CN101880304A - 24(R)-pseudoginsenoside-GQ as well as semisynthesis method and medicinal application thereof - Google Patents
24(R)-pseudoginsenoside-GQ as well as semisynthesis method and medicinal application thereof Download PDFInfo
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- CN101880304A CN101880304A CN 201010204031 CN201010204031A CN101880304A CN 101880304 A CN101880304 A CN 101880304A CN 201010204031 CN201010204031 CN 201010204031 CN 201010204031 A CN201010204031 A CN 201010204031A CN 101880304 A CN101880304 A CN 101880304A
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- Prior art keywords
- ginsenoside
- pseudo
- semisynthesis
- pseudoginsenoside
- glucopyranosyl
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Abstract
The invention relates to 24(R)-pseudoginsenoside-GQ as well as a semisynthesis method and medicinal application thereof, belonging to a new compound as well as a synthesis method and medicinal application thereof. In the invention, 20(S)-ginsenoside Rg3 or 20(R)-ginsenoside Rg3 is used as a raw material, and under an acid condition, a new compound is synthesized through the steps of oxidization, cyclization, and the like, wherein the chemical name of the new compound is 3-O-[beta-D-glucopyranose-(1-2)-beta-D-glucopyranose group]-damma-20S, 24R-epoxy-3beta, 12beta, 25-triol being short for 24(R)-pseudoginsenoside-GQ, the productivity of which reaches higher than 80 percent. The 24(R)-pseudoginsenoside-GQ has wide medicinal application in preparing medicaments for treating coronary heart diseases, myocardial ischemia, ischemic shocks, arrhythmia and reperfusion damages and resisting cancer.
Description
Technical field
The present invention relates to 24 (R)-pseudo-ginsenoside-GQ and semisynthesis thereof and its application in preparation treatment myocardial ischemia, ischemic shock, arrhythmia and reperfusion injury and cancer therapy drug.
Background technology
After the main effective constituent, chemists are devoted to the conversion of the synthetic and effective monomer of some monomer saponin in ginsenoside is proved conclusively to genseng and Radix Panacis Quinquefolii.At present, mainly contain following several method in research and using, for example acid-hydrolysis method, alkali hydrolysis method, enzymolysis process, condensation method etc.First three methods mainly is between total saponins and monomer saponin, falls in the molecule certain part or several parts by hydrolysis and realizes that a certain monomer saponin or several monomer saponin are after transforming; The back is a kind of then to obtain a certain monomeric compound with aglycon by becoming the glycosides reaction by sugar.
Nineteen eighty-two, Hart B H reported first with under the gentle sour condition, make ginsenoside degraded and measured the structure of degraded product.For example, with ginsenoside-Rg1, use 0.1M HCl, under 37 ℃ of conditions with without handling pitch time, obtain the degraded product ginsenoside Rh1, Li Pingya, prepare the monomer ginsenoside Rg3 (patent No.: ZL98103433.0) Deng having studied through acid hydrolysis from ginsenoside glycol group, Chen Yingjie waits first and finds, under suitable reaction conditions, the alkali catalyzed hydrolysis method, to ginsenoside degraded have reaction temperature and, advantage such as control is successfully synthesized ginsenoside Rh1 from the ginsenoside Rg2 with this method easily.Song Changchun in 1992 etc. use with quadrat method and have prepared monomer ginsenoside Rh1 and Rh2 from the stem and leaf of Radix Panacis Quinquefolii saponin(e.Also have some with the acid-base method degraded, with the example of enzymic degradation, repeat no more.Li Pingya waits and has reported that relevant oxidation, the cyclization method of utilizing makes ginsenoside Rg3 change into pseudo-ginsenoside-Pgq (patent No.: ZL 0012837.9).
Do not see the synthetic method of relevant 24 (R)-pseudo-ginsenoside-GQ and the report of compound at present, this compound belongs to new compound, belongs to synthetic first; The new pharmaceutical use of this compound belongs to first to be found.
Summary of the invention
The object of the present invention is to provide a kind of compound: 24 (R)-pseudo-ginsenoside-GQ:
Its chemical name is: 3-O-[β-D-Glucopyranose-(1-2)-β-D-glucopyranosyl]-Da Ma-20S, 24R-epoxy-3 β, 12 β, the 25-triol (3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-dammar-20S, 24R-epoxy-3 β, 12 β, 25-triol).Mp:231.7 ℃～232.2 ℃, white powder is soluble in methyl alcohol, ethanol, propylene glycol etc.Because of this compound is a new compound, be to obtain through semisynthesis with the protopanoxadiol saponin(e, its constitutional features C17 position has similar residue to pseudo-ginsenoside F 11, difference is that the C-24 position is configured as the R type, it also is one of endemic element in the Radix Panacis Quinquefolii, so called after 24 (R)-pseudo-ginsenoside-GQ is called for short 24 (R)-PGQ (P: intend; G: genseng; Q: Radix Panacis Quinquefolii: promptly change into the compound with Radix Panacis Quinquefolii constitutional features by the protopanoxadiol saponin(e, the C-24 position is configured as the R type).
The present invention also aims to utilize 20 (S)-ginsenoside Rg3s is precursor, through organic chemistry synthetic methods such as peroxidation, cyclisation, prepares a kind of novel substance that has than strong biological activity.
For achieving the above object, invent the semisynthesis of taking is:
A, semisynthesis are got 1.0g 20 (S)-ginsenoside Rg3, are dissolved in 50ml 1, in the 4-dioxane, and enriching H
2S0
4Regulate pH value 3-5, under agitation dropwise add oxygenant 5ml, in 75 ℃～85 ℃ reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution was 7.0, filtration, and filtrate is concentrated into dried, slightly 24 (R)-pseudo-ginsenoside-GQ:0.7g～0.9g;
The purifying of b, 24 (R)-pseudo-ginsenoside-GQ: get thick 24 (R)-pseudo-ginsenoside-GQ and carry out column chromatography or adopt the solvent extraction way to carry out purifying, get pure 24 (R)-pseudo-ginsenoside-GQ:0.5g～0.7g.
24 (R)-pseudo-ginsenoside-GQ structure is identified and is resolved
1HNMR (500MHz, C
5D
5N) spectrum provides 8 methyl proton signals at High-Field, is respectively δ
H0.95 (3H, s), 0.75 (3H, s), 1.26 (3H, s), 1.24 (3H, s), 1.45 (3H, s), 1.26 (3H, s), 1.07 (3H, s), 0.89 (3H s), provides the proton signal of 2 groups of glucose, wherein δ in the midfield
H4.92 (1H, d, J=7.5Hz), 5.37 (1H, d are the anomeric proton signal of 2 groups of glucose J=8.0Hz), according to its coupling constant, in conjunction with
13The CNMR spectrum determines to be beta comfiguration, provides all the other proton signals simultaneously; From
13CNMR (125MHz, C
5D
5N) in the spectrum, provide 42 carbon signals altogether, wherein provide 2 molecule glucose signals, all the other 30 carbon signal ownership are triterpenoid sapogenin, wherein δ
C56.5 be the characteristic signal of ginsenoside glycol group; By the HMQC and the HMBC spectrum of further this compound of parsing, proved conclusively the structure of this compound.
Chemical reaction is as follows:
20 (S)-ginsenoside Rg3 24 (R)-pseudo-ginsenoside-GQ
In above-mentioned semisynthesis, 20 (S)-ginsenoside Rg3 saponin(es can replace with 20 (R)-ginsenoside Rg3s.
In above-mentioned semisynthesis, oxygenant comprises inorganic oxidizer and organic oxidizing agent; Inorganic oxidizer is H
2O
2Or KMnO
4Organic oxidizing agent be Peracetic Acid ,-chlorine peroxybenzoic acid or right-chlorine peroxybenzoic acid.
The application of the present invention 24 (R)-pseudo-ginsenoside-GQ in preparation treatment coronary heart disease, myocardial ischemia, ischemic shock, arrhythmia and reperfusion injury and cancer therapy drug.
When the present invention is used for preparation treatment coronary heart disease, myocardial ischemia, ischemic shock, when arrhythmia and reperfusion injury and anticancer medicine, its oral or parenteral admin, all be safe, under oral situation, it can any conventionally form administration, as powder, granula, tablet, capsule, pill, solution, suspension, syrup, buccal tablets, sublingual lozenge etc.: when this medicine administered parenterally, can take any conventionally form, for example injection: as intravenous injection, ointment, suppository, percutaneous dosing, inhalation etc.
It is to be made of effective constituent monomer or the effective constituent vehicle with solid or liquid that the present invention prepares treatment coronary heart disease, myocardial ischemia, ischemic shock, arrhythmia and reperfusion injury and anticancer medicine, the vehicle of solid used herein or liquid is well known in the art, lift several object lessons below, powder is the powder agent that takes orally, its vehicle has lactose, starch, paste essence, lime carbonate, synthetic or puritan filler aluminium, magnesium oxide, Magnesium Stearate, sodium bicarbonate, dry yeast etc.; The vehicle of solution has water, glycerine, 1,2-propylene glycol, simple syrup, ethanol, ethylene glycol, polyoxyethylene glycol, Sorbitol Powder etc.; The vehicle of ointment can use fatty oil, and hydrous wool, Vaseline, glycerine, honeybee is cured, wood is cured, white oil, resin, senior hydrophobizing agent or the hydrophilizing agent that is combined into such as cured.
Beneficial effect of the present invention is, new compound 24 (R)-pseudo-ginsenoside-GQ can be used for preparation treatment coronary heart disease, myocardial ischemia, ischemic shock, arrhythmia and reperfusion injury and anticancer medicine, compare with precursor compound 20 (S)-ginsenoside Rg3 or with its enantiomorph pseudoginsenoside GQ, have the characteristics that are better than the two evident in efficacy.
Because of containing fat-soluble pair of key in 20 (S)-ginsenoside Rg3 side chain C24-35 positions, water-soluble relatively poor, oral administration biaavailability is low, through 24 (R)-pseudo-ginsenoside-GQ behind the structural modification, when having eliminated two key, increase by 1-OH, thereby increased water-soluble widely, improved oral administration biaavailability, biological activity obviously improves, and makes it have more into the property of medicine.
The dosage of active substance can be according to the mode of taking, and patient's age and body weight and the degree that is in a bad way change with other similar factor, and oral dose is: 8.0～16.0mg/kg, and every day, secondary was taken: injection 6.0～9.0mg/kg, once a day.
Description of drawings
Fig. 1 is the present invention 24 (R)-pseudo-ginsenoside-GQ
1The HNMR spectrogram;
Fig. 2 is the present invention 24 (R)-pseudo-ginsenoside-GQ
13The CNMR spectrogram;
Fig. 3 is the HMQC spectrogram of the present invention 24 (R)-pseudo-ginsenoside-GQ;
Fig. 4 is the HMBC spectrogram of the present invention 24 (R)-pseudo-ginsenoside-GQ.
Embodiment
The present invention can further specify by following experimental example.
Experimental example one, 24 (R)-pseudo-ginsenoside-GQ are to the influence of hemorrhagic shock
One, experiment material and method
Material: 6 of beagle dogs; 24 (R)-PGQ:10mg/ml aqueous solution
Method: dog with Nembutal vein anesthetic (1ml he), is lain on the back and is fixed on the operating table, separate tracheae, insert trachea cannula.Separate arteria carotis communis, connect RM-6000 four and lead physiograph, survey: BP (SBP/DBP); Separate right side bone artery, survey LVSP, LVEDP, ± dp/dt; Separate the right lateral thigh vein, be equipped with administrable.
Separate Right deviation side femoral artery, be equipped with arterial blood letting usefulness, connect cardiac diagnosis lead, survey ECG and calculate HR, xiphoid-process skin place connects force transducer with silk thread, surveys respiratory rate, after operation finishes, stablized 10 minutes, and write down every normal index, store in the blood bottle to filling 0.1% heparin-saline through the femoral artery bloodletting then, making the artery average pressure drop is that shock is (after bloodletting to 40mmHg, BP sharply descends, and can make the artery mean pressure maintain 40mmHg with in the defeated object that reverses of blood).Stablized 20 minutes, the artery mean pressure does not rise, and presses the 10mg/kgb administration, and observe 120 minutes every indexs and change, after the record administration 1,3,5,10,20,30,45,60,90,120 minutes.Venous blood collection, centrifugal, get serum, measure LPO (Ba Mushi improved method) and SOD.
Two, experimental result:
1, to the influence of mean arterial blood pressure (MBP)
24 (R)-PGQ small dose group 20 ', 30 ' MBP after administration significantly raise, and compare with the saline control group, and notable difference (p＜0.05) is arranged.The rising percentage of 5 '～45 ' MBP is compared for two groups apparently higher than the saline control group, significant difference (p＜0.05, p＜0.01, p＜0.001).
The heavy dose of group of 24 (R)-PGQ 5 '～120 ' MBP and rising percentage after administration have the highly significant meaning all apparently higher than saline control group (p＜0.05, p＜0.01, p＜0.001).
Dopamine HCL group 5 '～20 ' MBP after administration obviously raises, and the rising percentage of 5 '～30 ' MBP is compared with the salt solution group variant significantly (p＜0.05, p＜0.01) apparently higher than the saline control group.The results are shown in Table 1-1.
Table 1-124 (R)-PGQ is to the influence of MBP (Kpa)
Continuous table 1-1
Continuous table .1-1
*P＜0.05,
*P＜0.01,
* *Compare with the 0.9%NaCl control group p＜0.001.
2, the influence of right+dp/dt
24 (R)-PGQ small dose group after administration 10 '～45 ' and 90 ', 120 '+dp/dt obviously increases the significant difference of comparing with the saline control group (p＜0.05, p＜0.01).The rising percentage of 30 '～120 '+dp/dt is significantly higher than the saline control group, compares that there were significant differences (p＜0.05, p＜0.01) for two groups.
The heavy dose of group of 24 (R)-PGQ is 30 '～120 '+dp/dt and all significantly increases of rising percentage after administration, have compared highly significant meaning (p＜0.05, p＜0.01) with the saline control group.
The Dopamine HCL group is 5 '～45 '+dp/dt and all significantly increases of rising percentage after administration, compare significant difference (p＜0.05, p＜0.01, p＜0.001) with the saline control group.The results are shown in Table 1-2.
Table 1-2 24 (R)-P GQ is right+influence of dp/dt (Kpa/s)
Continuous table 1-2
Continuous table 1-2
Continuous table 1-2
Continuous table 1-2
P＜005,
*P＜0.01,
* *Compare with the 0.9%NaC1 control group p＜0.001.
3, the influence of right-dp/dt
The rising percentage of 24 (R)-PGQ small dose group 45 '-dp/dt after administration is apparently higher than the saline control group, the significant difference (p＜0.05) of comparing with the saline control group.
The heavy dose of group of 24 (R)-PGQ 60 '-dp/dt after administration obviously raises, and the rising percentage of 10 '～60 '-dp/dt is compared (p＜0.05, p＜0.01) for two groups apparently higher than the saline control group.
Dopamine HCL group 5 ', 10 '-dp/dt after administration compares significant difference (p＜0.01) apparently higher than the saline control group with the saline control group.The rising percentage of 5 '～20 '-dp/dt is compared significant difference (p＜0.05, p＜0.01) apparently higher than the saline control group with the saline control group.The results are shown in Table 1-3.
Table 1-3 24 (R)-PGQ is right-influence of dp/dt (Kpa/s)
Continuous table 1-3
Continuous table 1-3
Continuous table 1-3
Continuous table 1-3
*P＜0.05,
*Compare with the 0.9%NaCl control group p＜0.01.
Heart rate and respiratory rate: compare no significant difference when each time point is with shock after administration.
The result shows: (24 (R)-PGQ) have the anti-hemorrhagic shock effect to 24 (R)-pseudo-ginsenoside-GQ.
Experimental example two, 24 (R)-pseudo-ginsenoside-GQ are to the hemodynamic influence of normal anesthetized dog (n=6)
One, experiment material and method
Material: 6 of Beagle dogs, body weight 13kg～15kg body weight, each 3 of male and female, 24 (R)-pseudo-ginsenoside-GQ:10mg/ml solution;
Method: method is with experiment one, so slightly.
Two, result
1, to the influence of lipid peroxide (LPO)
Little, the heavy dose of group of 24 (R)-PGQ content of 120 ' LPO after administration is starkly lower than the saline control group, two groups of comparing differences remarkable (p＜0.05).
The content of Dopamine HCL group 120 ' LPO after administration is starkly lower than the saline control group, two groups of comparing differences remarkable (p＜0.05).The results are shown in Table 2-1.
Table 2-124 (R)-PGQ is to the influence of LPO (A/ml)
Compare with the 0.9%NaCl control group p＜0.05.
2, to the influence of superoxide-dismutase (SOD)
The content of 24 (R)-PGQ small dose group 120 ' SOD after administration and percentage and saline control group relatively do not have significant difference.
The content of the heavy dose of group of 24 (R)-PGQ 120 ' SOD after administration and rising percentage be apparently higher than the saline control group, and two groups of comparing differences are (p＜0.05, p＜0.01) significantly.
The content of Dopamine HCL group 120 ' SOD after administration and rising percentage are apparently higher than the saline control group, and two groups of comparing differences remarkable (p＜0.01) the results are shown in Table 2-2.
Table 2-2 24 (R)-P GQ is to the influence of SOD (U/l)
*P＜0.05,
*Compare with the NaCl control group p＜0.01.
The result shows: 24 (R)-pseudo-ginsenoside-GQ can significantly reduce LPO and improve SOD content, and anti-radical action is arranged.
Experimental example three, MTT (tetrazolium salts) method are measured the selection of 24 (R)-pseudo-ginsenoside-GQ to the lethal effect of tumour cell
(1) test design
Use the knurl strain: MCF-7 human breast cancer cell, PC3M Human Prostate Cancer Cells, NCI-H446 human lung carcinoma cell, Helas human cervical carcinoma cell, H8 human colon cancer cell, SHG-44 people's glioma cell, SK-OV-3 Proliferation of Human Ovarian Cell, seven kinds of human tumour cell lines.
(annotate: different cells adopt different nutrient solutions: RPMI1640, IMDM, DMEM.)
Test grouping: 24 (R)-pseudo-ginsenoside-GQ dosage group:
1.0μg/ml、2.5μg/ml、5μg/ml、7.5μg/ml、10μg/ml、12.5μg/ml、15μg/ml、17.5μg/ml、20μg/ml；
Blank group: solvent;
Positive controls: 5 FU 5 fluorouracil (1.0 μ g/ml).
(2) method:
1. the preparation of MTT liquid: 250mgMTT puts into small beaker, and (pH7.4 0.01M), stirs 30min, and being mixed with concentration is 5mg/ml solution, and is with the millipore filter bacteriological filtration of 0.22um, packing, 4 ℃ of preservations, effective in two weeks to add 50mlPBS.
The tumour cell of 2. taking the logarithm vegetative period adds an amount of 0.25% trypsinase, and attached cell is come off, and does cell counting, and general non-staining viable cell should be made into 6 * 10 more than 97%
4/ ml cell suspension.
3. get 96 hole flat boards, every hole adds cell suspension 100ul.Flat board is put 37 ℃ of 5%CO
2Incubator 24h.
4. after hatching 24h, add the SPG-Rg3 (SPG-Rg3 dilutes with serum free medium, the furnishing desired concn) of 100 μ l/ hole different concns, put 37 ℃ of 5%CO in 96 orifice plates
2Incubation 72h.
5. the every hole adding 20ulMTT liquid of 96 orifice plates (MTT is made into 5mg/ml solution with serum-free RPMI RPMI-1640) continue to hatch 4h, stop cultivating.
6. careful the suction abandoned supernatant liquor, and every hole adds 150ul DMSO, and concussion 10min fully dissolves crystallisate;
7. measure the optical density(OD) (OD value) of each aperture at the 570nm place with the dull and stereotyped reader of automatization spectrophotometric.
8. the result judges:
A. calculate cell survival rate:
(when calculating cell survival rate, the OD value of each test hole is deducted background OD value, the OD value of each repeating hole is got mean ± SD)
Drug level (IC when b. obtaining T/C=50%
50) and the drug level (IC during T/C=10%
90).
C. data use SPSS software analysis system to handle (weighted linear regression method).
[3] result: the result sees Table 3～table 10 respectively:
Table 3 24 (R)-pseudo-ginsenoside-GQ is to the influence of MCF-7 human breast cancer cell
Table 4 24 (R)-pseudo-ginsenoside-GQ is to the influence of PC3M Human Prostate Cancer Cells
Table 5 24 (R)-pseudo-ginsenoside-GQ is to the influence of NCI-H446 human lung carcinoma cell
Table 6 24 (R)-pseudo-ginsenoside-GQ is to the influence of Helas human cervical carcinoma cell MCF-7 human breast cancer cell
Table 7 24 (R)-pseudo-ginsenoside-GQ is to the influence of H8 human colon cancer cell
Table 8 24 (R)-pseudo-ginsenoside-GQ is to the influence of SK-OV-3 Proliferation of Human Ovarian Cell
Table 9 24 (R)-pseudo-ginsenoside-GQ is to the influence of SHG-44 people's glioma cell
Table 10MTT method records the IC of 24 (R)-pseudo-ginsenoside-GQ to 7 kinds of human body tumour cell effects
50(μ g/ml)
The result shows: 24 (R)-pseudo-ginsenoside-GQ all have certain lethal effect to 7 kinds of cancer cells.
Embodiment one:
A, semisynthesis are got 1.0g 20 (S)-ginsenoside Rg3, are dissolved in 50ml 1, in the 4-dioxane, and enriching H
2SO
4Regulate pH value 3, between under agitation dropwise adding-chlorine peroxybenzoic acid 5ml, in 75 ℃ of reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution was 7.0, filtration, and filtrate is concentrated into dried, gets slightly 24 (R)-pseudo-ginsenoside-GQ 0.9g;
The purifying of b, 24 (R)-pseudo-ginsenoside-GQ is got thick 24 (R)-pseudo-ginsenoside-GQ of obtaining of step and is carried out silica gel column chromatography, pure 24 (R)-pseudo-ginsenoside-GQ:0.7g.
Embodiment two:
A. semisynthesis is got 1.0g 20 (S)-ginsenoside Rg3, is dissolved in 50ml CHCl
3In, enriching H
2SO
4Regulate pH value 4, under agitation dropwise add right-chlorine peroxybenzoic acid 5ml, in 80 ℃ of reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution was 7.0, filtration, and filtrate is concentrated into dried, slightly 24 (R)-pseudo-ginsenoside-GQ 0.8g.
B.24 the purifying of (R)-pseudo-ginsenoside-GQ: it is soluble in water to get thick 24 (R)-pseudo-ginsenoside GQ that the step obtains, and adopts n-butanol extraction, carries out purifying, pure 24 (R)-pseudo-ginsenoside-GQ:0.6g.
Embodiment three:
A, semisynthesis are got 1.0g 20 (S)-ginsenoside Rg3, are dissolved in 50ml 1, in the 4-dioxane, and enriching H
2SO
4Regulate pH value 5, under agitation dropwise add H
2O
25ml, in 85 ℃ of reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution was 7.0, filters, filtrate is concentrated into dried, 24 (R)-pseudo-ginsenoside-GQ 0.7g slightly;
The purifying of b, 24 (R)-pseudo-ginsenoside-GQ is got thick 24 (R)-pseudo-ginsenoside-GQ of obtaining of step and is carried out silica gel column chromatography, pure 24 (R)-pseudo-ginsenoside-GQ:0.5g.
Embodiment four:
A, semisynthesis are got 1.0g 20 (R)-ginsenoside Rg3, are dissolved in 50ml 1, in the 4-dioxane, and enriching H
2SO
4Regulate pH value 3, under agitation dropwise add KMnO
45ml, in 75 ℃ of reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution was 7.0, filters, filtrate is concentrated into dried, 24 (R)-pseudo-ginsenoside-GQ 0.9g slightly;
The purifying of b, 24 (R)-pseudo-ginsenoside-GQ is got thick 24 (R)-pseudo-ginsenoside-GQ of obtaining of step and is carried out silica gel column chromatography, pure 24 (R)-pseudo-ginsenoside-GQ:0.7g.
Embodiment five:
A. semisynthesis is got 1.0g 20 (R)-ginsenoside Rg3, is dissolved in 50ml CHCl
3In, enriching H
2SO
4Regulate pH value 4, under agitation dropwise add Peracetic Acid 5ml, in 80 ℃ of reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution was 7.0, filtration, and filtrate is concentrated into dried, slightly 24 (R)-pseudo-ginsenoside-GQ 0.8g.
B.24 the purifying of (R)-pseudo-ginsenoside-GQ: it is soluble in water to get thick 24 (R)-pseudo-ginsenoside GQ that the step obtains, and adopts n-butanol extraction, carries out purifying, pure 24 (R)-pseudo-ginsenoside-GQ:0.6g.
The embodiment one of preparation medicament:
24 (R)-pseudo-ginsenoside-GQ 35g, 1,2-propylene glycol 10000ml packs into after the mixing 1000 and pacifies in the bottle, and every 10ml contains 24 (R)-pseudo-ginsenoside-GQ35mg.
The embodiment two of preparation medicament:
24 (R)-pseudo-ginsenoside-GQ20.0g, medical starch 480g, the two thorough mixing, encapsulated, make 1000 capsules, every heavy 0.5g contains 24 (R)-pseudo-ginsenoside-GQ20mg.
Claims (7)
- One kind as shown in the formula 24 (R)-pseudo-ginsenoside-GQ,
Its chemical name is: 3-O-[β-D-Glucopyranose-(1-2)-β-D-glucopyranosyl]-Da Ma-20S, 24R-epoxy-3 β, 12 β, the 25-triol (3-O-[β-D-glucopyranosyl-(1-2)-β-D-glucopyranosyl]-dammar-20S, 24R-epoxy-3 β, 12 β, 25-triol). - 2. the semisynthesis of (R)-pseudo-ginsenoside-GQ: it is characterized in that:A, semisynthesis get 1,0g 20 (S)-ginsenoside Rg3, be dissolved in 50ml 1, in the 4-dioxane, add the vitriol oil and regulate pH value 3-5, under agitation dropwise add oxygenant 5ml, in 75 ℃～85 ℃ reflux 90 minutes, after the cooling, regulating pH with the 0.1M NaOH aqueous solution is 7.0, filters, filtrate is concentrated into dried, gets slightly 24 (R)-pseudo-ginsenoside-GQ:0.7g～0.9g;The purifying of b, 24 (R)-pseudo-ginsenoside-GQ: get thick 24 (R)-pseudo-ginsenoside-GQ and carry out column chromatography or adopt the solvent extraction way to carry out purifying, get pure 24 (R)-pseudo-ginsenoside GQ 0.5g-0.7g.
- 3. the semisynthesis of 24 (R)-pseudo-ginsenoside-GQ according to claim 2 is characterized in that: 20 (S)-ginsenoside Rg3s can replace with 20 (R)-ginsenoside Rg3s.
- 4. the semisynthesis of 24 (R)-pseudo-ginsenoside-GQ according to claim 2 is characterized in that: oxygenant comprises inorganic oxidizer and organic oxidizing agent.
- 5. the semisynthesis of 24 (R)-pseudo-ginsenoside-GQ according to claim 4 is characterized in that: inorganic oxidizer is H 2O 2Or KMnO 4
- 6. the semisynthesis of 24 (R)-pseudo-ginsenoside-GQ according to claim 4 is characterized in that: organic oxidizing agent be Peracetic Acid ,-chlorine peroxybenzoic acid or right-chlorine peroxybenzoic acid.
- 7. the application of 24 (R)-pseudo-ginsenoside-GQ as claimed in claim 1 in preparation treatment coronary heart disease, myocardial ischemia, ischemic shock, arrhythmia and reperfusion injury and cancer therapy drug.
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| CN102924556A (en) * | 2012-11-05 | 2013-02-13 | 烟台大学 | (20S, 24R)-ocotillol type ginsenoside derivative having antibacterial activity and preparation method and application thereof |
| CN102924556B (en) * | 2012-11-05 | 2017-08-22 | 烟台大学 | (20S, 24R) ocotillol type ginsenosides analog derivative, preparation method and the usage with antibacterial activity |
| CN103059088A (en) * | 2013-01-16 | 2013-04-24 | 烟台大学 | Dammarane saponin derivatives with novel structure as well as preparation method and anti-microbial application thereof |
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| US20150112048A1 (en) * | 2013-10-17 | 2015-04-23 | Macau University of Science and Tehnology | Novel Ginsenoside Derivative Compounds And The Use Thereof In Protection Against Ischemia/Reperfusion Injury |
| US9273088B2 (en) * | 2013-10-17 | 2016-03-01 | Macau University Of Science And Technology | Ginsenoside derivative compounds and the use thereof in protection against ischemia/reperfusion injury |
| CN104926910A (en) * | 2015-06-01 | 2015-09-23 | 吉林大学 | Synthesis method and pharmaceutical application of compound |
| CN104926910B (en) * | 2015-06-01 | 2016-03-02 | 吉林大学 | A kind of synthetic method of compound and its pharmaceutical use |
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