阅读说明：本技术 一种具有酸降解、还原性敏感功能的单体及其制备方法和应用 (Monomer with acid degradation and reducibility sensitive functions and preparation method and application thereof ) 是由 李智慧 李大爱 赵琳 李钟玉 于 2021-09-03 设计创作，主要内容包括：本发明公开了一种具有酸降解、还原性敏感功能的单体制备及其在高分子中的应用,其制备方法是：将2,2’-二硫二乙醇的衍生物、2-(乙烯氧基)乙基丙烯酸酯在室温条件下,用二氯甲烷作溶剂,对甲苯磺酸作催化剂,催化得到。该方法制备过程简单,在功能性高分子合成领域内有广泛的应用前景。(The invention discloses a preparation method of a monomer with acid degradation and reducibility sensitive functions and application thereof in macromolecules, wherein the preparation method comprises the following steps: the catalyst is prepared by catalyzing a derivative of 2, 2' -dithiodiethanol and 2- (ethyleneoxy) ethyl acrylate at room temperature by using dichloromethane as a solvent and p-toluenesulfonic acid as a catalyst. The method has simple preparation process and wide application prospect in the field of functional polymer synthesis.)

1. A monomer with acid degradation and reducibility sensitive functions is characterized in that:

the structure of the substance is as follows:

wherein R is:

2. the method of claim 1 for preparing a monomer having acid degradation and reducibility sensitive function, wherein:

the method comprises the following steps: .

The method comprises the following steps: adding 2, 2' -dithiodiethanol into a reaction vessel filled with a first solvent, stirring and mixing to form a first mixture, adding an organic base, placing in an ice bath, and stirring by adopting a magnetic force;

step two: taking a first solvent, dissolving an acyl halide substance in the first solvent, slowly and dropwise adding the acyl halide substance containing the first solvent into the first mixture, reacting at room temperature for 3-5h, filtering to remove triethylamine hydrochloride, extracting once, collecting an organic phase, drying, performing reduced pressure rotary evaporation to obtain a crude product of the 2, 2 '-dithiodiethanol derivative, and further purifying by adopting a column chromatography method to obtain a purified 2, 2' -dithiodiethanol derivative;

step three: adding a proper amount of purified 2, 2' -dithiodiethanol derivative into a first solvent, adding a catalyst, stirring at room temperature for 1-2min, adding 2- (ethyleneoxy) ethyl acrylate into a system, reacting for 2-3h, adding an organic base into the system, adjusting the pH value of the system to 8-9 to obtain a crude product, further purifying by adopting a column chromatography method, and thus obtaining the monomer with acid degradation and reducing sensitive functions.

3. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

the first solvent is dichloromethane.

4. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

the organic base is triethylamine.

5. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

the catalyst is p-toluenesulfonic acid.

6. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

the acyl halide substance is:

acryloyl chloride or bromoisobutyryl bromide or 4-bromobutyryl bromide or bromoacetyl bromide or 4-bromobutyryl chloride.

7. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

the mass fraction of the 2, 2' -dithiodiethanol in the first mixture is 10% -20%;

the molar charge ratio of the 2, 2' -dithiodiethanol to the acyl halide substance is as follows: 2: 1.1-1.3.

8. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

the feeding molar weight ratio of the organic base to the acyl halide is as follows: 1-1.2: 1;

the molar charge ratio of the 2, 2' -dithiodiethanol derivative to the 2- (ethyleneoxy) ethyl acrylate is as follows: 1: 1-1.2.

9. The method of claim 2, wherein the monomer with acid degradation and reducibility sensitivity is prepared by:

in the first step, the adding mass of the first solvent is 4-9 times of that of the 2, 2' -dithiodiethanol;

in the second step, the adding mass of the first solvent is 1-3 times of that of the acyl halide substance;

in the third step, the mass of the first solvent is 3-10 times of that of the 2, 2' -dithiodiethanol derivative;

the adding mass of the catalyst is 0.04-0.08% of the mass of the first solvent in the third system.

10. The use of the acid-degradable, reductively-sensitive monomer of claim 1, wherein: the polymer drug carrier with acid degradation and reductive sensitivity functions is prepared by using the method.

Technical Field

The invention belongs to the field of organic synthesis and polymer synthesis, and particularly relates to preparation of a monomer with acid degradation and reducibility sensitive functions and application of the monomer in macromolecules.

Background

The monomer with acid degradation and reducibility sensitive functions is an important component for designing and synthesizing functional polymer materials, and is very important particularly in the field of designing intelligent response high-molecular drug carriers.

Generally, amphiphilic block polymers are frequently used as drug carriers and are receiving more and more attention and widely applied because of being capable of self-assembling in water to form polymer micelles, but non-functional block polymers are generally stable and often cannot completely release drugs. This brings the benefits of: the drug is slowly released to a certain extent, so that the rapid clearing of the kidney and the escape from a reticuloendothelial system are avoided; but also has disadvantages such as: the residual medicine not only reduces the utilization rate of the medicine, but also increases the side effect.

In order to improve the condition and realize the targeted release of the drug so as to improve the curative effect of the drug, subsequent researchers design functional polymer drug carriers by combining the specific properties of the focus part, such as: compared with the pH value of normal physiological tissues of human (about 7.4), the environment of tumor parts is acidic, the pH value is about 6.75, the pH value in the tumor is about 6.0, the pH value of lysosome in cells is lower and is 4.0-5.0, and the weak acidic environment of the tumor tissues provides a theoretical basis for designing molecular chain segments which are decomposed or degraded under acidic conditions, such as: designing a chain segment containing hydrazone bonds, acetal bonds or ketal bonds; meanwhile, Glutathione (GSH) with high concentration is contained in tumor cells to present a reducing environment, which provides a basis for designing a reduction sensitive drug delivery system, the reduction sensitive chain segment is mostly researched as disulfide bond (S-S), the bond of the disulfide bond has higher stability, but the disulfide bond is easy to degrade and break under the reducing environment of the tumor cells and is also easy to be effectively reduced by dithiothreitol, and a polymer drug carrier based on the disulfide bond is researched and shows good application prospect.

Current methods for imparting functionality to polymeric drug carriers are: (1) it can be made to have certain functionality by polymer post-modification methods, such as: polymers containing hydroxyl groups can impart acid-degradable properties to the polymer by reaction with vinyl ethers; polymers containing carboxyl groups can impart photodegradation properties to the polymer by reaction with 2-nitrobenzol. (2) Functional monomers are designed and then used for polymerization to give functional polymers. Among them, the latter is a more common method. In view of the present, functional monomers have been designed for polymerization, which have relatively single functionality, such as: the designed functional monomer has only acid sensitivity or only light sensitivity, and the number of monomers with multiple sensitivities is small. Therefore, the design of the functional monomer with multiple sensitivities has important value and significance.

Disclosure of Invention

Aiming at the defects in the prior art, the invention aims to provide a method for preparing a monomer with acid degradation and reducibility sensitive functions

In order to achieve the purpose, the invention provides the following technical scheme:

1. a monomer with acid degradation and reducibility sensitive functions is characterized in that:

the structure of the substance is as follows:

wherein R is:

as another object of the present invention, there is provided a method for preparing a monomer having acid degradation and reducing sensitivity,

the method comprises the following steps: .

The method comprises the following steps: adding 2, 2' -dithiodiethanol into a reaction vessel filled with a first solvent, stirring and mixing to form a first mixture, adding an organic base, placing in an ice bath, and stirring by adopting a magnetic force;

step two: taking a first solvent, dissolving an acyl halide substance in the first solvent, slowly and dropwise adding the acyl halide substance containing the first solvent into the first mixture, reacting at room temperature for 3-5h, filtering to remove triethylamine hydrochloride, extracting once, collecting an organic phase, drying, performing reduced pressure rotary evaporation to obtain a crude product of the 2, 2 '-dithiodiethanol derivative, and further purifying by adopting a column chromatography method to obtain a purified 2, 2' -dithiodiethanol derivative;

step three: adding a proper amount of purified 2, 2' -dithiodiethanol derivative into a first solvent, adding a catalyst, stirring at room temperature for 1-2min, adding 2- (ethyleneoxy) ethyl acrylate into a system, reacting for 2-3h, adding an organic base into the system, adjusting the pH value of the system to 8-9 to obtain a crude product, further purifying by adopting a column chromatography method, and thus obtaining the monomer with acid degradation and reducing sensitive functions.

As a further improvement of the present invention,

the first solvent is dichloromethane.

As a further improvement of the present invention,

the organic base is triethylamine.

As a further improvement of the present invention,

the catalyst is p-toluenesulfonic acid.

As a further improvement of the present invention,

the acyl halide substance is:

acryloyl chloride or bromoisobutyryl bromide or 4-bromobutyryl bromide or bromoacetyl bromide or 4-bromobutyryl chloride.

As a further improvement of the present invention,

the mass fraction of the 2, 2' -dithiodiethanol in the first mixture is 10% -20%;

the molar charge ratio of the 2, 2' -dithiodiethanol to the acyl halide substance is as follows: 2: 1.1-1.3.

As a further improvement of the present invention,

the feeding molar weight ratio of the organic base to the acyl halide is as follows: 1-1.2: 1;

the molar charge ratio of the 2, 2' -dithiodiethanol derivative to the 2- (ethyleneoxy) ethyl acrylate is as follows: 1: 1-1.2.

As a further improvement of the present invention,

in the first step, the adding mass of the first solvent is 4-9 times of that of the 2, 2' -dithiodiethanol;

in the second step, the adding mass of the first solvent is 1-3 times of that of the acyl halide substance;

in the third step, the mass of the first solvent is 3-10 times of that of the 2, 2' -dithiodiethanol derivative;

the adding mass of the catalyst is 0.04-0.08% of the mass of the first solvent in the third system. As another object of the invention, the invention provides an application of a monomer with acid degradation and reducibility sensitive functions, which is characterized in that: the polymer drug carrier with acid degradation and reductive sensitivity functions is prepared by using the method.

The principle of the invention is as follows: reacting 2, 2 '-dithiodiethanol with acyl halide to obtain 2, 2' -dithiodiethanol derivative, and reacting with 2- (ethyleneoxy) ethyl acrylate at room temperature, wherein when the acyl halide is acryloyl chloride, the reaction route is as follows:

the reaction is similar to the reaction by using other acyl halide reagents, and the optional acyl halide substances in the invention are described in the specification.

The invention has the beneficial effects that: 1. the method has the advantages of cheap and easily-obtained raw materials, high reaction rate, mild reaction conditions and simple and easy operation;

2. the monomer substance obtained by the invention can be degraded into corresponding aldehyde and alcohol under an acidic condition, and can generate disulfide bond breakage in the presence of dithiothreitol, wherein the degradation routes are respectively as follows:

drawings

FIG. 1 is a nuclear magnetic hydrogen spectrum of 2- (ethyleneoxy) ethyl acrylate and 2, 2' -dithiodiethanol monoacrylate provided in example 1 of the present invention;

FIG. 2 is a nuclear magnetic hydrogen spectrum of the product of the acid-addition of the monomer with acid degradation and reducibility sensitivity provided in example 1 of the present invention;

FIG. 3 is a nuclear magnetic spectrum of the product of dithiothreitol addition of the monomer with acid degradation and reducibility sensitivity provided in example 1 of the present invention;

FIG. 4 is a reaction scheme for preparing a polymer, provided in example 1 of the present invention;

FIG. 5 is a gel permeation chromatogram before and after the degradation of the polymer acid and before and after the reduction of the disulfide bond of the polymer by dithiothreitol provided in example 1 of the present invention;

FIG. 6 is a nuclear magnetic hydrogen spectrum before and after acid degradation of a polymer prepared by using a monomer substance with acid degradation and reducibility sensitivity provided in example 1 of the present invention;

FIG. 7 shows the particle size of the polymer-assembled micelle provided in example 1 of the present invention;

FIG. 8 is an electron micrograph of a polymer micelle provided in example 1 of the present invention;

FIG. 9 is a fluorescence change curve of the polymer-encapsulated Nile Red micelle provided in example 1 of the present invention in a pH5.4 environment;

FIG. 10 is a graph showing the fluorescence change of the polymer-encapsulated Nile Red micelle in a dithiothreitol environment, as provided in example 1 of the present invention.

Detailed Description

The invention will be further described in detail with reference to the following examples, which are given in the accompanying drawings.

Example 1

The method comprises the following steps: dissolving 6.16g of 2, 2' -dithiodiethanol in 30g of dichloromethane, and stirring for about 2 min; 4.24g of triethylamine was added and the mixture was placed in an ice bath and stirred magnetically.

Step two: adding 3.8g of acryloyl halide into a constant-pressure dropping funnel containing 10g of dichloromethane, slowly dropwise adding the acryloyl halide into the mixed system in the step one, reacting at room temperature for 4 hours after dropwise adding is finished, filtering the system, extracting with dichloromethane for 1 time, collecting an organic layer, drying and concentrating to obtain a crude product;

purifying the obtained crude product by column chromatography, using ethyl acetate petroleum ether (volume ratio 1: 4) as developing agent to obtain pure 2, 2' -dithiodiethanol monoacrylate, dissolving 20mg with deuterated chloroform, and performing nuclear magnetic treatment, as shown in B diagram of figure 1: the nuclear magnetic information is:

1H NMR(500MHz，CDCl3)δ6.44(d，J＝17.3Hz，1H)，6.14(dd，J＝17.3，10.5Hz，1H)，5.87(d，J＝10.4Hz，1H)，4.44(t，J＝6.7Hz，2H)，3.89(t，J＝5.8Hz，2H)，2.98(t，J＝6.7Hz，2H)，2.89(t，J＝5.8Hz，2H).

the same raw material, namely 20mg of 2- (ethyleneoxy) ethyl acrylate, is dissolved in 0.65mL of deuterated chloroform, the solution is transferred into a nuclear magnetic tube, and nuclear magnetism is performed, wherein nuclear magnetism hydrogen spectrum information is as follows: 1H NMR (400MHz, CDCl3)1H NMR (400MHz, CDCl3) δ 6.54-6.43(m, 2H), 6.18(dd, J ═ 17.3, 10.4Hz, 1H), 5.88(dd, J ═ 10.4, 1.4Hz, 1H), 4.44-4.40(m, 2H), 4.23(dd, J ═ 14.3, 2.3Hz, 1H), 4.07(dd, J ═ 6.8, 2.3Hz, 1H), 3.97-3.93(m, 2H), nuclear magnetic spectrum as in fig. 1A.

By contrast, it is apparent that between 6.5 and 5.5ppm, both species show hydrogen at the acrylate-activated double bond, while a peak of hydrogen at 4.44ppm on the methylene group attached to the ester bond is observed, and the mass structure of the product is confirmed to be that shown in the B diagram in FIG. 1 by the integration of the data of the respective portions.

Step three: and (2) putting 1.54g of 2, 2' -dithiodiethanol monoacrylate obtained in the step two into 10g of dichloromethane, magnetically stirring, adding 5mg of p-toluenesulfonic acid into the system, stirring for 1-2min, adding 1.2g of 2- (ethyleneoxy) ethyl acrylate into the system, reacting for 3h, adding triethylamine into the system, adjusting the system to be alkalescent, carrying out reduced pressure rotation and concentration to obtain a crude product, and further purifying by adopting a column chromatography method to obtain a monomer with acid degradation and reducibility sensitive functions.

Step four: taking 40mg of the monomer with acid degradation and reducibility sensitive functions in the third step into deuterated chloroform, halving, respectively adding no acid into the first part, performing nuclear magnetic resonance, and obtaining nuclear magnetic information as shown in A diagram of figure 2: 1H NMR (400MHz, CDCl3) δ 6.43(t, J ═ 13.2Hz, 2H), 6.16(dt, J ═ 17.4, 8.8Hz, 2H), 5.91-5.79(m, 2H), 4.88-4.73(m, 1H), 4.50-4.38(m, 2H), 4.32(s, 2H), 3.83(s, 2H), 3.72(s, 2H), 3.03-2.85(m, 4H), 1.35(d, J ═ 5.0Hz, 3H).

And the second part is added with 5 mu L of concentrated hydrochloric acid to rapidly seal the nuclear magnetic tube, the nuclear magnetic tube is vibrated for 2 to 3 times up and down, nuclear magnetic resonance is performed, and the nuclear magnetic spectrum is as shown in a B diagram in a figure 2, so that the nuclear magnetic spectrum is obviously seen, after the acid is added, a hydrogen peak on aldehyde groups of acetaldehyde appears at 9.80ppm, a hydrogen peak on methyl groups connected with the aldehyde groups appears at 2.19ppm, the acetaldehyde generated by acid degradation appears at a ratio of 1: 3 of the two positions through integration, and meanwhile, the hydrogen peak on acetal bonds at 4.88 to 4.73ppm is obviously weakened and almost ignored, and the hydrogen peak on the methyl groups on the acetal bonds completely disappears, which fully indicates that the acetal bonds are actually degraded under the acidic condition. The nuclear magnetism of acetaldehyde obtained by integration is: 1H NMR (400MHz in CDCl3) delta 9.80(s, 1H), 2.19(s, 3H) acetal bond degradation, and the resulting alcoholic species were also clearly assigned by comparison of integral ratios and peak positions.

Step five: taking 15mg of the monomer with acid degradation and reducibility sensitive functions in the third step, adding a proper amount of dithiothreitol, shaking up and down for 2-3 times, and performing nuclear magnetism. The obtained nuclear magnetic spectrum, as shown in B diagram in figure 3, shows that the peak of hydrogen atoms on the substance structure is not changed greatly before and after the disulfide bond is broken, and whether the substance is degraded or not can not be judged from the nuclear magnetic spectrum, however, the point plate is obtained by using ethyl acetate petroleum ether (volume ratio: 1: 4) as a developing solvent, a new point is really generated above the functional monomer, and the molecular weight of the corresponding substance is obtained by measuring the mass spectrum by combining a high-resolution mass spectrometer, which shows that the product is really generated by the sulfhydryl reagent corresponding to the B diagram in figure 3 after the dithiothreitol is added.

FIG. 3A is a comparison of the effect of FIG. 3A on the structure of the substance of FIG. 3A, as essentially shown in FIG. 2A, and FIG. 3B is a comparison of the effect of dithiothreitol on the degradation of the disulfide bonds in the substance to obtain a nuclear magnetic spectrum of the degraded substance.

Step six: taking 0.23g of the monomer with acid degradation and reducibility sensitive function in the fourth step and 92mg of 3, 6-oxaoctanediol into 1mL of dichloromethane, adding 3 muL of tetramethylguanidine catalyst into the dichloromethane, reacting for 10min, adding 0.5g of mercaptopolyethylene glycol monomethyl ether (2000) and 1.5mL of dichloromethane into the mixture, supplementing 3 muL of tetramethyl catalyst, and reacting at room temperature for 1h, wherein the reaction route is shown in FIG. 4. And slowly dropwise adding the system into a large amount of anhydrous ether to obtain a precipitate, collecting the precipitate, placing the precipitate in a vacuum drying oven, and drying for 24 hours for later use.

Step seven: taking 30mg of the polymer in the sixth step, dividing into three parts, adding no other reagent into the first part, adding hydrochloric acid into the second part, adding Dithiothreitol (DTT) into the third part, taking sulfhydryl polyethylene glycol monomethyl ether (2000) from the fourth part, and measuring the change of the peak time by using gel permeation chromatography to obtain a gel permeation chromatogram shown in figure 5. It can be seen from the comparison of retention times that the addition of acid or dithiothreitol produces a significant peak-lag in the polymer, indicating that the polymer degrades under both the addition of acid and dithiothreitol, and the number-average molecular weight of the polymer is found by integration as follows: 5337, after addition of an acid, the number average molecular weight is determined as: 2654; after addition of dithiothreitol, the number average molecular weight was determined as: 1902, which further demonstrates that the material has acid degradation, reductively sensitive functionality. Wherein, the mercapto-polyethylene glycol monomethyl ether (2000) is used as a raw material for reaction, and compared with the molecular weight difference between the raw material and the polymer before and after degradation, the polymer is degraded to be basically consistent with the position of the peak of the mercapto-polyethylene glycol monomethyl ether (2000) after degradation, which shows that the degradation is thorough.

Step eight: and (3) taking 40mg of the polymer in the sixth step into deuterated chloroform, halving, adding no acid into the first part, adding hydrochloric acid into the second part, and performing nuclear magnetic resonance respectively to obtain a nuclear magnetic spectrum as shown in figure 6. In panel a of fig. 6, it is clearly observed at 6.No hydrogen peak is observed between 43ppm, 6.16ppm and 5.91-5.79ppm, which indicates that unsaturated acrylate ester bonds in the monomer participate in the reaction, and the hydrogen peaks on other saturated hydrocarbon chains can be seen to be retained, which indicates that double bonds completely participate in the reaction to form polymers, while the nuclear magnetic spectrum after adding acid is shown as B picture in figure 6, from which it is obvious that the hydrogen peak on acetal bonds at 4.82ppm after adding acid completely disappears, the hydrogen peak on methyl groups at 1.36ppm on acetal bonds completely disappears, and the hydrogen peak on aldehyde groups on nuclear magnetic aldehyde groups at 9.83ppm can be seen, the hydrogen peak on methyl groups on acetaldehyde appears at 2.23ppm, the ratio of two points of integration is 1: 3, and the acetaldehyde substances produced by degradation are shown as:¹H NMR(400MHz，CDCl₃) δ 9.83(s, 1H), 2.23(s, 3H) it can be seen that, after the cleavage of the acetal bond, the hydrogen evolution peak position of the produced acetaldehyde species is relatively large, and the hydrogen evolution peak position of the produced corresponding alcohol species is not large.

Taking 20mg of the polymer in the sixth step into deuterated chloroform, adding 5 mu L of concentrated hydrochloric acid, rapidly sealing a nuclear magnetic tube, oscillating up and down for 2-3 times, standing for 2h, performing nuclear magnetic resonance, and obtaining a nuclear magnetic spectrum as a B diagram in a figure 6, wherein the nuclear magnetic spectrum is compared with a nuclear magnetic hydrogen spectrum of the polymer without acid, and as can be clearly seen from the B diagram, after acid is added, the hydrogen evolution peak of the original acetal bond at 4.82ppm completely disappears, the hydrogen evolution peak of the methyl group at 1.36ppm on the acetal bond also completely disappears, and simultaneously the hydrogen evolution peak of the aldehyde group on the acetaldehyde appears at 9.83ppm, the hydrogen evolution peak of the methyl group on the acetaldehyde appears at 2.23ppm, the ratio of the two integral points is 1: 3, and the acetaldehyde substance generated by degradation is the nuclear magnetic resonance information:¹H NMR(400MHz，CDCl₃) δ 9.83(s, 1H), 2.23(s, 3H) it can be seen that, after the cleavage of the acetal bond, the hydrogen evolution peak position of the produced acetaldehyde species is relatively large, and the hydrogen evolution peak position of the produced corresponding alcohol species is not large.

Step nine: taking 20mg of the polymer in the sixth step, adding the polymer into 0.5mL of tetrahydrofuran slowly and dropwise, adding the polymer into 20mL of distilled water, stirring for 24h, taking out a little, and measuring the particle size, wherein the result is shown in a figure 7; and dripping a small amount of sample on the silicon chip, airing, spraying gold, testing a mirror, and measuring the result of the electron microscope as shown in figure 8, wherein the micelle is basically spherical.

Step ten: and (3) taking 20mg of the polymer in the sixth step and 2mg of nile red in 0.5mL of tetrahydrofuran, slowly dripping the polymer into 20mL of distilled water, stirring for 24h, taking out 2mL of micelle solution, adding a certain amount of sodium acetate buffer solution, adjusting the pH value of the system to be 5.4, taking another part of 2mL of micelle solution, adding a certain concentration of dithiothreitol solution, finally measuring the change of fluorescence intensity after 0h, 2h, 4h, 8h, 12h, 24h, 36h and 48h, wherein the concentration of dithiothreitol in the system is 500mM, and respectively measuring the change of fluorescence intensity, as shown in the graph 9 and 10. It can be clearly seen that the fluorescence intensity is reduced in sequence with the time, which indicates that the encapsulated nile red is released and the nile red in the micelle is reduced, which indicates that the synthesized polymer can be used as a high molecular drug carrier. (the curves from top to bottom in FIGS. 9 and 10 are 0h, 2h, 4h, 8h, 12h, 24h, 36h and 48h in sequence).

The principle of the invention is as follows: reacting 2, 2 '-dithiodiethanol with acyl halide to obtain 2, 2' -dithiodiethanol derivative, and reacting with 2- (ethyleneoxy) ethyl acrylate at room temperature, wherein when the acyl halide is acryloyl chloride, the reaction route is as follows:

the reaction is similar to the reaction by using other acyl halide reagents, and the optional acyl halide substances in the invention are described in the specification.

The invention has the beneficial effects that: 1. the method has the advantages of cheap and easily-obtained raw materials, high reaction rate, mild reaction conditions and simple and easy operation;

2. the monomer substance obtained by the invention can be degraded into corresponding aldehyde and alcohol under an acidic condition, and can generate disulfide bond breakage in the presence of dithiothreitol, wherein the degradation routes are respectively as follows:

the above description is only a preferred embodiment of the present invention, and the protection scope of the present invention is not limited to the above embodiments, and all technical solutions belonging to the idea of the present invention belong to the protection scope of the present invention. It should be noted that modifications and embellishments within the scope of the invention may occur to those skilled in the art without departing from the principle of the invention, and are considered to be within the scope of the invention.