CN103446894A - Vancomycin chiral composite membrane and application thereof in resolution of phenylglycine racemate - Google Patents

Abstract

The invention discloses a vancomycin chiral composite membrane and application thereof to resolution of phenylglycine racemate. The composite membrane is prepared through the following steps: soaking a commercial polysulfone membrane with de-ionized water for one day, drying in air and placing in 0.012 g/mL of vancomycin solution to soak for 1 hour; taking out and drying in air, and performing interfacial polymerization with 0.01g/ml of 1,6-diisocyanate solution for 35 seconds; taking out to volatize a surface reagent, placing in a drying box to perform thermal treatment for 20 minutes at the temperature of 110 DEG C, washing with the de-ionized water and soaking for later use; holding the prepared composite membrane in a conventional dialysis device, and resolving phenylglycine racemate aqueous solution with concentration of 0.1 mg/mL at room temperature under the driving of concentration difference of 0-0.1 mg/mL, wherein the purity of permeate D-phenylglycine enantiomer is over 70 percent. The composite membrane has the advantages that the purity of the obtained enantiomer is high (e.e. percent), the energy is saved, the environment is protected, the cost is low and continuous operation and large-scale industrial production are easy.

Description

Vancomycin chirality composite membrane and the application in the phenylglycine racemic modification splits thereof

Technical field:

The invention belongs to chiral polymer membrane separation technique field, particularly, relate to the application of a kind of vancomycin chirality composite membrane in the phenylglycine racemic modification splits.

Background technology;

Chiral drug refers to the medicine be comprised of the chipal compounds with pharmacologically active, interior medicine dynamics process difference due to two enantiomers of chiral drug, therefore two enantiomers of chiral drug often pharmacologically active, metabolic process, metabolic rate and toxicity etc. in vivo exist significant difference concrete, may there is following several situation: only have a kind of enantiomer that pharmacologically active is arranged, and another kind of without significant pharmacological action; In enantiomer, one has activity and antagonism can occur for another; Two enantiomers have and are equal to or close pharmacologically active, and two enantiomers have close activity sometimes, but still should select single enantiomer from overall balance; Two enantiomers have diverse physiologically active, and for example wherein a kind of enantiomer is appetite inhibitor, and another kind is revitalizer; In two enantiomers, one has activity, and another does not only have activity toxic side effect on the contrary.Because the deficiency of before chiral drug being familiar with has had many bitter lessons, these recognize people, and medicine must be noted that the configuration that they are different.

The production of chipal compounds is generally synthesized and the large approach of chiral resolution two by chirality.But the synthetic scope of using at present of chirality is narrower, and the superfluous value of enantiomer (e.e.%) is often lower; Although the chiral resolution technology has direct crystallization Split Method, diastereoisomer Split Method, extraction, enzyme Split Method, chromatogram Split Method etc., both has been suitable for large-scale production, energy-saving and environmental protection again, low cost surely belong to chiral polymer film Split Method.

Phenylglycine is a kind of production β-antibiotic important intermediate of Nei acyl Ammonia, be usually used in the preparation of vertical new, the born of the same parents' chlorine ammonia benzyl in a born of the same parents Crow, ampicillin, a born of the same parents, piperacillin and Cefradine etc., it still synthesizes the important intermediate of polypeptide hormone, Multiple Pesticides simultaneously, and its medical market has a extensive future.Phenylglycine has optical activity, and they are left-handed different from dextrorotation, and for medicine and agricultural chemicals is mainly L-Phenylglycine.

So far, have no the open report of vancomycin-isocyanates composite membrane and the application in the phenylglycine racemic modification splits thereof.

Summary of the invention:

The object of the invention is to overcome the deficiency of prior art, a kind of vancomycin-isocyanates composite membrane and application and its preparation method in the phenylglycine racemic modification splits are provided.

Above-mentioned purpose of the present invention is to be achieved by following technical scheme:

A kind of chirality composite membrane, be fixed on vancomycin on film base material and form.

As described chirality composite membrane, be by making vancomycin be reacted and be fixed on film base material with the function groups compound.

As described chirality composite membrane, described function groups compound comprises multicomponent isocyanate or polynary acyl chlorides or multi-anhydride compound, or contains plural isocyanates, acyl chlorides, acid anhydrides functional group simultaneously.

Above-mentioned vancomycin-polysulfone composite membrane is obtained by following step preparation:

A, commodity PS membrane, as basement membrane, soak one day by deionized water, dry, and put into 0.012g/mL vancomycin solution and soak 1h;

B, take out PS membrane dry from vancomycin solution, with 0.01g/mL1, hexamethylene-diisocyanate solution carries out interfacial polymerization;

C, polyase 13 5s, take out PS membrane, treats the surface reagent volatilization, puts into drying box, 110 ℃ of lower heat treatment 20min;

D, vancomycin-polysulfone composite membrane are cleaned by deionized water, put into deionized water and soak standby.

A kind of method for optical resolution of amino acid racemization body, used the described chirality composite membrane of above-mentioned any one.

As the method for optical resolution of described amino acid racemization body, wherein said amino acid is any in D-pHPG, phenylglycine.

The application of the described chirality composite membrane of above-mentioned any one in the phenylglycine racemic modification splits.

Described application, be to utilize vancomycin to prepare diffusion barrier as the chirality function material of film, for the fractionation of phenylglycine racemic modification.

Described application, be describedly to split the phenylglycine racemic modification with vancomycin-polysulfone composite membrane and comprise the steps:

A, commodity PS membrane, as basement membrane, soak one day by deionized water, dry, and put into 0.012g/mL vancomycin solution and soak 1h;

B, take out PS membrane dry from vancomycin solution, with 0.01g/mL1, hexamethylene-diisocyanate solution carries out interfacial polymerization;

C, polyase 13 5s, take out PS membrane, treats the surface reagent volatilization, puts into drying box, 110 ℃ of lower heat treatment 20min;

D, vancomycin-polysulfone composite membrane are cleaned by deionized water, put into deionized water and soak standby;

E, the above-mentioned vancomycin-polysulfone composite membrane prepared is packed in conventional electrodialysis apparatus, under the 0-0.1mg/mL concentration difference drives, room temperature splits the phenylglycine racemic modification aqueous solution that concentration is 0.1mg/mL.

The present invention is using vancomycin-isocyanates composite membrane as the application that splits the phenylglycine racemic modification.

Compared with prior art, the invention has the advantages that:

1, vancomycin-isocyanates composite membrane fractionation phenylglycine racemic modification gained enantiomeric purity (e.e.%) reaches more than 70%, can realize the separation of high antimer purity;

2, because splitting, film carries out at normal temperatures, undergoing phase transition not, so energy consumption is low;

3, because the film split process is not added new chemical reagent, so environmental protection, cost is low;

4, the film separation is easy to continued operation, easily carries out large-scale industrial production.

The accompanying drawing explanation:

The molecular structural formula that Fig. 1 is vancomycin;

Fig. 2 is that the enantiomter sample is crossed the detection spectrogram of film liquid through the chirality high performance liquid chromatography.

The specific embodiment:

Below in conjunction with accompanying drawing, by embodiments of the invention, essentiality content of the present invention is described in detail, but content of the present invention is not limited to this.

Embodiment 1:

The vancomycin that the present invention adopts-isocyanates composite membrane following steps are prepared from:

A, commodity PS membrane soak one day by deionized water as basement membrane, dry, and put into 0.012g/mL vancomycin solution and soak 1h.

B, take out PS membrane dry from vancomycin solution, rear and 0.01g/mL1, hexamethylene-diisocyanate solution carries out interfacial polymerization.

C, polyase 13 5s time, take out PS membrane, treat the surface reagent volatilization, put into 110 ℃ of lower heat treatment 20min of drying box.

D, polysulfone composite membrane are cleaned by deionized water, put into deionized water and soak standby.

E, the above-mentioned vancomycin prepared-isocyanates composite membrane is packed in conventional electrodialysis apparatus, under the 0-0.1mg/mL concentration difference drives, room temperature splits the phenylglycine racemic modification aqueous solution that concentration is 0.1mg/mL.

F, by dialysis, the purity that sees through D-PG enantiomer in liquid reaches more than 70%.

Experimental result shows: utilize vancomycin-isocyanates composite membrane to split the phenylglycine racemic modification, cross the D-PG enantiomter sample obtained after film and show that through high-efficient liquid phase chromatogram its purity is more than 70%.Vancomycin of the present invention-isocyanates composite membrane splits phenylglycine racemic modification gained enantiomeric purity (e.e.%) and reaches more than 70%, can realize the separation of high antimer purity; Because splitting, film carries out at normal temperatures, undergoing phase transition not, so energy consumption is low; Because the film split process is not added new chemical reagent, so environmental protection, cost is low; The film separation is easy to continued operation, easily carries out large-scale industrial production.

Claims (9)

1. a chirality composite membrane, be fixed on vancomycin on film base material and make.

2. chirality composite membrane as claimed in claim 1, is characterized in that by making vancomycin be reacted and be fixed on film base material with the function groups compound.

3. chirality composite membrane as claimed in claim 2, is characterized in that, described function groups compound comprises multicomponent isocyanate or polynary acyl chlorides or multi-anhydride compound, or contain plural isocyanates, acyl chlorides, acid anhydrides functional group simultaneously.

4. chirality composite membrane as claimed in claim 1 is characterized in that it by following step preparation and obtains:

A, commodity PS membrane, as basement membrane, soak one day by deionized water, dry, and put into 0.012g/mL vancomycin solution and soak 1h;

B, take out PS membrane dry from vancomycin solution, with 0.01g/mL1, hexamethylene-diisocyanate solution carries out interfacial polymerization;

C, polyase 13 5s, take out PS membrane, treats the surface reagent volatilization, puts into drying box, 110 ℃ of lower heat treatment 20min;

D, vancomycin-polysulfone composite membrane are cleaned by deionized water, put into deionized water and soak standby.

5. the method for optical resolution of an amino acid racemization body, is characterized in that in method, right to use requires the described chirality composite membrane of any one in 1～4.

6. the method for optical resolution of amino acid racemization body as claimed in claim 5, is characterized in that, described amino acid is any in D-pHPG, phenylglycine.

7. the application of the described chirality composite membrane of any one in the phenylglycine racemic modification splits in claim 1～4.

8. application as claimed in claim 7, is characterized in that utilizing vancomycin to prepare diffusion barrier as the chirality function material of film, for the fractionation of phenylglycine racemic modification.

9. application as claimed in claim 7, is characterized in that describedly splitting the phenylglycine racemic modification with vancomycin-polysulfone composite membrane and comprising the steps:

A, commodity PS membrane, as basement membrane, soak one day by deionized water, dry, and put into 0.012g/mL vancomycin solution and soak 1h;

B, take out PS membrane dry from vancomycin solution, with 0.01g/mL1, hexamethylene-diisocyanate solution carries out interfacial polymerization;

C, polyase 13 5s, take out PS membrane, treats the surface reagent volatilization, puts into drying box, 110 ℃ of lower heat treatment 20min;

D, vancomycin-polysulfone composite membrane are cleaned by deionized water, put into deionized water and soak standby;

E, the above-mentioned vancomycin-polysulfone composite membrane prepared is packed in conventional electrodialysis apparatus, under the 0-0.1mg/mL concentration difference drives, room temperature splits the phenylglycine racemic modification aqueous solution that concentration is 0.1mg/mL.

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