CN103923151A - Pseudoginsenoside Rh2 and preparation method of derivatives thereof - Google Patents
Pseudoginsenoside Rh2 and preparation method of derivatives thereof Download PDFInfo
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Abstract
The invention discloses pseudoginsenoside Rh2 and a preparation method of derivatives thereof. The preparation method comprises the following steps: an acetylation preparation method, an acid catalysis preparation method and a saponification preparation method and purification steps thereof. The pseudoginsenoside Rh2 and derivatives thereof are obtained for the first time through acid catalytic reaction of an acetylation product at a low temperature, and elimination and alcoholization processes can be generated at different carbon chain positions of a side chain of ginsenoside simultaneously through one-step reaction. The processes are simpler compared with other organic target synthesis steps, and strong in operability, as well as strong in target compared with simple acid hydrolysis, and is strong in generalizability, and suitable for modifying the side chain of the majority of ginsenoside monomers. The yield of the preparation process is up to more than 60%, and the method is simple to operate, and the reagent is general to use, and suitable for production.
Description
Technical field
The invention discloses the preparation method of a kind of pseudo-ginsenoside Rh2 and derivative thereof, comprise acetylize preparation method, acid catalysis preparation method and saponification preparation method and purification step thereof, belong to ginsenoside preparing technical field.
Background technology
Ginseng (Panax ginseng C.A.Meyer) is Araliaceae (Araliaceae) Panax (Panax) plant.The weather that happiness is shady and cool, moistening, because root hypertrophy often has bifurcated, overall picture is people's shape quite seemingly, so be called ginseng (having another name called god's grass).By people, be called " kings of hundred grass ", be have won fame both at home and abroad, rare medicinal herbs that old children all knows.In ginseng, mainly contain compound and the various trace elements such as volatile oil, amino acids, vitamins, carbohydrate, flavonoid.Ginsenoside is the significant composition of ginseng, by the difference of its sapogenin structure, can be divided into five types: the ginsenoside of oleanolic acid type saponin(e, protopanoxadiol type saponin(e, Protopanaxatriol's type saponin(e, the Losec grand type saponin(e of ladder and other types.
Because the content of most ginsenosides in ginseng is less, the kind of saponin derivative is deficient, nowadays people for ginsenoside, the method by acid degradation, alkaline degradation, enzyme liberating and microbiological deterioration obtains secondary and novel ginsenoside.Wherein ginsenoside Rg3 (patent: ZL98103433.0) is prepared in the employing acid hydrolysis such as Li Pingya; The employing alkaline degradations such as Chen Yingjie obtain ginsenoside Rh1.Aforesaid method is from principle, and a part or the several part by hydrolysis, fallen on ginsenoside obtain a certain monomer saponin.
2007, Chinese patent 101054400A adopted acid hydrolysis to obtain the ginsenoside PPD that a kind of side chain changes; The ginsenoside Rh2 that Chinese patent CN102391345A utilizes acid-hydrolyzed a kind of side chain to change.Novel ginsenoside side chain in above-mentioned report has identical constitutional formula, but configuration is completely different, and wherein Chinese patent 101054400A report is Z-type, and what Chinese patent CN102391345A reported is E type.The effect both with good anti-tumor activity and treatment specified disease, and it adopts high-temperature hydrolysis process under method or acidic conditions, the complicated component producing in conversion process, reaction there is no purpose, and productive rate is lower, Chinese patent CN102391345A utilizes the productive rate of the ginsenoside Rh2 that acid-hydrolyzed a kind of side chain changes less than 1%.The E type that is configured as of pseudoginsenoside Rh2 prepared by the present invention; its process use first acetylate at low temperatures acid catalyzed reaction obtain pseudo-ginsenoside Rh2 and derivative thereof; utilize single step reaction in ginsenoside side chain different carbon chain position, to occur to eliminate and alcoholization process simultaneously; preparation process productive rate is up to more than 60%; simple to operate; reagent is used has general applicability, is applicable to producing.
summary of the invention
The invention provides the preparation method of a kind of pseudo-ginsenoside Rh2 and derivative thereof; use acetylate at low temperatures acid catalyzed reaction obtains pseudo-ginsenoside Rh2 and derivative thereof; utilize single step reaction in ginsenoside side chain different carbon chain position, to occur to eliminate and alcoholization process, be a kind of new preparation method simultaneously.Other ginsenoside is had general applicability and is applicable to suitability for industrialized production.
The preparation method who the invention provides a kind of pseudo-ginsenoside Rh2 and derivative thereof is as follows:
Wherein, a is acetylation; B is acid catalysis process; C is saponification process.
Wherein, pseudo-ginsenoside Rh2 is following structure:
Molecular formula: C
36h
62o
8; Molecular weight: 622; CAS:1370264-16-6.
Chemical name: 3-O-β-D-glucopyranosyl-3 β, 12 β, 25-trihydroxy-Da Ma-(E)-20 (22) alkene;
[3-O-β-D-glucopyranosyl-3β,12β,25-trihydroxyldammar-(E)-20(22)-ene]
Wherein, the derivative of pseudo-ginsenoside Rh2 is following structure:
Protopanoxadiol type saponin(e side connects modified outcome Protopanaxatriol type saponin(e side and connects modified outcome
R
1=H, for intending protopanoxadiol; R
2=H, for intending Protopanaxatriol;
R
1=glc-glc is pseudo-ginsenoside Rg3; R
2=glc is pseudo-ginsenoside Rh1;
R
2=glc-rha is pseudo-ginsenoside Rg2;
It is characterized in that: its side-chain structure identical with pseudo-ginsenoside Rh2 (C-20 and C-21 position are the two keys of E type, and C-25 position is hydroxyl), the sugared kind just connecting in female ring, the difference of quantity and position.
the preparation method of a kind of pseudo-ginsenoside Rh2 provided by the invention and derivative thereof, concrete steps comprise:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in organic solvent, add diacetyl oxide 50ml and pyridine 50ml, in 20 ~ 40 ℃ of water bath with thermostatic control reflux 10 ~ 30 hours, underpressure distillation, except desolventizing, obtains ginsenoside Rh2 acetylate;
Diacetyl oxide and pyridine are generally 5 times of amounts; Organic solvent is a kind of of methyl alcohol, acetone, methylene dichloride, acetonitrile;
B. pseudo-ginsenoside Rh2 acetylate preparation (acid catalysis): get ginsenoside Rh2 acetylate 10g, be dissolved in organic solvent, adding concentration is 1 ~ 25% sour 10ml, in-50 ~ 22 ℃ of thermostatic baths, reflux 5 ~ 20 hours, adding alkaline solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate;
Organic solvent is one of dioxane, pyridine, methylene dichloride or methyl alcohol or its mixture; Acid is one of hydrochloric acid, sulfuric acid, phosphoric acid, Glacial acetic acid or oxalic acid or its mixture, and concentration range is 1 ~ 25%, and the reaction times is 5 ~ 20 hours;
C. the preparation of pseudo-ginsenoside Rh2 (saponification): get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 50 ~ 75%V/V organic solvent 50ml, add 50 ~ 60% alkali 5ml, in 80 ~ 100 ℃ of water bath with thermostatic control reflux 2 ~ 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
Organic solvent is one of dioxane, ethanol, methylene dichloride or methyl alcohol or its mixture; Alkali is that one of sodium hydroxide, potassium hydroxide, basic metal, rudimentary sodium alkoxide are planted.
In the present invention, ginsenoside Rh2 can use ginsenoside Rh1, ginsenoside PPD, ginsenoside PPT, ginsenoside Rg3, ginsenoside Rg2 to replace, and product is the derivative (having identical side-chain structure: C-20 and C-21 is the two keys of E type, and C-25 is hydroxyl) of pseudo-ginsenoside Rh2.
In the present invention, pseudo-ginsenoside Rh2 acetylate is prepared in (acid catalysis) method; comprehensive cost art breading; the factors such as industrialized feasibility; organic solvent is with methyl alcohol and ethanol; acid is with hydrochloric acid, sulfuric acid or Glacial acetic acid; concentration is 1 ~ 25%, and temperature of reaction is-50 ~ 22 ℃, and the time is within 5 ~ 20 hours, to be the best.
positively effect of the present invention is:use first acetylate at low temperatures acid catalyzed reaction obtain pseudo-ginsenoside Rh2 and derivative thereof, utilize single step reaction in ginsenoside side chain different carbon chain position, to occur to eliminate and alcoholization process simultaneously.Other organic target synthesis step is simple, workable relatively for this process, is compared to simple acid hydrolysis simultaneously, and its targeted is strong, and general applicability is strong, is applicable to the modification of most of this side chain of ginseng saponin monomer.This preparation process productive rate is up to more than 60%, simple to operate, and reagent is used has general applicability, is applicable to producing.
Accompanying drawing explanation
Fig. 1 is ginsenoside Rh2 acetylize mass spectrum;
Fig. 2 is ginsenoside Rh2 acetylize
1h-NMR figure;
Fig. 3 is ginsenoside Rh2 acetylize
13c-NMR figure;
Fig. 4 is pseudo-ginsenoside Rh2 acetylize mass spectrum;
Fig. 5 is pseudo-ginsenoside Rh2 acetylize
1h-NMR figure;
Fig. 6 is pseudo-ginsenoside Rh2 acetylize
13c-NMR figure;
Fig. 7 is the mass spectrum of pseudo-ginsenoside Rh2;
Fig. 8 is pseudo-ginsenoside Rh2's
1h-NMR figure;
Fig. 9 is pseudo-ginsenoside Rh2's
13c-NMR figure;
Figure 10 is the HMQC figure of pseudo-ginsenoside Rh2;
Figure 11 is the HMBC figure of pseudo-ginsenoside Rh2.
embodiment:
By following examples, the present invention is further described for example, and do not limit the present invention in any way, any change that those of ordinary skills made for the present invention easily realize or change do not deviating under the prerequisite of technical solution of the present invention, within all will fall into claim scope of the present invention.
pseudo-ginsenoside Rh2 preparation process
embodiment 1:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in 50ml methylene dichloride, add diacetyl oxide 50ml and pyridine 50ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh2 acetylate; Ginsenoside Rh2 acetylize mass spectrum is shown in Fig. 1; Ginsenoside Rh2 acetylize
1h-NMR figure is shown in Fig. 2; Ginsenoside Rh2 acetylize
13c-NMR figure is shown in Fig. 3.
B. 3-O-BETA-D-glucopyranosyl-3BETA,12BETA,25-trihydroxyldammar-(E)-20(22)-ene acetylate preparation (acid catalysis): get ginsenoside Rh2 acetylate 10g, be dissolved in 100ml methylene dichloride, adding concentration is 5% sulfuric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate; Pseudo-ginsenoside Rh2 acetylize mass spectrum is shown in Fig. 4; Pseudo-ginsenoside Rh2 acetylize
1h-NMR figure is shown in Fig. 5; Pseudo-ginsenoside Rh2 acetylize
13c-NMR figure is shown in Fig. 6.
C. the preparation of pseudo-ginsenoside Rh2 (saponification): get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 25ml dioxane and 25ml ethanolic soln, add 50% sodium hydroxide solution 5ml, in 100 ℃ of water bath with thermostatic control reflux 2 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
D. the purifying of pseudo-ginsenoside Rh2: get pseudo-ginsenoside Rh2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:2:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=8:2, and flow velocity 10ml/min detects wavelength: 203), moisture 10% recrystallizing methanol, obtains pseudo-ginsenoside Rh2, and productive rate is 57.2%.The mass spectrum of pseudo-ginsenoside Rh2 is shown in Fig. 7; Pseudo-ginsenoside Rh2's
1h-NMR figure is shown in Fig. 8; Pseudo-ginsenoside Rh2's
13c-NMR figure is shown in Fig. 9; For the HMQC figure of pseudo-ginsenoside Rh2 is shown in Figure 10; The HMBC figure of pseudo-ginsenoside Rh2 is shown in Figure 11.
embodiment 2:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in 50ml methylene dichloride, add diacetyl oxide 50ml and pyridine 50ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh2 acetylate;
B. pseudo-ginsenoside Rh2 acetylate preparation (acid catalysis): get ginsenoside Rh2 acetylate 10g, be dissolved in 100ml methylene dichloride, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate; C. the preparation of pseudo-ginsenoside Rh2 (saponification): get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 25ml dioxane and 25ml ethanolic soln, add 50% sodium hydroxide solution 5ml, in 100 ℃ of water bath with thermostatic control reflux 2 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
D. the purifying of pseudo-ginsenoside Rh2: get pseudo-ginsenoside Rh2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:2:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=8:2, and flow velocity 10ml/min detects wavelength: 203), moisture 10% recrystallizing methanol, obtains pseudo-ginsenoside Rh2, and productive rate is 62.1%.
embodiment 3:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in 50ml methylene dichloride, add diacetyl oxide 50ml and pyridine 50ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh2 acetylate;
B. pseudo-ginsenoside Rh2 acetylate preparation (acid catalysis): get ginsenoside Rh2 acetylate 10g, be dissolved in 100ml acetic acid, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate;
C. the preparation of pseudo-ginsenoside Rh2 (saponification): get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 25ml dioxane and 25ml ethanolic soln, add 50% sodium hydroxide solution 5ml, in 100 ℃ of water bath with thermostatic control reflux 2 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
D. the purifying of pseudo-ginsenoside Rh2: get pseudo-ginsenoside Rh2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:2:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=8:2, and flow velocity 10ml/min detects wavelength: 203), moisture 10% recrystallizing methanol, obtains pseudo-ginsenoside Rh2, and productive rate is 61.2%.
embodiment 4:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in 50ml methylene dichloride, add diacetyl oxide 50ml and pyridine 50ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh2 acetylate;
B. pseudo-ginsenoside Rh2 acetylate preparation (acid catalysis): get ginsenoside Rh2 acetylate 10g, be dissolved in 100ml acetic acid, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate;
C. the preparation of pseudo-ginsenoside Rh2 (saponification): get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 25ml dioxane and 25ml methanol solution, add 50% sodium hydroxide solution 5ml, in 100 ℃ of water bath with thermostatic control reflux 2 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
D. the purifying of pseudo-ginsenoside Rh2: get pseudo-ginsenoside Rh2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:2:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=8:2, and flow velocity 10ml/min detects wavelength: 203), moisture 10% recrystallizing methanol, obtains pseudo-ginsenoside Rh2, and productive rate is 61.1%.
embodiment 5:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in 50ml methylene dichloride, add diacetyl oxide 50ml and pyridine 50ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh2 acetylate;
B. pseudo-ginsenoside Rh2 acetylate preparation (acid catalysis): get ginsenoside Rh2 acetylate 10g, be dissolved in 100ml acetic acid, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate;
C. the preparation of pseudo-ginsenoside Rh2 (saponification): get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 25ml dioxane and 25ml methanol solution, add 50% sodium hydroxide solution 5ml, in 90 ℃ of water bath with thermostatic control reflux 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
D. the purifying of pseudo-ginsenoside Rh2: get pseudo-ginsenoside Rh2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:2:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=8:2, and flow velocity 10ml/min detects wavelength: 203), moisture 10% recrystallizing methanol, obtains pseudo-ginsenoside Rh2, and productive rate is 55.6%.
pseudo-ginsenoside Rh2 derivative preparation process
embodiment 6:
A. the acetylize of ginsenoside PPD preparation: get 10g ginsenoside PPD, be dissolved in 25ml methylene dichloride, add diacetyl oxide 25ml and pyridine 25ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside PPD acetylate;
B. pseudo-ginsenoside PPD acetylate preparation (acid catalysis): get ginsenoside PPD acetylate 10g, be dissolved in 50ml acetic acid, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside PPD acetylate;
C. the preparation of pseudo-ginsenoside PPD (saponification): get 5g pseudo-ginsenoside PPD acetylate, be dissolved in 25ml dioxane and 25ml methanol solution, add 50% sodium hydroxide solution 5ml, in 90 ℃ of water bath with thermostatic control reflux 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside PPD;
D. the purifying of pseudo-ginsenoside PPD: get pseudo-ginsenoside PPD crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:1.5:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=9:1, and flow velocity 10ml/min detects wavelength: 203), moisture 5% recrystallizing methanol, obtains pseudo-ginsenoside PPD, and productive rate is 55.6%.
embodiment 7:
A. the acetylize of ginsenoside PPT preparation: get 10g ginsenoside PPT, be dissolved in 25ml methylene dichloride, add diacetyl oxide 25ml and pyridine 25ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside PPT acetylate;
B. pseudo-ginsenoside PPT acetylate preparation (acid catalysis): get ginsenoside PPT acetylate 10g, be dissolved in 50ml acetic acid, adding concentration is 5% sulfuric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside PPT acetylate;
C. the preparation of pseudo-ginsenoside PPT (saponification): get 5g pseudo-ginsenoside PPT acetylate, be dissolved in 25ml dioxane and 25ml methanol solution, add 50% sodium hydroxide solution 5ml, in 90 ℃ of water bath with thermostatic control reflux 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside PPT;
D. the purifying of pseudo-ginsenoside PPT: get pseudo-ginsenoside PPT crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:1.5:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=9:1, and flow velocity 10ml/min detects wavelength: 203), moisture 5% recrystallizing methanol, obtains pseudo-ginsenoside PPT, and productive rate is 58.6%.
embodiment 8:
A. the acetylize of ginsenoside Rh1 preparation: get 10g ginsenoside Rh1, be dissolved in 25ml methylene dichloride, add diacetyl oxide 50ml and pyridine 50ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh1 acetylate;
B. pseudo-ginsenoside Rh1 acetylate preparation (acid catalysis): get ginsenoside Rh1 acetylate 10g, be dissolved in 50ml acetic acid, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh1 acetylate;
C. the preparation of pseudo-ginsenoside Rh1 (saponification): get 5g pseudo-ginsenoside Rh1 acetylate, be dissolved in 25ml dioxane and 25ml methanol solution, add 50% sodium hydroxide solution 5ml, in 90 ℃ of water bath with thermostatic control reflux 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh1;
D. the purifying of pseudo-ginsenoside Rh1: get pseudo-ginsenoside Rh1 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:1.5:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=9:1, and flow velocity 10ml/min detects wavelength: 203), moisture 5% recrystallizing methanol, obtains pseudo-ginsenoside Rh1, and productive rate is 62.7%.
embodiment 9:
A. ginsenoside Rg2's acetylize preparation: get 10g ginsenoside Rg2, be dissolved in 25ml methylene dichloride, add diacetyl oxide 75ml and pyridine 75ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rg2's acetylate;
B. pseudo-ginsenoside Rg2 acetylate preparation (acid catalysis): get ginsenoside Rg2's acetylate 10g, be dissolved in 50ml acetic acid, adding concentration is 5% sulfuric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rg2 acetylate;
C. the preparation of pseudo-ginsenoside Rg2 (saponification): get 5g pseudo-ginsenoside Rg2 acetylate, be dissolved in 30ml dioxane and 30ml methanol solution, add 50% sodium hydroxide solution 5ml, in 90 ℃ of water bath with thermostatic control reflux 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rg2;
D. the purifying of pseudo-ginsenoside Rg2: get pseudo-ginsenoside Rg2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:1.5:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=7:3, and flow velocity 10ml/min detects wavelength: 203), moisture 5% recrystallizing methanol, obtains pseudo-ginsenoside Rg2, and productive rate is 64.1%.
embodiment 10:
A. the acetylize of ginsenoside Rg3 preparation: get 10g ginsenoside Rg3, be dissolved in 25ml methylene dichloride, add diacetyl oxide 75ml and pyridine 75ml, in 40 ℃ of water bath with thermostatic control reflux 10 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rg3 acetylate;
B. pseudo-ginsenoside Rg3 acetylate preparation (acid catalysis): get ginsenoside Rg3 acetylate 10g, be dissolved in 50ml acetic acid, adding concentration is 5% hydrochloric acid 10ml, in 4 ℃ of thermostatic baths, reflux 20 hours, adding sodium hydroxide solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rg3 acetylate;
C. the preparation of pseudo-ginsenoside Rg3 (saponification): get 5g pseudo-ginsenoside Rg3 acetylate, be dissolved in 30ml dioxane and 30ml methanol solution, add 50% sodium hydroxide solution 5ml, in 90 ℃ of water bath with thermostatic control reflux 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rg3;
D. the purifying of pseudo-ginsenoside Rg3: get pseudo-ginsenoside Rg3 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:1.5:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=7:3, and flow velocity 10ml/min detects wavelength: 203), moisture 5% recrystallizing methanol, obtains pseudo-ginsenoside Rg3, and productive rate is 56.1.
Claims (6)
1. pseudo-ginsenoside Rh2 and derivative thereof, have following structural formula:
Protopanoxadiol type saponin(e side connects modified outcome Protopanaxatriol type saponin(e side and connects modified outcome
R
1=H, for intending protopanoxadiol; R
2=H, for intending Protopanaxatriol;
R
1=glc is pseudo-ginsenoside Rh2; R
2=glc is pseudo-ginsenoside Rh1;
R1=glc-glc is pseudo-ginsenoside Rg3; R
2=glc-rha is pseudo-ginsenoside Rg2.
2. the preparation method of pseudo-ginsenoside Rh2 and derivative thereof, its preparation method is as follows:
Wherein a is acetylation; B is acid catalysis process; C is saponification process.
3. the preparation method of pseudo-ginsenoside Rh2 claimed in claim 1 and derivative thereof, is characterized in that: be included in ginsenoside Rh2 acetylation, pseudo-ginsenoside Rh2 acetylate acid catalysis preparation process, pseudo-ginsenoside Rh2 saponification preparation process and separation thereof, purification step;
Ginsenoside Rh2 reacts after acetylize in organic solvent in acid catalysis, and then in alkaline solution, saponification obtains pseudo-ginsenoside Rh2; Wherein:
A. the acetylize of ginsenoside Rh2 preparation: get 10g ginsenoside Rh2, be dissolved in organic solvent, add diacetyl oxide 50ml and pyridine 50ml, in 20 ~ 40 ℃ of water bath with thermostatic control reflux 10 ~ 0 hours, underpressure distillation, except desolventizing, obtained ginsenoside Rh2 acetylate;
B. pseudo-ginsenoside Rh2 acetylate acid catalysis preparation: get ginsenoside Rh2 acetylate 10g, be dissolved in organic solvent, adding concentration is 1 ~ 25% sour 10ml, in-50 ~ 22 ℃ of thermostatic baths, reflux 5 ~ 20 hours, adding alkaline solution to adjust pH is 7.0, reclaim solvent, obtain pseudo-ginsenoside Rh2 acetylate;
C. the saponification of pseudo-ginsenoside Rh2 preparation: get 5g pseudo-ginsenoside Rh2 acetylate, be dissolved in 50 ~ 75%V/V organic solvent 50ml, add 50 ~ 60% alkali 5ml, in 80 ~ 100 ℃ of water bath with thermostatic control reflux 2 ~ 5 hours, adding acid solution to regulate pH is 7.0, reclaim organic solvent, obtain pseudo-ginsenoside Rh2;
D. the purifying of pseudo-ginsenoside Rh2: get pseudo-ginsenoside Rh2 crude product and carry out silica gel column chromatography, chloroform: methyl alcohol: ethyl acetate: water is that 2:2:4:1 upper strata is eluent; Above-mentionedly must be prepared liquid phase separation compared with pure products (eluent is methyl alcohol: water=9:1, and flow velocity 10ml/min detects wavelength: 203), aqueous methanol recrystallization, obtains pseudo-ginsenoside Rh2;
Organic solvent prepared by wherein said ginsenoside Rh2 acetylate is a kind of of methyl alcohol, ethanol, acetone, methylene dichloride, acetonitrile;
Organic solvent prepared by wherein said pseudo-ginsenoside Rh2 acetylate acid catalysis is one of dioxane, pyridine, methylene dichloride or methyl alcohol or its mixture; Acid is one of hydrochloric acid, sulfuric acid, phosphoric acid, Glacial acetic acid oxalic acid or its mixture;
Organic solvent prepared by wherein said pseudo-ginsenoside Rh2 saponification is one of dioxane, ethanol, methylene dichloride or methyl alcohol or its mixture; Alkali is that one of sodium hydroxide, potassium hydroxide, basic metal, rudimentary sodium alkoxide are planted.
4. according to the pseudo-ginsenoside Rh2 described in claim 3 and the preparation method of derivative thereof; it is characterized in that: in pseudo-ginsenoside Rh2 acetylate acid catalysis preparation process; when using the mixing acid of hydrochloric acid, sulfuric acid or acetic acid; concentration the best is 1 ~ 25%; temperature of reaction the best is-50 ~ 22 ℃, reaction times the best 5 ~ 20 hours.
5. according to the pseudo-ginsenoside Rh2 described in claim 3 and the preparation method of derivative thereof, it is characterized in that: the purge process of pseudo-ginsenoside Rh2, reaction solution is with after acid neutralization, steam except organic solvent, pseudo-ginsenoside Rh2 crude product, column chromatography repeatedly, recrystallization.
6. according to the preparation process of the pseudo-ginsenoside Rh2 described in claim 3, be also applicable to other ginsenoside monomer, as ginsenoside Rg3, Rg2, Rh1, PPT, PPD etc., thereby obtain the derivative of pseudo-ginsenoside Rh2, it is characterized in that: except female ring difference, its side-chain structure is identical with pseudo-ginsenoside Rh2, C-20 and C-21 position are the two keys of E type, and C-25 position is hydroxyl.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104761610A (en) * | 2015-02-10 | 2015-07-08 | 江西本草天工科技有限责任公司 | Novel alpha-hederin derivative and preparation method and use thereof |
| CN106389442A (en) * | 2016-01-14 | 2017-02-15 | 孙妙囡 | Application of pseudo protopanoxadiol |
| CN106866769A (en) * | 2017-03-07 | 2017-06-20 | 吉林大学 | Pseudo-ginsenoside derivative and preparation method thereof |
| CN107188918A (en) * | 2017-06-05 | 2017-09-22 | 吉林大学 | A kind of pseudo-ginsenoside Rg3, Rh2, PPD preparation method |
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| -: "CAS RN：1370264-16-6等", 《STN ON WEB》, 20 April 2012 (2012-04-20), pages 1 - 17 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104761610A (en) * | 2015-02-10 | 2015-07-08 | 江西本草天工科技有限责任公司 | Novel alpha-hederin derivative and preparation method and use thereof |
| CN106389442A (en) * | 2016-01-14 | 2017-02-15 | 孙妙囡 | Application of pseudo protopanoxadiol |
| CN106866769A (en) * | 2017-03-07 | 2017-06-20 | 吉林大学 | Pseudo-ginsenoside derivative and preparation method thereof |
| CN107188918A (en) * | 2017-06-05 | 2017-09-22 | 吉林大学 | A kind of pseudo-ginsenoside Rg3, Rh2, PPD preparation method |
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