CN104031206A - Method for synthesizing galactose copolymer by adopting RAFT method - Google Patents

Abstract

The invention relates to a method for synthesizing galactose copolymer by RAFT method, comprising: dissolving divinyl adipate and galactose in a solvent, adding alkaline protease, and stirring for 4-5 days under the condition of 40-50°C To obtain vinyl adipate galactosyl ester OVNG, dissolve the above OVNG and diethylene glycol dimethacrylate DEGMA in a solvent, then add an initiator and a chain transfer agent, and react at 90°C under nitrogen protection in an oil bath for 10- 12h, terminate the reaction, purify, and obtain it. The invention adopts an enzymatic method to synthesize reaction monomers, which has strong selectivity, high yield, and high purity of the sugar-containing monomers obtained; the galactose-containing copolymer is synthesized by using the RAFT method, and the synthesis reaction is stable without implosion, and the reaction The molecular weight dispersion width of the obtained product is low; the obtained copolymer has biocompatibility and low toxicity, and can be widely used in the field of biomedicine.

Description

A method for synthesizing galactose copolymer by RAFT method

technical field

The invention belongs to the field of preparation of galactose copolymers, in particular to a method for synthesizing galactose 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 free radical 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 copolymer by RAFT method, which adopts enzymatic method to synthesize reaction monomer, has strong selectivity, high yield and high purity of obtained sugar-containing monomer.

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

(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 OVNG; The molar ratio of divinyl adipate to galactose is 1:1-4:1, the mass ratio of alkaline protease to galactose is 1:2-1:4; various related solutes divinyl adipate, galactose The mass ratio of the mass sum of lactose and alkaline protease to the solvent pyridine is 1:10 to 1:5;

(2) Dissolve the above-mentioned OVNG and diethylene glycol dimethacrylate DEGMA in a solvent, then add an initiator and a chain transfer agent, react for 10-12h under the condition of 90°C oil bath nitrogen protection, terminate the reaction, and purify, that is Get galactose copolymer P (DEGMA-OVNG), wherein the mol ratio of OVNG and DEGMA is 1:3; The mol ratio of chain transfer agent and initiator is 20:1, and the mol ratio of chain transfer agent and OVNG and DEGMA summation is 1:100, the mass ratio of monomer to solvent is 1:1-1:3.

The solvent in the step (1) is anhydrous pyridine.

In the step (1), the alkaline protease is subtilisin.

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

The solvent in the step (2) is dimethylformamide DMF.

The initiator in the step (2) is VAZO-88.

The chain transfer agent in the step (2) is S-dodecyl-S'-(α,α'-dimethyl-α″-acetic acid)-trithiocarbonate.

The termination reaction in the step (2) is an ice-water bath termination reaction.

The purification in the step (2) 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.

The present invention utilizes RAFT method to prepare the reaction 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 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 copolymer synthesized by the present invention, because DEGMA has temperature-sensitive property, the obtained copolymer also has temperature sensitivity, and can be used for biomedical materials.

Description of drawings

Figure 1: Infrared spectrum of P(DEGMA-OVNG);

Figure 2: Chemical structure of P(DEGMA-OVNG).

Detailed ways

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 Galactosyl adipate (OVNG).

(2) Dissolve the synthesized OVNG and diethylene glycol dimethacrylate (DEGMA) in 2 mL of DMF, add VAZO-88 as an initiator, and add a chain transfer agent with a molar ratio of 80:20:1:0.05 to 90 ℃ under the protection of nitrogen in an oil bath for 14 hours, put into 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, P(DEGMA-OVNG) was obtained with a yield of 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 Galactosyl diacid (OVNG).

(2) Dissolve the synthesized OVNG and diethylene glycol dimethacrylate (DEGMA) in 2 mL of DMF, add VAZO-88 as an initiator, and add a chain transfer agent with a molar ratio of 25:75:1:0.1 at 90 ℃ under the protection of nitrogen in an oil bath for 14 hours, put into an ice-water bath to terminate the reaction, dissolve ether with methanol to precipitate, and repeat this process 3 times. After purification, P(DEGMA-OVNG) was obtained with a yield of 83%.

Claims (10)

1. a method for synthesizing galactose copolymer by RAFT method, 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 OVNG; 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 the above-mentioned OVNG and diethylene glycol dimethacrylate DEGMA in a solvent, then add an initiator and a chain transfer agent, react for 10-12h under the condition of 90°C oil bath nitrogen protection, terminate the reaction, and purify, that is Get galactose copolymer P (DEGMA-OVNG), wherein the mol ratio of OVNG and DEGMA is 1:3; The mol ratio of chain transfer agent and initiator is 20:1, and the mol ratio of chain transfer agent and OVNG and DEGMA summation is 1:100, the mass ratio of the sum of OVNG and DEGMA to the solvent is 1:1-1:3. 2. the method for a kind of RAFT method synthetic galactose copolymer according to claim 1 is characterized in that: in described step (1), solvent is anhydrous pyridine. 3. the method for a kind of RAFT method synthetic galactose copolymer according to claim 1 is characterized in that: in described step (1), alkaline protease is subtilisin. 4. the method for a kind of RAFT synthesis galactose copolymer according to claim 1, is characterized in that: in described step (1), stirring rate is 150-200rpm. 5. the method for a kind of RAFT method synthesis galactose copolymer according to claim 1 is characterized in that: in described step (2), solvent is dimethylformamide DMF. 6. the method for a kind of RAFT method synthesis galactose copolymer according to claim 1 is characterized in that: in the described step (2), initiator is VAZO-88. 7. the method for a kind of RAFT method synthesis galactose copolymer according to claim 1, is characterized in that: in described step (2), chain transfer agent is S-dodecyl-S'-(α, α '-Dimethyl-α"-acetic acid)-trithiocarbonate. 8. the method for a kind of RAFT synthesis galactose copolymer according to claim 1, is characterized in that: in described step (2), termination reaction is ice-water bath termination reaction. 9. the method for a kind of RAFT synthesis galactose copolymer according to claim 1, is characterized in that: in described step (2), purifying is dissolving with solvent, then precipitating agent precipitation, repeats 3-4 times. 10. the method for a kind of RAFT synthesis galactose copolymer according to claim 9 is characterized in that: described solvent is methylene chloride, and precipitating agent is n-hexane.