CN104004037B - 8-position methylamine like derivative of baicalin and ester thereof and preparation method thereof - Google Patents
8-position methylamine like derivative of baicalin and ester thereof and preparation method thereof Download PDFInfo
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Abstract
The present invention discloses 8 methylamine like derivative of a kind of baicalin and ester thereof and preparation method thereof, employing baicalin is raw material, in polar solvent, Mannich reaction is carried out with formalin or paraformaldehyde and amine or amine salt, it is prepared as 8 methylamine like derivative of baicalin, 8 methylamine like derivative of baicalin again with halohydrocarbons reaction, prepare 8 methylamine like derivative of baicalin ester, or in alcohol, add SOCl2With 8 methylamine like derivative that 8 methylamine like derivative of baicalin prepare baicalin ester.8 methylamine like derivative of baicalin of the present invention have preferable sour water dissolubility and aqueous alkali dissolubility, and 8 methylamine like derivative of baicalin ester have preferable water solublity and alcohol-soluble, significantly compensate for fat-soluble, the problem that water solublity is poor of baicalin.Its reaction condition is gentle, and product easily refines, and preparation technology is simple, it is easy to preparation of industrialization.
Description
Technical field:
The present invention relates to field of medicaments one scutellaria glycosides derivant and preparation method thereof, a kind of especially baicalin and ester thereof
8-position methylamine like derivative and preparation method thereof.
Background technology:
The effect of baicalin and character: baicalin is the main active extracted from baikal skullcap root, be a kind of flavone
Compounds, molecular formula C21H18 O11, there is the effects such as antiviral, anti-inflammatory, antitumor and immunomodulating, be clinically used for urgency
Property, chronic persistent and chronic active hepatitis it can also be used to treatment nephritis, pyelonephritis, acute biliary infection, lead poisoning and
Anaphylactic disease.Baicalin is as cardiac and cerebral vascular diseases such as antithrombotic clinically, blood pressure lowering, treatment diabetes and coronary heart disease
Medicine, prospect is the most wide.Baicalin is soluble in DMF, pyridine, dissolve in sodium bicarbonate, sodium carbonate,
In the alkaline solutions such as sodium hydroxide, it is slightly soluble in methanol, ethanol, is insoluble in acetone, ethyl acetate, chloroform, be practically insoluble in water.
The bioavailability of baicalin: baicalin exists with molecularity in stomach and duodenal cap, can be absorbed,
But baicalin is insoluble in stomach and duodenal cap, therefore in stomach and duodenal cap, the absorbed amount of baicalin is very
Few.Owing to baicalin Middle molecule having carboxyl, in ionic condition in small intestinal Digestive system, it is difficult to through biomembrane, with molecularity
State baicalin is not the most absorbed.After it arrives ileocecus and colon site, under intestinal microbial population hydrolysis, generate Radix Scutellariae
Element is absorbed, and is then restored to baicalin in protection of intestinal mucosal barrier cells.Owing to intestinal microbial population hydrolysis is limited, its amount absorbed is less.
Skullcapflavone and complexing of metal ion: baicalin and complexing of metal ion, can improve water solublity, and can improve anti-
Bacterium activity.Wu Ronglan etc. prove Cu2+ 、Fe2+ 、A l3+ 、M n2+ 、Zn2+ 、N i2+6 metal ion species all can strengthen Radix Scutellariae
Glycosides suppression O2 -The activity generated, and the activity of Baicalin metal complex is all better than simple baicalin or metal ion ([1]
Wu Ronglan, Feng Shun, Wang Jide, etc. the antioxidant research of baicalin and metal complex thereof. science and technology Leader, 2005,24 (1)
: 36-37).The complex of the baicalins such as Luo Guoan and zinc, pharmacological evaluation shows, this complex can prepare antibacterial, antiinflammatory, resist
Medicine in terms of ulcer is applied ([2] Luo Guoan, Xiao Shengyuan, Wang Yiming, etc. a kind of acceptable complex two baicalin zinc
And preparation method thereof [P]. China, 2003, CN1462754).Baicalin is joined with slaine (mantoquita, iron salt, lanthanum salt or yttrium salt)
Closing, antibacterial, the anti-tumor activity of its coordination compound are obviously stronger than that baicalin, can be used for preparing antibacterials and antitumor drug
([3] Li Zhubo, Liu Yanji, Zhang Qixiong, etc. Baicalin metal complex and its preparation method and application [P]. China, 2012,
CN102516341A)。
Baicalin soluble ester compound: though baicalin has preferably understands oxygen-derived free radicals, arrhythmia, expansion heart and brain
Blood vessel, alleviating heart and brain tissues ischemic damage and reperfusion damage, anti-isoproterenol causes acute sugar myocardial cell injury, protects brain
Neurocytes etc. act on, but baicalin oral administration biaavailability is low, and in water, dissolubility is the least, makes injection difficulty relatively
Greatly, the performance of its drug effect is limited.Baicalin is prepared water miscible ethoxy baicalin or hydroxypropyl baicalin by Pei Yuehu etc.,
Such compound water soluble is fine, can be combined with pharmaceutically acceptable carrier easily make Aqueous injection agent or
Freeze-dried powder,Available
In preventing and treating cardiovascular and cerebrovascular disease, senile dementia, cerebral infarction, cerebral ischemia and other the various diseases etc. caused by cerebral ischemia.
([4] Pei Yuehu, Hua Huiming, Gao Huiyuan, etc. new scutellaria glycosides compounds and application [P] thereof. China 2008,
CN101220064).Mo Jingang has carried out esterification research to the-6-position carboxyl of glucuronic acid in baicalin structure, has obtained Huang
The products such as a kind of reed mentioned in ancient books glycosides N-butyl, baicalin isopropyl ester, baicalin benzyl ester, baicalin methyl ester, baicalin ethyl ester, the wherein positive fourth of baicalin
Ester all has stronger inhibitory activity to tested HeLa cell, H7402 cell, L929 cell, is that dose-dependant closes with medicine
System ([5] Mo Jingang. the extraction separation of baicalin and structural modification [D]. Northeast Normal University, 2007,31-34).Cheng Changmei etc.
Spread out the preparation compound containing following radicals :-OSO by baicalin3H、-OPO3H2、-OAc、-CH3、-CH3CH2、-CH3CH2CH3
With-CH3CH2CH2CH2, remaining is-OH, and spreading out the phosphate ester of wherein baicalin has the activity of anti-SARS virus, can be used for
Preparation prevention and/or treatment anti-SARS virus medicine ([6] Cheng Changmei, Chen Zhenchang, Lu Kui, etc. baicalin derivant and system thereof
Preparation Method and application [P]. China, 2005, CN1634954).
The potentiation of baicalin hydrolyzate is modified: when having amino, substituted-amino or nitro to replace on flavone A ring 8-position,
Then cytotoxicity will strengthen.Baicalin hydrolyzate is baicalin, also referred to as noroxylin.The substituted methylamine in baicalin 8-position
Derivant, with DMSO as solvent, carries out antivirus test, and the methylamine like derivative of result baicalin, compared with baicalin, has relatively
Strong suppression Protein kinase C (PKC) and the activity of suppression HIV (human immunodeficiency virus) HIV/IIIB, can be used as preparing anticancer and anti-AIDS
Sick medicine.([7] Hu Changqi, Sun Xun, Huang Xiaodong, etc. the substituted methylamine like derivative in baicalin 8-position and preparation side thereof
Method [P]. China, 2003, CN1427003).The structure activity study surface of flavone compound, if exist on its A ring simultaneously
Hydroxyl and amino, may show higher antiinflammatory, bacteriostatic activity, especially show good to the suppression aspect of tyrosine kinase
Activity well ([8] Sun Yucui. the synthesis [D] of several 8-amino Scutellarein derivatives. Yunnan University, 2012).Zhang Shixuan etc.
With baikal skullcap root extract skullcapflavone aglycon as lead compound, mix with formalin and organic amine compound, generate
Scutellaria flavonoid organic amine derivatives.This derivant cell cycle element dependent kinases inhibition strength and Flavopiridol and
P276-00 is similar to, and improves about more than 50 times than baicalin, energy selective induction proliferation period apoptosis of tumor cells, and normal tissue
Almost without impact, ([9] Zhang Shixuan, wraps Yongming, and Sun Yuming, etc. cell week to belong to cell cycle inhibitor series antineoplastic medicament
Phase element dependent kinases inhibitor scutellaria flavonoid organic amine derivatives and preparation method thereof and purposes [P]. China, 2009,
CN101591322).(I) baicalin, (II) baicalin, also referred to as noroxylin, the substituted methylamine in (III) baicalin 8-position
Derivant；(i) wogonoside, (ii) wogonin, also referred to as wogonin, the (iii) substituted methylamine in wogonin 8-position
Derivant.
The pluses and minuses that baicalin and aglycone structure are modified: the most briefly illustrate that the structural modification of baicalin and aglycon thereof is existing
Shape, baicalin or baicalin and complexing of metal ion, though its water solublity can be increased, but become salt with complexing of metal ion, band
There are the metal ion of positive charge, the most electronegative carboxyl, cause it to be difficult to be absorbed.It is really for clinical medicine only
There is baicalin (noroxylin) aluminium glue capsule, owing to not absorbed, for gastroenteropathy, as enteritis, bacillary dysentery, its
Range of application is the narrowest.Compared with metal ion complex, the esterification of baicalin, abolish the hydrogen in carboxyl and polyhydroxylated molecule
Key, is possible not only to increase water solublity, and then can make it in intestinal, exist with molecular state, be conducive to absorbing, improve biological utilisation
Degree, improves curative effect, therefore esterification is modified preferably.Flavone A ring is carrying out introducing in potentiation, only baicalin molecule amino, is introducing
After amino, its multiple pharmacological effect strengthens, but does not see introducing amino in baicalin molecule.Therefore baicalin molecule introduces ammonia
Base, it is desirable to be able to play potentiation；Baicalin ester is introduced amino, it is desirable to esterification, amination are dual improves its water by having
Dissolubility, fat-soluble, there is more preferable, higher effect.
Summary of the invention:
Present invention 8-position methylamine like derivative providing a kind of baicalin and ester thereof and preparation method thereof, is to enter with baicalin
Row Mannich reacts, and introduces substituted methylamine base in the molecule, is prepared as the 8-position methylamine like derivative of baicalin, to strengthening
The effect of baicalin；Carboxyl on 8-position its glucuronic acid of methylamine like derivative of baicalin, becomes ester with halohydrocarbons reaction, system
The 8-position methylamine like derivative of standby one-tenth baicalin ester.Purpose be improve baicalin 8-position methylamine like derivative water solublity and
Fat-soluble, to it, there is preferable bioavailability and activity.
The 8-position methylamine like derivative of a kind of baicalin of the present invention, its general structure is as shown in (I),
Wherein: R1R2N represents amine formula, R1, R2Can be identical or different, each representative-H ,-CH3、-CH2CH3、-
CH2CH2CH3、-CH2CH2CH2CH3Or R1, R2It is interconnected to 5 atom rings or 6 atom rings with nitrogen-atoms.
The 8-position methylamine like derivative of the present invention a kind of baicalin ester, its general structure is as shown in (II),
Wherein: R1R2N represents amine formula, R1, R2Can be identical or different, each representative-H ,-CH3、-CH2CH3、-
CH2CH2CH3、-CH2CH2CH2CH3Or R1, R2It is interconnected to 5 atom rings or 6 atom rings with nitrogen-atoms；R3Expression-CH3、-
CH2CH3、-CH2CH2CH3、-CH2CH2CH2CH3、-CH2CH2CH2OH、-CH2CH2OH。
The method of a kind of 8-position methylamine like derivative preparing baicalin of the present invention, it is with baicalin as raw material, in pole
Property solvent in, with formalin and amine or amine salt direct polycondensation single step reaction, the 8-position methylamine preparing baicalin derives
Thing.
The method of a kind of 8-position methylamine like derivative preparing baicalin ester of the present invention, it is with the 8-position methylamine of baicalin
Derivant is raw material, with halohydrocarbons reaction in polar solvent, prepares the 8-position methylamine like derivative of baicalin ester or with Radix Scutellariae
The 8-position methylamine like derivative of glycosides is raw material, adds SOCl at alcohol apoplexy due to endogenous wind2React, prepare the 8-position methylamine of baicalin ester
Derivant.
Polar solvent of the present invention is DMSO, DMF, glacial acetic acid and alcohols, described alcohols be methanol, ethanol, third
Alcohol, n-butyl alcohol, ethylene glycol, glycerol.
Halogenated hydrocarbons of the present invention is XCH3、XCH2CH3、XCH2CH2CH3、XCH2CH2CH2CH3、XCH2CH2CH2OH、
XCH2CH2OH, wherein X is Cl, Br, I.
The present invention utilizes Mannich reaction to prepare the 8-position methylamine like derivative of baicalin on baicalin molecule C-8；Yellow
The 8-position methylamine like derivative of a kind of reed mentioned in ancient books glycosides becomes ester with halohydrocarbons reaction again, prepares the 8-position methylamine like derivative of baicalin ester；
It is to improve the water solublity, fat-soluble of the 8-position methylamine like derivative of baicalin, to it, there is preferable biology
Availability and activity.
The present invention uses the baicalin of structural formula (1) to be raw material, in polar solvent, with formalin and amine or amine
Salt direct polycondensation single step reaction, prepares the 8-position methylamine like derivative of the baicalin of structural formula (2)；
The present invention uses the 8-position methylamine like derivative of the baicalin of structural formula (2), is prepared as structure with halohydrocarbons reaction
The 8-position methylamine like derivative of the baicalin ester of formula (3).
Reaction equation is expressed as follows:
If wherein X=Cl in halogenated hydrocarbons, then can be by alcohols and SOCl2The most directly preparing, its reaction equation is as follows:
Its reaction condition is gentle, and preparation technology is simple, beneficially industrialized production.
Reaction equation of the present invention, wherein R1R2N represents amine formula；R1, R2Can be identical or different, each representative-
H、-CH3、-CH2CH3、-CH2CH2CH3、-CH2CH2CH2CH3Or R1, R2Be interconnected to 5 atom rings with nitrogen-atoms or 6 former
Subring；R3Expression-CH3、-CH2CH3、-CH2CH2CH3、-CH2CH2CH2CH3、-CH2CH2CH2OH、-CH2CH2OH。
In reaction method of the present invention, its described polar solvent is DMSO, DMF, glacial acetic acid and alcohols, wherein alcohol
Class fingernail alcohol, ethanol, propanol, n-butyl alcohol, ethylene glycol, glycerol.
In reaction method of the present invention, halogenated hydrocarbons refers to XCH3、XCH2CH3、XCH2CH2CH3、XCH2CH2CH2CH3、
XCH2CH2CH2OH、XCH2CH2OH, wherein X refers mainly to Cl, Br, I.
The compound of the present invention, the 8-position methylamine like derivative sour water dissolubility of baicalin, aqueous alkali dissolubility are preferable；Baicalin ester
8-position methylamine like derivative there is preferable water solublity, alcohol-soluble, significantly compensate for baicalin fat-soluble, water solublity is poor
Problem.8-position methylamine like derivative relatively baicalin on dissolubility of the compound of the present invention, baicalin and ester thereof is had
Innate advantage so that it is oral relatively baicalin is easier to dissolve at gastrointestinal tract, makes injection and is also possibly realized；Make it have into
One step understands the meaning of medical value, potential potential applicability in clinical practice and potential economic benefit and social benefit.
Detailed description of the invention:
Being described in further detail the present invention below in conjunction with detailed description of the invention, embodiment can help the skill of this area
Art personnel are more fully appreciated with the present invention, but limit the present invention never in any form.In embodiment, the concentration of each material is matter
Amount concentration.
Embodiment 1:8-(N, N-diethyl-amine methyl) preparation of-baicalin；
Take the baicalin 5g that content is 85%, add glacial acetic acid 20ml, add the formaldehyde 5ml that mass concentration is 40%, add
Mass concentration is the diethylamine 3ml of 99%, after 90 DEG C of water-baths dissolve to baicalin, is further continued for reacting 1h, filters, take filter
Liquid, 70 DEG C of decompression and solvent recoveries, add distilled water 100ml, 60 DEG C of warm 10min, filtered while hot, 50g macroporous absorption on filtrate
Resin, distilled water 100ml washs, and mass concentration is the ethanol 200ml washing of 80%, reclaims ethanol, obtains 8-(N, N-diethyl
Base-amine methyl)-baicalin 4.1g, HPLC mensuration, its content is 88.6%.MS (ESI) m/z:532.4060 [M+H]+；13CNMR (100MHz, DMSO-d6): 162.41(C2), 104.82(C3), 181.43(C4) and, 146.69(C5), 130.82
(C6), 150.18(C7), 106.72(C8) and, 148.05(C9), 104.31(C10) and, 51.44(C11), 51.58(C12, C13),
9.58(C14, C15), 130.77(C1 '), 129.57 (C2 ', C4 '), 127.86(C3 ', C5 '), 130.42(C4 '),
100.18(C1 ' '), 72.86(C2 ' '), 75.63(C3 ' ') and, 71.52(C4 ' '), 75.37(C5 ' ') and, 169.42(C6 ' ')；
Its structural formula is as follows:
It is this example structural formula.
Embodiment 2:8-(N, N-dimethyl-amines methyl)-baicalin；
Take the baicalin 10g that content is 85%, add glacial acetic acid 60ml, add the formaldehyde 10ml that mass concentration is 40%, add
Enter dimethylamine 7ml that mass concentration is 40%, 90 DEG C of water-bath 8h, filter, take filtrate, 70 DEG C of decompression and solvent recoveries, add and steam
Distilled water 100ml, heating for dissolving, filtered while hot, filtrate lets cool, and places crystallize, sucking filtration, takes filtering residue 40 DEG C drying, obtain 8-(N, N-
Dimethyl-amines methyl)-baicalin 6.8g, measure through HPLC, its content is 87.4%.MS (ESI) m/z:504.2567 [M+H
]+；13CNMR (100MHz, DMSO-d6): 162.44(C2), 104.83(C3), 181.45(C4) and, 146.71(C5), 130.84
(C6), 150.20(C7), 106.73(C8) and, 148.07(C9), 104.33(C10) and, 51.48(C11), 42.43(C12, C13),
130.83(C1 '), 129.60 (C2 ', C4 '), 127.91(C3 ', C5 '), 130.43(C4 '), 100.21(C1 ' '), 72.91
(C2 ' '), 75.65(C3 ' '), 71.53(C4 ' ') and, 75.41(C5 ' '), 169.45(C6 ' ')；Its structural formula is as follows:
It is this example structural formula.
Embodiment 3:8-(N, N-diethyl-amine methyl)-baicalin；
Take the baicalin 5g that content is 85%, add DMSO 20ml, add the formaldehyde 5ml that mass concentration is 40%, add matter
Amount concentration is diethylamine 3ml, 90 DEG C of water-bath 10h of 99%, filters, and filtrate adds distilled water 100ml, 60 DEG C of warms
30min, filtered while hot, 50g macroporous adsorbent resin on filtrate, distilled water 100ml washs, and mass concentration is the ethanol of 80%
200ml washs, and reclaims ethanol, obtains 8-(N, N-diethyl-amine methyl)-baicalin 4.3g, HPLC mensuration, its content is
88.1%.Its structural formula is the same.
Embodiment 4:8-(nafoxidine-amine methyl)-baicalin；
Take the baicalin 5g that content is 85%, add DMSO 20ml, add the formaldehyde 5ml that mass concentration is 40%, add matter
Amount concentration is nafoxidine 3ml, 85 DEG C of water-bath 10h of 99%, filters, and filtrate adds distilled water 100ml, 60 DEG C of warms
30min, filtered while hot, 50g macroporous adsorbent resin on filtrate, distilled water 100ml washs, and mass concentration is the ethanol of 80%
200ml washs, and reclaims ethanol, obtains 8-(nafoxidine-amine methyl)-baicalin 3.9g, HPLC mensuration, its content is
86.4%.MS (ESI) m/z:530.2867 [M+H]+；13, 104.84 CNMR (100MHz, DMSO-d6): 162.47(C2)
(C3), 181.46(C4), 146.72(C5) and, 130.85(C6), 150.21(C7) and, 106.74(C8), 148.09(C9) and, 104.35
(C10), 51.49(C11), 42.44(C12, C13) and, 25.73(C14, C15), 130.79(C1 '), 129.64 (C2 ', C4 '),
127.93(C3 ', C5 '), 130.45(C4 '), 100.21(C1 ' ') and, 72.90(C2 ' '), 75.61(C3 ' ') and, 71.49
(C4 ' '), 75.42(C5 ' '), 169.43(C6 ' ')；Its structural formula is as follows:
It is this example structural formula.
Embodiment 5:8-(N, N-diethyl-amine methyl) preparation of-baicalin ethyl ester；
Take dehydrated alcohol 50ml, add SOCl22ml, shakes up, and after reaction 1h, adds 8-(N, N-diethyl-amine methyl)-
Baicalin 5g, reacts 2h, TLC and checks to substrate complete, add NaHCO under room temperature33g, stirring reaction, filter, take filtrate, rotation
Turning vaporizer and reclaim the 1/5 of ethanol extremely former submission, limit shakes, while be slowly added into 50ml ether, stands overnight, and filters, takes filtering residue
40 DEG C of drying, obtain 8-(N, N-diethyl-amine methyl)-baicalin ethyl ester, measure through HPLC, its content is 87.6%.MS
(ESI) m/z:560.4537 [M+H]+；13CNMR (100MHz, DMSO-d6): 162.40(C2), 104.81(C3), 181.39
(C4), 146.67(C5), 130.78(C6) and, 150.17(C7), 106.71(C8) and, 148.05(C9), 104.30(C10) and, 51.44
(C11), 42.43(C12, C13), 25.72(C14, C15) and, 130.74(C1 '), 129.61 (C2 ', C4 '), 127.85(C3 ',
C5 '), 130.38(C4 '), 100.20(C1 ' ') and, 72.91(C2 ' '), 75.62(C3 ' ') and, 71.53(C4 ' '), 75.42
(C5 ' '), 170.46(C6 ' '), 60.48(C7 ' ') and, 13.87(C8 ' ')；Its structural formula is as follows:
It is this example structural formula.
Embodiment 6:8-(N, N-diethyl-amine methyl)-baicalin butyl ester；
Take butanol 40ml, add SOCl22ml, shakes up, and after reaction 1h, adds 8-(N, N-diethyl-amine methyl)-Radix Scutellariae
Glycosides 5g, reacts 2h, TLC and checks to substrate complete, add NaHCO under room temperature33g, stirring reaction, pour out supernatant to another circle
In end beaker, under stirring, while be slowly added into ether 100ml, stand overnight, filter, take filtering residue 40 DEG C drying, obtain 8-(N, N-
Diethyl-amine methyl)-baicalin butyl ester, measure through HPLC, its content is 87.2%.
Embodiment 7:8-(nafoxidine-amine methyl)-baicalin ethyl ester；
Take dehydrated alcohol 50ml, add SOCl23ml, shakes up, and after reaction 1h, adds 8-(nafoxidine-amine methyl)-yellow
A kind of reed mentioned in ancient books glycosides 5g, reacts 2h, TLC and checks to substrate complete, add NaHCO under room temperature33g, stirring reaction, filter, take filtrate, rotate
Vaporizer reclaims ethanol and shakes to the 1/5 of former submission, limit, while be slowly added into ether 50ml, stand overnight, and filters, takes filtering residue 40
DEG C dry, obtain 8-(nafoxidine-amine methyl)-baicalin ethyl ester, through HPLC measure, its content is 85.1%.MS(ESI)
M/z:558.4289 [M+H]+；13CNMR (100MHz, DMSO-d6): 162.37(C2), 104.75(C3), 181.39(C4),
146.69(C5), 130.75(C6), 150.20(C7) and, 106.71(C8), 148.08(C9) and, 104.35(C10), 51.48
(C11), 42.43(C12, C13), 25.72(C14, C15) and, 130.69(C1 '), 129.45 (C2 ', C4 '), 127.67(C3 ',
C5 '), 130.28(C4 '), 100.17(C1 ' ') and, 72.87(C2 ' '), 75.61(C3 ' ') and, 71.52(C4 ' '), 75.43
(C5 ' '), 170.44(C6 ' '), 60.48(C7 ' ') and, 14.01(C8 ' ').Its structural formula is as follows:
。
Claims (4)
1. a 8-position methylamine like derivative for baicalin, is characterized in that its structure is as follows,
。
2. a 8-position methylamine like derivative for baicalin, is characterized in that its structure is as follows,
。
3. the method preparing the 8-position methylamine like derivative of baicalin described in claim 1 or 2, is characterized in that with Radix Scutellariae
Glycosides is raw material, in polar solvent, reacts with formalin and corresponding amine or amine salt compound direct polycondensation, preparation Huang
The 8-position methylamine like derivative of a kind of reed mentioned in ancient books glycosides；
Controlling its reaction temperature is 40 DEG C-120 DEG C.
4., according to the method for the 8-position methylamine like derivative preparing baicalin described in claim 3, it is characterized in that described pole
Property solvent is DMSO, DMF, glacial acetic acid and alcohols, described alcohols be methanol, ethanol, propanol, n-butyl alcohol, ethylene glycol, the third three
Alcohol.
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| CN114306362A (en) * | 2021-12-30 | 2022-04-12 | 华南理工大学 | Application of baicalin ester derivative with enhanced antibacterial and antioxidant activities |
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| WO2001049697A1 (en) * | 2000-01-04 | 2001-07-12 | Teva Pharmaceutical Industries Ltd. | Preparation method of azithromycin dihydrate |
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| CN1634954A (en) * | 2003-12-25 | 2005-07-06 | 清华大学 | Baicailin derivative, method for preparation and use |
| CN101337957A (en) * | 2008-08-22 | 2009-01-07 | 四川大学 | Scutellarin derivates, preparation method and application thereof |
| CN101642487A (en) * | 2009-09-15 | 2010-02-10 | 韩桂茹 | Simultaneous extraction and separation process of baicalin and baicalein in baikal skullcap root |
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| 黄芩苷结构修饰及抗氧化构效关系;韩宝瑞;《食品科学》;20110131;第32卷(第1期);第50页左栏 * |
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