CN105561959A - Chiral stationary phase prepared by taking quinine-tertiary butyl carbamate as a chiral selector and preparation method and application of chiral stationary phase - Google Patents
Chiral stationary phase prepared by taking quinine-tertiary butyl carbamate as a chiral selector and preparation method and application of chiral stationary phase Download PDFInfo
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Abstract
The invention discloses a chiral stationary phase prepared by taking quinine-tertiary butyl carbamate as a chiral selector and a preparation method and application of the chiral stationary phase, and aims at preparing the UHPLC chiral stationary phase with the maximum pressure resistance of 1300 bar and applying the UHPLC chiral stationary phase to UHPLC chiral separation. The chiral stationary phase suitable for ultra-high pressure liquid chromatography chiral separation is successfully prepared through the steps that the chiral selector is catalyzed with azodiisobutyronitrile, covalently bonded to the surface of mercaptopropyl-derived full porous spherical silica gel and then subjected to endcapping through 1-hexene by adopting a one-pot method. Accordingly, bonding of the chiral selector and endcapping of the stationary phase are completed through the one-pot method, and therefore the preparation efficiency is improved; the prepared chiral stationary phase is used for 12 acid chiral amino acid derivative enantiomers in ultra-high pressure liquid chromatography chiral separation and shows the good chiral separation capacity; under the selected chromatographic separation condition, most of the acid chiral amino acid derivative enantiomers can achieve baseline separation in about one minutes.
Description
Technical field
The present invention relates to chiral separation technology, be specifically related to chiral stationary phase prepared for chiral selector with quinine-t-butylcarbamate and its preparation method and application.
Background technology
The compound with chirality refer to have in kind can not the compound of complete overlapping character with mirror image, containing chiral drug, Chiral pesticide, chirality organic synthesis intermediate, chiral environmental pollutants etc.Compound containing a chiral centre has a pair enantiomer, and the equal amount of mixture of this pair enantiomer forms a racemic modification.Chiral drug is usually with the form medication of racemic modification.A pair enantiomer of chiral drug has different metabolism behaviors and physiologic effect in human body, a usual isomers has good curative effect (excellent isomers), and another is invalid even has the effect such as strong side effect, toxicity (carcinogenic, teratogenesis) (bad isomers).So Chiral Separation should be opened the character of rear each isomers of further investigation for chiral drug, and with the excellent isomers medication of chiral purity.
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.The chiral stationary phase (ChiralStationaryPhase, CSP) being applicable to HPLC is of a great variety, has shiploads of merchandiseization to originate simultaneously.The chiral stationary phase being applicable to HPLC is normally by chiral selector coating or be bonded to prepared by the surface of 3-10 micron grain size spherical silica gel, the stainless steel chromatogram column internal diameter of filling is generally 4.6-10mm, length is 15-25cm, and disengaging time is from several minutes to several tens minutes.The needs of all Chiral Separation in practical study work can be met, in the urgent need to developing the new CSP with high separability energy without any a kind of CSP.
Ultrahigh pressure liquid phase chromatogram and Ultra Performance Liquid Chromatography (UltraHighPerformanceLiquidChromatography, UHPLC) are the latest developments of modern liquid chromatography compartment analysis science and technology.UHPLC by reducing the particle diameter (extremely) of fixed phase stuffing, less internal diameter chromatographic column (being generally 2.1mm internal diameter), comparatively shorter chromatogram column length (5cm or 10cm is long), high flow rate (the highest 5ml/min) obtain higher post effect and shortening analysis time.UHPLC chromatographic column needs the pressure of superelevation (being up to 1300bar) to drive mobile phase.The UHPLC chromatographic column of current commercial source only has C18, non-bonding SiO
2on achirality post.
Summary of the invention
In order to solve the deficiencies in the prior art, the invention provides chiral stationary phase prepared for chiral selector with quinine-t-butylcarbamate and its preparation method and application.
Technical scheme of the present invention is: with quinine-t-butylcarbamate for chiral selector prepares the method for chiral stationary phase, comprise the following steps successively: step one, 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 and prepares chiral stationary phase by quinine-t-butylcarbamate chiral selector.
Further improvement of the present invention comprises:
Described step one specifically comprises: accurately take the full porous spherical silica gel that 5.0g diameter is 1.1-1.9 micron, join in the round-bottomed flask of 100ml, then add 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 each 60ml washing of dry toluene, methyl alcohol, ether, n-hexane successively, often walking centrifugal rotational speed is 5000rpm, and centrifugation time is 10min; 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 quinine-t-butylcarbamate chiral selector, 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, nitrogen protection device is installed, magnetic agitation, back flow reaction 12 hours; Post processing: centrifuge washing product, use each 60ml washing of anhydrous chloroform, methyl alcohol, ether, n-hexane successively, often walk centrifugal, 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.
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, take chloroform as homogenate and displacement fluid, under 12000psi pressure condition, the chiral stationary phase obtained with said method is inserted in the stainless steel chromatogram void column pipe of internal diameter 2.1mm, length 50mm, obtain the chiral column that can use on ultrahigh-pressure liquid chromatograph.
Described a kind of ultrahigh pressure liquid phase chromatogram chiral column, before use, makes it under 1ml/min flow conditions, use ethanol to rush post 10min, then uses mobile phase to balance 10min under setting chromatographic condition.
Present invention also offers a kind of ultrahigh pressure liquid phase chromatogram chiral column chiral stationary phase obtained according to above-mentioned method.
Invention further provides the application of chiral stationary phase in ultrahigh pressure liquid phase chromatogram chiral separation prepared for chiral selector with quinine-t-butylcarbamate.
Described application, its chiral separation sample is the amino acid of amino upper band blocking group, in acid, specifically comprise: N-dansyl-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 benzoyl)-DL-serine (S9), N-(3, 5-dinitro benzoyl)-DL-METHIONINE (S10), N-(3, 5-dinitro benzoyl)-DL-Alanine (S11) and N-(2, 4-dinitrophenyl)-DL-LEUCINE (S12).
Described application, the chromatographic condition of ultrahigh-pressure liquid chromatograph is: rp mode, mobile phase is acetonitrile by volume: the mixed solution of 0.1M ammonium acetate solution=80:20, be 6.0 with acetic acid adjust pH, flow velocity is 3.0ml/min, column temperature 20 DEG C, sample size is 0.5 microlitre, determined wavelength 254nm; Polar organic solvent pattern, mobile phase is the methyl alcohol mixed by volume: acetic acid: triethylamine=98:2:0.2, and flow velocity is 2.5ml/min, column temperature 20 DEG C, and sample size is 0.5 microlitre, determined wavelength 254nm.
The present invention be intended to prepare the highest withstand voltage 1300bar UHPLC chiral stationary phase and for UHPLC chiral separation.Adopt " one kettle way " by chiral selector, use azodiisobutyronitrile catalysis, be covalently bound on the full porous spherical Silica Surface of mercapto propyl group derivatization of mercapto propyl group derivatization, and utilize the sealing of 1-hexene, successfully prepared the chiral stationary phase being applicable to ultrahigh pressure liquid phase chromatogram chiral separation.
The bonding of chiral selector and the sealing " one kettle way " of Stationary liquid complete, and improve preparation efficiency.The chiral stationary phase of preparation, for the acid chiral amino acid derivative enantiomer of ultrahigh pressure liquid phase chromatogram chiral separation 12 kinds, demonstrates good Chiral Separation Ability.Under selected chromatographic separation condition, most of acid chiral amino acid derivative enantiomer can obtain baseline separation (separating degree Rs > 1.5) in about one minute.Successfully can be separated some aobvious acid chiral amino acid derivative enantiomers at about one minute, for the Chiral Separation problem solved in the process of producing product such as chiral drug, Chiral pesticide, chirality organic synthesis intermediate, there is important value.
Evaluated by UHPLC chiral separation, result shows that prepared UHPLCCSP has good chiral recognition, can be separated acid chiral amino acid derivative, can be applicable to amino acid derivativges enantiomter and analyzes and quality of production control.
Accompanying drawing explanation
Fig. 1 is N-(3,5-dinitro benzoyl)-DL-LEUCINE (S6) chirality separating resulting on CSP under polarity mobile phase pattern.
Fig. 2 is N-under rp mode (3,5-dinitro benzoyl)-DL-serine (S8) 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 quinine (Quinine, QN, 97%, 3.01g); Add 60ml dry toluene again, water knockout drum and nitrogen protection device are installed, magnetic agitation, backflow azeotropic water removing 1 hour.Reaction unit is cooled to room temperature, removes water knockout drum, add 10.0mmol derivatization reagent t-butylisocyanate (97%; 1.17ml), add 3 catalyst dibutyltin dilaurylate, nitrogen protection device is installed; magnetic agitation, back flow reaction 4 hours.Post processing: first use Rotary Evaporators removing solvent toluene, then 60ml n-hexane is added in the crude product, room temperature condition lower magnetic force stirs and spends the night, sand core funnel suction filtration, uses a small amount of n-hexane product, drains, finally utilize cyclohexane for recrystallization solvent, through recrystallization operation purified product, 60 DEG C of vacuum drying 24 hours, obtain the quinine-t-butylcarbamate of the chiral selector after purifying (tert-BuCQN):
13CNMR(101MHz,CDCl
3)δ158.00(s),147.64(s),144.91(s),144.37(s),142.09(s),131.78(s),127.57(s),121.94(s),118.91(s),118.62(s),114.54(s),101.65(s),60.13(s),59.14(s),56.63(s),55.78(s),50.76(s),42.50(s),39.98(s),28.99(s),27.93(s),27.71(s),27.04(s).
Embodiment 2
The preparation of the full porous spherical silica gel of 3-mercapto propyl group derivatization, accurately takes the full porous spherical silica gel that 5.0g diameter is 1.1-1.9 micron, adds 100ml round-bottomed flask; add 60ml dry toluene again; 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 each 60ml washing of dry toluene, methyl alcohol, ether, n-hexane successively, often walking centrifugal rotational speed is 5000rpm, and 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 0.27g quinine-t-butylcarbamate chiral selector, 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, installs nitrogen protection device, magnetic agitation, back flow reaction 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, use each 60ml washing of anhydrous chloroform, methyl alcohol, ether, n-hexane successively, often walk centrifugal, 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.
Utilize high-pressure homogenization, take chloroform as homogenate and displacement fluid, under 12000psi pressure condition, the chiral stationary phase obtained with said method is inserted in the stainless steel chromatogram void column pipe of internal diameter 2.1mm, length 50mm, obtain the chiral column that can use on ultrahigh-pressure liquid chromatograph.Before use, make it under 1ml/min flow conditions, use ethanol to rush post 10min, then use mobile phase to balance 10min under setting chromatographic condition.
Embodiment 4
With the application of chiral stationary phase in ultrahigh pressure liquid phase chromatogram chiral separation that quinine-t-butylcarbamate is prepared for chiral selector.Its chiral separation sample is the amino acid of amino upper band blocking group, in acid, specifically comprise: N-dansyl-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 benzoyl)-DL-serine (S9), N-(3, 5-dinitro benzoyl)-DL-METHIONINE (S10), N-(3, 5-dinitro benzoyl)-DL-Alanine (S11) and N-(2, 4-dinitrophenyl)-DL-LEUCINE (S12).Its chemical structural formula is as follows:
The chromatographic condition of ultrahigh-pressure liquid chromatograph is: rp mode, and mobile phase is acetonitrile by volume: the mixed solution of 0.1M ammonium acetate solution=80:20 is 6.0 with acetic acid adjust pH, flow velocity is 3.0ml/min, column temperature 20 DEG C, sample size is 0.5 microlitre, determined wavelength 254nm; Polar organic solvent pattern, mobile phase is the methyl alcohol mixed by volume: acetic acid: triethylamine=98:2:0.2, and flow velocity is 2.5ml/min, column temperature 20 DEG C, and sample size is 0.5 microlitre, determined wavelength 254nm.
12 kinds of acid chiral amino acid derivatives on chiral stationary phase chirality separating resulting respectively see 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 quinines-t-butylcarbamate UHPLCCSP
1:Mobilephase:ACN:0.1MCH
3COONH
4＝80:20(v/v),pH＝6.0,3.0ml/min,254nm,20℃,0.5μl.
2:Mobilephase:MeOH:CH
3COOH:(CH
3CH
2)
3N＝98:2:0.2(v/v/v),2.5ml/min,254nm,20℃,0.5μl.
Embodiment 5
As shown in Figure 1, N-(3,5-dinitro benzoyl)-DL-LEUCINE (S6) chirality separating resulting on CSP under polarity mobile phase pattern.Wherein mobile phase: MeOH:CH
3cOOH:(CH
3cH
2)
3n=98:2:0.2 (v/v/v), flow velocity 2.5ml/min, determined wavelength 254nm, 20 DEG C, sample size 0.5 μ l.The chromatographic condition of ultrahigh-pressure liquid chromatograph is with embodiment 4.
Embodiment 6
As shown in Figure 2, N-(3,5-dinitro benzoyl)-DL-serine (S8) chirality separating resulting on chiral stationary phase under rp mode.Wherein mobile phase A CN:0.1MCH
3cOONH
4=80:20 (v/v), pH=6.0, flow velocity 3.0ml/min, determined wavelength 254nm, 20 DEG C, sample size 0.5 μ l.The chromatographic condition of ultrahigh-pressure liquid chromatograph is with embodiment 4.
The present invention be intended to prepare the highest withstand voltage 1300bar UHPLC chiral stationary phase and for UHPLC chiral separation.Adopt " one kettle way " by chiral selector, use azodiisobutyronitrile catalysis, be covalently bound on the full porous spherical Silica Surface of 3-mercapto propyl group derivatization, and utilize the sealing of 1-hexene, successfully prepared the chiral stationary phase being applicable to ultrahigh pressure liquid phase chromatogram chiral separation.
The bonding of chiral selector and the sealing " one kettle way " of Stationary liquid complete, and improve preparation efficiency.The chiral stationary phase of preparation, for the acid chiral amino acid derivative enantiomer of ultrahigh pressure liquid phase chromatogram chiral separation 12 kinds, demonstrates good Chiral Separation Ability.Under selected chromatographic separation condition, most of acid chiral amino acid derivative enantiomer can obtain baseline separation (separating degree Rs > 1.5) in about one minute.Successfully can be separated some aobvious acid chiral amino acid derivative enantiomers at about one minute, for the Chiral Separation problem solved in the process of producing product such as chiral drug, Chiral pesticide, chirality organic synthesis intermediate, there is important value.
Evaluated by UHPLC chiral separation, result shows that prepared UHPLCCSP has good chiral recognition, can be separated acid chiral amino acid derivative, can be applicable to amino acid derivativges enantiomter and analyzes and quality of production control.
More than show and describe general principle of the present invention and principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements all fall in the claimed scope of the invention.Application claims protection domain is defined by appending claims and equivalent thereof.
Claims (9)
1. with quinine-t-butylcarbamate for chiral selector prepares the method for chiral stationary phase, it is characterized in that, comprise the following steps successively: step one, prepare the full porous spherical silica gel of mercapto propyl group derivatization; Step 2, is bonded to quinine-t-butylcarbamate chiral selector on the full porous spherical Silica Surface of mercapto propyl group derivatization and prepares chiral stationary phase.
2. according to claim 1 with quinine-t-butylcarbamate for chiral selector prepares the method for chiral stationary phase, it is characterized in that, described step one specifically comprises: the diameter accurately taking 5.0g is the full porous spherical silica gel of 1.1-1.9 micron, add in 100ml round-bottomed flask, add 60ml dry toluene again, 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 each 60ml washing of dry toluene, methyl alcohol, ether, n-hexane successively, often walking centrifugal rotational speed is 5000rpm, and centrifugation time is 10min; End product vacuum drying 24 hours under 60 DEG C of conditions.
3. according to claim 1 with quinine-t-butylcarbamate for chiral selector prepares the method for chiral stationary phase, it is characterized in that, described step 2 specifically comprises: in 100ml round-bottomed flask, add 0.27g quinine-t-butylcarbamate chiral selector, 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, nitrogen protection device is installed, magnetic agitation, back flow reaction 12 hours; Post processing: centrifuge washing product, use each 60ml washing of anhydrous chloroform, methyl alcohol, ether, n-hexane successively, often walk centrifugal, 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, take chloroform as homogenate and displacement fluid, under 12000psi pressure condition, the chiral stationary phase obtained with method described in claim 1 is inserted in the stainless steel chromatogram void column pipe of internal diameter 2.1mm, length 50mm, obtain the chiral column that can use on ultrahigh-pressure liquid 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 to balance 10min under setting chromatographic condition.
6. a ultrahigh pressure liquid phase chromatogram chiral column chiral stationary phase, is characterized in that, obtain in accordance with the method for claim 1.
7. with the application of chiral stationary phase in ultrahigh pressure liquid phase chromatogram chiral separation that quinine-t-butylcarbamate is prepared for chiral selector.
8. application according to claim 7, it is characterized in that, chiral separation sample is the amino acid of amino upper band blocking group, in 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 benzoyl)-DL-serine, N-(3, 5-dinitro benzoyl)-DL-METHIONINE, N-(3, 5-dinitro benzoyl)-DL-Alanine and N-(2, 4-dinitrophenyl)-DL-LEUCINE.
9. application according to claim 7, it is characterized in that, the chromatographic condition of ultrahigh-pressure liquid chromatograph is: rp mode, mobile phase is acetonitrile by volume: the mixed solution of 0.1M ammonium acetate solution=80:20, be 6.0 with acetic acid adjust pH, flow velocity is 3.0ml/min, column temperature 20 DEG C, sample size is 0.5 microlitre, determined wavelength 254nm; Polar organic solvent pattern, mobile phase is the methyl alcohol mixed by volume: acetic acid: triethylamine=98:2:0.2, and flow velocity is 2.5ml/min, column temperature 20 DEG C, and sample size is 0.5 microlitre, determined 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 CN201610079349.8A patent/CN105561959A/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 |
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| 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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Application publication date: 20160511 |