CN105642261A - Chiral stationary phase prepared with cinchonine-Boc-amide as chiral selector and preparation method and application thereof - Google Patents
Chiral stationary phase prepared with cinchonine-Boc-amide as chiral selector and preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a chiral stationary phase prepared with cinchonine-Boc-amide as a chiral selector and a preparation method and application thereof. The UHPLC chiral stationary phase with the maximally-endured pressure of 1,300 bar is prepared and used for UHPLC chiral separation. The chiral selector is catalyzed through azodiisobutyronitrile and covalently bound to a mercaptopropyl derived fully-porous spherical silica gel surface through a one-pot method, 1-hexene is used for end-capping, and the chiral stationary phase suitable for ultra-high pressure liquid chromatography chiral separation is successfully prepared. Bonding of the chiral selector and end-capping of the stationary phase are completed through the one-pot method, and preparation efficiency is improved. The prepared chiral stationary phase is used for ultra-high pressure liquid chromatography chiral separation of 12 acid chiral amino acid derivative enantiomers, and good chiral separation capacity is shown.
Description
Technical field
The present invention relates to chiral separation technology, be specifically related to the hand of preparing as chiral selector taking Xin Kening-tert-butyl group carbamateProperty fixing phase and its preparation method and application.
Background technology
The compound with chirality refers to has the compound that in kind and mirror image can not complete overlapping character, containing chiral drug, handProperty agricultural chemicals, chirality organic synthesis intermediate, chiral environmental pollutants etc. The compound that contains a chiral centre has a pair of rightReflect body, the equal amount of mixture of this pair of enantiomer forms a racemic modification. Chiral drug is conventionally with the form medication of racemic modification.The a pair of enantiomer of chiral drug has different metabolism behavior and physiologic effect in human body, and a common isomers has wellCurative effect (excellent isomers), another is invalid, and even to have the effect such as strong side effect, toxicity (carcinogenic, teratogenesis) (badIsomers). So Chiral Separation should be opened to the character of rear each isomers of further investigation for chiral drug, and with handThe excellent isomers medication that property is pure.
In numerous chiral separation methods, high performance liquid chromatography (HighPerformanceLiquidChromatography,HPLC) Chiral Stationary Phases is most widely used general, the most successful chiral chromatogram technology. Be applicable to the chiral stationary phase of HPLC(ChiralStationaryPhase, CSP) is of a great variety, has shiploads of merchandiseization source simultaneously. Be applicable to the chirality of HPLCFixing phase normally applies chiral selector or be bonded to prepared by the surface of 3-10 micron grain size spherical silica gel, and filling is notRust steel chromatographic column internal diameter is generally 4.6-10mm, and length is 15-25cm, and disengaging time was from several minutes to tens of minutes. NoAny CSP can meet the needs of all Chiral Separation in practical study work, in the urgent need to developing the new high score that hasFrom the CSP of performance.
Ultrahigh pressure liquid phase chromatogram be Ultra Performance Liquid Chromatography (UltraHighPerformanceLiquidChromatography,UHPLC) be the latest developments of modern liquid chromatography compartment analysis science and technology. UHPLC by reduce fixed phase stuffing particle diameter (extremely),Less internal diameter chromatographic column (being generally 2.1mm internal diameter), compared with shorter chromatogram column length (5cm or 10cm long), high flow rate (High 5ml/min) obtain higher post effect and shorten analysis time. UHPLC chromatographic column needs the pressure of superelevation (to be up to 1300Bar) drive mobile phase. The UHPLC chromatographic column at present commercialization source only has C18, bonding SiO not2On achirality post.
Summary of the invention
In order to solve the deficiencies in the prior art, the invention provides the preparation taking Xin Kening-tert-butyl group carbamate as chiral selectorChiral stationary phase and its preparation method and application.
Technical scheme of the present invention is: taking Xin Kening-tert-butyl group carbamate as side that chiral selector is prepared chiral stationary phaseMethod, comprises the following steps successively: step 1, prepare the full porous spherical silica gel of mercapto propyl group derivatization; Step 2, by Xin Kening-Tert-butyl group carbamate chirality chooser is bonded to the full porous spherical silica gel of mercapto propyl group derivatization and prepares chiral stationary phase.
Further improvement of the present invention comprises:
Described step 1 specifically comprises: accurately taking 5.0g diameter is the full porous spherical silica gel of 1.1-1.9 micron, adds 100Ml round-bottomed flask, then add 60ml dry toluene, water knockout drum and nitrogen protection device are installed, magnetic agitation, backflow azeotropicDewater 3 hours; Reaction unit is cooled to room temperature, removes water knockout drum, add 10ml derivatization reagent 3-mercapto propyl group three ethoxiesBase silane, installs nitrogen protection device, magnetic agitation, back flow reaction 72 hours; Post processing: centrifuge washing product, makes successivelyWith dry toluene, methyl alcohol, ether, the each 60ml washing of n-hexane, every step centrifugal rotational speed is 5000rpm, and centrifugation time is10min; End product vacuum drying 24 hours under 60 DEG C of conditions.
Described step 2 specifically comprises: in 100ml round-bottomed flask, add 0.27g Xin Kening-tert-butyl group carbamateChiral selector, 0.40g diameter is the full porous spherical silica gel of mercapto propyl group derivatization of 1.1-1.9 micron, 27.0mg azo twoIsobutyronitrile, 40ml anhydrous chloroform, installs nitrogen protection device, magnetic agitation, back flow reaction 12 hours; Reaction unit is coldBut to room temperature, add sealing reagent 0.27ml1-hexene, 27.0mg azodiisobutyronitrile, installs nitrogen protection device, magneticPower stirs, back flow reaction 12 hours; Post processing: centrifuge washing product, uses anhydrous chloroform, methyl alcohol, ether, just own successivelyThe each 60ml washing of alkane, every step is centrifugal, and rotating speed is 5000rpm, and the time is 10min; Last product chiral stationary phase existsVacuum drying 24 hours under 60 DEG C of conditions.
Ultrahigh pressure liquid phase chromatogram chiral stationary phase (CSP) preparation flow is as follows:
Another object of the present invention is to provide a kind of ultrahigh pressure liquid phase chromatogram chiral column, utilize high-pressure homogenization method, taking chloroform as evenSlurries and displacement fluid, under 12000psi pressure condition, the chiral stationary phase making with said method is inserted internal diameter 2.1mm,In the stainless steel chromatogram void column pipe of length 50mm, obtain the chiral column that can use on ultrahigh pressure liquid phase chromatograph.
Described a kind of ultrahigh pressure liquid phase chromatogram chiral column, before use, makes it under 1ml/min flow conditions, use ethanolRush post 10min, then use mobile phase setting balance 10min under chromatographic condition.
The present invention also provides a kind of ultrahigh pressure liquid phase chromatogram chiral column chiral stationary phase making according to above-mentioned method.
The present invention further provides the chiral stationary phase of preparing taking Xin Kening-tert-butyl group carbamate as chiral selector superApplication in high pressure liquid chromatography chiral separation.
Described application, its chiral separation sample is the amino acid with blocking group on amino, is acid, specifically comprises: N-pelletSulfonyl-DL-phenylalanine (S1), N-benzoyl-DL-METHIONINE (S2), N-benzoyl-DL-leucine (S3), N-Benzoyl-DL-phenylalanine (S4), N-benzoyl-DL-Alanine (S5), N-benzoyl-DL-valine (S6),N-(3,5-dinitrobenzoyl)-DL-leucine (S7), N-(3,5-dinitrobenzoyl)-DL-phenylalanine (S8),N-(3,5-dinitro benzene formyl)-DL-serine (S9), N-(3,5-dinitro benzene formyl)-DL-METHIONINE (S10), N-(3,5-dinitro benzene formyl)-DL-Alanine (S11) and N-(2,4-dinitrophenyl)-DL-leucine (S12).
Described application, the chromatographic chromatographic condition of ultrahigh pressure liquid phase is: under rp mode, mobile phase is acetonitrile by volume:The mixed solution of 0.1M ammonium acetate solution=80:20, with acetic acid adjust pH be 6.0, flow velocity is 3ml/min, 20 DEG C of column temperatures,Sample size is 0.5 microlitre, detects wavelength 254nm; Under polar organic solvent pattern, mobile phase is the methyl alcohol mixing by volume:Acetic acid: triethylamine=98:2:0.2, flow velocity is 2.5ml/min, 20 DEG C of column temperatures, sample size is 0.5 microlitre, detects wavelength254nm。
The present invention be intended to preparation the highest withstand voltage 1300bar UHPLC chiral stationary phase and for UHPLC chiral separation. Adopt " onePot method " by chiral selector, use azodiisobutyronitrile catalysis, be covalently bound to the full porous spherical silica gel table of mercapto propyl group derivatizationOn face, and utilize the sealing of 1-hexene, successfully prepared the chiral stationary phase that is applicable to ultrahigh pressure liquid phase chromatogram chiral separation.
The bonding of chiral selector and the sealing of fixing phase " one kettle way " complete, and have improved preparation efficiency. The chirality of preparation is fixedPhase, for 12 kinds of acid chiral amino acid derivative enantiomers of ultrahigh pressure liquid phase chromatogram chiral separation, demonstrates good chirality and dividesFrom ability. Under selected chromatographic separation condition, most of acid chiral amino acid derivative enantiomers can be about one minute inObtain baseline separation (separating degree Rs > 1.5). About one minute, can successfully separate some aobvious acid chiral amino acid derivativesEnantiomer, divides for the enantiomer solving in the process of producing product such as chiral drug, Chiral pesticide, chirality organic synthesis intermediateThere is important value from problem.
Evaluate by UHPLC chiral separation, result shows that prepared UHPLCCSP has good chiral Recognition ability, canAcid chiral amino acid derivative is separated, can be applicable to amino acid derivativges enantiomter and analyze and quality of production control.
Brief description of the drawings
Fig. 1 is (3,5-dinitro benzene the formyl)-DL-serine (S8) of N-under polarity mobile phase pattern chiral separation on CSPResult.
Fig. 2 is (3,5-dinitro benzene the formyl)-DL-serine (S8) of N-under rp mode chirality separating resulting on CSP.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is elaborated.
Embodiment 1
In 100ml round-bottomed flask, first add 9.0mmol Xin Kening (Cinchonidine, CN, 98%, 2.70g);Add again 60ml dry toluene, water knockout drum and nitrogen protection device are installed, magnetic agitation, backflow azeotropic water removing 1 hour. WillReaction unit is cooled to room temperature, removes water knockout drum, adds 10.0mmol derivatization reagent tert-butyl group isocyanates (97%, 1.17Ml), add 3 catalyst dibutyl tin laurates, nitrogen protection device is installed, magnetic agitation, back flow reaction 4 hours.Post processing: first use Rotary Evaporators to remove solvent toluene, then add 60ml n-hexane, room temperature condition in crude productLower magnetic force stirs and spends the night, and sand core funnel suction filtration, uses a small amount of n-hexane washed product, drains, and finally utilizes the cyclohexane knot of attaching most importance toBrilliant solvent, through recrystallization operation purified product, 60 DEG C of vacuum drying 24 hours, obtain chiral selector Xin Kening after purifying-Tert-butyl group carbamate (tert-BuCCN):
13CNMR(101MHz,CDCl3)δ153.76(s),150.37(s),150.11(s),148.65(s),146.53(s),140.78(s),130.43(s),129.17(s),126.79(s),123.74(s),118.59(s),114.75(s),73.14(s),59.98(s),50.75(s),49.91(s),49.17(s),40.00(s),28.99(s),27.99(s),26.64(s),23.72(s).
Embodiment 2
The preparation of the full porous spherical silica gel of mercapto propyl group derivatization, accurately taking 5.0g diameter is the full porous ball of 1.1-1.9 micronShape silica gel, adds 100ml round-bottomed flask, then adds 60ml dry toluene, water knockout drum and nitrogen protection device is installed, magneticPower stirs, backflow azeotropic water removing 3 hours. Reaction unit is cooled to room temperature, removes water knockout drum, add the examination of 10ml derivatizationAgent 3-mercaptopropyltriethoxysilane, installs nitrogen protection device, magnetic agitation, back flow reaction 72 hours. Post processing: fromHeart washed product, is used dry toluene, methyl alcohol, ether, the each 60ml washing of n-hexane successively, and every step centrifugal rotational speed is 5000Rpm, centrifugation time is 10min. End product vacuum drying 24 hours under 60 DEG C of conditions.
Embodiment 3
The preparation of chiral stationary phase and chiral column, described step 2 specifically comprises: in 100ml round-bottomed flask, add 0.27gXin Kening-tert-butyl group carbamate chirality chooser, 0.40g diameter is the full porous of mercapto propyl group derivatization of 1.1-1.9 micronSpherical silica gel, 27.0mg azodiisobutyronitrile, 40ml anhydrous chloroform, installs nitrogen protection device, and magnetic agitation refluxes anti-Answer 12 hours; Reaction unit is cooled to room temperature, adds sealing reagent 0.27ml1-hexene, 27.0mg azodiisobutyronitrile,Nitrogen protection device is installed, magnetic agitation, back flow reaction 12 hours; Post processing: centrifuge washing product, uses anhydrous chlorine successivelyImitative, methyl alcohol, ether, the each 60ml washing of n-hexane, every step is centrifugal, and rotating speed is 5000rpm, and the time is 10min; ?After the vacuum drying 24 hours under 60 DEG C of conditions of product chiral stationary phase.
Utilize high-pressure homogenization method, taking chloroform as homogenate with displacement fluid, will be with said method system under 12000psi pressure conditionThe chiral stationary phase obtaining is inserted in the stainless steel chromatogram void column pipe of internal diameter 2.1mm, length 50mm, and obtaining can be at ultrahigh pressure liquid phaseThe chiral column using on chromatograph. Before use, make it under 1ml/min flow conditions, use ethanol to rush post 10min, soRear use mobile phase is being set balance 10min under chromatographic condition.
Embodiment 4
The chiral stationary phase of preparing taking Xin Kening-tert-butyl group carbamate as chiral selector divides in ultrahigh pressure liquid phase chromatogram chiralityFrom in application. Its chiral separation sample is the amino acid with blocking group on amino, is acid, specifically comprises: the red sulphonyl of N-Base-DL-phenylalanine (S1), N-benzoyl-DL-METHIONINE (S2), N-benzoyl-DL-leucine (S3), N-benzene firstAcyl group-DL-phenylalanine (S4), N-benzoyl-DL-Alanine (S5), N-benzoyl-DL-valine (S6), N-(3,5-dinitrobenzoyl)-DL-leucine (S7), N-(3,5-dinitrobenzoyl)-DL-phenylalanine (S8),N-(3,5-dinitro benzene formyl)-DL-serine (S9), N-(3,5-dinitro benzene formyl)-DL-METHIONINE (S10), N-(3,5-dinitro benzene formyl)-DL-Alanine (S11) and N-(2,4-dinitrophenyl)-DL-leucine (S12). ItsChemical structural formula is as follows:
The chromatographic chromatographic condition of ultrahigh pressure liquid phase is: under rp mode, mobile phase is acetonitrile by volume: 0.1M ammonium acetateThe mixed solution of the aqueous solution=80:20, with acetic acid adjust pH be 6.0, flow velocity is 3ml/min, 20 DEG C of column temperatures, sample sizeBe 0.5 microlitre, detect wavelength 254nm; Under polar organic solvent pattern, mobile phase is the methyl alcohol mixing by volume: acetic acid:Triethylamine=98:2:0.2, flow velocity is 2.5ml/min, 20 DEG C of column temperatures, sample size is 0.5 microlitre, detects wavelength 254nm.
12 kinds of acid chiral amino acid derivatives on chiral stationary phase chirality separating resulting respectively referring to table 1. Wherein chromatographic parameter:T, retention time; α, separation factor; Rs, separating degree.
The chiral separation result of table 112 derived from amino acid thing on 1.9 microns of Xin Kening-tert-butyl group carbamate UHPLCCSP
1:Mobilephase:ACN:0.1MCH3COONH4＝80:20(v/v),pH＝6.0,3.0ml/min,254nm,20℃,0.5μl.
2:Mobilephase:MeOH:CH3COOH:(CH3CH2)3N＝98:2:0.2(v/v/v),2.5ml/min,254nm,20℃,0.5μl.
Embodiment 5
As shown in Figure 1, under polarity mobile phase pattern N-(3,5-dinitro benzene formyl)-DL-serine (S8) at CSP left-hand seatProperty separating resulting, wherein mobile phase: MeOH:CH3COOH:(CH3CH2)3N=98:2:0.2 (v/v/v), flow velocity 2.5ml/min, inspectionSurvey wavelength 254nm, 20 DEG C, sample size 0.5 μ l. The chromatographic chromatographic condition of ultrahigh pressure liquid phase is with embodiment 4.
Embodiment 6
As shown in Figure 2, N-(3,5-dinitro benzene formyl)-DL-serine (S8) chiral separation on CSP under rp modeAs a result, mobile phase A CN:0.1MCH wherein3COONH4=80:20 (v/v), pH=6.0, flow velocity 3.0ml/min, detectsWavelength 254nm, 20 DEG C, sample size 0.5 μ l. The chromatographic chromatographic condition of ultrahigh pressure liquid phase is with embodiment 4.
The present invention be intended to preparation the highest withstand voltage 1300bar UHPLC chiral stationary phase and for UHPLC chiral separation. Adopt " onePot method " by chiral selector, use azodiisobutyronitrile catalysis, be covalently bound to the full porous spherical silica gel table of mercapto propyl group derivatizationOn face, and utilize the sealing of 1-hexene, successfully prepared the chiral stationary phase that is applicable to ultrahigh pressure liquid phase chromatogram chiral separation.
The bonding of chiral selector and the sealing of fixing phase " one kettle way " complete, and have improved preparation efficiency. The chirality of preparation is fixedPhase, for 12 kinds of acid chiral amino acid derivative enantiomers of ultrahigh pressure liquid phase chromatogram chiral separation, demonstrates good chirality and dividesFrom ability. Under selected chromatographic separation condition, most of acid chiral amino acid derivative enantiomers can be about one minute inObtain baseline separation (separating degree Rs > 1.5). About one minute, can successfully separate some aobvious acid chiral amino acid derivativesEnantiomer, divides for the enantiomer solving in the process of producing product such as chiral drug, Chiral pesticide, chirality organic synthesis intermediateThere is important value from problem.
Evaluate by UHPLC chiral separation, result shows that prepared UHPLCCSP has good chiral Recognition ability, canAcid chiral amino acid derivative is separated, can be applicable to amino acid derivativges enantiomter and analyze and quality of production control.
More than show and described general principle of the present invention and principal character and advantage of the present invention. The technical staff of the industry shouldThis understanding, the present invention is not restricted to the described embodiments, and just illustrating of describing in above-described embodiment and description is of the present invention formerReason, without departing from the spirit and scope of the present invention, the present invention also has various changes and modifications, these changes and improvementsAll fall in the claimed scope of the invention. The claimed scope of the present invention is defined by appending claims and equivalent thereof.
Claims (9)
1. the method for preparing chiral stationary phase taking Xin Kening-tert-butyl group carbamate as chiral selector, is characterized in that, comprises the following steps successively: step 1, prepare the full porous spherical silica gel of mercapto propyl group derivatization; Step 2, is bonded to the full porous spherical silica gel of mercapto propyl group derivatization by Xin Kening-tert-butyl group carbamate chirality chooser and prepares chiral stationary phase.
2. the method for preparing chiral stationary phase taking Xin Kening-tert-butyl group carbamate as chiral selector according to claim 1, it is characterized in that, described step 1 specifically comprises: accurately taking 5.0g diameter is the full porous spherical silica gel of 1.1-1.9 micron, add 100ml round-bottomed flask, add again 60ml dry toluene, water knockout drum and nitrogen protection device are installed, magnetic agitation, backflow azeotropic water removing 3 hours; Reaction unit is cooled to room temperature, removes water knockout drum, add 10ml derivatization reagent 3-mercaptopropyltriethoxysilane, nitrogen protection device is installed, magnetic agitation, back flow reaction 72 hours; Post processing: centrifuge washing product, use successively dry toluene, methyl alcohol, ether, the each 60ml washing of n-hexane, every step centrifugal rotational speed is 5000rpm, centrifugation time is 10min; End product vacuum drying 24 hours under 60 DEG C of conditions.
3. the method for preparing chiral stationary phase taking Xin Kening-tert-butyl group carbamate as chiral selector according to claim 1, it is characterized in that, described step 2 specifically comprises: in 100ml round-bottomed flask, add 0.27g Xin Kening-tert-butyl group carbamate chirality chooser, 0.40g diameter is the full porous spherical silica gel of mercapto propyl group derivatization of 1.1-1.9 micron, 27.0mg azodiisobutyronitrile, 40ml anhydrous chloroform, nitrogen protection device is installed, magnetic agitation, back flow reaction 12 hours; Reaction unit is cooled to room temperature, adds sealing reagent 0.27ml1-hexene, 27.0mg azodiisobutyronitrile, installs nitrogen protection device, magnetic agitation, back flow reaction 12 hours; Post processing: centrifuge washing product, use successively anhydrous chloroform, methyl alcohol, ether, the each 60ml washing of n-hexane, every step is centrifugal, and rotating speed is 5000rpm, and the time is 10min; The vacuum drying 24 hours under 60 DEG C of conditions of last product chiral stationary phase.
4. a ultrahigh pressure liquid phase chromatogram chiral column, it is characterized in that, utilize high-pressure homogenization method, taking chloroform as homogenate with displacement fluid, under 12000psi pressure condition, the chiral stationary phase making with method described in claim 1 is inserted in the stainless steel chromatogram void column pipe of internal diameter 2.1mm, length 50mm, obtained the chiral column that can use on ultrahigh pressure liquid phase chromatograph.
5. a kind of ultrahigh pressure liquid phase chromatogram chiral column according to claim 4, is characterized in that, before described chiral column uses, makes it under 1ml/min flow conditions, use ethanol to rush post 10min, then uses mobile phase setting balance 10min under chromatographic condition.
6. a ultrahigh pressure liquid phase chromatogram chiral column chiral stationary phase, is characterized in that, makes in accordance with the method for claim 1.
7. the application of the chiral stationary phase of preparing taking Xin Kening-tert-butyl group carbamate as chiral selector in ultrahigh pressure liquid phase chromatogram chiral separation.
8. application according to claim 7, it is characterized in that, chiral separation sample is the amino acid with blocking group on amino, be acid, specifically comprise: N-dansyl-DL-phenylalanine, N-benzoyl-DL-METHIONINE, N-benzoyl-DL-leucine, N-benzoyl-DL-phenylalanine, N-benzoyl-DL-Alanine, N-benzoyl-DL-valine, N-(3, 5-dinitrobenzoyl)-DL-leucine, N-(3, 5-dinitrobenzoyl)-DL-phenylalanine, N-(3, 5-dinitro benzene formyl)-DL-serine, N-(3, 5-dinitro benzene formyl)-DL-METHIONINE, N-(3, 5-dinitro benzene formyl)-DL-Alanine and N-(2, 4-dinitrophenyl)-DL-leucine.
9. application according to claim 7, it is characterized in that, the chromatographic chromatographic condition of ultrahigh pressure liquid phase is: under rp mode, mobile phase is acetonitrile by volume: the mixed solution of 0.1M ammonium acetate solution=80:20, with acetic acid adjust pH be 6.0, flow velocity is 3ml/min, 20 DEG C of column temperatures, sample size is 0.5 microlitre, detects wavelength 254nm; Under polar organic solvent pattern, mobile phase is the methyl alcohol mixing by volume: acetic acid: triethylamine=98:2:0.2, and flow velocity is 2.5ml/min, 20 DEG C of column temperatures, sample size is 0.5 microlitre, detects wavelength 254nm.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009137853A1 (en) * | 2008-05-13 | 2009-11-19 | Universität Wien | Enantioselective zwitterionic ion-exchanee material |
| CN102172517A (en) * | 2011-02-24 | 2011-09-07 | 贾正平 | Chiral column chromatographic packing and synthesis method thereof |
| CN104860939A (en) * | 2015-04-10 | 2015-08-26 | 昆明理工大学 | Cinchona alkaloids compound and preparation method thereof |
-
2016
- 2016-02-04 CN CN201610077782.8A patent/CN105642261A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009137853A1 (en) * | 2008-05-13 | 2009-11-19 | Universität Wien | Enantioselective zwitterionic ion-exchanee material |
| CN102172517A (en) * | 2011-02-24 | 2011-09-07 | 贾正平 | Chiral column chromatographic packing and synthesis method thereof |
| CN104860939A (en) * | 2015-04-10 | 2015-08-26 | 昆明理工大学 | Cinchona alkaloids compound and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| NORBERT M.MAIER,ET AL: "Enantioselective anion exchangers based on cinchona alkaloid-derived carbamates: Influence of C8/C9 stereochemistry on chiral recognition", 《CHIRALITY》 * |
| 蒋生祥等: "全多孔球形硅胶基质高效液相色谱填料研究进展", 《中国科学B辑：化学》 * |
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