CN101967105B - Beta-hydroxy protected didecyl quaternary ammonium salt with anticancer activity and preparation method thereof - Google Patents
Beta-hydroxy protected didecyl quaternary ammonium salt with anticancer activity and preparation method thereof Download PDFInfo
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Abstract
The invention relates to the synthesis of an emodin derivative with anticancer function, in particular to beta-hydroxy protected didecyl quaternary ammonium salt with anticancer activity and a preparation method thereof. The didecyl quaternary ammonium salt is methyl didecyl-[2-(4,5-dihydroxy-7-methoxy-9,10-anthraquinonyl)methyl] ammonium salt and is prepared from emodin serving as a raw material through a series of synthetic reactions. In the invention, the emodin derivative has proliferation inhibiting functions with different degrees for five cancer cells such as liver cancer HepG2, gastric cancer BGC, neuroma SH-SY5Y, gastric cancer AGS and cervical cancer Hela and the normal human embryonic lung fibroblast HELF, and can be used for preparing medicaments for treating cancers.
Description
Technical field
The present invention relates to emodin derivates synthetic that a class has anti-cancer function, relate more specifically to two decyl quaternary ammonium salts of a kind of beta-hydroxy protection with antitumour activity and preparation method thereof.
Technical background
Schuttgelb be a kind of in polygonaceae plant the higher anthraquinone compounds of content, have multiple biological activity, such as anti-infective, antiviral, immunosuppression, protect the liver, the transfer of antitumor, inhibition of cell proliferation, cell death inducing, prevention tumour and arrestin kinases etc.But the poorly water-soluble of Schuttgelb own, toxicity is high, and biological activity is good not, and biological activity mechanism neither be very clear and definite, so Schuttgelb also is not used for the report of clinicing aspect.Therefore Schuttgelb being carried out chemically modified is very important to improve antitumour activity.
Summary of the invention
The object of the present invention is to provide two decyl quaternary ammonium salts of a kind of beta-hydroxy protection with antitumour activity and preparation method thereof.
Two decyl quaternary ammonium salts of beta-hydroxy of the present invention protection are methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] ammonium salt, and structural formula is suc as formula shown in the I,
Represent negatively charged ion.
Described pair of decyl quaternary ammonium salt is methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio,
Expression Br
-., its preparation method may further comprise the steps:
(1) Schuttgelb and methyl-sulfate are at K
2CO
3There is lower reaction, generates 1,3,8-trimethoxy-6-methyl-9, the 10-anthraquinone;
(2) 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone and the reaction of N-bromo-succinimide generate 1,3,8-trimethoxy-6-brooethyl-9, the 10-anthraquinone;
(3) 1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone and Hydrogen bromide reaction generate 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9, the 10-anthraquinone;
(4) 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone and the reaction of N-methyl didecylamine, synthesizing methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio.
Above-mentioned preparation method's concrete steps are as follows:
(1) 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone synthetic: get the 1.6g Schuttgelb and be dissolved in 120～200ml acetone, add 10～12g Anhydrous potassium carbonate, be heated to backflow, under the state that refluxes, slowly drip 4～8ml (CH
3O)
2SO
2, the 20～24h that refluxes is cooled to room temperature, and is concentrated, adds 50～100ml water and stirs 30min, and suction filtration is used washing with acetone, obtains the thick product of yellow powder, and the silica gel column chromatography separation obtains 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone;
(2) 1,3,8-trimethoxy-6-brooethyl-9, synthesizing of 10-anthraquinone: get 0.8g 1,3,8-trimethoxy-6-methyl-9, the 10-anthraquinone, 1.2～1.6g N-bromo-succinimide (NBS), the CCl of 0.2～0.3g benzoyl peroxide and 60～160ml
4Add in the there-necked flask, reflux 15～25h is cooled to room temperature, filters, and filter residue is used respectively CCl
4, H
2O and washing with acetone, the separation of recycle silicon plastic column chromatography obtains 1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone;
(3) 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone synthetic: add 280～800mg 1,3 in the 100mL there-necked flask, 8-trimethoxy-6 brooethyls-anthraquinone, 30～50mL glacial acetic acid are heated to backflow; Under nitrogen protection, drip 5～9mL 47%(weight ratio) hydrobromic acid aqueous solution, continue back flow reaction 4～6 h; Reactant is poured in 200～300mL frozen water, suction filtration after stirring, and the filter residue oven dry obtains 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone with the silica gel column chromatography separation;
(4) positive decyl-[2-(4 for methyl two, 5-dihydroxyl-7-methoxyl group-9, the 10-anthraquinonyl) methyl] brometo de amonio synthetic: add 125～500mg1 in the 100mL there-necked flask, 8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone, 50～150mL chloroform and 127～468 mg N-methyl didecylamine; Back flow reaction under nitrogen protection is followed the tracks of reaction process with TLC, and 20～24 h afterreactions finish; The rotary evaporation desolventizing, enriched material is with being chloroform-ethanol gradient elution gradually of 4:1 again with volume ratio with chloroform first on the silica gel column chromatography, from last elutriant, separate and obtain methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio.
Wherein the elutriant of step (1), (2) described silica gel column chromatography is methylene dichloride; The elutriant of the described silica gel column chromatography of step (3) is chloroform.
Two decyl quaternary ammonium salts of above-described beta-hydroxy protection, it has antitumour activity, is used for the treatment of the preparation of Cancerous disease medicine.
The synthetic route of synthesizing methyl two positive decyls of the present invention-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio is as follows:
Above-mentioned compound 1-5 represents respectively Schuttgelb, 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone, 1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone, 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone, methyl two are positive, and decyl-[2-(4,5-dihydroxyl-7-methoxyl group-9, the 10-anthraquinonyl) methyl] brometo de amonio.Wherein Schuttgelb is available from Xi'an China extraction biotechnology limited liability company, and N-methyl didecylamine is available from the chemical industry that circles in the air (Zhangjiagang) company limited.
Suppressing experiment by cancer cell in vitro shows, the emodin derivates methyl two of the present invention report is positive, and decyl-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio can effectively kill 5 kinds of cancer cells such as liver cancer HepG2, cancer of the stomach BGC, neuroma SH-SY5Y, cancer of the stomach AGS, cervical cancer Hela.
Embodiment
The present invention will be further described by the following examples, but the present invention is not limited only to this.
Embodiment 1: intermediate product
2The synthetic a of (1,3,8-trimethoxy-6-methyl-9,10-anthraquinone)
Get 1.6g (5.8mmol) Schuttgelb and be dissolved in the 120ml acetone, add 12g (87mmol) Anhydrous potassium carbonate, under the state that refluxes, slowly drip (the CH of 8ml (87mmol)
3O)
2SO
2, backflow 24h cools off room temperature, and concentrated solution adds 100ml water and stirs 30min, and suction filtration with a small amount of cold washing with acetone, obtains the thick product of yellow powder, and the silica gel column chromatography separation obtains glassy yellow solid 1.52g, productive rate 82.6%.The product structure warp
1H NMR, IR, fusing point are determined.Intermediate product
2Characterization data as follows:
m.p.?226~228℃;?IR(KBr)
ν max/cm-1:?2941,2843,1662,1601,1322,1241,1022,759.?
1HNMR?(400MHz,?CDCl
3),?
δ:?7.65(s,?1H,?Ar-H),?7.34(d,?1H,
?J=2.4Hz,?Ar-H),?7.11(s,?1H,?Ar-H),?6.78(d,?1H,?
J=2.0Hz,?Ar-H),?4.00(s,?3H,?OCH
3),?3.97(s,?3H,?OCH
3),?3.96(s,?3H,?OCH
3),?2.48(s,?3H,?CH
3).
Embodiment 2: intermediate product
2The synthetic b of (1,3,8-trimethoxy-6-methyl-9,10-anthraquinone)
Get 1.6g (5.9mmol) Schuttgelb and be dissolved in the 200ml acetone, add 10g (73mmol) Anhydrous potassium carbonate, under the state that refluxes, slowly drip (the CH of 4ml (43mmol)
3O)
2SO
2, backflow 24h cools off room temperature, and concentrated solution adds 80ml water and stirs 30min, and suction filtration with a small amount of cold washing with acetone, obtains the thick product of yellow powder, and the silica gel column chromatography separation obtains glassy yellow solid 1.34g, productive rate 72.8%.
Embodiment 3: intermediate product
2The synthetic c of (1,3,8-trimethoxy-6-methyl-9,10-anthraquinone)
Get 1.6g (5.9mmol) Schuttgelb and be dissolved in the 180ml acetone, add 10g (73mmol) Anhydrous potassium carbonate, under the state that refluxes, slowly drip (the CH of 4ml (43mmol)
3O)
2SO
2, backflow 20h cools off room temperature, and concentrated solution adds 60ml water and stirs 30min, and suction filtration with a small amount of cold washing with acetone, obtains the thick product of yellow powder, and the silica gel column chromatography separation obtains glassy yellow solid 1.30g, productive rate 70.6%.
Embodiment 4: intermediate product
3 (1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone) synthetic a
Get the compound of 0.8g embodiment 1 preparation
2(2.56mmol), 1.6g N-bromo-succinimide (NBS) (9.0mmol), the CCl of 0.20g benzoyl peroxide (BPO) and 60ml
4Add in the there-necked flask, reflux 25h, the cooling room temperature is filtered and is obtained yellow solid, uses respectively a small amount of CCl
4, H
2O and washing with acetone obtain yellow solid, separate obtaining yellow solid 0.83g, productive rate 83% with silica gel column chromatography.The product structure warp
1H NMR, IR, fusing point are determined.Intermediate product
3Characterization data:
m.p.217.0~219.0℃;?IR(KBr)
ν max/cm-1:3436,1662,1597,1314,1253,1021,943.?
1HNMR?(400MHz,?CDCl
3),?
δ:7.83(d,?1H,?
J=1.2Hz,?Ar-H),?7.33(d,?1H,?
J=2.4Hz,?Ar-H),?7.11(d,?1H,?
J=1.2Hz,?Ar-H),?6.78(d,?1H,?
J=2.4Hz,?Ar-H),?4.52(s,?2H,-CH
2),?4.02(s,?3H,?OCH
3),?3.97?(s,?3H,?OCH
3),?3.96?(s,?3H,?OCH
3).
Embodiment 5: intermediate product
3 (1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone) synthetic b
Get the compound of 0.8g embodiment 2 preparations
2(2.56mmol), 1.2g N-bromo-succinimide (NBS) (6.74mmol), the CCl of 0.24g BPO and 100ml
4Add in the there-necked flask, reflux 18h, the cooling room temperature is filtered and is obtained yellow solid, uses respectively a small amount of CCl
4, H
2O and washing with alcohol obtain yellow solid, separate obtaining yellow solid 0.84g, productive rate 84% with silica gel column chromatography.
Embodiment 6: intermediate product
3 (1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone) synthetic c
Get the compound of 0.8g embodiment 3 preparations
2(2.56mmol), 1.60g N-bromo-succinimide (NBS) (9.0mmol), the CCl of 0.30g BPO and 160ml
4Add in the there-necked flask, reflux 15h, the cooling room temperature is filtered and is obtained yellow solid, uses respectively a small amount of CHCl
3, H
2O and washing with alcohol obtain yellow solid, separate obtaining yellow solid 0.80g, productive rate 80% with silica gel column chromatography.
Embodiment 7: compound
4(1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone) synthesizes a
Add 1,3 of 280.7mg (0.72mmol) embodiment 4 preparations in the 100mL there-necked flask, 8-trimethoxy-6 brooethyls-anthraquinone, the 30mL glacial acetic acid is heated to backflow.Under nitrogen protection, drip 5mL Hydrogen bromide (47% aqueous solution).After adding, continue back flow reaction 6 h, separate out a large amount of orange solids, finish reaction.Mixture is poured in the 200mL frozen water, suction filtration after stirring, and the solid oven dry obtains the 224.3mg sterling with silica gel column chromatography, productive rate 85.8%.
Compound
4Characterization data as follows:
m.p.246~247℃;?IR(KBr),?
ν max/cm-1:?3435,?3080,?1667,?1633,?1486,?1328,?1262,?763.?
1H?NMR(400MHz,?CDCl
3),?
δ:?12.23(s,?H,?OH),?12.17(s,?H,?OH),?7.82(d,?1H,?
J=1.6Hz,?Ar-H),?7.40(d,?1H,?
J=1.6Hz,?Ar-H),?7.30(d,?1H,?
J=1.6Hz,?Ar-H),?6.71(d,?1H,?
J=2.8Hz,?Ar-H),?4.47(s,?2H,?CH
2-N),?3.95(s,?3H,?OCH
3).
Embodiment 8: compound
4(1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone) synthesizes b
Add 1,3 of 800mg (2.05mmol) embodiment 5 preparations in the 100mL there-necked flask, 8-trimethoxy-6 brooethyls-anthraquinone, the 50mL glacial acetic acid is heated to backflow.Under nitrogen protection, drip 9mL Hydrogen bromide (47% aqueous solution).After adding, continue back flow reaction 5 h, separate out a large amount of orange solids, finish reaction.Mixture is poured in the 300mL frozen water, suction filtration after stirring, and the solid oven dry obtains the 641.2mg sterling with silica gel column chromatography, productive rate 86.2%.
Embodiment 9: compound
5(methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio) synthesize a
The compound that adds 125.0mg (0.34mmol) embodiment 7 preparations in the 100mL there-necked flask
4(1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone), 50mL chloroform and 127.9 mg (0.41mmol) N-methyl didecylamine.Back flow reaction under nitrogen protection is followed the tracks of reaction process with TLC, and 24 h afterreactions finish.Rotary evaporation desolventizing, residuum are used gradually gradient elution of chloroform-ethanol with chloroform first again on silica gel column chromatography, separate to obtain product 128.6mg, yield 56.1%
Compound
5Characterization data as follows:
M.p.148.8-150.8 ℃; IR (KBr),
ν Max/cm-1: 3379,2924,2853,1678,1630,1483,1222,1164,758.
1H NMR (400MHz, CD
3COCD
3),
δ: 12.09 (s, 2H, OH), 7.87 (d, 1H,
J=1.2Hz, Ar-H), 7.59 (d, 1H,
J=1.2Hz, Ar-H), 7.25 (d, 1H,
J=2.4Hz, Ar-H), 6.95 (d, 1H,
J=2.4Hz, Ar-H), 4.65 (s, 2H, CH
2-N), 3.96 (s, 3H, OCH
3), 3.16 ~ 3.27 (m, 4H, C
H 2-N-C
H 2), 2.97 (s, 3H, N-CH
3), 1.26 ~ 1.29 (m, 32H, 2 * (CH
2)
8), 0.86 (t, 6H,
J=6.8Hz, 2 * CH
3). ultimate analysis, C
37H
56BrNO
5%, measured value (calculated value), %: C 65.65 (65.86); H 8.61 (8.37); N 1.99 (2.08).
Embodiment 10: compound
5(methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio) synthesize b
The compound that adds 500.0mg (1.38mmol) embodiment 8 preparations in the 250mL there-necked flask
4(1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone), 150mL chloroform and 468.0 mg (1.50mmol) N-methyl didecylamine back flow reaction under nitrogen protection are followed the tracks of reaction process with TLC, and 20 h afterreactions finish.Rotary evaporation desolventizing, residuum are used gradually gradient elution of chloroform-ethanol with chloroform first again on silica gel column chromatography, separate to obtain product 484.2mg, yield 52.0%
Embodiment 11: compound 5 cell in vitro active testings
5 kinds of cancer cells such as liver cancer HepG2, cancer of the stomach BGC, neuroma SH-SY5Y, cancer of the stomach AGS, cervical cancer Hela and normal human embryonic lung fibroblast HELF cell density are adjusted into 1.5 * 10
5/ ml is inoculated in 96 well culture plates, and every hole 100ul puts 37 ℃, 5% CO
2Cultivate 24h in the incubator; Remove old substratum, add tested derivative (with the dilution of tested derivative storage liquid, setting different activities with substratum), every hole 100uL, other establishes blank group, Schuttgelb group and raw material N-methyl didecylamine group, establishes 6 multiple holes for every group.Behind drug effect 24 h, inhale and to abandon the pastille substratum, in every hole, add serum-free, without phenol red 1640 substratum, 100 uL, add again MTT solution 10 uL, continue to hatch 4 h, stop cultivation; The careful suction abandoned supernatant liquor in 96 orifice bores, and every hole adds 150uL DMSO, and 10 min that vibrate are in mensuration each hole absorbance value (OD value) on the microplate reader, calculation of half inhibitory concentration IC50 value in 490 nm wavelength.The result is as shown in table 1.
Table 1. compound 5 and Schuttgelb etc. are to JEG-3 not of the same race and normal cell toxicity IC50 (μ mol/L)
Mean(± SD fold, n 〉=4), compared with Schuttgelb, *
P＜0.05; *
P＜0.01. compared with N,
a P＜0.05;
b P＜0.01
Use the half-inhibition concentration (IC50) that SPSS16.0 software carries out data processing and calculates cancer cell multiplication, the results are shown in Table 1.
Shown in table 1 result, 5 pairs of different tumour cells of the compound that is synthesized all have certain inhibited proliferation, but very large for different cyto-inhibition difference on effect.For the same cell, Schuttgelb, compound 5 and synthesis material N-methyl didecylamine are widely different equally to the IC50 value of cytosis.Wherein all greater than 100umol/L, Schuttgelb itself is also larger to the IC50 value of each cell for the IC50 value of each cytosis for synthesis material N-methyl didecylamine.The IC50 value of Schuttgelb is more than 20 times of its derivative I C50 value.Wherein, the IC50 value of compound 5 antithetical phrase s is minimum, is 1.7umol/L, to the IC50 value of other cancer cells also all less than 7umol/L; And its IC50 value to normal people's embryo lung fibroblast HELF is relatively large, reaches 18.07umol/L, proves that it has preferably specific selectivity to cancer cells.
Claims (5)
1. two decyl quaternary ammonium salts of beta-hydroxy protection, it is characterized in that: described pair of decyl quaternary ammonium salt is methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio, structural formula is suc as formula shown in the I,
2. the preparation method of two decyl quaternary ammonium salts of a beta-hydroxy as claimed in claim 1 protection is characterized in that: said method comprising the steps of:
(1) Schuttgelb and methyl-sulfate are at K
2CO
3There is lower reaction, generates 1,3,8-trimethoxy-6-methyl-9, the 10-anthraquinone;
(2) 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone and the reaction of N-bromo-succinimide generate 1,3,8-trimethoxy-6-brooethyl-9, the 10-anthraquinone;
(3) 1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone and Hydrogen bromide reaction generate 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9, the 10-anthraquinone;
(4) 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone and N, the reaction of N-didecyl methylamine, synthesizing methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio.
3. the preparation method of two decyl quaternary ammonium salts of beta-hydroxy according to claim 2 protection, it is characterized in that: concrete steps are as follows:
(1) 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone synthetic: get the 1.6g Schuttgelb and be dissolved in 120～200ml acetone, add 10～12g Anhydrous potassium carbonate, be heated to backflow, under the state that refluxes, slowly drip 4～8ml (CH
3O)
2SO
2, the 20～24h that refluxes is cooled to room temperature, and is concentrated, adds 50～100ml water and stirs 30min, and suction filtration is used washing with acetone, obtains the thick product of yellow powder, and the silica gel column chromatography separation obtains 1,3,8-trimethoxy-6-methyl-9,10-anthraquinone;
(2) 1,3,8-trimethoxy-6-brooethyl-9, synthesizing of 10-anthraquinone: get 0.8g 1,3,8-trimethoxy-6-methyl-9, the 10-anthraquinone, 1.2～1.6g N-bromo-succinimide (NBS), the CCl of 0.2～0.3g benzoyl peroxide and 60～160ml
4Add in the there-necked flask, reflux 15～25h is cooled to room temperature, filters, and filter residue is used respectively CCl
4, H
2O and washing with acetone, the separation of recycle silicon plastic column chromatography obtains 1,3,8-trimethoxy-6-brooethyl-9,10-anthraquinone;
(3) 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone synthetic: add 280～800mg 1,3 in the 100mL there-necked flask, 8-trimethoxy-6-brooethyl-anthraquinone, 30～50mL glacial acetic acid are heated to backflow; Under nitrogen protection, drip 5～9mL 47%(weight ratio) hydrobromic acid aqueous solution, continue back flow reaction 4～6 h; Reactant is poured in 200～300mL frozen water, suction filtration after stirring, and the filter residue oven dry obtains 1,8-dihydroxyl-3-methoxyl group-6-brooethyl-9,10-anthraquinone with the silica gel column chromatography separation;
(4) positive decyl-[2-(4 for methyl two, 5-dihydroxyl-7-methoxyl group-9, the 10-anthraquinonyl) methyl] brometo de amonio synthetic: add 125～500mg1 in the 100mL there-necked flask, 8-dihydroxyl-3-methoxyl group-6-brooethyl-9, the two decyl amine of 10-anthraquinone, 50～150mL chloroform and 127～468 mg N-methyl; Back flow reaction under nitrogen protection is followed the tracks of reaction process with TLC, and 20～24 h afterreactions finish; The rotary evaporation desolventizing, enriched material is with being chloroform-ethanol gradient elution gradually of 4:1 again with volume ratio with chloroform first on the silica gel column chromatography, from last elutriant, separate and obtain methyl two positive decyls-[2-(4,5-dihydroxyl-7-methoxyl group-9,10-anthraquinonyl) methyl] brometo de amonio.
4. the preparation method of two decyl quaternary ammonium salts of beta-hydroxy according to claim 3 protection, it is characterized in that: the elutriant of step (1), (2) described silica gel column chromatography is methylene dichloride; The elutriant of the described silica gel column chromatography of step (3) is chloroform.
5. the application of two decyl quaternary ammonium salts of beta-hydroxy protection as claimed in claim 1 in preparation treatment Cancerous disease medicine.
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| CN102173997A (en) * | 2011-02-24 | 2011-09-07 | 福州大学 | Liver cancer, gastric cancer and cervical cancer-resistant archen derivative and preparation method thereof |
| CN102249941A (en) * | 2011-05-24 | 2011-11-23 | 福州大学 | Monohydroxy di(n-decyl) emodin quaternary ammonium salt with anticancer activity |
| CN102304091B (en) * | 2011-05-30 | 2013-06-05 | 徐州师范大学 | Emodin and fluorouracil combined compound having antitumor activity and preparation method thereof |
| CN103896790B (en) * | 2014-04-29 | 2015-04-15 | 福州大学 | Aloe emodin quaternary ammonium salt as well as preparation and application thereof |
| CN105152941B (en) * | 2015-07-27 | 2017-05-10 | 福州大学 | Anthraquinone compound with both alkylation reactive group and lipophilic positive ion |
| CN105399640B (en) * | 2015-12-22 | 2017-06-06 | 福州大学 | Aloe-emodin bi-quaternary ammonium salt and its preparation with water-soluble and active anticancer |
| CN105924364B (en) * | 2016-05-10 | 2017-11-17 | 福州大学 | Aloe-emodin quaternary ammonium salt Alkyl Iodoacetates with more re-association anticancer mechanisms |
| CN111039806B (en) * | 2019-12-27 | 2021-04-27 | 福州大学 | Hydroxy benzoquinone biquaternary ammonium salt and preparation and application thereof |
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| US4966918A (en) * | 1989-01-27 | 1990-10-30 | Sloan-Kettering Institute For Cancer Research | Derivatives of chryosphanol |
| CN1546451A (en) * | 2003-12-05 | 2004-11-17 | 中山大学 | Hydroxyanthraquinone derivatives and their application in preparation of anticancer medicines |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4966918A (en) * | 1989-01-27 | 1990-10-30 | Sloan-Kettering Institute For Cancer Research | Derivatives of chryosphanol |
| CN1546451A (en) * | 2003-12-05 | 2004-11-17 | 中山大学 | Hydroxyanthraquinone derivatives and their application in preparation of anticancer medicines |
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| Intercalating Agents with Covalent Bond Forming Capability.A Novel Type of Potential Anticancer Agents.2.Derivatives of Chrysophanol and Emodin;Masao Koyama,et al.;《J.Med.Chem.》;19891231;第32卷(第7期);1594-1599 * |
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