CN103193898A - Synthesis and application of L-phenylalanine derived Beta-cyclodextrin bonded silica gel for separating alanine enantiomer - Google Patents
Synthesis and application of L-phenylalanine derived Beta-cyclodextrin bonded silica gel for separating alanine enantiomer Download PDFInfo
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Abstract
The invention belongs to the field of analytic chemistry, relates to synthesis of a chiral column material, and in particular relates to synthesis and an application of L-phenylalanine derived Beta-cyclodextrin bonded silica gel for separating an alanine enantiomer. According to the technical scheme, the synthesis process comprises the following steps: firstly, preparing activated silica gel; then synthesizing Beta-cyclodextrin bonded silica gel; next, synthesizing tosylated Beta-cyclodextrin bonded silica gel; and finally, derivatizing an obtained product by using L-phenylalanine. The prepared L-phenylalanine derived Beta-cyclodextrin bonded silica gel is yellow solid powder which is insoluble in water and organic solvents such as N,N-dimethyl formamide and the like as well as difficult to dissolve in acid solutions. If the synthesized L-phenylalanine derived Beta-cyclodextrin bonded silica gel is served as a chromatographic filling material to perform adsorption separation on an aqueous solution containing the alanine enantiomer at the constant temperature and under the normal pressure, the good chiral separation effect can be achieved. When the L-phenylalanine derived Beta-cyclodextrin bonded silica gel is used for separating the alanine enantiomer, the operation is simple, the cost is low and the adsorption effect is good. Therefore, the L-phenylalanine derived Beta-cyclodextrin bonded silica gel has a definite practical value.
Description
Technical field
The invention belongs to the analytical chemistry field, relate to the synthetic of a kind of chiral column material, particularly derive the synthetic of beta-cyclodextrin bonded silica gel and the L-Ala Separation of Enantiomers used of a kind of L-phenylalanine.
Background technology
The chirality feature of compound is very general, and it causes extensive concern at medicine, agricultural chemicals and life chemistry.In view of three-dimensional arrangement and its biological activity of organic molecule has special relation, set up mapping fractionation and the measuring method of high specificity, high separation, to improving molecular activity, reduce side effect, the further investigation mechanism of action etc. will have important in theory and practical significance.
Chiral stationary phase is to make chiral stationary phase on silica gel or other polymkeric substance and make the difference that presents physical features between enantiomer by introducing chiral environment by having optically active monomer, being fixed on, thereby reaches the purpose that optical isomer splits.At least have the interaction more than three kinds between chipal compounds molecule and the chiral stationary phase, these interactions comprise hydrogen bond, dipole-dipole effect, π-π effect, electrostatic interaction, hydrophobic interaction or space behavior.Realizing chiral recognition and separating effect, then is the coefficient result of multiple interaction.These interact and to change the chiral separation result by the bonding of formation, special site and the analyte that influences the embedding mixture etc.
The cyclodextrin stationary phase is that the beginning of the eighties in last century is by the respectively nitrogenous spacer preparation of two Japanology groups as a kind of stable chiral stationary phase the earliest.In recent years, (range of application of bonded silica gel stationary phase of β-CD), people have synthesized multiple derivatized beta-CD bonded silica gel stationary phase in order to enlarge beta-cyclodextrin.The main achievement of research is at present:
(1) Beijing Institute of Technology's journal, 2007,27:1022-1026, be research object with the synthetic novel Serine in this laboratory beta-cyclodextrin bonded silica gel stationary phase of deriving, adopt high-pressure homogenization method filling performance liquid chromatographic column, filling process is optimized, obtain good chromatogram column efficiency and dress post circulation ratio. investigated the β that derives-CD chromatographic column separation point position isomer and chipal compounds, and compare with the β that do not derive-CD chromatographic column, centrifugation mechanism is discussed.
(2) analytical chemistry, 2010,28:158-162, adopt the β-CD bonded silica gel chiral column of short full phenyl isocyanate derivatize of 5 cm, under the RP-HPLC condition, H-56/28, Proprasylyte, Mei Xijin, metoprolol and 5 kinds of beta-blocker classes of Visken medicine have been carried out the research of chiral separation.
(3) Journal of Pharmaceutical and Biomedical Analysis, 2010,51:84-89, the chiral stationary phase that has synthesized full methyl-6-mono amino-6-deoxidation-beta-cyclodextrin, use high performance liquid chromatography separate the racemic modification of coumarin derivatives and chiral stationary phase are estimated.
(4) Journal of Colloid and Interface Science, 2011,354:483-492, having studied magnetic silica dioxide nano particles is attached on the carboxymethyl-beta-cyclodextrin, absorption behavior to the enantiomorph of some chirality aromatic amino acid, by to the research as selective adsorbent of the magnetic silica particle of CM-β-CD, understand the host-guest interaction mechanism in depth.
(5) nuclear chemistry and radiological chemistry, 2012,34:40-45, utilize amino functional silica gel to be solid phase carrier, but the epoxy chloropropane with two-way reaction is the link agent, the beta-cyclodextrin sorbing material is grafted to the silica gel surface, has prepared the beta-cyclodextrin bonded silica gel solid phase adsorption enrichment material of stable performance, resistance to acids and bases, by metal ion chelation agent diphenylpropane-1,3-dione(DPPO) booster action thorium ion is adsorbed fast.
There are clear superiority in beta-cyclodextrin bonded silica gel and derivative thereof aspect chiral separation, and utilize the beta-cyclodextrin bonded silica gel of L-phenylalanine modification and be applied to L-Ala and other chirality Separation of Enantiomers, and Shang Weijian openly reports.
Summary of the invention
The objective of the invention is that beta-cyclodextrin is carried out the L-phenylalanine and modify and to derive, and the L-phenylalanine of the preparation beta-cyclodextrin bonded silica gel of deriving is applied to L-Ala (Ala) Separation of Enantiomers.
The present invention is the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic and be applied to the L-Ala Separation of Enantiomers, concrete technical scheme of the present invention is to make activated silica gel earlier, then synthetic beta-cyclodextrin bonded silica gel (β-CD/SiO
2), resynthesis tosylation beta-cyclodextrin bonded silica gel is prepared from products therefrom at last with L-phenylalanine derivatize.
Activated silica gel of the present invention is to adopt following steps to make: press the volume mass of hydrochloric acid soln and silica gel than being 20mL/g, with dense HCl – H
2(v/v) with particle diameter be the silica gel of 5 ~ 7 μ ms be mixed with mixture room temperature dipping 24h to O at 1: 3, and then at 120 ℃ of following backflow 10h, suction filtration also is washed till neutrality with bi-distilled water, uses washing with acetone again, in 150 ℃ of following vacuum-drying 10h, places moisture eliminator standby.
Beta-cyclodextrin bonded silica gel (β-CD/SiO of the present invention
2), preparation process comprises as follows:
A, be the ratio of 20g/mL in mass volume ratio, beta-cyclodextrin is dissolved in anhydrous N, be mixed with solution among the N '-dimethyl formamide (DMF), adding the NaH that accounts for beta-cyclodextrin quality 6% is catalyzer, stirs 1h under the room temperature, filters;
B, in nitrogen atmosphere, drip KH-560(γ-(2,3-epoxy, third oxygen) propyl trimethoxy silicane to filtrate), in 85-90 ℃ of reaction 5h, the volume of described KH-560 is 1.96% of filtrate;
C, add the activated silica gel with quality such as beta-cyclodextrin in the reaction system, be warming up to 110-115 ℃ of reaction 24h, to be cooled to room temperature, suction filtration;
D, will filter solids use anhydrous N successively, methanol wash is used in N '-dimethyl formamide, methyl alcohol, bi-distilled water washing at last again, filter is done the back in 120 ℃ of vacuum-drying 3h, places moisture eliminator standby.
Tosylation beta-cyclodextrin bonded silica gel (TsCD/ SiO of the present invention
2), its preparation comprises the steps:
A, by anhydrous pyridine and Tosyl chloride volume mass than being mixed with solution for 25mL/g, add the beta-cyclodextrin bonded silica gel (β-CD/SiO with quality such as Tosyl chloride
2), stir 24h under the room temperature;
B, place ice bath to continue reaction 18h, suction filtration reaction system;
C, will filter product successively with anhydrous pyridine, ether, methyl alcohol, ether washing for several times, in 100 ℃ of following vacuum-drying 24 h, drying for standby.
L-phenylalanine derivatize preparation process of the present invention comprises:
A, press L-phenylalanine and tosylation beta-cyclodextrin bonded silica gel (TsCD/ SiO
2) mixing quality and the solid-to-liquid ratio of anhydrous pyridine be the preferred 40g/mL of 25 ~ 75g/mL() ratio, take by weighing dry L-phenylalanine and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) in anhydrous pyridine, described L-phenylalanine and tosylation beta-cyclodextrin bonded silica gel (TsCD/ SiO
2) mass ratio be 1:2 ~ 2:1, preferred 1:1;
B, in nitrogen atmosphere with solution in 70 ~ 90 ℃ of stirring reaction 40 ~ 52h, preferred 80 ℃ of temperature, preferred 48h of reaction times is cooled to the room temperature suction filtration;
C, will filter product use anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 100 ~ 130 ℃ of following vacuum-drying 3 ~ 5 h, preferred 120 ℃ of bake out temperature, the preferred 4h of drying time.
Beta-cyclodextrin bonded silica gel (the L-Phe-CD/SiO that the L-phenylalanine that the present invention is prepared is modified
2) as the application of chromatograph packing material, as moving phase, under the constant temperature normal pressure, can finish the chromatographic separation of L-Ala enantiomorph with the racemize solution of L-Ala.
The prepared L-phenylalanine of the present invention beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2), outward appearance is yellow, pressed powder is water insoluble, also is insoluble to N, N '-organic solvents such as dimethyl formamide, indissoluble in acidic solution.
L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala.Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts it in the Water Tank with Temp.-controlled, reaches balance up to absorption.The temperature of absorption can be between 25 ~ 50 ℃, preferred 35 ℃.After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place; Measure the specific rotation of clear liquid with polarimeter.
Used beta-cyclodextrin among the present invention, the D-L-Ala, the L-L-Ala, sodium hydride (80%), the L-phenylalanine is available from Chemical Reagent Co., Ltd., Sinopharm Group; Available from Haiyang Chemical Plant, Qingdao, other chemical and reagent are analytical pure to spherical silica gel (5-7 μ m), also all available from Chemical Reagent Co., Ltd., Sinopharm Group.
Beneficial effect
The invention discloses a kind of synthesis of chiral sorbent material L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic method, the prepared L-phenylalanine beta-cyclodextrin bonded silica gel of deriving is the yellow solid powder, and is water insoluble, also is insoluble to N, N '-organic solvents such as dimethyl formamide, indissoluble in acidic solution.The present invention derives the beta-cyclodextrin bonded silica gel as the chromatogram packing material with the L-phenylalanine that is synthesized, and under the constant temperature normal pressure aqueous solution that contains the L-Ala enantiomorph is carried out fractionation by adsorption, has good chiral separation effect.Separate the L-Ala enantiomorph with this material, simple to operate, cost is lower, and advantages of good adsorption effect has certain practical value.
Embodiment
The present invention is described in detail below in conjunction with embodiment, so that those skilled in the art understands the present invention better, but the present invention is not limited to following examples.
In the embodiments of the invention, the preparation process of activated silica gel is as follows: the silica gel 10g that takes by weighing particle diameter and be 5 ~ 7 μ m is immersed in the dense HCl – of 200 mL H
2O (1: 3, v/v; ) 24 h in the solution, at 120 ℃ of following backflow 10h, with bi-distilled water silica gel is washed till neutrality then, use washing with acetone again; The gained activated silica gel places moisture eliminator standby in 150 ℃ of following vacuum-drying 10h.
In the embodiments of the invention, beta-cyclodextrin bonded silica gel (β-CD/SiO
2) preparation process comprise as follows: take by weighing through the beta-cyclodextrin 5g of vacuum-drying and add the anhydrous N of 100mL, among the N '-dimethyl formamide (DMF), adding 0.3gNaH is catalyzer, stirring reaction 1h at room temperature, the solid matter of elimination unreacted; In filtrate, drip KH-560(γ-(2,3-epoxy third oxygen) 2mL propyl trimethoxy silicane) in 85-90 ℃ of reaction 5h, adds the 5g activated silica gel then temperature of reaction is brought up to 110-115 ℃ of continuation reaction 24h in nitrogen atmosphere, after question response liquid is cooled to room temperature, suction filtration; Product is used anhydrous N successively, and methanol wash is used in N '-dimethyl formamide (DMF), methyl alcohol, bi-distilled water washing at last again, and filter is done the back in 120 ℃ of following vacuum-drying 3h, places moisture eliminator standby.
In the embodiments of the invention, tosylation beta-cyclodextrin bonded silica gel (TsCD/ SiO
2) preparation process comprise as follows: take by weighing 2. 0 g Tosyl chlorides and be dissolved in the 50 mL anhydrous pyridines, add 2. 0 g beta-cyclodextrin bonded silica gel (β-CD/SiO
2) under the room temperature behind stirring reaction 24 h, place ice bath (0～2 ℃) to continue reaction 18 h, suction filtration; Product is successively with pyridine, ether, methyl alcohol, ether washing several, 100 ℃ of following vacuum-drying 24 h, drying for standby.
Embodiment 1
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 0.5g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 60mL anhydrous pyridine, in the nitrogen atmosphere in 70 ℃ of stirring reaction 40h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 100 ℃ of following vacuum-drying 3 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 25 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.03 ~ 1.58.
Embodiment 2
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 1g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 50mL anhydrous pyridine, in the nitrogen atmosphere in 70 ℃ of stirring reaction 52h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 120 ℃ of following vacuum-drying 5 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 30 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.31 ~ 1.78.
Embodiment 3
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 2g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 40mL anhydrous pyridine, in the nitrogen atmosphere in 70 ℃ of stirring reaction 40h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 130 ℃ of following vacuum-drying 5 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 45 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.39 ~ 1.88.
Embodiment 4
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 1g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 60mL anhydrous pyridine, in the nitrogen atmosphere in 70 ℃ of stirring reaction 48h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 120 ℃ of following vacuum-drying 4 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 30 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.45 ~ 1.89.
Embodiment 5
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 2g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 50mL anhydrous pyridine, in the nitrogen atmosphere in 90 ℃ of stirring reaction 48h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 100 ℃ of following vacuum-drying 3 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 50 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.13 ~ 1.67.
Embodiment 6
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 0.5g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 50mL anhydrous pyridine, in the nitrogen atmosphere in 80 ℃ of stirring reaction 48h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 100 ℃ of following vacuum-drying 3 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 45 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.63 ~ 2.09.
Embodiment 7
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 0.5g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 60mL anhydrous pyridine, in the nitrogen atmosphere in 70 ℃ of stirring reaction 40h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 130 ℃ of following vacuum-drying 4 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 35 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 1.93 ~ 2.58.
Embodiment 8
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 1g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 50mL anhydrous pyridine, in the nitrogen atmosphere in 80 ℃ of stirring reaction 48h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 120 ℃ of following vacuum-drying 4 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 35 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) between 2.07 ~ 3.02.
Embodiment 9
(1) the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives
2) synthetic: take by weighing dry L-phenylalanine 2g and tosylation beta-cyclodextrin bonded silica gel (the TsCD/ SiO that crosses
2) 1g places the 60mL anhydrous pyridine, in the nitrogen atmosphere in 90 ℃ of stirring reaction 48h; Suction filtration is removed reaction solution, and product is used anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 130 ℃ of following vacuum-drying 5 h, namely.
(2) L-Ala Separation of Enantiomers: L-L-Ala (L-Ala) and the D-L-Ala (D-Ala) of quality such as get, be dissolved in after the mixing in the water, obtain the racemize solution of L-Ala; Insert the L-phenylalanine beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO that derives at the Glass tubing of bottom end-blocking
2), the L-Ala racemize solution of adding certain volume seals, and puts into 30 ℃ of Water Tanks with Temp.-controlled, reaches balance up to absorption; After absorption finished, the UV-2450 spectrophotometer was used in centrifugation, measured the absorbancy of clear liquid at 190nm wavelength place, measured the specific rotation of clear liquid with polarimeter.The L-phenylalanine derive the beta-cyclodextrin bonded silica gel to the selectivity coefficient of L-L-Ala (L-Ala) 1.36 ~ 1. between 81.
The result shows, with L-phenylalanine derivatized beta-cyclodextrin bonded silica gel (L-Phe-CD/SiO
2) be chiral separation adsorption column material, be separate object with racemic L-Ala, have the recognition capability stronger to the L-L-Ala, simple to operate, cost is low, selectivity is high and separation efficiency is good, has certain practical value.
The above only is embodiments of the invention; be not so limit claim of the present invention; every equivalent structure or equivalent flow process conversion that utilizes specification sheets of the present invention to do, or directly or indirectly be used in other relevant technical fields, all in like manner be included in the scope of patent protection of the present invention.
Claims (8)
- The beta-cyclodextrin bonded silica gel is synthetic 1.L-phenylalanine is derived; it is characterized in that preparation process comprises: make activated silica gel earlier, then synthetic beta-cyclodextrin bonded silica gel; resynthesis tosylation beta-cyclodextrin bonded silica gel is used products therefrom L-phenylalanine derivatize at last.
- 2. L-phenylalanine according to claim 1 the synthetic of beta-cyclodextrin bonded silica gel that derive is characterized in that described activated silica gel makes with following steps: press the volume mass of hydrochloric acid soln and silica gel than being 20mL/g, with dense HCl – H 2(v/v) with particle diameter be the silica gel of 5 ~ 7 μ ms be mixed with mixture room temperature dipping 24h to O at 1: 3, and then at 120 ℃ of following backflow 10h, suction filtration also is washed till neutrality with bi-distilled water, uses washing with acetone again, in 150 ℃ of following vacuum-drying 10h, places moisture eliminator standby.
- 3. L-phenylalanine according to claim 1 is derived synthesizing of beta-cyclodextrin bonded silica gel, it is characterized in that described beta-cyclodextrin bonded silica gel comprises the steps:A, be the ratio of 20g/mL in mass volume ratio, beta-cyclodextrin is dissolved in anhydrous N, be mixed with solution in N '-dimethyl formamide, adding the NaH that accounts for beta-cyclodextrin quality 6% is catalyzer, stirs 1h under the room temperature, filters;B, drip KH-560 to filtrate in nitrogen atmosphere, in 85-90 ℃ of reaction 5h, the volume of described KH-560 is 1.96% of filtrate;C, add the activated silica gel with quality such as beta-cyclodextrin in the reaction system, be warming up to 110-115 ℃ of reaction 24h, to be cooled to room temperature, suction filtration;D, will filter solids use anhydrous N successively, methanol wash is used in N '-dimethyl formamide, methyl alcohol, bi-distilled water washing at last again, filter is done the back in 120 ℃ of vacuum-drying 3h, places moisture eliminator standby.
- 4. L-phenylalanine according to claim 1 is derived synthesizing of beta-cyclodextrin bonded silica gel, it is characterized in that the synthesis step of described tosylation beta-cyclodextrin bonded silica gel comprises as follows:A, by anhydrous pyridine and Tosyl chloride volume mass than being mixed with solution for 25mL/g, add the beta-cyclodextrin bonded silica gel with quality such as Tosyl chloride, stir 24h under the room temperature;B, place ice bath to continue reaction 18h, suction filtration reaction system;C, will filter product successively with anhydrous pyridine, ether, methyl alcohol, ether washing for several times, in 100 ℃ of following vacuum-drying 24 h, drying for standby.
- 5. L-phenylalanine according to claim 1 is derived synthesizing of beta-cyclodextrin bonded silica gel, it is characterized in that described L-phenylalanine derivatize preparation process comprises:A, be the ratio of 25 ~ 75g/mL in the mixing quality of L-phenylalanine and tosylation beta-cyclodextrin bonded silica gel and the solid-to-liquid ratio of anhydrous pyridine, take by weighing the dry L-phenylalanine of crossing and tosylation beta-cyclodextrin bonded silica gel in anhydrous pyridine, the mass ratio of described L-phenylalanine and tosylation beta-cyclodextrin bonded silica gel is 1:2 ~ 2:1;B, in nitrogen atmosphere with solution in 70 ~ 90 ℃ of stirring reaction 40 ~ 52h, be cooled to the room temperature suction filtration;C, will filter product use anhydrous pyridine, methyl alcohol, ether, dehydrated alcohol, methyl alcohol, distilled water, washing with acetone successively, behind the suction filtration, in 100 ~ 130 ℃ of following vacuum-drying 3 ~ 5 h.
- 6. L-phenylalanine according to claim 5 is derived synthesizing of beta-cyclodextrin bonded silica gel, it is characterized in that:The mixing quality of the phenylalanine of L-described in the steps A and tosylation beta-cyclodextrin bonded silica gel and the solid-to-liquid ratio of anhydrous pyridine are 40g/mL; Described L-phenylalanine and tosylation beta-cyclodextrin bonded silica gel mass ratio are 1:1;Among the step B in nitrogen atmosphere solution be cooled to the room temperature suction filtration in 80 ℃ of stirring reaction 48h;Among the step C behind the suction filtration, in 120 ℃ of following vacuum-drying 4 h.
- 7. according to the L-phenylalanine of the arbitrary described method preparation of the claim 1 ~ 6 beta-cyclodextrin bonded silica gel of deriving.
- 8. the described L-phenylalanine of claim 7 is derived the beta-cyclodextrin bonded silica gel as the application of chromatograph packing material, it is characterized in that, as moving phase, under the constant temperature normal pressure, finish the chromatographic separation of L-Ala enantiomorph with the racemize solution of L-Ala.
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Cited By (5)
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| CN103965484A (en) * | 2014-04-09 | 2014-08-06 | 南昌大学 | Preparation method and application of omega-diamine derivatization beta-cyclodextrin bonded SBA-15 chiral stationary phase |
| CN104289210A (en) * | 2014-07-02 | 2015-01-21 | 苏州苏凯路化学科技有限公司 | Preparation method of novel phenylalanine chiral chromatographic column stationary phase |
| CN109513431A (en) * | 2017-09-19 | 2019-03-26 | 中国科学院大连化学物理研究所 | The nucleocapsid silica gel chiral resolution material of bonding beta-cyclodextrin and its preparation and application |
| CN113117653A (en) * | 2021-04-19 | 2021-07-16 | 中国科学院兰州化学物理研究所 | Preparation and application of carboxylic acid modified cyclodextrin chiral chromatographic stationary phase material |
| CN113929590A (en) * | 2021-11-03 | 2022-01-14 | 上海工程技术大学 | Method for splitting chiral aspartic acid by heterogeneous nucleation crystallization method |
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| CN103965484A (en) * | 2014-04-09 | 2014-08-06 | 南昌大学 | Preparation method and application of omega-diamine derivatization beta-cyclodextrin bonded SBA-15 chiral stationary phase |
| CN103965484B (en) * | 2014-04-09 | 2017-02-22 | 南昌大学 | Preparation method and application of omega-diamine derivatization beta-cyclodextrin bonded SBA-15 chiral stationary phase |
| CN104289210A (en) * | 2014-07-02 | 2015-01-21 | 苏州苏凯路化学科技有限公司 | Preparation method of novel phenylalanine chiral chromatographic column stationary phase |
| CN109513431A (en) * | 2017-09-19 | 2019-03-26 | 中国科学院大连化学物理研究所 | The nucleocapsid silica gel chiral resolution material of bonding beta-cyclodextrin and its preparation and application |
| CN113117653A (en) * | 2021-04-19 | 2021-07-16 | 中国科学院兰州化学物理研究所 | Preparation and application of carboxylic acid modified cyclodextrin chiral chromatographic stationary phase material |
| CN113117653B (en) * | 2021-04-19 | 2022-03-25 | 中国科学院兰州化学物理研究所 | Preparation and application of carboxylic acid modified cyclodextrin chiral chromatographic stationary phase material |
| CN113929590A (en) * | 2021-11-03 | 2022-01-14 | 上海工程技术大学 | Method for splitting chiral aspartic acid by heterogeneous nucleation crystallization method |
| CN113929590B (en) * | 2021-11-03 | 2023-09-05 | 上海工程技术大学 | Method for separating chiral aspartic acid by heterogeneous nucleation crystallization method |
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