Methyl-the 2,3a of-hydroxyl -2,2,5,7,7,10,10- seven1,7,
8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de] quinoline -4 (6H) -one；Using acetone/
The mixed solvent of methanol is extracted, and obtains total alkali by the heavy legal system of sour molten alkali, ethyl acetate extract is obtained by solvent distribution method,
Recycle RP chromatography isolated new skeleton alkaloids compound 1 and compound 2.
There is the alkaloid compound of the type skeleton of dimeric piperidine I and II, the change in its root of a kind of arna of the present invention
Compound (1) and the structural formula of compound (2) are：
Wherein：
(I) it is the type skeleton of dimeric piperidine class I, corresponding compound (1) chemical name is：2,2,4,5,7,7,8a- seven
Methyl -2,6,7,8,8a, 9- hexahydro -3H- cyclopentas [1,2-b:3,4-c'] double pyridine -3- ketone；
(II) it is the type skeleton of dimeric piperidine class II, corresponding compound (2) chemical name is：3a1- hydroxyl -2,2,5,
Methyl-the 2,3a of 7,7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-
De] quinoline -4 (6H) -one.
The preparation method of the alkaloid compound with the type skeleton of dimeric piperidine I and II, is pressed in its root of described arna
Row step is carried out：
A, arna its root crushed, with volume ratio 2:1-1:2 acetone:It is methanol mixed solvent cold soaking, backflow, diacolation, super
Sound or Microwave Extraction 2-10 times, merge extract solution and drying, obtain total extract；
B, by the total extract in step a with 5% dissolving with hydrochloric acid filter, collect filtrate, filtrate is extracted with dichloromethane
Take to remove non-alkaloid impurity, the filtrate of decontamination adjusts pH to 10-14, obtains alkaline solution with saturated sodium bicarbonate aqueous solution；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain total alkaloid；
D, the total alkaloid in step c fully distributed with n-hexane/methanol, collect methanol position, dry, obtain
Methanol position, methanol position ethyl acetate is fully dissolved and filtered, and is collected ethyl acetate lysate, is spin-dried for, produces acetic acid
Ethyl ester position；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation, chromatographic condition with automatic purification system
For：Chromatographic column is XSelect CSH C185 μm of 19 × 150mm, 230 nanometers of absorbing wavelength, 20 milliliters of flow velocity is per minute, flowing
Xiang Wei：0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol, collects the stream of 14 minutes to 18.5 minutes
Part, the stream part that collection is obtained passes through reverse-phase chromatography again after drying further isolated compound 2 is 3a1- hydroxyl -2,2,5,
Methyl-the 2,3a of 7,7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-
De] quinoline -4 (6H) -one；The stream part of 18.5 minutes to 21 minutes will be collected, collected after obtained stream part is dried again by anti-phase
Further isolated compound 1 is methyl -2,6,7,8,8a, the 9- hexahydro -3H- rings penta 2 of 2,2,4,5,7,7,8a- seven to chromatogram
Alkene simultaneously [1,2-b:3,4-c'] double pyridine -3- ketone.
Alkaloid compound with the type skeleton of dimeric piperidine I and II and preparation side in its root of arna of the present invention
Method, wherein the Structural Identification of the alkaloid compound 1 with the type skeleton of dimeric piperidine class I：
Compound 1：Methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas [1,2-b of 2,2,4,5,7,7,8a- seven:
3,4-c'] double pyridine -3- ketone physics and chemistry and spectroscopic data and Structural Identification：Yellow amorphous powder, UV (MeOH) λmax(log
ε) 450 (4.47) nm, 271 (4.01) nm and 247 (3.93) nm；Dragendorff reagent reactings are positive；HR-ESI(+)MS：
[M+H]+287.2119；Molecular formula：C18H26N2O；1H-NMR(CD3OD, 400MHz)：δ 2.06 (1H, d, J=13.6Hz, H-8),
1.47 (1H, d, J=13.2Hz, H-8), 2.54 (1H, d, J=16.8Hz, H-9), 2.15 (1H, d, J=16.0Hz, H-9),
1.38 (3H, s, H-10), 1.27 (3H, s, H-11), 1.85 (3H, s, H-12), 1.87 (3H, s, H-13), 1.35 (3H, s, H-
14), 1.31 (3H, s, H-15), 1.17 (3H, s, H-16)；13C-NMR(CD3OD, 100MHz)：δ 15.1 (q, C-12), 21.1
(q, C-13), 27.8 (q, C-10), 29.0 (q, C-14), 29.5 (q, C-11), 29.9 (q, C-16), 32.1 (q, C-15),
40.5 (s, C-8a), 47.5 (t, C-8), 51.7 (s, C-7), 52.9 (t, C-9), 66.5 (s, C-2), 111.2 (s, C-4b),
120.2 (s, C-4), 146.6 (s, C-5), 146.7 (s, C-4a), 173.4 (s, C-9a), 206.1 (s, C-3)；Pass through 2D nuclear-magnetisms
Spectrum HMBC determines structure such as Fig. 1 of compound 1；
The Structural Identification of alkaloid compound 2 with the type skeleton of dimeric piperidine class II：
Compound 2：3a1Methyl-the 2,3a of-hydroxyl -2,2,5,7,7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos
[4',3':3,4] physics and chemistry and spectroscopic data and Structural Identification of cyclopenta [1,2,3-de] quinoline -4 (6H) -one：Yellow
Amorphous powder, UV (MeOH) λmax(log ε) 366 (4.18) nm and 243 (3.80) nm；Dragendorff reagent reactings are in sun
Property；HR-ESI(+)MS：[M+H]+343.2394；Molecular formula：C21H30N2O2；1H-NMR(CD3OD, 400MHz)：δ6.85(1H,s,
H-3), 2.81 (1H, d, J=12.0Hz, H-11), 2.10 (1H, d, J=12.0Hz, H-11), 2.22 (1H, d, J=14.0Hz,
H-8), 2.11 (1H, d, J=14.0Hz, H-8), 1.95 (1H, d, J=14.4Hz, H-9), 0.64 (1H, d, J=14.4Hz, H-
9), 1.37 (3H, s, H-16), 1.30 (3H, s, H-17), 0.80 (3H, s, H-18), 1.48 (3H, s, H-15), 1.47 (3H, s,
H-12), 1.43 (3H, s, H-13), 2.38 (3H, s, H-14)；13C-NMR(CD3OD, 100MHz)：δ 19.5 (q, C-14), 29.2
(q, C-13), 30.8 (q, C-12), 31.4 (q, C-15), 32.6 (q, C-17), 32.6 (q, C-18), 33.6 (q, C-16),
36.6 (t, C-8), 44.4 (t, C-11), 46.0 (t, C-9), 47.2 (s, C-8a), 49.3 (s, C-10), 53.4 (s, C-7),
61.0 (s, C-2), 71.6 (s, C-3a1), 110.3 (s, C-4a), 142.3 (d, C-3), 143.1 (s, C-3a), 158.4 (s, C-
5), 173.7 (s, C-11a), 187.1 (s, C-4)；Structure such as Fig. 4 that HMBC determines compound 2 is composed by 2D nuclear-magnetisms.
Brief description of the drawings
Fig. 1 schemes for the crucial HMBC correlations of alkaloid compound 1 of the present invention；
Fig. 2 is alkaloid compound 1 of the present invention1H-NMR schemes；
Fig. 3 is alkaloid compound 1 of the present invention13C-NMR schemes；
Fig. 4 schemes for the crucial HMBC correlations of alkaloid compound 2 of the present invention；
Fig. 5 is alkaloid compound 2 of the present invention1H-NMR schemes；
Fig. 6 is alkaloid compound 2 of the present invention13C-NMR schemes.
Embodiment
Embodiment 1
A, by the arna of crushing its root powder 4.5kg, add 10 liter 1:1 acetone:Methanol solution soaking at room temperature 24 hours,
Repeat to extract 10 times, merge extract solution and drying, obtain total extract 1.2kg；
B, the dissolving with hydrochloric acid for being 5% with 1 liter of concentration by the total extract in step a are filtered, and collect filtrate, filtrate is used
Dichloromethane extraction is to remove non-alkaloid impurity, and the filtrate of decontamination is adjusted pH to 10, obtained with saturated sodium bicarbonate aqueous solution
Alkaline solution；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain 660 grams of total alkaloid；
D, the total alkaloid in step c dissolved with 1 liter of methanol, and add 1 liter of n-hexane and fully distributed, collection first
Alcohol position, is dried, obtains 140 grams of methanol position, then 140 grams of methanol position ethyl acetate are fully dissolved and filtered, and is collected
Ethyl acetate lysate, is spin-dried for, and produces 70 grams of ethyl acetate extract；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation, chromatographic condition with automatic purification system
For：Chromatographic column is XSelect CSH C185μm 19×150mm；230 nanometers of absorbing wavelength；20 milliliters of flow velocity is per minute；Flowing
Xiang Wei：0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol；The stream of collection 14 minutes to 18.5 minutes
Part, the stream part that collection is obtained passes through reverse-phase chromatography again after drying further isolated compound 2 is 3a1- hydroxyl -2,2,5,7,
Methyl-the 2,3a of 7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de]
Quinoline -4 (6H) -one；The stream part of collection 18.5 minutes to 21 minutes, collects after obtained stream part is dried by reverse-phase chromatography to enter again
The isolated compound 1 of one step be methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas of 2,2,4,5,7,7,8a- seven [1,
2-b:3,4-c'] double pyridine -3- ketone.
Embodiment 2
A, by the arna of crushing its root powder 4.5kg, add 10 liter 1:1 acetone:Methanol solution refluxing extraction 4 hours,
Repeat to extract 6 times, merge extract solution and drying, obtain total extract 1.7kg；
B, by the total extract in step a with 1 liter of concentration for 5% dissolving with hydrochloric acid filter, collect filtrate, filtrate is used two
Chloromethanes extraction is to remove non-alkaloid impurity, and the filtrate of decontamination adjusts pH to 11, obtains alkali with saturated sodium bicarbonate aqueous solution
Change liquid；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain 725 grams of total alkaloid；
D, the total alkaloid in step c dissolved with 1 liter of methanol, and add 1 liter of n-hexane and fully distributed, collection first
Alcohol position, is dried, obtains 164 grams of methanol position, then 164 grams of methanol position ethyl acetate are fully dissolved and filtered, and is collected
Ethyl acetate lysate, is spin-dried for, and produces 87 grams of ethyl acetate extract；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation, chromatographic condition with automatic purification system
For：Chromatographic column is XSelect CSH C185μm 19×150mm；230 nanometers of absorbing wavelength；20 milliliters of flow velocity is per minute；Flowing
Xiang Wei：0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol；The stream of collection 14 minutes to 18.5 minutes
Part, the stream part that collection is obtained passes through reverse-phase chromatography again after drying further isolated compound 2 is 3a1- hydroxyl -2,2,5,7,
Methyl-the 2,3a of 7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de]
Quinoline -4 (6H) -one；The stream part of collection 18.5 minutes to 21 minutes, collects after obtained stream part is dried by reverse-phase chromatography to enter again
The isolated compound 1 of one step be methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas of 2,2,4,5,7,7,8a- seven [1,
2-b:3,4-c'] double pyridine -3- ketone.
Embodiment 3
A, by the arna of crushing its root powder 4.5kg, add 10 liter 1:1 acetone:Methanol solution seepage pressure effects 24 hours,
Repeat to extract 8 times, merge extract solution and drying, obtain total extract 1.4kg；
B, by the total extract in step a with 1 liter of concentration for 5% dissolving with hydrochloric acid filter, collect filtrate, filtrate is used two
Chloromethanes extraction is to remove non-alkaloid impurity, and the filtrate of decontamination adjusts pH to 12, obtains alkali with saturated sodium bicarbonate aqueous solution
Change liquid；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain 689 grams of total alkaloid；
D, the total alkaloid in step c dissolved with 1 liter of methanol, and add 1 liter of n-hexane and fully distributed, collection first
Alcohol position, is dried, obtains 147 grams of methanol position, then 147 grams of methanol position ethyl acetate are fully dissolved and filtered, and is collected
Ethyl acetate lysate, is spin-dried for, and produces 78 grams of ethyl acetate extract；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation, chromatographic condition with automatic purification system
For：Chromatographic column is XSelect CSH C185μm 19×150mm；230 nanometers of absorbing wavelength；20 milliliters of flow velocity is per minute；Flowing
Xiang Wei：0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol；The stream of collection 14 minutes to 18.5 minutes
Part, the stream part that collection is obtained passes through reverse-phase chromatography again after drying further isolated compound 2 is 3a1- hydroxyl -2,2,5,7,
Methyl-the 2,3a of 7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de]
Quinoline -4 (6H) -one；The stream part of collection 18.5 minutes to 21 minutes, collects after obtained stream part is dried by reverse-phase chromatography to enter again
The isolated compound 1 of one step be methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas of 2,2,4,5,7,7,8a- seven [1,
2-b:3,4-c'] double pyridine -3- ketone.
Embodiment 4
A, by the arna of crushing its root powder 4.5kg, add 10 liter 2:1 acetone:Methanol solution ultrasonic extraction 3 hours,
Repeat to extract 4 times, merge extract solution and drying, obtain total extract 1.5kg；
B, by the total extract in step a with 1 liter of concentration for 5% dissolving with hydrochloric acid filter, collect filtrate, filtrate is used two
Chloromethanes extraction is to remove non-alkaloid impurity, and the filtrate of decontamination adjusts pH to 13, obtains alkali with saturated sodium bicarbonate aqueous solution
Change liquid；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain 720 grams of total alkaloid；
D, the total alkaloid in step c dissolved with 1 liter of methanol, and add 1 liter of n-hexane and fully distributed, collection first
Alcohol position, is dried, obtains 155 grams of methanol position, then 155 grams of methanol position ethyl acetate are fully dissolved and filtered, and is collected
Ethyl acetate lysate, is spin-dried for, and produces 81 grams of ethyl acetate extract；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation, chromatographic condition with automatic purification system
For：Chromatographic column is XSelect CSH C185μm 19×150mm；230 nanometers of absorbing wavelength；20 milliliters of flow velocity is per minute；Flowing
Xiang Wei：0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol；The stream of collection 14 minutes to 18.5 minutes
Part, the stream part that collection is obtained passes through reverse-phase chromatography again after drying further isolated compound 2 is 3a1- hydroxyl -2,2,5,7,
Methyl-the 2,3a of 7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de]
Quinoline -4 (6H) -one；The stream part of collection 18.5 minutes to 21 minutes, collects after obtained stream part is dried by reverse-phase chromatography to enter again
The isolated compound 1 of one step be methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas of 2,2,4,5,7,7,8a- seven [1,
2-b:3,4-c'] double pyridine -3- ketone.
Embodiment 5
A, by the arna of crushing its root powder 4.5kg, add 10 liter 1:2 acetone:Methanol solution Microwave Extraction 1 hour,
Repeat to extract 2 times, merge extract solution and drying, obtain total extract 1.1kg；
B, by the total extract in step a with 1 liter of concentration for 5% dissolving with hydrochloric acid filter, collect filtrate, filtrate is used two
Chloromethanes extraction is to remove non-alkaloid impurity, and the filtrate of decontamination adjusts pH to 14, obtains alkali with saturated sodium bicarbonate aqueous solution
Change liquid；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain 579 grams of total alkaloid；
D, the total alkaloid in step c dissolved with 1 liter of methanol, and add 1 liter of n-hexane and fully distributed, collection first
Alcohol position, is dried, obtains 125 grams of methanol position, then 125 grams of methanol position ethyl acetate are fully dissolved and filtered, and is collected
Ethyl acetate lysate, is spin-dried for, and produces 58 grams of ethyl acetate extract；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation, chromatographic condition with automatic purification system
For：Chromatographic column is XSelect CSH C185μm 19×150mm；230 nanometers of absorbing wavelength；20 milliliters of flow velocity is per minute；Flowing
Xiang Wei：0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol；The stream of collection 14 minutes to 18.5 minutes
Part, the stream part that collection is obtained passes through reverse-phase chromatography again after drying further isolated compound 2 is 3a1- hydroxyl -2,2,5,7,
Methyl-the 2,3a of 7,10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de]
Quinoline -4 (6H) -one；The stream part of collection 18.5 minutes to 21 minutes, collects after obtained stream part is dried by reverse-phase chromatography to enter again
The isolated compound 1 of one step be methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas of 2,2,4,5,7,7,8a- seven [1,
2-b:3,4-c'] double pyridine -3- ketone.
Claims (2)
1. there is the alkaloid compound of the type skeleton of dimeric piperidine I and II, it is characterised in that the compound in a kind of its root of arna
And the structural formula of compound (2) is (1)：
Wherein：
(I) it is the type skeleton of dimeric piperidine class I, corresponding compound (1) chemical name is：The methyl of 2,2,4,5,7,7,8a- seven-
2,6,7,8,8a, 9- hexahydro -3H- cyclopentas [1,2-b:3,4-c'] double pyridine -3- ketone；
(II) it is the type skeleton of dimeric piperidine class II, corresponding compound (2) chemical name is：3a1- hydroxyl -2,2,5,7,7,
Methyl-the 2,3a of 10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de] quinoline
Quinoline -4 (6H) -one.
2. the preparation of the alkaloid compound with the type skeleton of dimeric piperidine I and II in its root of arna as claimed in claim 1
Method, it is characterised in that follow these steps to carry out：
A, arna its root crushed, with volume ratio 2:1-1:2 acetone:Methanol mixed solvent cold soaking, backflow, diacolation, ultrasound or
Microwave Extraction 2-10 times, merges extract solution and drying, obtains total extract；
B, by the total extract in step a with 5% dissolving with hydrochloric acid filter, collect filtrate, by filtrate with dichloromethane extract with
Non-alkaloid impurity is removed, the filtrate of decontamination adjusts pH to 10-14, obtains alkaline solution with saturated sodium bicarbonate aqueous solution；
C, the alkaline solution in step b fully extracted with dichloromethane, obtain total alkaloid；
D, the total alkaloid in step c fully distributed with n-hexane/methanol, collect methanol position, dry, obtain methanol
Position, methanol position ethyl acetate is fully dissolved and filtered, and is collected ethyl acetate lysate, is spin-dried for, produces ethyl acetate
Position；
E, the ethyl acetate extract obtained in step d is subjected to ON-LINE SEPARATION segmentation with automatic purification system, chromatographic condition is：Color
Spectrum post is XSelect CSH C185 μm of 19 × 150mm, 230 nanometers of absorbing wavelength, 20 milliliters of flow velocity is per minute, and mobile phase is：
0-30 minutes concentration is that 10% methanol aqueous solution is incremented to 100% methanol, collects the stream part of 14 minutes to 18.5 minutes, will
The stream part that collection is obtained is again 3a by the further isolated compound 2 of reverse-phase chromatography after drying1- hydroxyl -2,2,5,7,7,
Methyl-the 2,3a of 10,10- seven1, 7,8,10,11- hexahydro -9H- pyridos [4', 3':3,4] cyclopenta [1,2,3-de] quinoline
Quinoline -4 (6H) -one；The stream part of 18.5 minutes to 21 minutes will be collected, collect after obtained stream part is dried by reverse-phase chromatography to enter again
The isolated compound 1 of one step be methyl -2,6,7,8,8a, the 9- hexahydro -3H- cyclopentas of 2,2,4,5,7,7,8a- seven [1,
2-b:3,4-c'] double pyridine -3- ketone.
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| CN117143100A (en) * | 2023-08-30 | 2023-12-01 | 中国科学院新疆理化技术研究所 | Analgesic compound with Nav1.2 inhibition effect in radix Arnafae, and preparation and application thereof |
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| HANANE ELAZZOUZI等: "Biocidal effects of alkaloids extracted from Anacyclus pyrethrum L. (Asteraceae) on Callosobruchus maculatus (Fab.) (Coleoptera: Bruchidae)", 《INTERNATIONAL JOURNAL OF INNOVATION AND APPLIED STUDIES》 * |
| 古丽娜尔.卡斯木: "阿纳其根化学成分及其酪氨酸酶活性筛选研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑 E056-88》 * |
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| CN117143100A (en) * | 2023-08-30 | 2023-12-01 | 中国科学院新疆理化技术研究所 | Analgesic compound with Nav1.2 inhibition effect in radix Arnafae, and preparation and application thereof |
| CN117143100B (en) * | 2023-08-30 | 2024-08-23 | 中国科学院新疆理化技术研究所 | Analgesic compound with Nav1.2 inhibition effect in radix Arnafae, and preparation and application thereof |
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