CN101077894A - Beta-cyclodextrins chiral selecting agent and preparation method thereof - Google Patents
Beta-cyclodextrins chiral selecting agent and preparation method thereof Download PDFInfo
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Abstract
The present invention provides one kind of beta-cyclodextrin-like chiral selecting agent and its preparation process. The beta-cyclodextrin-like chiral selecting agent in the molecule expression of (ROC6H5NHCO)n(C42H49O34)(N3)m, where, n=21-m, m=1-7, and R is C1-C5 alkyl radical, is prepared through substituting H in the hydroxyl radical of beta-cyclodextrin with ROC6H5NHCO- radical and -N3 radical. Specifically, ROC6H5NHCO- radical substitutes H of the hydroxyl radical in position 2' s, position 3' s and partial position 6' s of beta-cyclodextrin, while -N3 radical substitutes H of the hydroxyl radical in position 6' s of beta-cyclodextrin. The present invention has the advantages of wide material source, mild reaction condition, relatively low cost, etc.
Description
Technical field
The present invention relates to a kind of beta-cyclodextrins chiral selecting agent and preparation method thereof, more particularly, the present invention relates to a kind of beta-cyclodextrins chiral selecting agent that can be used for the chemically bonded chiral stationary phase and preparation method thereof.
Background technology
Determining of the identification of chiral isomer and component content is very important for some chiral drug molecules especially, because different its biological actions of chiral molecules is distinct in the life system.The chirality phenomenon resembles " masonry of building life ", as, carbohydrate tends to have D-form in the vital process, and amino acid almost all exists with the L-configuration, and life is built according to this D, L configuration.Because the function of most drug is to interact by the biological substance with chirality just to manifest.And the isomer of each chiral drug might show as different pharmacological properties at aspects such as activity, the efficacy of a drug, toxicity, transporting mechanism and metabolism passages.Therefore, the chiral purity of medicine becomes the problem of a key in the medicine effect check, all formulate relevant rules in many countries, if there is different chiral structures in promptly a kind of medicine, the content of different chiral isomers must be determined and be described with relevant physiologically active.
Chiral isomer has closely similar physicochemical property, only just shows otherness when interacting to polarized light and with other chiral molecules.Therefore, the quantitative analysis method at the generalization compound commonly used at present is like water off a duck's back for chiral isomer.1966; (Gil-Av E.etal. such as Gil-Av; Tetrahedron Lett.1966; 1009) method of employing gas-chromatography (GC); reported first the method that the chiral isomer of some amino acid whose trifluoroacetyl derivatives is carried out quantitative analysis, the chiral stationary phase that its utilization contains N-TFA base-L-phenylpropylamine acid cyclohexyl is discerned chiral isomer and is separated.After this, the analysis that the isolation technique of chiral stationary phase is widely used in chiral chromatography with separate, so far, be considered to the means of the most effective chiral separation and quantitative analysis.The present more general analytical procedure that grows up therefrom is the high pressure liquid chromatography (HPLC) of band chiral separation post or gas-chromatography (GC), capillary electrophoresis (CE), supercritical fluid chromatography (SFC) etc.
At present, the chiral selector of employing is generally: as disclosed glycopeptide class macrocyclic antibiotic-Norvancomycin in the Chinese patent application 200410021198; As disclosed R-(+)-1 in the Chinese patent application 200510046924,1 '-binaphthylyl-2,2 '-diamine derivative; As disclosed chirr polymer compound in the Chinese patent application 200410013305; And contain derivative of cyclodextrin structure etc.
The molecular formula of cyclodextrin is C
42H
49O
34It is to have the strong-hydrophobicity cavity of being made up of 4,5 hydrogen atoms and glucosides Sauerstoffatom, with the wetting ability periphery that constitutes by hydroxyl (seeing accompanying drawing 1), can form the inclusion title complex with many molecules, and to shape, volume and the polarity of molecule, particularly in the identification of chiral molecules, show very strong selectivity.So owing to its, broad spectrum isolating efficiently to chirality, present many commercialization chiral separation posts all adopt this compounds as chiral selector to the cyclodextrin derivative class as chiral selector.
The multiple technology of utilizing the cyclodextrin derivative class as chiral selector is disclosed in the prior art, for example, disclose in the Chinese patent application 200410013253 utilize cyclodextrin sodium salt and bonding halopropyl on the silica gel surface through solid phase condensation reaction, cyclodextrin bonded silica stationary phase; Disclose in the Chinese patent application 200410068142 and utilized cyclodextrin as chiral selector, bonding matrix is that the glycidyl methacrylate-EDMA ethylene dimethacrylate polymkeric substance of porous build is as chiral stationary phase; 200510051451 of Chinese patent application provide a kind of synthetic method of utilizing beta-cyclodextrin aldehyde to obtain novel alpha-Schiff base derivatized beta-cyclodextrin, this invention is applied in the chiral separation, can carry out qualitative and quantitative research to the optical isomer of amino acid, ferrocene amino-complex, medicine, sulfocompound, alcohol compound, amino-complex and multiple chipal compounds.U.S. Pat P 6,017,458, USP 6,921,02 2 and USP 6,296,768 derivatives that the hydroxyl that discloses on the class cyclodextrin is functionalized, it can be used as chiral selector, be used for bonded silica gel and be prepared into chiral stationary phase, and then be applied to chiral separation post of HPLC etc., wherein, the group of its functionalization can be methyl (CH
3), phenyl (C
6H
5), benzoyl (C
6H
5CO-), carbaniloyl,phenylcarbamoyl (C
6H
5NHCO-), right-phenmethyl (C
6H
5CH
3), naphthyl (C
10H
7), naphthylamino formyl radical (C
10H
7NHCO-) etc.
But the common drawback of the cyclodextrin derivative class chiral selector of prior art is that separation efficiency is not ideal enough.
Thereby, be necessary to provide a kind of and have than high separating efficiency, novel cyclodextrins chiral selecting agent.
Summary of the invention
Purpose of the present invention provide a kind of new, that can be used as chiral selector, contain palkoxy benzene formamyl (CH
3OC
6H
5The beta-cyclodextrin derivative of functional group NHCO-).But this chiral selector bonded silica gel is prepared into chiral stationary phase.
In order to realize purpose of the present invention, on the one hand, the invention provides a kind of beta-cyclodextrins chiral selecting agent, this beta-cyclodextrins chiral selecting agent is by using palkoxy benzene formamyl (ROC
6H
5NHCO-) and azido-(N
3) hydroxyl hydrogen that replaces beta-cyclodextrin forms, its general molecular formula is: [(ROC
6H
5NHCO)
n(C
42H
49O
34) (N
3)
m], wherein, n=21-m, m=1-7, R are the alkyl of 1-5 carbon atom; And the palkoxy benzene formamyl replaces is hydrogen, the hydrogen on 3 hydroxyls and the hydrogen on 6 hydroxyls of part on 2 hydroxyls of beta-cyclodextrin, and the hydrogen on 6 hydroxyls of the beta-cyclodextrin that azido-replaces.
In beta-cyclodextrins chiral selecting agent of the present invention; owing to contain π-power supply in the palkoxy benzene formamyl group; its have a plurality of can with the site (NH of analyte generation interaction of hydrogen bond; C=O); can produce certain space multistory chemical action, and be the group of electron rich alkoxyl group, thereby; this chipal compounds applicable surface is wider, and separating effect is better.
Preferably, in the above-mentioned beta-cyclodextrins chiral selecting agent, R is methyl or ethyl.
In the further preferably above-mentioned beta-cyclodextrins chiral selecting agent, m=1 or m=7.
When R was methyl, beta-cyclodextrins chiral selecting agent had the structure as shown in the formula (I):
Formula (I)
In formula (I), when R is methyl, m=1, be single nitrine that replaces, this beta-cyclodextrins chiral selecting agent is single replacement 6
A-nitrine-20 replaces the amino formyl radical-beta-cyclodextrin of anisole, abbreviates MAZ-MeOPh-β-CD as; When R was methyl, m=7, this beta-cyclodextrins chiral selecting agent was seven replacements 6
A-nitrine-14 replaces the amino formyl radical-beta-cyclodextrin of anisole, abbreviates HAZ-MeOPh-β-CD as.
On the other hand, the present invention also provides the method for preparing above-mentioned beta-cyclodextrins chiral selecting agent, and wherein a kind of preparation method comprises the steps:
(1) with beta-cyclodextrin, right-Methyl benzenesulfonyl chlorine, pyridine beta-cyclodextrin in molar ratio: right-Methyl benzenesulfonyl chlorine: pyridine=1.00: (0.80～0.90): the mixed of (10～14), and react, obtain the intermediate product of white;
(2) step (1) products therefrom and sodiumazide are reacted in deionized water; Filtering reacting liquid, and add sym.-tetrachloroethane in filtrate produces white precipitate, filter white solid product AZ-β-CD;
(3) product with step (2) is dissolved in the pyridine, add the p-methoxyphenyl isocyanic acid, the consumption of the p-methoxyphenyl isocyanic acid of adding and the proportionlity mol ratio of AZ-β-CD are: p-methoxyphenyl isocyanic acid: AZ-β-CD=1: (40.00～45.00); After the reaction, separate purification with column chromatography and promptly make single replacement 6
A-nitrine-20 replaces the amino formyl radical-beta-cyclodextrin of anisole.
Another kind of preparation method then comprises the steps:
(1) with beta-cyclodextrin, iodine, triphenyl phosphorus, imidazoles beta-cyclodextrin: I in molar ratio
2: triphenyl phosphorus: imidazoles=1.00: (8～10): (7～8): the ratio of (7～8) is mixed in solvent, reacts under nitrogen protection, obtains intermediate product;
(2) step (1) products therefrom and sodiumazide are reacted in deionized water; Filtering reacting liquid, and add sym.-tetrachloroethane in filtrate produces white precipitate, filter white solid product AZ-β-CD;
(3) product with step (2) is dissolved in the pyridine, adds the p-methoxyphenyl isocyanic acid and reacts; After the reaction, separate purification with column chromatography and promptly make seven replacements 6
A-nitrine-14 replaces the amino formyl radical-beta-cyclodextrin of anisole.
The step of these two kinds of methods (2), raw materials used, the reaction conditions basically identical of step (3).
The compound of the beta-cyclodextrin structure that the present invention makes can be bonded to it on carrier by the method for chemical bonding.Chiral selector of the present invention is suitable on high pressure liquid chromatography (HPLC), gas-chromatography (GC), capillary electrophoresis (CE), the supercritical fluid chromatography instruments such as (SFC) as the chiral separation stationary phase.Prepared stationary phase has very strong chiral recognition ability and good stability, can realize separating to the chiral drug of number of different types.
Compared with prior art, the present invention has following advantage or effect:
1, products material wide material sources of the present invention, reaction conditions gentleness, cost are lower;
2, product of the present invention is because to contain π-power supply be palkoxy benzene formamyl group, have a plurality of can with the site of analyte generation interaction of hydrogen bond (NH, C=O), can produce certain space multistory chemical action, thereby isolating chipal compounds is widely applicable, and effect is good;
3, product of the present invention is owing to be substituted with azido group on the hydroxyl of cyclodextrin, make this product be easy to be connected to silica gel by bonding as chiral selector, on the quartz capillary inwall, thereby can make stable chiral stationary phase, be used for high pressure liquid chromatography (HPLC) or gas-chromatography (GC), capillary electrophoresis (CE), supercritical fluid chromatography (SFC) etc.;
4, product of the present invention makes us can regulate and control firm degree, density and chiral selectivity that chiral selector is bonded to matrix because the replacement azido group of different numbers is arranged on the hydroxyl of cyclodextrin.
Description of drawings
Fig. 1 is the beta-cyclodextrin molecular structure, and wherein, a is the molecular structure of beta-cyclodextrin; B is the schematic arrangement of beta-cyclodextrin.
Embodiment
The preparation of embodiment 1:MAZ-MeOPh-β-CD)
(1) 6
AThe preparation of-O-P-Methyl benzenesulfonyl group-beta-cyclodextrin:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, 30ml makes solvent with pyridine, adds beta-cyclodextrin 20mmol successively, and is right-Methyl benzenesulfonyl chlorine 16mmol.The control reaction conditions is 25 ± 2 ℃, and the reaction times is 20h; After reaction finishes, remove pyridine under reduced pressure, wash 3 times with 200ml acetone at every turn, obtain after the vacuum-drying about the product TS-β-CD8 gram of white.
(2) 6
A-nitrine-6
AThe preparation of-deoxidation-beta-cyclodextrin:
Get step (1) gained TS-β-CD 6mmol and sodiumazide 124mmol, add in the 400ml deionized water, in the three-necked bottle that magnetic stirring apparatus, thermometer and reflux condensing tube are housed, control reaction temperature is 60～65 ℃, and the reaction times is 4h; Filtering reacting liquid adds sym.-tetrachloroethane 2ml in filtrate, produce white precipitate, filters.Solid product is washed 2-3 time with boiling water, and vacuum-drying gets about white solid product AZ-β-CD 6 grams.
(3) single replacement 6
A-nitrine-20 replaces the preparation to the amino formyl radical-beta-cyclodextrin of anisole:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, under the normal temperature, the product A Z-β-CD 5mmol of step (2) is dissolved in the 90ml pyridine, add 200mmol p-methoxyphenyl isocyanic acid; Reaction 24h.Add 300ml water in product, come extraction product with the 450ml ethyl acetate.Organic phase is concentrated, separate purification with column chromatography (is that hexanaphthene-ethyl acetate of 1: 1 is as eluent with volume ratio) and make chiral selector MAZ-MeOPh-β-CD of the present invention about 10 and restrain.
The preparation of embodiment 2:MAZ-MeOPh-β-CD)
(1) 6
AThe preparation of-O-P-Methyl benzenesulfonyl group-beta-cyclodextrin:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, 30ml makes solvent with pyridine, adds beta-cyclodextrin 20mmol successively, and is right-Methyl benzenesulfonyl chlorine 18mmol.The control reaction conditions is 25 ± 2 ℃, and the reaction times is 24h; After reaction finishes, remove pyridine under reduced pressure, wash 3 times with 200ml acetone at every turn, obtain after the vacuum-drying about product TS-β-CD 8.8 grams of white.
(2) 6
A-nitrine-6
AThe preparation of-deoxidation-beta-cyclodextrin:
Get step (1) gained TS-β-CD 6mmol and sodiumazide 132mmol, add in the 400ml deionized water, in the three-necked bottle that magnetic stirring apparatus, thermometer and reflux condensing tube are housed, control reaction temperature is 85～90 ℃, and the reaction times is 4h; Filtering reacting liquid adds sym.-tetrachloroethane 5ml in filtrate, produce white precipitate, filters.Solid product is washed 2-3 time with boiling water, and vacuum-drying gets about white solid product AZ-β-CD 7 grams.
(3) single replacement 6
A-nitrine-20 replaces the preparation to the amino formyl radical-beta-cyclodextrin of anisole:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, under the normal temperature, the product A Z-β-CD 5mmol of step (2) is dissolved in the 90ml pyridine, add 225mmol p-methoxyphenyl isocyanic acid; Reaction 30h.Add 300ml water in product, come extraction product with the 450ml ethyl acetate.Organic phase is concentrated, separate purification with column chromatography (is that hexanaphthene-ethyl acetate of 1: 1 is as eluent with volume ratio) and make chiral selector MAZ-MeOPh-β-CD of the present invention about 11 and restrain.
The structure of chiral selector MAZ-MeOPh-β-CD that embodiment 1 and embodiment 2 make records by ultimate analysis, infrared spectra (IR) and nucleus magnetic resonance (NMR) and confirms.
Chiral selector MAZ-MeOPh-β-CD:IR (cm
-1) 3407,3318 (N-H str), 2101 (N
3Str), 1719 (C=O str), 1610,1543,1489 (C=C aromatic nucleus str), 1051 (sym C-O-C);
13C-NMR (CDCl
3) δ (ppm) 153.73,153.12,152.65 (Ar-NH-CO-), 136.97,136.79,123.49,119.65,118.90 (aromatic nucleus hydrogen-containing carbon atoms), 128.77, (128.50 aromatic nucleus quaternary carbon atom), 98.75 (C-1), 78.64 (C-4), 73.48 (C-2), 71.66 (C-3), 60.22 (CH
3O), 52.12 (C-6a-N
3); ESI-MS m/z is by molecular formula C
202H
208O
74N
23Calculate molecular weight 4141, measured value 4164 is by [M+Na
+]; Ultimate analysis is by molecular formula C
202H
208O
74N
23Calculated value: C, 58.53%; H, 5.02%; N, 7.78%. measured value: C, 58.25%; H, 5.20%; N, 7.67%.
The preparation of embodiment 3:HAZ-MeOPh-β-CD)
(1) seven replaces 6
AThe preparation of-I-beta-cyclodextrin:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, 60ml makes solvent with ethylene dichloride, adds beta-cyclodextrin 20mmol successively, iodine 160mmol, triphenyl phosphorus 140mmol, imidazoles 140mmol.The control reaction conditions is 25 ± 2 ℃, is 3h in the following reaction times of nitrogen protection; After reaction finishes, remove by filter filtrate, solid is washed 3 times with the 80ml ether at every turn, obtains xanchromatic product seven after the vacuum-drying and replaces 6
AAbout-I-β-CD 11 grams.
(2) seven replace 6
A-nitrine-6
AThe preparation of-deoxidation-beta-cyclodextrin:
Get step (1) gained seven and replace 6
A-I-β-CD 6mmol and sodiumazide 848mmol add in the 600ml deionized water, and in the three-necked bottle that magnetic stirring apparatus, thermometer and reflux condensing tube are housed, control reaction temperature is 60～65 ℃, and the reaction times is 4h; Filtering reacting liquid adds sym.-tetrachloroethane 2ml in filtrate, produce white precipitate, filters.Solid product is washed 2-3 time with boiling water, and vacuum-drying gets white solid product seven and replaces about AZ-β-CD 11 grams.
(3) seven replace 6
A-nitrine-14 replaces the preparation to the amino formyl radical-beta-cyclodextrin of anisole:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, under the normal temperature, the product seven of step (2) is replaced AZ-β-CD 5mmol be dissolved in the 90ml pyridine, add 70mmol p-methoxyphenyl isocyanic acid; Reaction 24h.Add 300ml water in product, come extraction product with the 450ml ethyl acetate.Organic phase is concentrated, separate purification with column chromatography (is that hexanaphthene-ethyl acetate of 1: 1 is as eluent with volume ratio) and make chiral selector HAZ-MeOPh-β-CD of the present invention about 7 and restrain.
The preparation of embodiment 4:HAZ-MeOPh-β-CD)
(1) seven replaces 6
AThe preparation of-I-beta-cyclodextrin:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, 60ml makes solvent with ethylene dichloride, adds beta-cyclodextrin 20mmol successively, iodine 200mmol, triphenyl phosphorus 160mmol, imidazoles 160mmol.The control reaction conditions is 25 ± 2 ℃, is 3h in the following reaction times of nitrogen protection; After reaction finishes, remove by filter filtrate, solid is washed 3 times with the 80ml ether at every turn, obtains xanchromatic product seven after the vacuum-drying and replaces 6
AAbout-I-β-CD 12 grams.
(2) seven replace 6
A-nitrine-6
AThe preparation of-deoxidation-beta-cyclodextrin:
Get step (1) gained seven and replace 6
A-I-β-CD 6mmol and sodiumazide 924mmol add in the 600ml deionized water, and in the three-necked bottle that magnetic stirring apparatus, thermometer and reflux condensing tube are housed, control reaction temperature is 85～90 ℃, and the reaction times is 4h; Filtering reacting liquid adds sym.-tetrachloroethane 5ml in filtrate, produce white precipitate, filters.Solid product is washed 2-3 time with boiling water, and vacuum-drying gets white solid product seven and replaces about AZ-β-CD 13 grams.
(3) seven replace 6
A-nitrine-14 replaces the preparation to the amino formyl radical-beta-cyclodextrin of anisole:
In the three-necked bottle that magnetic stirring apparatus and thermometer are housed, the product seven replacement AZ-β-CD 5mmol with step (2) under the normal temperature are dissolved in the 90ml pyridine, add 80mmol p-methoxyphenyl isocyanic acid; Reaction 24h.Add 300ml water in product, come extraction product with the 450ml ethyl acetate.Organic phase is concentrated, separate purification with column chromatography (is that hexanaphthene-ethyl acetate of 1: 1 is as eluent with volume ratio) and make chiral selector HAZ-MeOPh-β-CD of the present invention about 7 and restrain.
The structure of chiral selector HAZ-MeOPh-β-CD that embodiment 3 and embodiment 4 make records by ultimate analysis, infrared spectra (IR) and nucleus magnetic resonance (NMR) and confirms.Chiral selector HAZ-MeOPh-β-CD:IR (cm
-1) 3407,3318 (N-H str), 2103 (N
3Str), 1719 (C=O str), 1610,1543,1489 (C=C aromatic nucleus str), 1051 (sym C-O-C);
13C-NMR (CDCl
3) δ (ppm) 153.73,153.12,152.65 (Ar-NH-CO-), 136.97,136.79,123.49,119.65,118.90 (aromatic nucleus hydrogen-containing carbon atoms), 128.77, (128.50 aromatic nucleus quaternary carbon atom), 98.75 (C-1), 78.64 (C-4), 73.48 (C-2), 71.66 (C-3), 60.22 (CH
3O), 52.12 (C-6a-N
3); ESI-MS m/z is by molecular formula C
154H
160O
56N
35Calculate molecular weight 3394, measured value 3417 is by [M+Na
+]; Ultimate analysis is by molecular formula C
154H
160O
56N
35Calculated value: C, 54.45%; H, 4.71%; N, 14.43%. measured value: C, 54.75%; H, 5.00%; N, 14.57%.
Claims (7)
1, a kind of beta-cyclodextrins chiral selecting agent, this beta-cyclodextrins chiral selecting agent are by using palkoxy benzene formamyl (ROC
6H
5NHCO-) and azido-(N
3) hydroxyl hydrogen that replaces beta-cyclodextrin forms, its general molecular formula is: [(ROC
6H
5NHCO)
n(C
42H
49O
34) (N
3)
m], wherein, n=21-m, m=1-7, R are the alkyl of 1-5 carbon atom; And the palkoxy benzene formamyl replaces is hydrogen, the hydrogen on 3 hydroxyls and the hydrogen on 6 hydroxyls of part on 2 hydroxyls of beta-cyclodextrin, and the hydrogen on 6 hydroxyls of the beta-cyclodextrin that azido-replaces.
2, beta-cyclodextrins chiral selecting agent as claimed in claim 1 is characterized in that, R is a methyl.
3, beta-cyclodextrins chiral selecting agent as claimed in claim 1 is characterized in that, R is an ethyl.
4, as the described beta-cyclodextrins chiral selecting agent of one of claim 1-3, it is characterized in that m=1.
5, as the described beta-cyclodextrins chiral selecting agent of one of claim 1-3, it is characterized in that m=7.
6, a kind of method for preparing beta-cyclodextrins chiral selecting agent, this method comprises the steps:
(1) with beta-cyclodextrin, right-Methyl benzenesulfonyl chlorine, pyridine beta-cyclodextrin in molar ratio: right-Methyl benzenesulfonyl chlorine: pyridine=1.00: (0.80～0.90): the mixed of (10～14), and react, obtain the intermediate product of white;
(2) step (1) products therefrom and sodiumazide are reacted in deionized water; Filtering reacting liquid, and add sym.-tetrachloroethane in filtrate produces white precipitate, filter white solid product AZ-β-CD;
(3) product with step (2) is dissolved in the pyridine, adds the p-methoxyphenyl isocyanic acid and reacts; After the reaction, separate purification with column chromatography and promptly make single replacement 6
A-nitrine-20 replaces the amino formyl radical-beta-cyclodextrin of anisole.
7, a kind of method for preparing beta-cyclodextrins chiral selecting agent, this method comprises the steps:
(1) with beta-cyclodextrin, iodine, triphenyl phosphorus, imidazoles beta-cyclodextrin: I2 in molar ratio: triphenyl phosphorus: imidazoles=1.00: (8～10): (7～8): the ratio of (7～8) is mixed in solvent, reacts under nitrogen protection, obtains intermediate product;
(2) step (1) products therefrom and sodiumazide are reacted in deionized water; Filtering reacting liquid, and add sym.-tetrachloroethane in filtrate produces white precipitate, filter white solid product AZ-β-CD;
(3) product with step (2) is dissolved in the pyridine, adds the p-methoxyphenyl isocyanic acid and reacts; After the reaction, separate purification with column chromatography and promptly make seven replacements 6
A-nitrine-14 replaces the amino formyl radical-beta-cyclodextrin of anisole.
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| CN101955552A (en) * | 2010-09-06 | 2011-01-26 | 南京理工大学 | Monosubstituted alkyl bond-connected amino and imidazolyl double-front point centre beta-cyclodextrin and preparation method thereof |
| CN102225974A (en) * | 2011-05-09 | 2011-10-26 | 南京理工大学 | A kind of 6-alkylimidazolium-6-ammonium-β-cyclodextrin with double substituted double positive center and preparation method thereof |
| CN103910812A (en) * | 2014-03-06 | 2014-07-09 | 广州研创生物技术发展有限公司 | Beta-cyclodextrin derivative and preparation method thereof, and polyurea-bond cyclodextrin chiral stationary phase prepared from beta-cyclodextrin derivative |
| CN105312039A (en) * | 2014-07-17 | 2016-02-10 | 中国科学院大连化学物理研究所 | Beta-cyclodextrin functionalized chiral stationary phase, preparation and application thereof |
| CN112010724A (en) * | 2020-09-04 | 2020-12-01 | 南京师范大学常州创新发展研究院 | Method for separating naphthalene derivative isomer and determining binding constant of naphthalene derivative isomer and cyclodextrin |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6017458A (en) * | 1997-08-27 | 2000-01-25 | National University Of Singapore | Separating materials for chromatography and electrophoresis applications comprising regiodefined functionalised cyclodextrins chemically bonded to a support via urethane functionalities |
| CN1289184C (en) * | 2004-06-02 | 2006-12-13 | 武汉大学 | Cyclodextrin linkage silica gel fixed phase, preparing method and use thereof |
| CN1603817A (en) * | 2004-11-12 | 2005-04-06 | 中国科学院上海有机化学研究所 | High performance liquid chromatography organic phase monolithic column bonded with cyclodextrin compounds and preparation method thereof |
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| CN101955552A (en) * | 2010-09-06 | 2011-01-26 | 南京理工大学 | Monosubstituted alkyl bond-connected amino and imidazolyl double-front point centre beta-cyclodextrin and preparation method thereof |
| CN101955552B (en) * | 2010-09-06 | 2013-01-23 | 南京理工大学 | Monosubstituted alkyl bond-connected amino and imidazolyl double-front point centre beta-cyclodextrin and preparation method thereof |
| CN102225974A (en) * | 2011-05-09 | 2011-10-26 | 南京理工大学 | A kind of 6-alkylimidazolium-6-ammonium-β-cyclodextrin with double substituted double positive center and preparation method thereof |
| CN103910812A (en) * | 2014-03-06 | 2014-07-09 | 广州研创生物技术发展有限公司 | Beta-cyclodextrin derivative and preparation method thereof, and polyurea-bond cyclodextrin chiral stationary phase prepared from beta-cyclodextrin derivative |
| CN103910812B (en) * | 2014-03-06 | 2016-05-11 | 广州研创生物技术发展有限公司 | Beta-cyclodextrin derivative and its preparation method and many ureas key cyclodextrin chiral prepared therefrom are fixed phase |
| CN105312039A (en) * | 2014-07-17 | 2016-02-10 | 中国科学院大连化学物理研究所 | Beta-cyclodextrin functionalized chiral stationary phase, preparation and application thereof |
| CN105312039B (en) * | 2014-07-17 | 2017-10-13 | 中国科学院大连化学物理研究所 | A kind of beta cyclodextrin functionalization chiral stationary phase and its preparation and application |
| CN112010724A (en) * | 2020-09-04 | 2020-12-01 | 南京师范大学常州创新发展研究院 | Method for separating naphthalene derivative isomer and determining binding constant of naphthalene derivative isomer and cyclodextrin |
| CN112010724B (en) * | 2020-09-04 | 2023-09-08 | 南京师范大学常州创新发展研究院 | Naphthalene derivative isomer separation and cyclodextrin binding constant determination method |
| CN113768151A (en) * | 2021-08-31 | 2021-12-10 | 海南师范大学 | Preparation method and detection method of tea polyphenol in Baisha green tea |
| CN113768151B (en) * | 2021-08-31 | 2024-05-31 | 海南师范大学 | Preparation method and detection method of tea polyphenol in white sand green tea |
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