CN104628892B - Preparation method and use of 6-benzyl phenylethylamine derivative beta-cyclodextrin bonded SBA-15 - Google Patents
Preparation method and use of 6-benzyl phenylethylamine derivative beta-cyclodextrin bonded SBA-15 Download PDFInfo
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Abstract
The invention discloses a preparation method of 6-benzyl phenylethylamine derivative beta-cyclodextrin bonded SBA-15. The preparation method comprises the following steps: with 6-p-tolylsulfonyl beta-cyclodextrin and N-benzyl-1-phenylethylamine as raw materials, preparing a 6-benzyl phenylethylamine derivative beta-cyclodextrin ligand; adding a coupling agent 3-isocyanate propyl siloxane, and reacting to prepare siloxane containing the 6-benzyl phenylethylamine derivative beta-cyclodextrin; with an ordered mesoporous SBA-15 silica gel as a bonding matrix, reacting the bonding matrix with the siloxane containing the 6-benzyl phenylethylamine derivative beta-cyclodextrin to obtain a coarse product of 6-benzyl phenylethylamine derivative beta-cyclodextrin bonded SBA-15; with acetone as a solvent, extracting and purifying via a soxhlet to prepare the 6-benzyl phenylethylamine derivative beta-cyclodextrin bonded SBA-15. The preparation method disclosed by the invention is simple and the convenient, the cost is lower, the adaptability is wide, the stereoselectivity is stronger, meanwhile the permeability is good, the mass transfer resistance is small, and the 6-benzyl phenylethylamine derivative beta-cyclodextrin bonded SBA-15 can be used as a stationary phase in chiral chromatography for the chiral separation and analysis of high performance Liquid chromatography.
Description
Technical field
The present invention relates to the preparation method of chiral stationary phase, in particular to a kind of 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-
The Preparation method and use of bonding SBA-15.
Background technology
Life system is complicated chiral systems, and such as protein, enzyme, polysaccharide, DNA etc. have chirality,
The absorption of chiral drug enantiomer, transhipment, metabolism etc. there is stereo selectivity so that drug enantiomer is in pharmacologically active, poison
Often there is obvious difference in the aspect such as property and pharmacokineticss.Beta-blocker is a class clinical treatment hypertension, heart strand
Bitterly, the modal chiral drug of the disease such as arrhythmia.Zoopery shows, (the S)-enantiomer of most of beta-blockers
It is typically 50～500 times of (R)-enantiomer activity.For example the most frequently used propranolol hydrochloride S- on beta-receptor blocking effect
Type is stronger than R- type enantiomer about 100 times, and (R)-type enantiomer can suppress libido, is a kind of male contraceptive pill, long-term taking pair
People's cognition causes very big injury.The activity that (the S)-enantiomer of spectinomycin hydrochloride blocks heart beta receptor is its (R)-right
Reflect 33 times of body.Early in 1992 FDA (Food and Drug Adminstration) (FDA) issued chiral drug guideline, this principles and requirements
U.S.'s listing all chiral drugs it is necessary to make explicitly stated to the pharmacokineticss of its enantiomer, and strictly monitor
The chiral purity of medicine.State Food and Drug Administration of China promulgated in 2006《Chiral drug quality controling research
Technological guidance's principle》, the sale of chiral medicine done relevant regulations (State Food and Drug Administration.《Chiral drug matter
Amount controls investigative technique guideline》(state's food medicine prison note [2006] 639) .2006.).Because chiral drug is in building-up process
In hardly result in single isomer, be therefore clinically mostly administered in the form of racemic modification, drug safety has hidden danger.Cause
This, the strict content monitoring enantiomers of chiral drugs, all have with guarantee drug safety to improving chiral drug quality control system
There is important Research Significance, wherein develop the new separation material of quick, easy, efficient, inexpensive Chiral Separation and new
Chiral separation method is extremely urgent.
The method for splitting of enantiomers of chiral drugs mainly includes high performance liquid chromatography and capillary electrophoresis etc. at present.Especially
It is high performance liquid chromatography because separation condition is gentle, easy and simple to handle, instrument commercialized degree high, become medicine at present chiral
One of detached prefered method.High performance liquid chromatography is related to develop new chiral separation material, prepares high selection
Property, high stability and the quick chiral column of high-permeability are hot research fields, and the preparation method of wherein fixing phase occupies importantly
Position.At present, fixing phase part mainly includes following a few class：Pirkle type, crown ether, cyclodextrin, macrocyclic antibiotic, protein, micro-
Crystalline cellulose, amylose, spiro-compound etc..What Commercialization application was the widest is derivatization cellulose family part, typically to apply
Based on deposited type, operate under the conditions of being useful in normal-phase chromatography, chiral separation object is wider, but the loss of coated stationary phase is usually
The service life of impact chiral column, along with being gradually reduced of separating degree and stability, so the selection of mobile phase and splitting die
Formula all exists certain restricted, and in addition the type commodity post is expensive, increased testing cost.Therefore, develop further
Selectivity height, good stability, preparation facility, lower-cost novel chiral fixing phase have important Research Significance and well should
Use prospect.
Cyclodextrin contains abundant supermolecule chirality recognition site, so that chiral separation selectivity is carried further by derivatization
Height, can use under positive, the anti-phase and organic multi-mode of polarity, there is extensive object, stability is high, and price is relatively just in addition
Preferably, it is one of rising chiral ligand.
Cyclodextrin is class D- type glucose oligomers, is connected with α-Isosorbide-5-Nitrae-glycosidic bond, common α, β, γ-CD contains respectively
There are 6,7,8 glucose units.Cyclodextrin has hydrophobic with hydrophilic outside the chamber unique texture of inner chamber, especially derivatized cyclodextrin
Part can identify R- by hydrogen bond, dipole, electrostatic, π-π and Inclusion property, and S- chirality object, due to forming inclusion complex stability
Difference enantiomer is separated, there is higher separation selectivity.
At present cyclodextrin derivatization mode mainly include methylating, acetylation, benzoylation, carbanilic acid esterification etc. several
Class, most is full derivatization or part derivatization, because the uncertainty of substitution value or position is it is difficult to ensure and effective control institute
The chiral stationary phase of preparation batch between chromatographic separation performance, full derivatization causes the congestion of cyclodextrin port sometimes, and impact is chiral
Separating effect.About the chiral stationary phase of mono-substituted benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-, there is not been reported.Therefore, prepare
Mono-substituted cyclodextrin part not only can make separating mechanism simple and clear, can improve chiral separation effect simultaneously.
Content of the invention
Present invention aim to overcoming the shortcomings of existing for prior art, provide a kind of 6- benzyl-1-phenylethylamine derivatization
Beta-schardinger dextrin-is bonded the Preparation method and use of SBA-15.
The preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 of the present invention, can pass through following technical side
Case is realizing：
1) under nitrogen atmosphere, with anhydrous DMF as solvent, raw material is pressed 6- tosylation β-ring
The mmol consumption of dextrin：The ratio 1.0 of the ml consumption of N- benzyl -1- phenethylamine：0.6～1.0 addition, stirring 1～2h makes raw material
Fully dissolving forms homogeneous phase solution；Under nitrogen protection, in 80～85 DEG C of oil baths, magnetic agitation reacts 4～6h；Then reduce pressure
Solvent is evaporated off, solid is dissolved in a small amount of hot water, stirring is lower to add acetone-water solution, collects white precipitate, and repeats above-mentioned
Operation 3 times, after 50 DEG C of vacuum drying, obtains 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-；
2) under nitrogen atmosphere, by step 1) 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin of obtaining is in anhydrous N, N- bis-
In methylformamide, add 3- isocyanatopropyl siloxanes, stirring reaction 1～2h under room temperature under ice bath, then protect in nitrogen
Under, continue reaction 4～6h in 80 DEG C of oil baths, obtain the solution of the siloxanes of the derivatization beta-schardinger dextrin-of benzyl-1-phenylethylamine containing 6-；Its
In, the mmol consumption of 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-：The mmol consumption of 3- isocyanate group propyl-siloxane：Anhydrous N,
The ratio of the ml consumption of dinethylformamide is 1.0：1.0～1.5：30～40；
3) under nitrogen atmosphere, by step 2) in 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-mmol consumption：SBA-15
G consumption ratio be 1.0：1.0～1.5, under stirring, pre-dry SBA-15 is added directly into step 2) gained molten
In liquid, be warming up to 110～120 DEG C, oil bath react 10～15h, after being cooled to room temperature, solid repeatedly use DMF and
Washing with acetone, till washing liquid is limpid, obtains 6- benzyl-1-phenylethylamine-beta-schardinger dextrin-bonding SBA-15 silica gel crude product；
4) press step 3) in add SBA-15 g consumption：The ratio of the ml consumption of acetone is 1.0：80～110, use third
Ketone makees solvent, by silica gel crude product surname extraction 15～20h, to remove unnecessary part and impurity in SBA-15 silica gel duct,
50 DEG C of vacuum drying 12h, obtain 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15.
The structure of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 is as follows：
Step 1 of the present invention) in, in described acetone-water solution, acetone and the volume ratio of water are 10～15：1.
Step 2 of the present invention) in, the mmol consumption of described 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-：3- isocyanate group third
The mmol consumption of radical siloxane：The optimum proportioning of the ml consumption of anhydrous N,N-dimethylformamide is 1.0：1.2：35.
Step 2 of the present invention) in, described 3- isocyanate group propyl-siloxane be 3- isocyanate group propyl trimethoxy silicane or
3- isocyanate group propyl-triethoxysilicane.
Step 3 of the present invention) in, the mmol consumption of 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-：The g consumption of SBA-15 is
1.0：1.2.
Step 4 of the present invention) in, the g consumption of described SBA-15：The ratio of the ml consumption of acetone is 1.0：100.
SBA-15 of the present invention is ordered mesoporous material, and aperture is 8～25nm, and specific surface area is 400～500m2/g.
Present invention also offers the purposes of above-mentioned 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15：Will be prepared
6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 as chiral stationary phase, load performance liquid chromatographic column, be used in combination
Chiral separation in compound enantiomer.
The present invention with 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-as part, with 3- isocyanate group propyl-siloxane for be coupled
Agent and order mesoporous SBA-15 silica gel are that bonding substrate prepares novel chiral fixing phase.The joining of one side fixing phase benzyl-1-phenylethylamine
The inclusion of position performance and cyclodextrin cavity carries out synergism, extends chiral separation object, simultaneously the hydrogen bond of port, π-π and
Dipole effect is enhanced, and is conducive to improving chiral Recognition effect；On the other hand mono-substituted cyclodextrin part does not result in ring
The congestion of dextrin port, affects chiral separation effect.Additionally, the orderly SBA-15 substrate with larger specific surface area can accommodate
More chiral ligands, permeability, resistance to mass tranfer is little, improves the comprehensive chromatographic performance of chiral stationary phase, in chiral medicine
The quality-monitoring of thing and enantiomer pharmacokinetic have preferable application prospect.
The present invention prepares gained novel chiral fixing phase and characterizes through infrared spectrum analysiss, elementary analysiss, thermogravimetric analysiss etc.
Its structure, with methanol/water (80/20, ν/ν) for mobile phase, flow velocity is 1mL/min, is visited for solute with 1,3,5- tri-butyl benzene
Pin, records its post and imitates as 12000 plates/rice under room temperature.
The present invention, with chiral separation, flavanone and beta-blocker for solute probe, systematically have studied this
The chiral chromatogram performance of fixing phase.Research finds that benzyl-1-phenylethylamine and the combination of cyclodextrin cavity more enrich chiral Recognition position
Point, by the multiple effects such as cooperative effects such as hydrogen bond, dipole, π-π, electric charge transfer and Inclusion property, is conducive to improving chiral point
From ability and scope.Test result indicate that, solid using the benzyl-1-phenylethylamine derivatized cyclodextrin bonded chiral prepared by the present invention
Fixed mutually have the features such as specific surface area is big, bonded amount is high, method is easy, preparation cost is relatively low, preparation method is widely applicable, due to
Cyclodextrin stable performance, and prepared chiral stationary phase is to be connected with silica gel by way of bonding, using this fixing phase
The chromatographic column service life loading is longer.The present invention prepares gained 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 handss
Property fixing phase silica gel specific surface area be 400～500m2/ g, fixing phase bonded amount is 0.13～0.17 μm of ol/m2.
Brief description
Fig. 1 is red sulfonylation leucic Chiral liquid chromatography figure.
Fig. 2 is the Chiral liquid chromatography figure of red sulfonylation tyrosine.
Fig. 3 is the Chiral liquid chromatography figure of 2'- hydroxyl flavanone.
Fig. 4 is the Chiral liquid chromatography figure of 4'- hydroxyl flavanone.
Fig. 5 is the Chiral liquid chromatography figure of metoprolol.
Fig. 6 is the Chiral liquid chromatography figure of Atenolol.
Specific embodiment
In order to preferably explain the present invention, below in conjunction with the drawings and specific embodiments, the present invention is made further specifically
Bright, but they do not constitute restriction to the present invention.
Embodiment 1
Take SBA-15 (400m2/ g) activated silica gel 2.5g be substrate.
1) under nitrogen atmosphere, with anhydrous DMF as solvent, by 6- tosylation beta-schardinger dextrin-
(mmol)：N- benzyl -1- phenethylamine (ml) is 1.0：0.6 ratio, by 6- tosylation beta-schardinger dextrin-and N- benzyl -1-
Phenethylamine adds in round-bottomed flask, and the lower 1h of stirring makes raw material fully dissolve formation homogeneous phase solution；Configuration condensing tube and calcium chloride are done
Dry pipe, under nitrogen protection, in 80 DEG C of oil baths, magnetic agitation reacts 4h；Then remove solvent under reduced pressure, solid is dissolved on a small quantity
Hot water in, stirring is lower to add acetone-water solution (10：1, v/v), collect white precipitate, and repeat aforesaid operations 3 times, 50 DEG C
After vacuum drying oven is dried, obtain 6- benzyl-1-phenylethylamine beta-schardinger dextrin-, this step reaction yield is 60%；
2) under nitrogen atmosphere, by 6- benzyl-1-phenylethylamine beta-schardinger dextrin-(mmol)：3- isocyanate group propyl-triethoxysilicane
(mmol)：Anhydrous N,N-dimethylformamide is 1.0：1.0：30 ratio, by step 1) 6- benzyl-1-phenylethylamine β-ring of obtaining
Dextrin is dissolved in anhydrous DMF, adds 3- isocyanatopropyl triethoxysilane, stir under room temperature under ice bath
Mix reaction 1h, then under nitrogen protection, continue reaction 4h in 80 DEG C of oil baths, obtain the silicon of the beta-schardinger dextrin-of benzyl-1-phenylethylamine containing 6-
The solution of oxygen alkane；This step does not carry out separating-purifying, proceeds next step reaction；
3) under nitrogen atmosphere, by step 2) in 6- benzyl-1-phenylethylamine beta-schardinger dextrin-(mmol)：SBA-15 (g) is 1.0：
Pre-dry SBA-15 is added directly into step 2 under stirring by 1.0 ratio) in the solution of gained, it is warming up to 110 DEG C, oil
Bath reaction 10h, after being cooled to room temperature, solid uses DMF and washing with acetone repeatedly, till washing liquid is limpid, obtains
It is bonded SBA-15 silica gel crude product to 6- benzyl-1-phenylethylamine beta-schardinger dextrin-；
4) press step 3) the middle SBA-15 (g) adding：Acetone (ml) is 1.0：80 ratio, with acetone as solvent, by silicon
Glue crude product surname extraction 15h, to remove unnecessary part and impurity in SBA-15 silica gel duct, 50 DEG C of vacuum drying 12h,
Obtain 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15.
The present embodiment is pressed elementary analysiss carbon content and is calculated obtained 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded
The surface ligand bonded amount measured data of SBA-15 is as shown in table 1：
Table 1：The surface ligand bonded amount of embodiment 1 products obtained therefrom
| C (%) | H (%) | N (%) | Bonded amount (μm ol/m2) |
| 3.91 | 1.05 | 0.48 | 0.13 |
Embodiment 2
Take SBA-15 (500m2/ g) activated silica gel 2.5g be substrate
1) under nitrogen atmosphere, solvent is made with anhydrous DMF, by 6- tosylation beta-schardinger dextrin-
(mmol)：N- benzyl -1- phenethylamine (ml) is 1.0：1.0 ratio, by 6- tosylation beta-schardinger dextrin-and N- benzyl -1-
Phenethylamine adds in round-bottomed flask, and the lower 2h of stirring makes raw material fully dissolve formation homogeneous phase solution；Configuration condensing tube and calcium chloride are done
Dry pipe, under nitrogen protection, in 85 DEG C of oil baths, magnetic agitation reacts 6h；Then remove solvent under reduced pressure, solid is dissolved on a small quantity
Hot water in, stirring is lower to add acetone-water solution (10:1, v/v), collect white precipitate, and repeat aforesaid operations 3 times, 50 DEG C
After vacuum drying oven is dried, obtain 6- benzyl-1-phenylethylamine beta-schardinger dextrin-, this step reaction yield is 68%；
2) under nitrogen atmosphere, by 6- benzyl-1-phenylethylamine beta-schardinger dextrin-(mmol)：3- isocyanate group propyl trimethoxy silicane
(mmol)：Anhydrous N,N-dimethylformamide is 1.0：1.5：40 ratio, 6- benzyl-1-phenylethylamine beta-schardinger dextrin-is dissolved in no
In water DMF, addition 3- isocyanatopropyl trimethoxy silane under ice bath, stirring reaction 2h under room temperature, then
Under nitrogen protection, continue reaction 6h in 80 DEG C of oil baths, obtain the solution of the siloxanes of the beta-schardinger dextrin-of benzyl-1-phenylethylamine containing 6-；Should
Step does not carry out separating-purifying, proceeds next step reaction；
3) under nitrogen atmosphere, by step 2) in 6- benzyl-1-phenylethylamine beta-schardinger dextrin-(mmol)：SBA-15 (g) is 1.0：
1.5 ratio, under stirring, pre-dry SBA-15 is added directly into step 2) in the solution of gained, it is warming up to 120 DEG C,
15h is reacted in oil bath, and after being cooled to room temperature, solid uses DMF and washing with acetone repeatedly, till washing liquid is limpid,
Obtain 6- benzyl-1-phenylethylamine beta-schardinger dextrin-bonding SBA-15 silica gel crude product；
4) press step 3) the middle SBA-15 (g) adding：Acetone (ml) is 1.0：110 ratio, with acetone as solvent, by silicon
Glue crude product surname extraction 20h, to remove unnecessary part and impurity in SBA-15 silica gel duct, 50 DEG C of vacuum drying 12h,
Obtain 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15.
The present embodiment is pressed elementary analysiss carbon content and is calculated obtained 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded
The surface ligand bonded amount measured data of SBA-15 is as shown in table 2：
Table 2：The surface ligand bonded amount of embodiment 2 products obtained therefrom
| C (%) | H (%) | N (%) | Bonded amount (μm ol/m2) |
| 5.65 | 1.38 | 0.69 | 0.15 |
Embodiment 3
Take SBA-15 (420m2/ g) activated silica gel 2.5g be substrate.
1) under nitrogen atmosphere, solvent is made with anhydrous DMF, by 6- tosylation beta-schardinger dextrin-
(mmol)：N- benzyl -1- phenethylamine (ml) is 1.0：0.8 ratio, by 6- tosylation beta-schardinger dextrin-and N- benzyl -1-
Phenethylamine adds in round-bottomed flask, and the lower 1.5h of stirring makes raw material fully dissolve formation homogeneous phase solution；Configuration condensing tube and calcium chloride
Drying tube, under nitrogen protection, in 85 DEG C of oil baths, magnetic agitation reacts 5h.Then remove solvent under reduced pressure, solid is dissolved in few
In the hot water of amount, stirring is lower to add acetone-water solution (10:1, v/v), collect white precipitate, and repeat aforesaid operations 3 times, 50
DEG C vacuum drying oven obtains 6- benzyl-1-phenylethylamine beta-schardinger dextrin-after being dried, and this step reaction yield is 70%；
2) under nitrogen atmosphere, by 6- benzyl-1-phenylethylamine beta-schardinger dextrin-(mmol)：3- isocyanate group propyl-triethoxysilicane
(mmol)：Anhydrous N,N-dimethylformamide is 1.0：1.2：35 ratio, 6- benzyl-1-phenylethylamine beta-schardinger dextrin-is dissolved in no
In water DMF, addition 3- isocyanatopropyl triethoxysilane under ice bath, stirring reaction 1.5h under room temperature, so
Afterwards under nitrogen protection, continue reaction 5h in 80 DEG C of oil baths, obtain the solution of the siloxanes of the beta-schardinger dextrin-of benzyl-1-phenylethylamine containing 6-.
This step does not carry out separating-purifying, proceeds next step reaction；
3) under nitrogen atmosphere, by step 2) in 6- benzyl-1-phenylethylamine beta-schardinger dextrin-(mmol)：SBA-15 (g) is 1.0：
Pre-dry SBA-15 is added directly under stirring in the reactant liquor of upper step by 1.2 ratio, is warming up to 115 DEG C of oil baths anti-
Answer 12h, after being cooled to room temperature, solid uses DMF and washing with acetone repeatedly, till washing liquid is limpid, obtains 6-
Benzyl-1-phenylethylamine beta-schardinger dextrin-is bonded SBA-15 silica gel crude product；
4) press step 3) the middle SBA-15 (g) adding：Acetone (ml) is 1.0：100 ratio, with acetone as solvent, by silicon
Glue crude product surname extraction 18h, to remove unnecessary part and impurity in SBA-15 silica gel duct, 50 DEG C of vacuum drying 12h,
Obtain 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15.
The present embodiment is pressed elementary analysiss carbon content and is calculated obtained 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded
The surface ligand bonded amount measured data of SBA-15 is as shown in table 3：
Table 3：The surface ligand bonded amount of embodiment 3 products obtained therefrom
| C (%) | H (%) | N (%) | Bonded amount (μm ol/m2) |
| 5.34 | 1.31 | 0.64 | 0.17 |
Application examples 4
Using the 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 prepared by embodiment 3 as chiral stationary phase
Split for high performance liquid chromatography chipal compounds.
Split object：Two chiral separations (red sulfonylation leucine, red sulfonylation tyrosine), two flavanones
Compound (2'- hydroxyl flavanone, 4'- hydroxyl flavanone) and two beta-blocker (metoprolol, Atenolol) structures
As follows：
Detailed process：Chromatographic column is loaded using slurry packing.Weigh the 6- benzyl of the embodiment of the present invention 3 that 2.5g is dried
Phenethylamine derivatized beta-cyclodextrin bonded SBA-15, adds 30mL acetone, ultrasonic mixing, with methanol as displacer, in 35MPa pressure
Under power, homogenate is filled in the chromatographic column (150mm × 4.6mmI.D.) having cleaned up, keeps pressure 30min.Take off filling
Good chromatographic column, puts chromatograph stigma, indicates mobile phase direction.Repeatedly rinse chromatographic column with water and methanol, use mobile phase used
Balance, sample introduction analysis after baseline is steady.Standard substance methanol solution is made into the stock solution of about 0.5mg/mL, in 4 DEG C of lucifuges
Preserve.With front through 0.45 μm of membrane filtration, ultrasonic degassing, direct injection analysis.
With 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 as chiral stationary phase, under reversed phase chromatography pattern,
Mobile phase is 1% vinegar triethylenetetraminehexaacetic acid ammonium (pH=5.0)/methanol, with front through 0.45 μm of membrane filtration, ultrasonic degassing.Flow velocity is
0.5mL/min；Column temperature is 20 DEG C；Sample size is 5 μ L；Detection wavelength is 330nm.Dead time is surveyed with 1,3,5- tri-butyl benzene
Fixed.The flowing phase composition of two dansyl Cl aminoacid dansyl Cl leucines and dansyl Cl tyrosine optimization is not all：1%
Vinegar triethylenetetraminehexaacetic acid ammonium (pH=5.0)/methanol, 70/30.The separating degree (Rs) obtaining is respectively：2.79 and 3.29.
With 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 as chiral stationary phase, under reversed phase chromatography pattern,
Mobile phase is the acetonitrile/formic acid of different proportion, with front through 0.45 μm of membrane filtration, ultrasonic degassing.Flow velocity is 0.5mL/min；Post
Temperature is 20 DEG C；Sample size is 5 μ L；Detection wavelength is 323nm.Two flavanone compound 2'- hydroxyl flavanone and 4'- hydroxyl
The flowing phase composition of flavanone optimization is respectively：(c) methanol/formic acid (40/60, ν/ν) and (d) acetonitrile/formic acid (20/80, ν/
ν).The separating degree (Rs) obtaining is respectively：3.25 and 3.65.
With 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 as chiral stationary phase, in polar organic solvent pattern
Under, mobile phase is the acetonitrile/methanol/glacial acetic acid/triethylamine of different proportion, with front through 0.45 μm of membrane filtration, ultrasonic degassing.Stream
Speed is 0.5mL/min；Column temperature is 20 DEG C；Sample size is 5 μ L；Detection wavelength is 275nm.Two beta-blocker metoprolols
Flowing phase composition with Atenolol optimization is respectively：Acetonitrile/methanol/glacial acetic acid/triethylamine (ν/ν/ν/ν), (e) 95/5/
0.5/0.4,(f)90/10/1.0/0.9.The separating degree (Rs) obtaining is respectively：1.67 and 1.62.
Split red sulfonylation leucine, red sulfonylation tyrosine, 2'- hydroxyl flavanone, 4'- hydroxyl flavanone, Mei Tuoluo
That and the chiral chromatogram figure of Atenolol, respectively as shown in figs. 1 to 6.
In Fig. 1：The retention time of the enantiomer of the leucic 2 kinds of chipal compounds of red sulfonylation be respectively 11.89min and
14.96min, separating degree is 2.79.
In Fig. 2：The retention time of the enantiomer of 2 kinds of chipal compounds of red sulfonylation tyrosine be respectively 14.21min and
20.62min, separating degree is 3.29.
In Fig. 3：The retention time of the enantiomer of 2 kinds of chipal compounds of 2'- hydroxyl flavanone be respectively 11.18min and
14.53min, separating degree is 3.25.
In Fig. 4：The retention time of the enantiomer of 2 kinds of chipal compounds of 4'- hydroxyl flavanone be respectively 12.07min and
15.20min, separating degree is 3.65.
In Fig. 5：The retention time of the enantiomer of 2 kinds of chipal compounds of metoprolol be respectively 14.04min and
16.19min, separating degree is 1.67.
In Fig. 6：The retention time of the enantiomer of 2 kinds of chipal compounds of Atenolol be respectively 17.92min and
20.40min, separating degree is 1.62.
Result shows：The present invention with 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 as chiral stationary phase, energy
It is successfully used to high performance liquid chromatography and split chiral separation, part beta-blocker and flavanone chipal compounds
Enantiomer.
Claims (7)
1. a kind of preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 it is characterised in that it include with
Lower step：
1) under nitrogen atmosphere, with anhydrous DMF as solvent, raw material is pressed 6- tosylation beta-schardinger dextrin-
Mmol consumption：The ratio 1.0: 0.6～1.0 of the mL consumption of N- benzyl -1- phenethylamine adds, and stirring 1～2h makes raw material abundant
Dissolving forms homogeneous phase solution；Under nitrogen protection, in 80～85 DEG C of oil baths, magnetic agitation reacts 4～6h；Then remove under reduced pressure
Solvent, solid is dissolved in a small amount of hot water, and stirring is lower to add acetone-water solution, collects white precipitate, and repeats aforesaid operations
3 times, after 50 DEG C of vacuum drying, obtain 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-；
2) under nitrogen atmosphere, by step 1) 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin of obtaining is in anhydrous N, N- dimethyl
In Methanamide, addition 3- isocyanatopropyl siloxanes under ice bath, stirring reaction 1～2h under room temperature, then under nitrogen protection, 80
Continue reaction 4～6h in DEG C oil bath, obtain the solution of the siloxanes of the derivatization beta-schardinger dextrin-of benzyl-1-phenylethylamine containing 6-；Wherein, 6-
The mmol consumption of benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-：The mmol consumption of 3- isocyanate group propyl-siloxane：Anhydrous N, N- bis-
The ratio of the mL consumption of methylformamide is 1.0: 1.0～1.5: 30～40；
3) under nitrogen atmosphere, by step 2) in 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-mmol consumption：The g of SBA-15 uses
The ratio of amount is 1.0: 1.0～1.5, under stirring, pre-dry SBA-15 is added directly into step 2) in the solution of gained,
It is warming up to 110～120 DEG C, 10～15h is reacted in oil bath, after being cooled to room temperature, solid uses DMF and acetone repeatedly
Washing, till washing liquid is limpid, obtains 6- benzyl-1-phenylethylamine-beta-schardinger dextrin-bonding SBA-15 silica gel crude product；
4) press step 3) in add SBA-15 g consumption：The ratio of the mL consumption of acetone is 1.0: 80～110, is made with acetone
Solvent, by silica gel crude product surname extraction 15～20h, to remove unnecessary part and impurity in SBA-15 silica gel duct, 50 DEG C
Vacuum drying 12h, obtains 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15.
2. the preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 according to claim 1, it is special
Levy and be：Step 1) in, in described acetone-water solution, acetone and the volume ratio of water are 10～15: 1.
3. the preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 according to claim 1, it is special
Levy and be：Step 2) in, the mmol consumption of described 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-：3- isocyanate group propyl-siloxane
Mmol consumption：The ratio of the mL consumption of anhydrous DMF is 1.0: 1.2: 35.
4. the preparation method of the 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 according to claim 1 or 3, its
It is characterised by：Step 2) in, described 3- isocyanate group propyl-siloxane is 3- isocyanate group propyl trimethoxy silicane or 3- is different
Cyanic acid base propyl-triethoxysilicane.
5. the preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 according to claim 1, it is special
Levy and be：Step 3) in, the mmol consumption of 6- benzyl-1-phenylethylamine derivatization beta-schardinger dextrin-：The g consumption of SBA-15 is 1.0: 1.2.
6. the preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 according to claim 1, it is special
Levy and be：Step 4) in, the g consumption of described SBA-15：The ratio of the mL consumption of acetone is 1.0: 100.
7. the preparation method of 6- benzyl-1-phenylethylamine derivatized beta-cyclodextrin bonded SBA-15 according to claim 1, it is special
Levy and be：Described SBA-15 is ordered mesoporous material, and aperture is 8～25nm, and specific surface area is 400～500m2/g.
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