CN102924670A - Synthesis and application of novel cyclodextrin polymer chiral resolving agent - Google Patents
Synthesis and application of novel cyclodextrin polymer chiral resolving agent Download PDFInfo
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Abstract
The invention discloses a synthesis method of a novel cyclodextrin polymer chiral resolving agent. According to the synthesis method, a derivative cyclodextrin chiral resolving agent having homogeneous substitution positions and substitution degree is obtained through a novel synthesis route; and the novel chiral resolving agent is prepared by performing polymerization and sulfonation reaction on cyclodextrin and can be used instead of inhomogeneous derivative cyclodextrin for the formation of a polymer through connection. The synthesis method has the advantages of simplicity, fewer steps, easy purification and recovery, low synthesis cost and the like, realizes the homogenization of cyclodextrin derivative substitution on the statistic meaning, enhances the column efficiency and degree of separation, and simultaneously improves cyclodextrin solubility and reduces Joule heat during electrophoretic separation. By synthesizing and characterizing the sulfonated beta-cyclodextrin polymer, results prove the advantages of the design concept of the invention; and the polymer can be used as a buffer solution additive for chiral compound separation through capillary electrophoresis.
Description
Technical field
The present invention relates to a class novel chiral resolving agent---synthetic method and the application of sulfonated cyclodextrin, this base polymer can be used as chiral resolving agent and is added in the capillary electrophoresis running buffer, be used for the separation of capillary electrophoresis chipal compounds, has synthetic method simple, step is few, purification and recovery are easily, synthetic low cost and other advantages, and realized that the cyclodextrin derivatize is substituted in the homogenization on the statistical significance, improve post effect and resolution, improved simultaneously cyclodextrin solubility, joule heating when having reduced electrophoretic separation, be conducive to large-scale industrialization and use, have preferably economic worth and application prospect.
Background technology
Chirality is natural a kind of universal phenomenon, consists of the base substance of organism, all is chiral molecules such as amino acid, carbohydrate etc.The chiral separation especially fractionation of chiral drug mainly has the meaning of two aspects: pharma-toxicology meaning and huge economic worth.
Compare with technology such as high performance liquid chromatography (HPLC), gas-chromatographies (GC), with capillary electrophoresis (CE, capillary electrophoresis) technology is carried out chiral separation to have expense low, analysis speed is fast, chiral derivatization abbreviation list, required sample size is few, sensitivity and post effect advantages of higher.
For the CE chiral separation, utilizing chiral selector to make up the stereoselectivity environment is the key that realizes that enantiomorph is distinguished.The kind of chiral selector is a lot, and wherein, cyclodextrin (CDs, cyclodextrins) and derivative thereof are class chiral resolving agents that is most widely used, and it demonstrates good chiral recognition ability to the different chipal compounds of various structures.The space structure of cyclodextrin has a hydrophobic tubbiness cavity, the difference of the clathration between cavity and enantiomorph, and the variation of mobility has caused the separation of enantiomorph behind the inclusion.Natural cyclodextrin and neutral derivant thereof, such as beta-cyclodextrin, though successfully separated some chipal compounds, but its solubleness is low and its practical application that has been difficult to split the drawbacks limit such as neutral enantiomorph, article " Fanali S.J.Chromatogr.A; 1996,735:77 ~ 121. " referring to Salvatore Fanali.Charged CDs derivative can be opened neutral Chiral Separation because having self electrophoretic mobility.Cyclodextrin is carried out derivatize not only can improve selectivity, can also enlarge the chiral separation scope.
The similar hydroxyl of a plurality of reactive behavioies is arranged in the cyclodextrin molecular, derivatize product take this cyclodextrin as parent also has its limitation: 1) the charged CDs derivative different ions group substitution value mixture different with the position of substitution normally, can have a negative impact to the separation of chipal compounds, low etc. such as poor reproducibility, post effect; 2) charged CDs derivative is high to the ionic strength contribution of damping fluid, produces higher running current thereupon, has increased the joule heating in the electrophoresis; 3) be difficult to realize recovery to the charged CDs derivative of costliness.The chirality selective power of Sulfonated cyclodextrin derivative is very strong, range of application very extensively, lot of documents has been put down in writing various types of sulfonated cyclodextrin and has been applied to the chirality capillary electrophoresis separation.Use the cyclodextrin that mixes replacement inevitably to cause chiral selectivity to descend, the post effect reduces, the problem of batch poor reproducibility, analyze scholars and adopted various chemosynthesis means, obtain the charged derivative of sulfonated cyclodextrin of high purity homogenization with expectation from the angle of chemical structure.Relatively be typically the isostructure a series of sulfonated cyclodextrin enantiomorph of Vincent, referring to " Vincent J B, Sokolowski A D; Nguyen T, Anal.Chem.1997,69:4226 ~ 4233 " and " Vincent J B; Kirby D M; Nguyen T V, Vigh G, Anal.Chem.1997; 69 (21): 4419 ~ 4428 " etc., they have used loaded down with trivial details chemosynthesis process, have obtained single sulfonated enantiomorph, and successful realization chiral separation.But the preparation process of this class negative electricity CDs derivative comprises protection and the deprotection of hydroxyl, and each goes on foot the complex steps such as chromatographic column purifying of product, and product is not only expensive and can't recycling, is widely used therefore limited to a great extent it.
In addition, the people such as Fu-Tai A.Chen high sulfonation cyclodextrin more early also is a class, and referring to " Chen F T; Shen G, Evangelista R A, J.Chromatogr.A; 2001; 924:523 ~ 532 " and " Chen F T, Evangelista R, American lavoratory; 2002; 8:30 ~ 37 " etc., they are by the spherical symmetric on the space, thereby has reached the purpose of acquisition homogenization cyclodextrin.The characteristics of the chemical structure of cyclodextrin own cause preparation and reclaim the cyclodextrin of homogeneous on these chemical structures very difficult, so that price is very expensive.
Summary of the invention
For above-mentioned prior art, the invention provides a kind of synthetic method of novel cyclodextrin chiral resolving agent, obtain the derivatized cyclodextrin chiral resolving agent of the position of substitution and substitution value homogeneous with novel synthetic thinking, to replace inhomogenous derivatized cyclodextrin and connect into polymkeric substance, it is simple that this method not only has synthetic method, step is few, purification and recovery are easily, synthetic low cost and other advantages, and realized that the cyclodextrin derivatize is substituted in the homogenization on the statistical significance, improve post effect and resolution, improved simultaneously cyclodextrin solubility, joule heating when having reduced electrophoretic separation.By synthetic sulfonated beta cyclo dextrin polymer and to the advantage of its characterization result proof design philosophy of the present invention of carrying out, and this polymkeric substance is respectively applied to during the CE chipal compounds separates as Buffer additive.
Main purpose of the present invention is as follows:
1. the difficult problems such as to set forth a kind of novel chiral resolving agent design philosophy water-soluble low to solve natural cyclodextrin (such as beta-cyclodextrin) as example to prepare charged cyclodextrin, and charged CDs derivative ionic strength is high, substitution value and the position of substitution are difficult to control, expensive;
2. prepare chiral resolving agent novel, efficient, inexpensive, recyclable recycling---sulfonated beta cyclo dextrin polymer by Raolical polymerizable.
3. sulfonated cyclodextrin is added into and is used for the chipal compounds fractionation in the CE damping fluid.
In order to solve the problems of the technologies described above, the chemical structure of the novel sulfonated cyclodextrin of the present invention is:
Wherein:
Represent beta-cyclodextrin, m, n are natural number and equal 〉=1.
The synthetic method of the novel sulfonated cyclodextrin of the present invention is: prepared through polymerization and sulfonated reaction by cyclodextrin, the reaction scheme of its preparation is as follows:
Wherein:
Represent beta-cyclodextrin, m, n are natural number and equal 〉=1.
Step according to the synthetic sulfonated beta cyclo dextrin polymer (SA-β-CDP, Sulfated acrylamide β-CD polymer) of above-mentioned reaction scheme is as follows:
1) under the room temperature beta-cyclodextrin of purifying is dissolved in 2% ~ 5% the sodium hydroxide solution; be stirred to fully dissolving; slowly drip the glycidyl allyl ether (AGE) of 1 ~ 5 times of equivalent under the nitrogen protection; holding temperature is reacted end in 36 ~ 60h hour at 40 ~ 65 ℃, and dilute hydrochloric acid conditioned reaction liquid is to neutral; and adding acetone precipitation product; filter, dry to get white solid allyl group cyclodextrin, porphyrize is for subsequent use.
2) vitriol oil is cooled to 0 ℃ in cryosel is bathed after, slowly add allyl group cyclodextrin fine powder, control temperature＜5 ℃, behind magnetic agitation reaction 1.5 ~ 3h with reaction solution to large water gaging, add the calcium carbonate neutralization, the elimination calcium sulfate precipitation adds ethanol in the filtrate, low temperature spends the night, filter, regulate filtrate pH to 10.50 with yellow soda ash, filter, filtrate decompression is concentrated.Concentrated solution is poured in a large amount of dehydrated alcohols, is precipitated, and precipitates dry that light yellow solid is sulfonated allyl group cyclodextrin.
The sulfonated allyl group cyclodextrin that 3) will synthesize is dissolved in the water, and vacuum outgas 30-60min adds the acrylamide (AM) of 1 ~ 5 times of equivalent, stirs 20-60min under the nitrogen, adds the Potassium Persulphate initiation reaction, 40 ~ 65 ℃ of lower stirring reactions 24 ~ 48 hours.After reacting completely, pour molecular weight cut-off after reaction solution diluted a little into and be in 14,000 the dialysis tubing and dialyse, freeze-drying obtains sulfonated cyclodextrin product behind the dialysate filter.
The sulfonated cyclodextrin of gained among the present invention, by the thin layer chromatography, infrared spectroscopy, the means such as elemental microanalysis method, Indirect UV method characterize, and the specific embodiments principle is as follows:
1) tlc
Thin-layer chromatography is again the thin plate chromatography, is a kind of in the chromatography, is a kind of very important experimental technique of sharp separation and a small amount of material of qualitative analysis.During experiment sample is dripped on the zero line of thin layer plate airing or dry up rearmounted thin layer plate in the separation chamber that fills developping agent with kapillary.Treat that solvent front, takes out chromatosheet approximately near the 1cm time from the top, dry after spray with developer, or under ultraviolet lamp, develop the color.
2) infrared spectroscopy
Infrared spectra (IR) often is used to the detection of product characteristic group in the chemosynthesis reaction, and we also characterize by IR p-sulfonic acid beta cyclo dextrin polymer in the test.
3) elemental microanalysis method
By measuring C element, the S constituent content of different sulfopropyl ether ring dextrin monomers, can calculate by the constituent content ratio content of sulfonate radical in the product, then obtain the average substitution degree of product.
4) Indirect UV method
The Indirect UV method can be used for analyzing those with detection in the capillary electrophoresis does not have the material of enough strong uv-absorbing.Here contrasted the substitution value homogeneity of sulfonated cyclodextrin and sulfonated cyclodextrin with the Indirect UV method.The background damping fluid is selected tosic acid-three (methylol) aminomethane (Tris) damping fluid with uv-absorbing, tosic acid wherein provides background absorption, negative peak will occur when the sulfopropyl ether ring dextrin that uv-absorbing is weak and sulfopropyl ether ring cyclodextrin poly compound process detection window.In order better to prove the electrical of molecules detected, we have added DMF as neutral marker in sample solution.Replace homogeneity by Information Authentication polymkeric substance such as peak area size and appearance time and numbers.
The novel sulfonated cyclodextrin that the present invention synthesized separates chiral compound enantiomer in capillary electrophoresis as Buffer additive, and concrete technical scheme is as follows:
Prepare the matrix damping fluid of different pH values, behind 0.45 μ m water system membrane filtration, get the electrophoresis running buffer to wherein adding sulfonated cyclodextrin; Use capillary electrophoresis apparatus equipment, after kapillary activation flushing, in kapillary, be full of the damping fluid that does not contain sulfonated cyclodextrin, in kapillary, push one section damping fluid that contains polymkeric substance, make it not arrive the detection window place, sample introduction is put into the kapillary two ends damping fluid making alive electrophoresis that does not contain sulfonated cyclodextrin.Open electrophoretic voltage, the electrophoresis field intensity is 50-1000V/cm, selects detection method test chipal compounds according to the character of different chiral drugs; Separation condition is: it is 0.1%-6.0% that described sulfonated cyclodextrin adds concentration; Electrophoresis running buffer pH1.50-12.50; Electrophoresis running buffer concentration is 5-200mmol/L; Running voltage 1-11kV; Temperature 17-37 ℃; Organic additive content 0-50%.
Compared with prior art, the invention has the beneficial effects as follows:
The present invention has synthesized sulfonated cyclodextrin and sulfonated cyclodextrin by radical polymerization, and used synthetic method is simple, and step is few, and agents useful for same economy will be far superior to other single monobasic derivatized cyclodextrin chiral resolving agents on synthetic cost.The more important thing is, the preparation cyclodextrin that this patent proposes has obtained confirmation with the thought that obtains cyclodextrin derivative the position of substitution and substitution value homogeneous by chiral separation, in addition, this polymkeric substance is also showing following advantage: a. for the small molecules cyclodextrin derivative in the CE chiral separation, the cyclodextrin of derivatize is less to the contribution of CE running current; B. synthetic derivatized cyclodextrin polymkeric substance can carry out recycling by simple methods such as dialysis.
Description of drawings
Fig. 1 is the sulfonated beta cyclo dextrin polymer that obtains of embodiment 1 (the Infrared Characterization spectrogram of SA-β-CDP);
Fig. 2 A Indirect UV method is measured the sulfonated beta-cyclodextrin (electrophorogram of SA-β-CD);
Fig. 2 B Indirect UV method is measured the electrophorogram of SA-β-CDP;
SA-β under Fig. 3 A optimal conditions-CDP separates the electrophorogram of Proprasylyte;
SA-β under Fig. 3 B optimal conditions-CDP separates the electrophorogram of terbutaline;
SA-β under Fig. 3 C optimal conditions-CDP separates the electrophorogram of warfarin;
SA-β under Fig. 3 D optimal conditions-CDP separates the electrophorogram of promethazine;
Fig. 4 A is the electrophorogram that the SA-β-CDP of different concns separates terbutaline;
Fig. 4 B is the electrophorogram that the SA-β-CDP of different concns separates Proprasylyte;
Fig. 5-1 is to Fig. 5-the 3rd, and running buffer pH is on the electrophorogram of the impact of promethazine transition time and resolution.
Embodiment
The present invention proposes the design philosophy that substitution value and the position of substitution behind the cyclodextrin derivatize easily reach the homogeneous on the statistical significance, thereby in chiral separation, obtain higher fractionation effect, and the derivatized cyclodextrin polymkeric substance has water-soluble height, economical, generation current is low during electrophoresis, the advantages such as recyclable recycling, this patent has been developed synthetic method and the application in the capillary electrophoresis chipal compounds splits thereof of sulfonated cyclodextrin on this basis, tell about by the following examples detailed process of the present invention, it is convenience in order to understand that embodiment is provided, and never is restriction the present invention.
Embodiment 1:SA-β-CDP's is synthetic
8.00g(7.05mmol) β-CD of purifying is dissolved in 20mL3%(w/v) in the NaOH solution, be stirred to fully dissolving, slowly drip 0.84mL(7.05mmol under the nitrogen protection) AGE, holding temperature is at 50 ℃, reaction 48h.After reaction finishes,, and pour in isopyknic acetone and be settled out product to neutral with hydrochloric acid neutralization reaction liquid, filter, dry to get white solid 5.02g, productive rate is 56.82%.
Get the 13mL80% vitriol oil, cryosel is cooled to 0 ℃ in bathing.The ACD that 5.02g is ground into fine powder slowly joins in the above-mentioned vitriol oil, keeps below temperature＜5 ℃ magnetic agitation reaction 2h.After reaction is finished reaction solution is poured in the 225mL water, added 25g CaCO
3Neutralisation of sulphuric acid, elimination CaSO
4Precipitation adds 50mL ethanol in the filtrate, low temperature spends the night.The elimination precipitation, filtrate is used Na
2CO
3Regulate pH to 10.50.The elimination precipitation, filtrate decompression is concentrated.Concentrated solution is poured in the 150mL dehydrated alcohol, is precipitated in a large number, precipitates the dry light yellow solid 4.20g of getting, and productive rate is 72.16%.
Top synthetic sulfonation ACD4.20g is dissolved in the 8mL water, and vacuum outgas 30min adds 0.32g AM again, stirs 30min under the nitrogen, adds 0.03g K
2S
2O
8, 50 ℃ of lower stirring reaction 24h.After reacting completely, pour molecular weight cut-off after reaction solution diluted a little into and be that dialysis is to remove unreacted monomer in 14,000 the dialysis tubing, freeze-drying obtains polymkeric substance 0.38g behind the dialysate filter, and productive rate is 8.41%.
Embodiment 2: utilize respectively tlc, infra-red chromatography and elemental microanalysis method that the embodiment 1 synthetic product that obtains is characterized
(1) tlc characterizes
With kapillary the ACD sample drop is added on the zero line of thin layer plate, dries up rearmounted thin layer plate in the separation chamber that fills developping agent, TLC analyzes, and developping agent is: Virahol: water: ammoniacal liquor=5:2:2, the Rf value Rf=0.63 of ACD, the Rf=0.43 of β-CD.
(2) infra-red chromatography
(infrared absorption spectra of SA-β-CDP) and poly-S-ACD and polyacrylamide (PAM) can find out that the Absorption Characteristics of multipolymer combines the characteristic absorbance of poly-S-ACD and polyacrylamide to have contrasted the S-ACD/AM multipolymer among Fig. 1.1030cm
-1C-O stretching vibration absorption peak in place's is from ehter bond in the cyclodextrin molecular of ACD and the side chain, 3418cm
-1The place is the stretching vibration absorption peak of O-H in the cyclodextrin molecular, and 1657cm
-1And 3192cm
-1The absorption peak at place is respectively from the stretching vibration of C=O and N-H in the acrylamide skeleton.Sulfonated β-CD polymkeric substance has above-mentioned several charateristic avsorption band simultaneously, and this shows and contains β-CD side chain and polyacrylamide skeleton in the synthetic polymkeric substance.
(3) utilize elemental microanalysis method that SA-β-CD is characterized
Use Vario Micro elemental analyser to measure each constituent content of SA-β-CD, the results of elemental analyses carbon element content is 33.37%, and element sulphur content is 5.01%, and carbon is 6.66 with the sulphur content ratio, and calculating sulfonate radical substitution value mean value is 2.0.
(4) Indirect UV method checking polymkeric substance replaces homogeneity
The tosic acid of preparation 20mmol/L pH8.0-Tris background damping fluid, and with 0.45 μ m water system membrane filtration, for subsequent use.Get SA-β-CD, SA-β-each 20mg of CDP sample and be dissolved in the 990uL deionized water, each adds the neutral marker DMF of 10uL, and vortex dissolving mixing namely obtains 20mg/mL, contains the sample solution of neutral marker 1%.Use the Bio-radHPE100 capillary electrophoresis apparatus to measure, the kapillary total length is 27cm, and useful length is 20cm, and internal diameter is 75 μ m, and coating is not used NaOH solution and H successively with kapillary
2Then the O flushing is full of damping fluid in kapillary, open electrophoretic voltage, 8kV sample introduction 5s, and 10kV carries out electrophoresis, and the room temperature test sample goes out the peak situation under 214nm.Can see from Fig. 2 A and Fig. 2 B, what go out the earliest the peak is the sodium ion of positively charged, is thereafter the peak of neutral marker, and electronegative sulfonated cyclodextrin (Fig. 2 A) and sulfonated cyclodextrin (Fig. 2 B) go out the peak at last.Contrast by Fig. 2 A and Fig. 2 B can see, form whole polymer molecule after the polymkeric substance the relative homogeneous of substitution value many.Polymkeric substance is because self molecular weight is large and be mixture, therefore peak shape is wider, but the nucleo plasmic relation difference between this explanation polymer molecule is smaller, and distribution is relatively even in electric field.And for the sulfonated cyclodextrin of small molecules, its sulfonated substitution value can be divided into several bands, because the situation of skewness can appear in the mobility speed difference, sepn process has a negative impact to chirality in electric field for it.Form after the polymkeric substance, the substitution value homogeneity obviously increases, the comparing result of substitution value also indirect proof synthetic polymer be successfully.
Embodiment 3: chiral drug separates
Phosphoric acid-triethylamine buffer solution of preparation 25mmol/L pH2.60 behind 0.45 μ m water system membrane filtration, adds synthetic SA-β-CDP in 1mL phosphoric acid-triethylamine buffer solution, obtain containing the electrophoresis running buffer of SA-β-CDP.Use the Beckman5000P/ACE capillary electrophoresis apparatus, the kapillary total length is 37cm, and useful length is 30cm, and internal diameter is 50 μ m, and coating is not used NaOH solution and H successively with kapillary
2The O flushing, then in kapillary, be full of the damping fluid that does not contain sulfonated cyclodextrin, in kapillary, push first one section damping fluid 0.8min that contains sulfonated cyclodextrin, 0.5psi hydrodynamic injection 5s, the kapillary two ends are put into the damping fluid making alive electrophoresis that does not contain sulfonated cyclodextrin, field intensity is+300V/cm, splits Proprasylyte (Fig. 3 A) and terbutaline (Fig. 3 B) under 37 ℃, 214nm.
Phosphoric acid-triethylamine buffer solution of preparation 25mmol/L pH5.50 behind 0.45 μ m water system membrane filtration, adds synthetic SA-β-CDP in 1mL phosphoric acid-triethylamine buffer solution, obtain containing the electrophoresis running buffer of SA-β-CDP.Instrument and kapillary pre-treatment are the same, and 0.5psi hydrodynamic injection 5s puts into the kapillary two ends damping fluid making alive electrophoresis that does not contain sulfonated cyclodextrin, and field intensity is+300V/cm, split warfarin (Fig. 3 C) under 37 ℃, 214nm.
Instrument and buffer conditions, the same Proprasylyte that separates of kapillary pre-treatment, 0.5psi hydrodynamic injection 5s, the kapillary two ends are put into the damping fluid making alive electrophoresis that does not contain sulfonated cyclodextrin, field intensity is+189V/cm, splits promethazine (Fig. 3 D) under 37 ℃, 214nm.
Embodiment 4: the damping fluid separating chiral compound of more different SA-β-CDP concentration
Phosphoric acid-triethylamine buffer solution of preparation 25mmol/L pH2.6 behind 0.45 μ m water system membrane filtration, adds the SA-β-CDP of different amounts in 1mL phosphoric acid-triethylamine buffer solution, obtain containing the electrophoresis running buffer of different concns SA-β-CDP.Instrument and kapillary pre-treatment are the same, 0.5psi hydrodynamic injection 5s, the kapillary two ends are put into the damping fluid making alive electrophoresis that does not contain sulfonated cyclodextrin, field intensity is+300V/cm, splits terbutaline (Fig. 4 A) and Proprasylyte (Fig. 4 B) under 37 ℃, 214nm.
Embodiment 5: the different pH damping fluid separating chiral compounds that relatively contain SA-β-CDP
Prepare respectively 25mmol/L pH2.5, phosphoric acid-triethylamine buffer solution of 3.5,4.5 behind 0.45 μ m water system membrane filtration, adds synthetic SA-β-CDP in 1mL phosphoric acid-triethylamine buffer solution, obtain containing the electrophoresis running buffer of SA-β-CDP.Instrument and kapillary pre-treatment are the same, 0.5psi hydrodynamic injection 5s, the kapillary two ends are put into the damping fluid making alive electrophoresis that does not contain sulfonated cyclodextrin, field intensity is+300V/cm, under 37 ℃, 214nm, split promethazine, Fig. 5-1, Fig. 5-2 and Fig. 5-3 show respectively that pH is 2.5, pH be 3.5 and pH be that 4.5 o'clock running buffers are on the impact of promethazine transition time and resolution.
Above embodiment is suitable for synthetic, the characterize and application of all sulfonated cyclodextrins that the present invention mentions, certainly, also can be used for all the other cyclodextrins, all sulfonated cyclodextrin synthesis conditions, separating power is slightly different, but general trend is identical.The above, only being part embodiment of the present invention, is not that the present invention is done any pro forma restriction, any simple modification that every foundation technical spirit of the present invention is done above-described embodiment, equivalent variations and modification all belong in the technical solution of the present invention scope.
Claims (7)
1. a novel synthetic thinking is characterized in that to obtain the derivatized cyclodextrin chiral resolving agent of the position of substitution and substitution value homogeneous, will replace inhomogenous derivatized cyclodextrin and connect into polymkeric substance.
2. novel sulfonated cyclodextrin, its chemical structure is:
Wherein:
Expression beta-cyclodextrin, m, n are natural number and equal 〉=1.
3. the synthetic method of described novel sulfonated cyclodextrin according to claim 2 is characterized in that, is prepared through polymerization and sulfonated reaction by beta-cyclodextrin, and the reaction scheme of preparation is as follows:
Wherein:
Represent beta-cyclodextrin, m, n are natural number and equal 〉=1.
4. the synthetic method of described novel sulfonated cyclodextrin according to claim 3 is characterized in that, may further comprise the steps:
1) under the room temperature beta-cyclodextrin of purifying is dissolved in 2% ~ 5% the sodium hydroxide solution, be stirred to fully dissolving, slowly drip the glycidyl allyl ether of 1 ~ 5 times of equivalent under the nitrogen protection, holding temperature is reacted end in 36 ~ 60h hour at 40 ~ 65 ℃, and dilute hydrochloric acid conditioned reaction liquid is to neutral, and adding acetone precipitation product, filter, dry to get white solid allyl group beta-cyclodextrin, porphyrize is for subsequent use;
2) vitriol oil is cooled to 0 ℃ in cryosel is bathed after, slowly add allyl group beta-cyclodextrin fine powder, control temperature＜5 ℃, behind magnetic agitation reaction 1.5 ~ 3h with reaction solution to large water gaging, add the calcium carbonate neutralization, the elimination calcium sulfate precipitation adds ethanol in the filtrate, low temperature spends the night, filter, regulate filtrate pH to 10.50 with yellow soda ash, filter, filtrate decompression is concentrated; Concentrated solution is poured in a large amount of dehydrated alcohols, is precipitated, and precipitates dry that light yellow solid is sulfonated allyl group beta-cyclodextrin;
The sulfonated allyl group beta-cyclodextrin that 3) will synthesize is dissolved in the water, and vacuum outgas 30-60min adds the acrylamide of 1 ~ 5 times of equivalent, stirs 20-60min under the nitrogen, adds the Potassium Persulphate initiation reaction, 40 ~ 65 ℃ of lower stirring reactions 24 ~ 48 hours; After reacting completely, pour molecular weight cut-off after reaction solution diluted a little into and be in 14,000 the dialysis tubing and dialyse, freeze-drying obtains sulfonated beta cyclo dextrin polymer product behind the dialysate filter.
5. the according to claim 2 application of novel sulfonated cyclodextrin in the capillary electrophoresis chipal compounds splits.
6. the according to claim 5 application of described novel sulfonated cyclodextrin in the capillary electrophoresis chipal compounds splits, be with sulfonated beta cyclo dextrin polymer as Buffer additive, in capillary electrophoresis, chiral compound enantiomer is separated.
7. the according to claim 6 application of described novel sulfonated cyclodextrin in the capillary electrophoresis chipal compounds splits, its concrete steps comprise:
Prepare the matrix damping fluid of different pH values, behind 0.45 μ m water system membrane filtration, get the electrophoresis running buffer to wherein adding sulfonated beta cyclo dextrin polymer;
Use capillary electrophoresis apparatus equipment, after kapillary activation flushing, in kapillary, be full of the damping fluid that does not contain sulfonated beta cyclo dextrin polymer, in kapillary, push one section damping fluid that contains sulfonated beta cyclo dextrin polymer, make it not arrive the detection window place, sample introduction is put into the kapillary two ends damping fluid making alive electrophoresis that does not contain sulfonated beta cyclo dextrin polymer; Open electrophoretic voltage, the electrophoresis field intensity is 50-1000V/cm, selects detection method test chipal compounds according to the character of different chiral drugs;
Separation condition is: it is 0.1%-6.0% that described sulfonated beta cyclo dextrin polymer adds concentration; Electrophoresis running buffer pH1.50-12.50; Electrophoresis running buffer concentration is 5-200mmol/L; Running voltage 1-11kV; Temperature 17-37 ℃; Organic additive content 0-50%.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN104031179A (en) * | 2014-05-15 | 2014-09-10 | 昆明理工大学 | 6-site monosubstituted-beta-cyclodextrin functional monomer and preparation method thereof |
| CN111495341A (en) * | 2020-05-09 | 2020-08-07 | 中南民族大学 | Preparation and application of novel amphoteric chiral selector CEC monolithic column |
| CN112824888A (en) * | 2020-07-21 | 2021-05-21 | 宁波大学 | Analytical reagent and method for aminobenzenesulfonic acid positional isomer based on beta cyclodextrin |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104031179A (en) * | 2014-05-15 | 2014-09-10 | 昆明理工大学 | 6-site monosubstituted-beta-cyclodextrin functional monomer and preparation method thereof |
| CN111495341A (en) * | 2020-05-09 | 2020-08-07 | 中南民族大学 | Preparation and application of novel amphoteric chiral selector CEC monolithic column |
| CN112824888A (en) * | 2020-07-21 | 2021-05-21 | 宁波大学 | Analytical reagent and method for aminobenzenesulfonic acid positional isomer based on beta cyclodextrin |
| CN112824888B (en) * | 2020-07-21 | 2022-07-12 | 常州磐诺仪器有限公司 | Analytical reagent and method for aminobenzenesulfonic acid positional isomer based on beta cyclodextrin |
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