CN102924670B - 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 capillary electrophoresis running buffer, for the separation of capillary electrophoresis chipal compounds, there is synthetic method simple, step is few, purify and reclaim easily, synthetic low cost and other advantages, and realize cyclodextrin derivatize and be substituted in the homogenization on statistical significance, post effect and resolution are improved, improve cyclodextrin solubility simultaneously, joule heating while having reduced electrophoretic separation, being conducive to large-scale industrialization uses, there is good economic worth and application prospect.
Background technology
Chirality is natural a kind of universal phenomenon, forms the base substance of organism, if amino acid, carbohydrate etc. are all chiral molecules.The chiral separation especially fractionation of chiral drug mainly has the meaning of two aspects: pharma-toxicology meaning and huge economic worth.
Compared with the technology such as high performance liquid chromatography (HPLC), gas-chromatography (GC), with capillary electrophoresis (CE, capillary electrophoresis) technology carries 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 CE chiral separation, utilizing chiral selector to build stereoselectivity environment is to realize the key that enantiomorph is distinguished.The kind of chiral selector is a lot, and wherein, cyclodextrin (CDs, cyclodextrins) and derivative thereof are the class chiral resolving agents being 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 after inclusion, the variation of mobility has caused the separation of enantiomorph.Natural cyclodextrin and neutral derivant thereof, as beta-cyclodextrin, though successfully separated some chipal compounds, but its solubleness is low and be difficult to split the drawbacks limit such as neutral enantiomorph its practical application, referring to the article " Fanali S.J.Chromatogr.A; 1996,735:77 ~ 121. " of Salvatore Fanali.Charged CDs derivative can be opened neutral Chiral Separation because having self electrophoretic mobility.Cyclodextrin is carried out to derivatize and not only can improve selectivity, can also expand chiral separation scope.
In cyclodextrin molecular, there is the similar hydroxyl of multiple reactive behavioies, derivatize product taking this cyclodextrin as parent also has its limitation: 1) the normally different ions group substitution value mixture different with the position of substitution of charged CDs derivative, can have a negative impact to the separation of chipal compounds, as low in poor reproducibility, post effect etc.; 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 electrophoresis; 3) be difficult to realize the recovery of charged CDs derivative to costliness.The chirality selective power of Sulfonated cyclodextrin derivative is very strong, range of application very extensively, lot of documents has been recorded various types of sulfonated cyclodextrin and has been applied to chirality capillary electrophoresis separation.Use the cyclodextrin that mixes replacement inevitably to cause chiral selectivity to decline, post effect reduces, the problem of batch poor reproducibility, analyze scholars and adopted various chemosynthesis means, to expect to obtain from the angle of chemical structure the charged derivative of sulfonated cyclodextrin of high purity homogenization.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 have successfully realized chiral separation.But the preparation process of this class negative electricity CDs derivative comprises protection and the deprotection of hydroxyl, respectively walk the complex steps such as the chromatographic column purifying of product, product is not only expensive and cannot recycling, is widely used therefore limited to a great extent it.
In addition, the people such as Fu-Tai A.Chen high sulfonation cyclodextrin is more early also 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 space, thereby has reached the object of acquisition homogenization cyclodextrin.The feature of the chemical structure of cyclodextrin own causes preparation and reclaims the cyclodextrin of homogeneous in these chemical structures very difficult, makes price 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, inhomogenous replacement derivatized cyclodextrin is connected into polymkeric substance, it is simple that this method not only has synthetic method, step is few, purify and reclaim easily, synthetic low cost and other advantages, and realize cyclodextrin derivatize and be substituted in the homogenization on statistical significance, post effect and resolution are improved, improve cyclodextrin solubility simultaneously, joule heating while having reduced electrophoretic separation.Prove the advantage of design philosophy of the present invention by the characterization result that synthesizes sulfonated beta cyclo dextrin polymer and it is carried out, and be respectively used to this polymkeric substance as Buffer additive in the separation of CE chipal compounds.
Main purpose of the present invention is as follows:
1. to prepare the charged cyclodextrin difficult problems such as to set forth a kind of novel chiral resolving agent design philosophy water-soluble low to solve natural cyclodextrin (as beta-cyclodextrin) as example, 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 in CE damping fluid and is split for chipal compounds.
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 is natural number and all>=1.
The synthetic method of the novel sulfonated cyclodextrin of the present invention is: prepared through polymerization and sulfonated reaction by cyclodextrin, its reaction scheme of preparing is as follows:
Wherein:
represent beta-cyclodextrin, m, n is natural number and all>=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 room temperature, the beta-cyclodextrin of purifying is dissolved in 2% ~ 5% sodium hydroxide solution; be stirred to completely and dissolve; under nitrogen protection, slowly drip the glycidyl allyl ether (AGE) of 1 ~ 5 times of equivalent; holding temperature, at 40 ~ 65 DEG C, is reacted end in 36 ~ 60h hour, and dilute hydrochloric acid regulates reaction solution to neutral; and add acetone precipitation product; filter, dry to obtain white solid allyl group cyclodextrin, porphyrize is for subsequent use.
2) vitriol oil in bathing, cryosel is cooled to after 0 DEG C, slowly add allyl group cyclodextrin fine powder, control temperature <5 DEG C, after magnetic agitation reaction 1.5 ~ 3h by reaction solution to large water gaging, add calcium carbonate neutralization, elimination calcium sulfate precipitation, adds ethanol in filtrate, low temperature spends the night, filter, with sodium carbonate adjusting filtrate pH to 10.50, to filter, filtrate decompression is concentrated.Concentrated solution is poured in a large amount of dehydrated alcohols, is precipitated, and precipitation is dry that light yellow solid is sulfonated allyl group cyclodextrin.
3) synthetic sulfonated allyl group cyclodextrin is dissolved in the water, vacuum outgas 30-60min, adds the acrylamide (AM) of 1 ~ 5 times of equivalent, under nitrogen, stirs 20-60min, adds Potassium Persulphate initiation reaction, stirring reaction 24 ~ 48 hours at 40 ~ 65 DEG C.After reacting completely, pour molecular weight cut-off into and be in 14,000 dialysis tubing and dialyse after reaction solution is diluted a little, after dialysate filter, freeze-drying obtains sulfonated cyclodextrin product.
The sulfonated cyclodextrin of gained in the present invention, by thin layer chromatography, infrared spectroscopy, the means such as elemental microanalysis method, Indirect UV method characterize, and specific embodiments principle is as follows:
1) tlc
Thin-layer chromatography is again thin plate chromatography, is the one in chromatography, is a kind of very important experimental technique of sharp separation and a small amount of material of qualitative analysis.When experiment, sample is dripped on the zero line of thin layer plate to airing or dry up rearmounted thin layer plate in filling the separation chamber of developping agent with kapillary., chromatosheet is taken out near the about 1cm in top time until solvent front, dry after spray with developer, or develop the color under ultraviolet lamp.
2) infrared spectroscopy
Infrared spectra (IR) is often used to the detection of product characteristic group in chemosynthesis reaction, and in test, we also characterize by IR p-sulfonic acid beta cyclo dextrin polymer.
3) elemental microanalysis method
By measuring C element, the S constituent content of different sulfopropyl ether cyclodextrin monomers, can calculate by constituent content ratio the content of sulfonate radical in product, then obtain the average substitution degree of product.
4) Indirect UV method
Indirect UV method can be used for analyzing those with detection in capillary electrophoresis does not have the material of enough strong uv-absorbing.Here contrasted the substitution value homogeneity of sulfonated cyclodextrin and sulfonated cyclodextrin by Indirect UV method.Background damping fluid is selected tosic acid-tri-(methylol) aminomethanes (Tris) damping fluid with uv-absorbing, tosic acid wherein provides background absorption, just there will be negative peak when the sulfopropyl ether ring dextrin that uv-absorbing is weak and sulfopropyl ether cyclodextrin 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 of synthesized of the present invention, as Buffer additive, separates chiral compound enantiomer in capillary electrophoresis, and concrete technical scheme is as follows:
Prepare the matrix damping fluid of different pH values, after 0.45 μ m water system membrane filtration, add wherein sulfonated cyclodextrin to obtain electrophoresis running buffer; Use capillary electrophoresis apparatus equipment, after kapillary activation is rinsed, in kapillary, be full of the not damping fluid containing sulfonated cyclodextrin, in kapillary, push one section of damping fluid that contains polymkeric substance, make it not arrive detection window place, sample introduction, puts into the not damping fluid making alive electrophoresis containing sulfonated cyclodextrin by kapillary two ends.Open electrophoretic voltage, 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 DEG C; 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 synthetic method used 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 cyclodextrin of preparing of this patent proposition 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 also shows following advantage: a. for small molecules cyclodextrin derivative in CE chiral separation, and 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.
Brief description of the drawings
Fig. 1 is the Infrared Characterization spectrogram of the sulfonated beta cyclo dextrin polymer (SA-β-CDP) that obtains of embodiment 1;
Fig. 2 A Indirect UV method is measured the electrophorogram of sulfonated beta-cyclodextrin (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. 5-3rd, the electrophorogram of the impact of running buffer pH on promethazine transition time and resolution.
Embodiment
The present invention proposes substitution value and the position of substitution after cyclodextrin derivatize and easily reaches the design philosophy of the homogeneous on statistical significance, thereby in chiral separation, obtain higher fractionation effect, and derivatized cyclodextrin polymkeric substance has water-soluble height, economical, when electrophoresis, generation current is low, the advantages such as recyclable recycling, this patent has been developed the synthetic method of sulfonated cyclodextrin and the application in capillary electrophoresis chipal compounds splits thereof on this basis, tell about by the following examples detailed process of the present invention, it is the convenience in order to understand that embodiment is provided, never 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 NaOH solution, be stirred to completely and dissolve, under nitrogen protection, slowly drip 0.84mL(7.05mmol) AGE, holding temperature is at 50 DEG C, 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 obtain white solid 5.02g, productive rate is 56.82%.
Get the 13mL80% vitriol oil, cryosel is cooled to 0 DEG C in bathing.The ACD that 5.02g is ground into fine powder slowly joins in the above-mentioned vitriol oil, keeps temperature below <5 DEG C, magnetic agitation reaction 2h.After having reacted, reaction solution is poured in 225mL water, added 25g CaCO
3neutralisation of sulphuric acid, elimination CaSO
4precipitation, adds 50mL ethanol in filtrate, low temperature spends the night.Elimination precipitation, filtrate Na
2cO
3regulate pH to 10.50.Elimination precipitation, filtrate decompression is concentrated.Concentrated solution is poured in 150mL dehydrated alcohol, is precipitated in a large number, and precipitation is dried to obtain light yellow solid 4.20g, and productive rate is 72.16%.
Synthetic above sulfonation ACD4.20g is dissolved in 8mL water, vacuum outgas 30min, then add 0.32g AM, and under nitrogen, stir 30min, add 0.03g K
2s
2o
8, stirring reaction 24h at 50 DEG C.After reacting completely, pour molecular weight cut-off into and be that in 14,000 dialysis tubing, dialysis is to remove unreacted monomer after reaction solution is diluted a little, after dialysate filter, freeze-drying obtains polymkeric substance 0.38g, and productive rate is 8.41%.
Embodiment 2: utilize respectively tlc, infra-red chromatography and elemental microanalysis method to characterize the synthetic product obtaining of embodiment 1
(1) tlc characterizes
ACD sample drop is added on the zero line of thin layer plate with kapillary, dries up rearmounted thin layer plate in filling the separation chamber of 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
In Fig. 1, contrasted the infrared absorption spectra of S-ACD/AM multipolymer (SA-β-CDP) with poly-S-ACD and polyacrylamide (PAM), can find out, the Absorption Characteristics of multipolymer combines the characteristic absorbance of poly-S-ACD and polyacrylamide.1030cm
-1c-O stretching vibration absorption peak in place's is from ehter bond in the cyclodextrin molecular of ACD and side chain, 3418cm
-1place is the stretching vibration absorption peak of O-H in cyclodextrin molecular, and 1657cm
-1and 3192cm
-1the absorption peak at place is respectively from the stretching vibration of C=O and N-H in acrylamide skeleton.Sulfonated β-CD polymkeric substance has above-mentioned several charateristic avsorption band simultaneously, and this shows to contain in synthetic polymkeric substance β-CD side chain and polyacrylamide skeleton.
(3) utilize elemental microanalysis method to characterize SA-β-CD
Use Vario Micro elemental analyser to measure each constituent content of SA-β-CD, results of elemental analyses carbon element content is 33.37%, and element sulphur content is 5.01%, and carbon is 6.66 with sulphur content ratio, and calculating sulfonate radical substitution value mean value is 2.0.
(4) Indirect UV method checking polymkeric substance replaces homogeneity
Tosic acid-Tris background damping fluid of preparation 20mmol/L pH8.0, and with 0.45 μ m water system membrane filtration, for subsequent use.Get the each 20mg of SA-β-CD, SA-β-CDP sample and be dissolved in 990uL deionized water, respectively add the neutral marker DMF of 10uL, vortex dissolves and mixes, and obtains 20mg/mL, sample solution containing neutral marker 1%.Use Bio-radHPE100 capillary electrophoresis apparatus to measure, kapillary total length is 27cm, and useful length is 20cm, and internal diameter is 75 μ m, and not coating, uses NaOH solution and H successively by kapillary
2o rinses, and then in kapillary, is full of damping fluid, opens electrophoretic voltage, 8kV sample introduction 5s, and 10kV carries out electrophoresis, and under 214nm, room temperature detection sample goes out peak situation.From Fig. 2 A and Fig. 2 B, can see, what go out the earliest 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) finally go out peak.Contrast by Fig. 2 A and Fig. 2 B can see, form whole polymer molecule after 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 in electric field, distribution is relatively even.And for the sulfonated cyclodextrin of small molecules, its sulfonated substitution value can be divided into several bands, it there will be the situation of skewness in electric field due to mobility speed difference, and to chirality, sepn process has a negative impact.Form after polymkeric substance, substitution value homogeneity obviously increases, the comparing result of substitution value also indirect proof the synthetic of polymkeric substance be successful.
Embodiment 3: chiral drug separates
Phosphoric acid-triethylamine buffer solution of preparation 25mmol/L pH2.60 after 0.45 μ m water system membrane filtration, adds synthetic SA-β-CDP in 1mL phosphoric acid-triethylamine buffer solution, obtains the electrophoresis running buffer containing SA-β-CDP.Use Beckman5000P/ACE capillary electrophoresis apparatus, kapillary total length is 37cm, and useful length is 30cm, and internal diameter is 50 μ m, and not coating, uses NaOH solution and H successively by kapillary
2o rinses, then in kapillary, be full of the not damping fluid containing sulfonated cyclodextrin, in kapillary, first push one section of damping fluid 0.8min that contains sulfonated cyclodextrin, 0.5psi hydrodynamic injection 5s, the not damping fluid making alive electrophoresis containing sulfonated cyclodextrin is put into in kapillary two ends, field intensity is+300V/cm, under 37 DEG C, 214nm, splits Proprasylyte (Fig. 3 A) and terbutaline (Fig. 3 B).
Phosphoric acid-triethylamine buffer solution of preparation 25mmol/L pH5.50 after 0.45 μ m water system membrane filtration, adds synthetic SA-β-CDP in 1mL phosphoric acid-triethylamine buffer solution, obtains the electrophoresis running buffer containing SA-β-CDP.Instrument and kapillary pre-treatment are the same, and the damping fluid making alive electrophoresis containing sulfonated cyclodextrin is put into not at kapillary two ends by 0.5psi hydrodynamic injection 5s, and field intensity is+300V/cm, under 37 DEG C, 214nm, split warfarin (Fig. 3 C).
Instrument and buffer conditions, the same Proprasylyte that separates of kapillary pre-treatment, 0.5psi hydrodynamic injection 5s, the damping fluid making alive electrophoresis containing sulfonated cyclodextrin is put into not in kapillary two ends, and field intensity is+189V/cm, under 37 DEG C, 214nm, splits promethazine (Fig. 3 D).
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 after 0.45 μ m water system membrane filtration, adds the SA-β-CDP of different amounts in 1mL phosphoric acid-triethylamine buffer solution, obtains the electrophoresis running buffer containing different concns SA-β-CDP.Instrument and kapillary pre-treatment are the same, 0.5psi hydrodynamic injection 5s, the damping fluid making alive electrophoresis containing sulfonated cyclodextrin is put into not in kapillary two ends, and field intensity is+300V/cm, under 37 DEG C, 214nm, splits terbutaline (Fig. 4 A) and Proprasylyte (Fig. 4 B).
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 after 0.45 μ m water system membrane filtration, adds synthetic SA-β-CDP in 1mL phosphoric acid-triethylamine buffer solution, obtains the electrophoresis running buffer containing SA-β-CDP.Instrument and kapillary pre-treatment are the same, 0.5psi hydrodynamic injection 5s, the not damping fluid making alive electrophoresis containing sulfonated cyclodextrin is put into in kapillary two ends, field intensity is+300V/cm, under 37 DEG C, 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 the impact on promethazine transition time and resolution of 4.5 o'clock running buffers.
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, be only part embodiment of the present invention, not the present invention done to any pro forma restriction, any simple amendment that every foundation technical spirit of the present invention is done above-described embodiment, equivalent variations and modification, all belong within the scope of technical solution of the present invention.
Claims (6)
1. a sulfonated cyclodextrin, its chemical structure is:
Wherein:
represent beta-cyclodextrin, m, n is natural number and all>=1.
2. a synthetic method for sulfonated cyclodextrin according to claim 1, 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 is natural number and all>=1.
3. the synthetic method of sulfonated cyclodextrin according to claim 2, is characterized in that, comprises the following steps:
1) under room temperature, the beta-cyclodextrin of purifying is dissolved in 2%～5% sodium hydroxide solution, be stirred to completely and dissolve, under nitrogen protection, slowly drip the glycidyl allyl ether of 1～5 times of equivalent, holding temperature, at 40～65 DEG C, is reacted end in 36～60h hour, and dilute hydrochloric acid regulates reaction solution to neutral, and add acetone precipitation product, filter, dry to obtain white solid allyl group beta-cyclodextrin, porphyrize is for subsequent use;
2) vitriol oil in bathing, cryosel is cooled to after 0 DEG C, slowly add allyl group beta-cyclodextrin fine powder, control temperature <5 DEG C, after magnetic agitation reaction 1.5～3h by reaction solution to large water gaging, add calcium carbonate neutralization, elimination calcium sulfate precipitation, adds ethanol in filtrate, low temperature spends the night, filter, with sodium carbonate adjusting filtrate pH to 10.50, to filter, filtrate decompression is concentrated; Concentrated solution is poured in a large amount of dehydrated alcohols, is precipitated, and precipitation is dry that light yellow solid is sulfonated allyl group beta-cyclodextrin;
3) synthetic sulfonated allyl group beta-cyclodextrin is dissolved in the water, vacuum outgas 30-60min, adds the acrylamide of 1～5 times of equivalent, under nitrogen, stirs 20-60min, adds Potassium Persulphate initiation reaction, stirring reaction 24～48 hours at 40～65 DEG C; After reacting completely, pour molecular weight cut-off into and be in 14,000 dialysis tubing and dialyse after reaction solution is diluted a little, after dialysate filter, freeze-drying obtains sulfonated beta cyclo dextrin polymer product.
4. the application in capillary electrophoresis chipal compounds splits according to the sulfonated cyclodextrin of claim 1.
5. the application of sulfonated cyclodextrin in capillary electrophoresis chipal compounds splits according to claim 4, is using sulfonated beta cyclo dextrin polymer as Buffer additive, in capillary electrophoresis, chiral compound enantiomer is separated.
6. the application of sulfonated cyclodextrin in capillary electrophoresis chipal compounds splits according to claim 5, its concrete steps comprise:
Prepare the matrix damping fluid of different pH values, after 0.45 μ m water system membrane filtration, add wherein sulfonated beta cyclo dextrin polymer to obtain electrophoresis running buffer;
Use capillary electrophoresis apparatus equipment, after kapillary activation is rinsed, in kapillary, be full of the not damping fluid containing sulfonated beta cyclo dextrin polymer, in kapillary, push one section of damping fluid that contains sulfonated beta cyclo dextrin polymer, make it not arrive detection window place, sample introduction, puts into the not damping fluid making alive electrophoresis containing sulfonated beta cyclo dextrin polymer by kapillary two ends; Open electrophoretic voltage, 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 DEG C; Organic additive content 0-50%.
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