CN104761694B - A kind of method of RAFT methods synthesis galactolipin block copolymer - Google Patents

Abstract

The present invention relates to a kind of method of RAFT methods synthesis galactolipin block copolymer, including：Vinyl hexanediacetate and galactolipin are dissolved in solvent; add alkali protease; under the conditions of 40 50 DEG C; the 5d of stirring reaction 4, obtains vinyl adipic acid gala sugar ester OVAG above-mentioned OVAG is polymerize into the macromolecular PDEGMA to be formed with diethylene glycol dimethacrylate DEGMA being dissolved in solvent as chain-transferring agent, then adds initiator A IBN; 48h is reacted under 70 DEG C of oil bath nitrogen protective conditions; terminating reaction, purification, is produced.The present invention uses enzymatic method synthetic reaction monomer, and selectivity is strong, and yield is high, and gained purity containing sugar monomer is high；Block copolymer containing galactolipin is synthesized using RAFT methods, synthetic reaction carries out stabilization, implode will not occur, and it is low to react products therefrom molecular weight dispersion width；Gained copolymer has biocompatibility, and toxicity is relatively low, can be widely used in biomedicine field.

Description

A kind of method of RAFT method synthesizing galactose block copolymer

technical field

The invention belongs to the field of preparation of galactose copolymers, in particular to a method for synthesizing galactose block copolymers by RAFT method.

Background technique

Sugar-containing polymers have become a research hotspot in the fields of biomedicine due to their good hydrophilicity, biocompatibility and easy degradability.

Rizzardo made a report on "Tailored polymers by freeradical processes" at the 37th International Polymer Congress, and for the first time proposed the concept of reversible addition-fragmentation chain transfer radical polymerization (RAFT). In the traditional free radical polymerization system, the concentration of free radicals is high, and the termination reaction of free radicals is prone to occur, resulting in an uncontrollable reaction. If a special chain transfer agent with a high chain transfer constant is added to the polymerization system, the degenerate transfer between the propagating free radical and the chain transfer agent is performed, thereby reducing the concentration of free radicals, and it is possible to realize living free radical polymerization. Polymers synthesized by reversible addition chain fragmentation transfer radical method (RAFT) have narrower molecular weight dispersion index (PDI), and have more excellent performance in application.

Contents of the invention

The technical problem to be solved by the present invention is to provide a method for synthesizing galactose block copolymers by the RAFT method. The present invention adopts an enzymatic method to synthesize reaction monomers, which has strong selectivity, high yield and high purity of the obtained sugar-containing monomers.

A kind of RAFT method of the present invention synthesizes the method for galactose block copolymer, comprising:

(1) Dissolve divinyl adipate and galactose in a solvent, add alkaline protease, and stir for 4-5 days at 40-50°C to obtain vinyl adipate galactose OVAG; The molar ratio of divinyl diacid to galactose is 1:1-4:1, the mass ratio of alkaline protease to galactose is 1:2-1:4; The mass ratio of the sum of the mass of protease to the solvent is 1:10～1:5;

(2) Dissolve diethylene glycol dimethacrylate DEGMA in a solvent, then add an initiator and a chain transfer agent, and react for 0.5-1h under the condition of nitrogen protection in an oil bath at 70°C, terminate the reaction, and purify to obtain polydimethacrylate Glycol dimethacrylate PDEGMA; the molar ratio of chain transfer agent to DEGMA is 1:100, the molar ratio of chain transfer agent to initiator is 5:1, and the mass ratio of DEGMA to solvent is 1:1-1:3 ;

(3) Dissolve the above-mentioned OVAG and polydiethylene glycol dimethacrylate PDEGMA (as a macromolecular chain transfer agent) in a solvent, then add an initiator, react for 48 hours under the condition of nitrogen protection in an oil bath at 70°C, and terminate the reaction. Purify to obtain the galactose block copolymer PDEGMA-b-POVAG, wherein the molar ratio of PDEGMA to OVAG is 1:63-80; the molar ratio of PDEGMA to AIBN is 1:0.21-0.4, the sum of PDEGMA and OVAG and solvent The mass ratio is 1:1-1:3.

In the step (1), the solvent is anhydrous pyridine; the alkaline protease is subtilisin.

The stirring rate in the step (1) is 150-200rpm.

The solvent in the steps (2) and (3) is dimethylformamide DMF.

In the step (2), the initiator is azobisisobutyronitrile AIBN; the chain transfer agent is S-cyanomethyl-N-methyl-N-(4-pyridyl)aminodithiocarbonate CMPCD.

The initiator in the step (3) is azobisisobutyronitrile AIBN.

Purification in the steps (2) and (3) is to dissolve with a solvent, then precipitate with a precipitating agent, and repeat 3-4 times.

The solvent is dichloromethane, and the precipitating agent is n-hexane.

Termination reaction in described step (2), (3) is ice-water bath termination reaction.

The present invention utilizes RAFT method to prepare the reaction equation of galactose copolymer as follows:

Beneficial effect

(1) The present invention adopts enzymatic method to synthesize reaction monomer, has strong selectivity, high yield, and the obtained sugar-containing monomer has high purity;

(2) The present invention uses the RAFT method to synthesize the galactose-containing block copolymer, the synthesis reaction is stable, no violent polymerization occurs, and the molecular weight dispersion width of the reaction product is low;

(3) The copolymer obtained by the reaction of the present invention has biocompatibility, low toxicity, and can be widely used in the field of biomedicine;

(4) The galactose block copolymer synthesized by the present invention has a regular structure, and because DEGMA has temperature-sensitive properties, the resulting copolymer also has temperature sensitivity and can be used in biomedical materials.

Description of drawings

Fig. 1 is the infrared spectrogram of PDEGMA-b-POVAG;

Figure 2 is the chemical structure of PDEGMA-b-POVAG.

detailed description

Below in conjunction with specific embodiment, further illustrate the present invention. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In addition, it should be understood that after reading the teachings of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Example 1

(1) Dissolve divinyl adipate and galactose at a molar ratio of 3:1 in 100 mL of anhydrous pyridine, add 0.5 g of alkaline protease, and react in a constant temperature water bath at 50 ° C and 200 rpm for 4 days to synthesize vinyl hexyl Diacid galactosyl ester (OVAG).

(2) Dissolve diethylene glycol dimethacrylate (DEGMA) in 2 mL of DMF, add AIBN as an initiator, and add a chain transfer agent at a molar ratio of 100:1:0.2, and react for 1 h at 70°C under nitrogen protection in an oil bath , placed in an ice-water bath to terminate the reaction, and dichloromethane was used to dissolve the n-hexane precipitate, and this was repeated 3 times to obtain PDEGMA after purification.

(3) Dissolve vinyl adipate galactose (OVAG) in 2mL DMF, add AIBN as an initiator, add chain transfer agent (polyethylene glycol dimethacrylate PDEGMA), its OVAG, PDEGMA, initiator The molar ratio of 63:1:0.21 was reacted under the protection of nitrogen in an oil bath at 70°C for 48 hours, and then placed in an ice-water bath to terminate the reaction, and dichloromethane was used to dissolve n-hexane to precipitate, and this was repeated 3 times. After purification, PDEGMA-b-POVAG was obtained. The yield was 85%.

Example 2

(1) Dissolve divinyl adipate and galactose at a molar ratio of 3:1 in 100 mL of anhydrous pyridine, add 0.5 g of alkaline protease, and react in a constant temperature water bath at 50 ° C and 200 rpm for 4 days to synthesize vinyl hexyl Diacid galactosyl ester (OVAG).

(2) Dissolve diethylene glycol dimethacrylate (DEGMA) in 2 mL of DMF, add AIBN as an initiator, and add a chain transfer agent at a molar ratio of 100:1:0.2, and react for 1 h at 70°C under nitrogen protection in an oil bath , placed in an ice-water bath to terminate the reaction, and dichloromethane was used to dissolve the n-hexane precipitate, and this was repeated 3 times to obtain PDEGMA after purification.

(3) Dissolve vinyl adipate galactose (OVAG) in 2mL DMF, add AIBN as an initiator, add chain transfer agent (polyethylene glycol dimethacrylate PDEGMA), its OVAG, PDEGMA, initiator The molar ratio of 80:1:0.4 was reacted under the protection of nitrogen in an oil bath at 70°C for 48 hours, and then placed in an ice-water bath to terminate the reaction, and dichloromethane was used to dissolve n-hexane to precipitate, and this was repeated 3 times. After purification, PDEGMA-b-POVAG was obtained. The yield was 83%.

Claims (9)

1. a kind of method of RAFT methods synthesis galactolipin block copolymer, including：

(1) vinyl hexanediacetate and galactolipin are dissolved in solvent, add alkali protease, under the conditions of 40-50 DEG C, stirring 4-5d is reacted, obtains vinyl adipic acid gala sugar ester OVAG；Wherein the mol ratio of vinyl hexanediacetate and galactolipin is 1: 1-4:1, the mass ratio of alkali protease and galactolipin is 1:2-1:4；Vinyl hexanediacetate, galactolipin and alkali protease The mass ratio of quality sum and solvent is 1:10~1:5；

(2) two polyethylene glycol monomethyl ethermethacrylic acid esters DEGMA are dissolved in solvent, then add initiator, chain-transferring agent, 0.5-1h is reacted under 70 DEG C of oil bath nitrogen protective conditions, terminating reaction, purification, that is, obtains poly- two poly glycol monomethyl ethers methyl Acrylate PDEGMA；Its Chain transfer agent and DEGMA mol ratio are 1:100, the mol ratio 5 of chain-transferring agent and initiator: 1, DEGMA and solvent mass ratio be 1:1-1:3；

(3) above-mentioned OVAG and poly- two polyethylene glycol monomethyl ethermethacrylic acid esters PDEGMA are dissolved in solvent, then add and draw Agent is sent out, 48h is reacted under 70 DEG C of oil bath nitrogen protective conditions, terminating reaction, purification, produces galactolipin block copolymer PDEGMA-b-POVAG, wherein PDEGMA and OVAG mol ratio are 1:63-80；The mol ratio of PDEGMA and initiator is 1: The mass ratio of 0.21-0.4, PDEGMA and OVAG sum and solvent is 1:1-1:3.

A kind of 2. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Solvent is anhydrous pyridine in step (1)；Alkali protease is Validase TSP Concentrate II.

A kind of 3. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Stir speed (S.S.) is 150-200rpm in step (1).

A kind of 4. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Solvent is dimethylformamide DMF in step (2), (3).

A kind of 5. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Initiator is azodiisobutyronitrile AIBN in step (2)；Chain-transferring agent is S- cyanogen methyl-N-methyls-N- (4- pyridine radicals) amino Dithiocarbonates CMPCD.

A kind of 6. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Initiator is azodiisobutyronitrile AIBN in step (3).

A kind of 7. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Purification is dissolves with solvent in step (2), (3), and then precipitating reagent precipitates, and repeats 3-4 times.

A kind of 8. method of RAFT methods synthesis galactolipin block copolymer according to claim 7, it is characterised in that：It is described Solvent is dichloromethane, and precipitating reagent is n-hexane.

A kind of 9. method of RAFT methods synthesis galactolipin block copolymer according to claim 1, it is characterised in that：It is described Terminating reaction is ice-water bath terminating reaction in step (2), (3).