CN103739653B - A kind of 23-fall oleanane acid compound and preparation method thereof and the purposes in preparing glycosidase inhibitor - Google Patents
A kind of 23-fall oleanane acid compound and preparation method thereof and the purposes in preparing glycosidase inhibitor Download PDFInfo
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Abstract
The invention discloses compound 2 hydroxyl 3 carbonyl 23 and drop olive 1,4,12 triolefin 28 acid and preparation method thereof and the application in preparing glycosidase inhibitor.The present invention extracts from Three Akebia Decne Species and separates potent a glucosidase inhibitor, source of plant material is enriched, extraction preparation method is easily operated, and plant itself also can be made to be utilized for a long time without destruction when using fruit to extract, can increase economic efficiency, the most environmentally friendly, and this monomeric compound is stable, easy to store.Pharmacological evaluation shows, olive Isosorbide-5-Nitrae drops in compound 2 hydroxyl 3 carbonyl 23, and a glucosidase inhibitory active of 12 triolefin 28 acid is than strong about 16 times of a line diabetes medicament acarbose, it is expected to be further development of the medicine of clinical treatment type Ⅱdiabetes mellitus, promise well.
Description
Technical field:
The invention belongs to field of natural medicinal chemistry, be specifically related to a kind of new 23-and drop oleanolic acid compounds, i.e. 2-
Olive-Isosorbide-5-Nitrae drops in hydroxyl-3-carbonyl-23-, 12-triolefin-28-acid, and the preparation method of this compound and this compound or its
Pharmaceutically useful salt or the application in preparing glycosidase inhibitor of its esterification derivative.
Background technology:
Diabetes are clinical common endocrine metabolism dysfunctional disease, and it is with cardiovascular disease and cancer etc. year by year
Occurred frequently have important dependency, is the potential important killer of human health.Progress and people's living standard along with society
Improving, the sickness rate of diabetes improves in the world, has more than the prevalence of 100,000,000 people in China especially, and presents
The trend increased year by year.Diabetes cause the most great loss just to our people's health and national economy.
Diabetes doctor trained in Western medicine is divided into type Ⅰ diabetes mellitus (or claim insulin-dependent, DM1) and type Ⅱdiabetes mellitus (or Chen Fei islets of langerhans
Element dependency, DM2), wherein type Ⅱdiabetes mellitus morbidity is all far above type Ⅰ diabetes mellitus with prevalence, thus harm is bigger.Competitive
Alpha-glucosidase inhibitor have postponement glucide digest and assimilate, alleviate kidney burden, control blood glucose after meal drastically raise and then
Blood sugar concentration can be made to change the functions such as fluctuating margin reduction in one day, and they are just becoming people and are finding and can be developed for treatment
The medicine of type Ⅱdiabetes mellitus.Listing and the important α-sugar of positive clinic trial work treatment type Ⅱdiabetes mellitus one line medication are the most developed
Glycosides enzyme inhibitor includes acarbose(acarbose), voglibose, miglitol and emigliate etc..
Diabetes are also known as diabetes in the traditional Chinese medical science, and recording the single medicinal material that can be used for treating diabetes in Compendium of Materia Medica has closely
200 kinds, display is excavated new alpha-glucosidase inhibitor from Chinese medicine or plant origin and is had important prospect.Existing document report
Disclosing, Lardizabalaceae Three Akebia Decne Species has the pharmacological function such as antiinflammatory, diuresis, and rich in compounds such as triterpene and fall triterpenes, but
On the general study of pharmacologically active and composition the most deep.We have found that this platymiscium tissue extract has in the recent period necessarily to press down
The activity of alpha-glucosidase processed, thus it has important in terms of exploring excavation alpha-glucosidase inhibitor new, highly effective and safe
Potentiality.
Summary of the invention:
First purpose of the present invention is to provide a kind of 23-fall triterpenes with alpha-glucosaccharase enzyme inhibition activity and newly changes
Compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid.
Olive-Isosorbide-5-Nitrae drops in the 2-hydroxyl-3-carbonyl-23-of the present invention, 12-triolefin-28-acid, its structural formula such as formula I institute
Show:
Second object of the present invention is to provide a kind of compound 2-hydroxyl-3-carbonyl-23-and drops olive-1,4,12-three
The preparation method of alkene-28-acid, it is characterised in that olive-Isosorbide-5-Nitrae, 12-triolefin-28-drop in compound 2-hydroxyl-3-carbonyl-23-
Acid is from Caulis Akebiae (Akebia quinata (Thumb.) Decne.), threeleaf akebia (Akebiatrifolia (Thumb.)
Koidz), long sequence Caulis Akebiae (Akebia longeracemosaMatsumura), Caulis Akebiae (Akebiatrifolia (Thumb.)
Koidz.Var.australis (Diels) Rehd) or long calyx threeleaf akebia (Akebiatrifolia (Thumb.)
Koidz..subsp.LongisepalaH.N.Qin) in stem, leaf or fruit, preparative separation obtains.Concrete material can be
Dry product or fresh goods, the fruit dry product of preferred plant.
Concrete steps are preferably:
A, prepare total extractum: by the Caulis Akebiae, threeleaf akebia, long sequence Caulis Akebiae, Caulis Akebiae or the stem of long calyx threeleaf akebia that gather,
Leaf or fruit material are pulverized, and then extract with ethanol water or aqueous acetone solution, and extracting solution concentrates after removing organic solvent and obtains
To total extractum crude extract, total extractum crude extract is suspended in water, extract, after extract is concentrated by petroleum ether or ethyl acetate
Obtain total extractum；
B, isolated and purified: total extractum is through purification on normal-phase silica gel column chromatography, with petroleum ether/acetone as eluant, successively from volume ratio
100:0,20:1,10:1,8:1,5:1,3:1,2:1,1:1,0:100 gradient elution, collects petroleum ether/acetone 5:1 and elutes
Fraction, then through purification on normal-phase silica gel column chromatography, with petroleum ether/acetone successively from volume ratio 100:0,10:1,8:1,6:1,4:1,2:
1,0:100 is eluent gradient eluting, collects the fraction of petroleum ether/acetone 6:1 eluting, then through SephadexLH-20 gel column
Isolated and purified with acetone eluting, eluent carries out recrystallization, obtains the pure compound 2-hydroxyl-3-carbonyl-23-shown in formula I
Fall olive-1,4,12-triolefin-28-acid.
Described ethanol water or aqueous acetone solution be preferably volume fraction more than or equal to 70% ethanol water or
Person's aqueous acetone solution.
Olive-Isosorbide-5-Nitrae drops in novel compound of present invention 2-hydroxyl-3-carbonyl-23-, and 12-triolefin-28-acid, through external medicine
Reason is it is experimentally confirmed that it has potent inhibitory action, its inhibitory activity (IC to alpha-glucosidase50=24.8 ± 0.28 μM) very
To than positive control acarbose (IC50=408.78 ± 5.67 μMs) the strongest.Therefore this noval chemical compound is more higher than acarbose
Alpha-glucosidase inhibitor, can develop for preparing prevention and the medicine for the treatment of type Ⅱdiabetes mellitus, and application potential quality is extensive.
Third object of the present invention be to provide 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid,
Its pharmaceutically useful salt or the application in preparing alpha-glucosidase inhibitor medicament of its esterification derivative.
Fourth object of the present invention is to provide a kind of alpha-glucosidase inhibitor medicament, it is characterised in that have
The compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid of effect amount or its officinal salt or its esterification are spread out
Biology, and pharmaceutically commonly use adjuvant or carrier.
5th purpose of the present invention is to provide Caulis Akebiae, threeleaf akebia, long sequence Caulis Akebiae, Caulis Akebiae or long calyx threeleaf akebia
The application in preparing compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid of stem, leaf or fruit.
Noval chemical compound 2-hydroxyl-3-carbonyl-23-of the present invention fall olive-1,4,12-triolefin-28-is sour or it can
Medicinal salt or esterification derivative, its substantive suppression glycosidase activity composition is all compound 2-hydroxyl-3-carbonyl-23-fall
Olive-1,4,12-triolefin-28-acid molecule.Described 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid
Pharmaceutically useful salt, its suppression alpha-glucosidase essence be in people's digestive tract, activity can be converted under the physiological conditions such as gastric acid
Molecule 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-is sour and works.Described compound 2-hydroxyl-3-carbonyl
The esterification derivative of base-23-fall olive-1,4,12-triolefin-28-acid refers to that neat pier drops in compound 2-hydroxyl-3-carbonyl-23-
Really the 2-position hydroxyl in-1,4,12-triolefin-28-acid molecule is by the 28-position carboxyl in esterifying organic acid or molecule and alcohols chemical combination
The derivative compound of thing esterification, described esterification derivative can be or two in 2-position hydroxyl and 28-position carboxyl functional group
The partial esterification of individual group or be entirely esterified, these drop olive-Isosorbide-5-Nitrae, 12-triolefin-28-acid based on 2-hydroxyl-3-carbonyl-23-
The esterification derivative of molecular skeleton, it can be converted into activity point in people's digestive tract under the physiological conditions such as gastric acid or intestinal alkali easily
Olive-Isosorbide-5-Nitrae drops in sub-2-hydroxyl-3-carbonyl-23-, 12-triolefin-28-acid, its essence be also compound 2-hydroxyl-3-carbonyl-
Olive-Isosorbide-5-Nitrae drops in 23-, and 12-triolefin-28-acid plays alpha-glucoside inhibiting activity, thus belongs to the strict protection scope of the present invention.
The organic acid and the Organic Alcohol that are esterified respectively with 2-position hydroxyl and 28-position carboxyl the most respectively can be phases under physiology acid-base condition
Close any form that can hydrolyze of ester bond, preferably can strengthen whole macromolecule water-solubility characteristic C1 to C4 small molecular organic acid with
Alcohol, and contain organic acid or the Organic Alcohol of the various small moleculars of C6 to the C10 of phenyl ring.
Novel compound of present invention 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-is sour or it is pharmaceutically acceptable
Salt or esterification derivative can with pharmaceutically commonly use adjuvant or pharmaceutical carrier is combined, prepare have 2-hydroxyl-3-carbonyl-
Olive-Isosorbide-5-Nitrae drops in 23-, 12-triolefin-28-acid suppression alpha-glucosidase activity, can be used for preventing and treating type Ⅱdiabetes mellitus
Medicine or pharmaceutical composition.This medicine or pharmaceutical composition can use wettable powder, tablet, granule, capsule, be administered orally
The dosage forms such as liquid, drop pill, injection, aerosol；Also can use the controlled release well known to modern pharmaceutical circle or slow release formulation or nanometer system
Agent.
The present invention uses to extract from the Three Akebia Decne Species that China is widely distributed and separates potent alpha-glucosidase inhibitor, material
Abundance, preparation process is easy, easily operated, and when using fruit to extract it is also possible that plant itself
Utilized for a long time without destruction, can also be environmentally friendly while obtaining good economic benefit, and this monomeric compound
Stable, easy to store.The alpha-glucosidase suppression of this compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid
Activity even above clinical application acarbose, is further development of effective, safe new prevention and treatment II type most probably
The alpha-glucosidase inhibitor class medicine of diabetes, marketization prospect is preferable.
Accompanying drawing illustrates:
Fig. 1 is compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid1HNMR collection of illustrative plates；
Fig. 2 is compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid13CNMR collection of illustrative plates；
Fig. 3 is the HMBC collection of illustrative plates of compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid.
Detailed description of the invention:
Following example are to further illustrate the present invention rather than limitation of the present invention, according to the reality of the present invention
The simple modifications that the confrontation present invention is carried out broadly falls into the scope of protection of present invention.
Embodiment 1: the system of 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid in Trilobed Caulis Akebiae fruit
Standby
1.1 instruments and reagent
Concentrating under reduced pressure use Tokyo physics and chemistry company N-1000 Rotary Evaporators, the circulating cooler bin of CCA-1110 and
SB-1000 electric-heated thermostatic water bath；HPLC uses Japan Shimadzu Corporation LC-20AT type chromatograph of liquid, SPD-M20A detector
With Shim-PackPRC-ODS chromatographic column (particle diameter 5 μm, aperture 12nm, 250mm × 20mm)；Electrospray Mass Spectrometry (ESIMS) uses
Applied biosystems's MDSSCIEXAPI2000LC/MS/MS instrument, measures with methanol for solvent direct injected；1HNMR
Spectrum and13CNMR spectrum uses BrukerDRX-400 nuclear magnetic resonance analyser, and measures with tetramethylsilane for internal standard.Coloration method uses
10% ethanol solution of sulfuric acid or sulphuric acid vanillin process post-heating colour developing or iodine vapor colour developing.
1.2 plant origins and qualification
For extraction vegetable material threeleaf akebia (Akebiatrifolia (Thumb.) Koidz.) fruit sample in
In JIUYUE, 2009 picks up from Hunan Province within the border, South China Botanical Garden Chinese Academy of Sciences Xing Fuwu researcher identify.
1.3 extract and separate
Sample (Trilobed Caulis Akebiae fruit, dry weight 2.0 kilograms) extracts with under volume fraction 95% ethanol water room temperature after pulverizing
Three times, merging filtrate concentrating under reduced pressure removes organic solvent, obtains total extractum crude extract.Total extractum crude extract is suspended in 500ml
In water, then using isopyknic petroleum ether extraction, extract is through being concentrated under reduced pressure to give the total extractum of petroleum ether (32g).By petroleum ether
The chloroform/methanol (100mL) of total extractum 1:1 is dissolved, and adds purification on normal-phase silica gel (80-100 mesh) and mixes sample with weight ratio 1:1.5
Volatilize, dry column-packing (200-300 mesh, 800 grams), dry method loading, successively with petroleum ether/acetone=100:0,20:1,10:1,8:
1,5:1,3:1,2:1,1:1,0:100v/v are eluent gradient eluting, detect according to lamellae, and each stream part is according to the difference of polarity
Collect 9 component E1 E9 the most successively；The fraction that E5(petroleum ether/acetone 5:1 is eluted) again through purification on normal-phase silica gel
Column chromatography (200-300 mesh, 50g gram) is isolated and purified, with petroleum ether/acetone=100:0,10:1,8:1,6:1,4:1,2:1,0:
100v/v is eluent gradient eluting (each gradient elution 300ml, every 15ml are collected as a component), according to positive lamellae
Detection is collected and appropriately merges eluent, obtains 7 component E5-1-E5-7；E5-4(petroleum ether/acetone 6:1 elution fraction) warp
SephadexLH-20 gel column (acetone) is isolated and purified, uses acetone eluting, detects according to lamellae, collects eluent,
To 7 component E5-4-1-E5-4-7, this component of component E5-4-7(carries out positive TLC with chloroform/methanol 9:0.25 for developing solvent
Detection, and spray heating colour developing with 10% sulphuric acid-ethanol, main constituent presents the mauve speckle of Rf=0.8) it is molten with methanol again
Agent carries out repeatedly recrystallization, obtains colourless (white) powdered compounds 1(2-hydroxyl-3-carbonyl-23-and drops olive-Isosorbide-5-Nitrae,
12-triolefin-28-acid) (8mg).
1.4 compound 1(2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid) Structural Identification
Obtained compound 1 is white amorphous powder, and molecular formula is C29H40O4；
UV(MeOH)λmaxNm (log ε): 203 (4.13), 262 (3.8)；HRESIMS(pos.)m/z475.2816
(calcd.forC29H40NaO4,475.2819)；ESIMS (pos.) m/z475 [M+Na]+, 491 [M+K]+, (neg.) m/z451
[M-H], 487 [M+Cl]–；1H-NMR and13C-NMR data are as shown in table 1:
The NMR data of table 1. obtained compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid
(inCD3OD)
According to the comprehensive analysis of the wave spectrum related datas such as above ultraviolet, mass spectrum and a peacekeeping two-dimensional nucleus magnetic, analytic derivation goes out
The chemical constitution of this noval chemical compound 1 is that olive-Isosorbide-5-Nitrae, 12-triolefin-28-acid, its structure such as formula drop in 2-hydroxyl-3-carbonyl-23-
(I) shown in.
Embodiment 2: the system of 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid in threeleaf akebia stem and leaf
Standby
2.1 instruments and reagent: with embodiment 1
2.2 plant origins and qualification: with embodiment 1
2.3 extract and separate
Sample (threeleaf akebia stem and leaf, dry weight 2.0 kilograms) extracts with under volume fraction 95% ethanol water room temperature after pulverizing
Three times, merging filtrate concentrating under reduced pressure removes organic solvent, obtains total extractum crude extract.Total extractum crude extract is suspended in 500ml
In water, then using isopyknic petroleum ether extraction, extract is through being concentrated under reduced pressure to give the total extractum of petroleum ether (24g).By petroleum ether
The chloroform/methanol (100mL) of total extractum volume ratio 1:1 is dissolved, and adds purification on normal-phase silica gel (80-100 mesh) with weight ratio 1:
1.5 mix sample volatilizes, dry column-packing (200-300 mesh, 800 grams), dry method loading, successively with petroleum ether/acetone=100:0,20:1,
10:1,8:1,5:1,3:1,2:1,1:1,0:100v/v are eluent gradient eluting, detect according to lamellae, and each stream part is according to pole
The difference of property collects 9 component F1 F9 the most successively；The fraction that F5(petroleum ether/acetone 5:1 is eluted) again through just
Phase silica gel column chromatography (200-300 mesh, 50g gram) is isolated and purified, with petroleum ether/acetone=100:0,10:1,8:1,6:1,4:1,
2:1,0:100v/v are eluent gradient eluting (each gradient elution 300ml, every 15ml are collected as a component), according to positive
Lamellae detection is collected and appropriately merges eluent, obtains 7 component F5-1-F5-7；F5-4(petroleum ether/acetone 6:1 eluting portion
Point) isolated and purified through SephadexLH-20 gel column (acetone), use acetone eluting, detect according to lamellae, collect eluting
Liquid, obtains 7 component F5-4-1-F5-4-7, and this component of component F5-4-7(is just being carried out with chloroform/methanol 9:0.25 for developing solvent
Phase TLC detects, and sprays heating colour developing with 10% sulphuric acid-ethanol, and main constituent presents the mauve speckle of Rf=0.8) again with first
Alcohol is that solvent carries out repeatedly recrystallization, obtains colourless (white) powdered compounds 2-hydroxyl-3-carbonyl-23-and drops olive-1,
4,12-triolefin-28-acid (5mg).
Embodiment 3:
With stem, leaf or the fruit of Caulis Akebiae, long sequence Caulis Akebiae, Caulis Akebiae or long calyx threeleaf akebia as sample, according to embodiment 1 institute
The extraction stated and separation method final purification obtain the pure compound 2,3,20-trihydroxy-29-fall olive-12-alkene of formula I-
28-acid.
The alpha-glucoside inhibiting activity of embodiment 4:2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid
Detection
4.1 instruments and reagent
Experimental apparatus: microplate reader Genoismicroplatereader(TecanGENios, Swizerland)
Reagent and compound sample: alpha-glucosidase is purchased from SigmaChemicalCo.(Sigma-Aldrich,
St.Louis, USA)；4-nitrophenols-alpha-D-glucose pyrans glycosides (PNPG) is purchased from TokyoChemicalIndustryCo.,
Ltd.(Japan)；Acarbose (Acarbose), purchased from TokyoChemicalIndustryCo., Ltd. (Japan)；2-hydroxyl
Base-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid is prepared by above experimental example
4.2 method of testings:
A) compounding pharmaceutical solution: by 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid and A Kabo
Sugar is not prepared 10mg/ml solution by dimethyl sulfoxide (DMSO), and prepares the phosphate buffer (ultra-pure water preparation) of 67mmol,
PNPG substrate solution (5mM, phosphate buffer is prepared), and the NaCO of 0.2M3Solution (phosphate buffer preparation).
B) use colorimetry, by 96 porocyte culture plates, olive-Isosorbide-5-Nitrae dropped with regard to compound 2-hydroxyl-3-carbonyl-23-,
The half-inhibition concentration of alpha-glucosidase is measured by 12-triolefin-28-acid.First by the alpha-glucosidase of 20 μ L
(0.8U) joining in sample well, then diluted by a certain percentage by test sample solution phosphate buffer, every hole adds sample
Product solution 120 μ L, makes test sample (olive-Isosorbide-5-Nitrae, 12-triolefin-28-acid or acarbose drop in 2-hydroxyl-3-carbonyl-23-)
Ultimate density be: 500 μ g/mL, 250 μ g/mL, 125 μ g/mL, 62.5 μ g/mL, 31.25 μ g/mL, 15.625 μ g/mL, finally
Add reaction substrate 4-nitrophenols-α-D-pyranglucoside 20 μ L (5mM).After 37 DEG C of water-bath 15min, each sample
Hole adds the NaCO of 80 μ L3(0.2M) reaction, colorimetric determination at 405nm wavelength are terminated.The phosphate buffer of same volume
Replace enzymatic solution.Compound suppression ratio is calculated for blank and comparison OD value by sample OD value, and computing formula is as follows: suppression ratio
(%)=(ODcontrol–ODneg)-(ODtest–ODtest control)/(ODcontrol–ODneg)×100%.Wherein test compound 2-hydroxyl
Base-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid half-inhibition concentration (the IC to alpha-glucosidase50) by agent
Graded effect curve obtains.
4.3 experimental datas see table 2:
The a-glucosidase inhibitory active of table 2.2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid
4.4 experiment conclusion:
A-glucosidase is the index tested enzyme of a-glycosidase inhibitor screening, the medicine of many treatment diabetes
Thing is based on to be had a-glucosidase competitive inhibition and develops into hypoglycemic medicine.Originally test result indicate that,
The noval chemical compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid that we excavate out has potent suppression a-
The effect of glucosidase, its inhibitory activity even the most about surpasses 16 times than positive reference substance that is line blood sugar lowering medication acarbose,
Thus there is stronger exploitation potential quality, it is expected to can be further developed into into new prevention and treatment type Ⅱdiabetes mellitus medication, should
Extensive by potential quality.
Claims (6)
1. olive-Isosorbide-5-Nitrae, 12-triolefin-28-acid or its pharmaceutically useful salt, its structure drop in compound 2-hydroxyl-3-carbonyl-23-
Formula is as shown in formula I:
2. olive-1,4,12-triolefin-28-acid drops in the compound 2-hydroxyl-3-carbonyl-23-described in a claim 1
Preparation method, it is characterised in that
A, prepare total extractum: Caulis Akebiae, threeleaf akebia, long sequence Caulis Akebiae, Caulis Akebiae or the stem of long calyx threeleaf akebia, the Ye Huo that will gather
Fruit material is pulverized, and then extracts with ethanol water or aqueous acetone solution, and extracting solution concentrates after removing organic solvent and always obtains
Extractum crude extract, suspends in water total extractum crude extract, with petroleum ether extraction, obtains total extractum after extract is concentrated；
B, isolated and purified: total extractum is through purification on normal-phase silica gel column chromatography, with petroleum ether/acetone as eluant, successively from volume ratio 100:
0,20:1,10:1,8:1,5:1,3:1,2:1,1:1,0:100 gradient elution, what collection petroleum ether/acetone 5:1 eluted evaporates
Point, then through purification on normal-phase silica gel column chromatography, with petroleum ether/acetone successively from volume ratio 100:0,10:1,8:1,6:1,4:1,2:1,0:
100 is eluent gradient eluting, collects the fraction of petroleum ether/acetone 6:1 eluting, then separates through Sephadex LH-20 gel column
Purification carries out recrystallization with acetone eluting, eluent, obtains compound 2-hydroxyl-3-carbonyl-23-and drops olive-Isosorbide-5-Nitrae, 12-tri-
Alkene-28-acid.
Preparation method the most according to claim 2, it is characterised in that described ethanol water or aqueous acetone solution are
Volume fraction is more than or equal to ethanol water or the aqueous acetone solution of 70%.
4. the 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-described in claim 1 is sour or it is pharmaceutically useful
Salt application in preparing alpha-glucosidase inhibitor medicament.
5. an alpha-glucosidase inhibitor medicament, it is characterised in that the compound described in the claim 1 containing effective dose
Olive-Isosorbide-5-Nitrae, 12-triolefin-28-acid or its officinal salt drop in 2-hydroxyl-3-carbonyl-23-, and pharmaceutically commonly use adjuvant or load
Body.
6. stem, leaf or the fruit of Caulis Akebiae, threeleaf akebia, long sequence Caulis Akebiae, Caulis Akebiae or long calyx threeleaf akebia is in preparation claim 1
The described application in compound 2-hydroxyl-3-carbonyl-23-fall olive-1,4,12-triolefin-28-acid.
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| US8129429B2 (en) * | 2008-01-11 | 2012-03-06 | Reata Pharmaceuticals, Inc. | Synthetic triterpenoids and methods of use in the treatment of disease |
Non-Patent Citations (2)
| Title |
|---|
| Constituents of the Fruit of Pseudopanax arboreum (Araliaceae);Bruce F.Bowden, et al.;《Aust.J.Chem.》;19751231;第28卷;第91-107页 * |
| 三叶木通齐墩果酸的超声提取工艺研究;刘卫国等;《中药材》;20050228;第28卷(第2期);第140-141页 * |
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