CN111793214A - Method for generating biological polyester - Google Patents

Abstract

The invention relates to a method for generating biological polyester, which comprises the following steps: firstly, synthesizing ethyl cellulose grafted poly-caprolactone; then grafting poly-caprolactone by using ethyl cellulose modified by pentynoic acid; synthesizing 6-p-toluenesulfonic acid-beta-cyclodextrin beta-CD-6-OTs; suspending beta-CD-6-OTs in N, N-dimethylformamide DMF, adding potassium iodide and sodium azide, and purifying to obtain azide cyclodextrin; and finally, dissolving the product B and azido cyclodextrin in N, N-dimethylformamide DMF, and adding cuprous bromide and pentamethyldiethylenetriamine serving as catalysts to obtain the product biological polyester. The biological polyester synthesized by the invention has good stability, biocompatibility and degradability.

Description

Method for generating biological polyester

Technical Field

The invention belongs to the technical field of biology, and particularly relates to a catalytic generation method of biological polyester.

Background

The science that the regular structures in different sizes are formed between the macromolecule and the macromolecule, the micromolecule, the nano particle or the substrate through the non-covalent bond effect. Among these, the study of the assembly of polymers in solution is undoubtedly one of the most thorough aspects. In particular, in recent years, the assembly of polymers in solution has many new progresses, the assembly objects are wider, the appearance is more novel, and the assembly driving force is more diversified, and in the molecules, cyclodextrin is noticed, on one hand, the cyclodextrin can selectively complex other molecules, for example, alpha-cyclodextrin can react with azo molecules, beta-cyclodextrin can react with ferrocene and adamantane molecules, Y-cyclodextrin can react with tricyclic aromatic hydrocarbon, and the like; on the other hand, cyclodextrin can induce the formation of an assembly, non-covalent bonds and micelles are formed through the complexation of cyclodextrin and adamantane, but the stability of the micelles needs to be enhanced; in the work of the document "Angew. chem. int. Ed 47(2008) 5573-5576", cyclodextrin is partially nested on a PCL chain segment, so that the chain segment has hydrophilicity, and the whole system obtains a core-shell micelle structure, but the cyclodextrin at the outer layer is difficult to react with other functional molecules because molecules are already nested, so that the functionality of the micelle is reduced.

Disclosure of Invention

Aiming at the defects, the invention provides a method for generating the biological polyester, and the biological polyester synthesized by the method has good stability, biocompatibility and degradability.

The technical scheme adopted by the invention is as follows:

a method for producing biological polyester, which is beta-cyclodextrin bonded ethyl cellulose grafted poly (-caprolactone) (EC-g-PCL-beta-CD), the structure of the biological polyester is shown as follows:

wherein p is 40-150, n is 10-40, Et is ethyl, the round platform is beta-cyclodextrin, and the number average molecular weight of the copolymer is 50000-400000.

A non-metal catalyzed method for synthesizing biological polyester is characterized by comprising the following steps:

1. dissolving ethyl cellulose EC in anhydrous xylene, adding caprolactone monomer CL and a catalyst, wherein the molar ratio of CL to EC is 140: 1-5000: 1, the catalyst is stannous octoate, the molar ratio of the stannous octoate to CL is 1: 1100-1: 600, vacuumizing, introducing inert gas, reacting at 90-140 ℃ for 1-24 hours to obtain a reaction solution, precipitating in petroleum ether, wherein the volume ratio of the petroleum ether to the reaction solution is more than 11: 1, performing suction filtration, and drying in vacuum to constant weight to obtain a product A, namely ethyl cellulose grafted poly-caprolactone;

2. dissolving the product A in trichloromethane, adding pentynoic acid, wherein the molar ratio of the product A to the pentynoic acid is 1: 133, the catalyst is 4-dimethylaminopyridine and 1, 3-Dicyclohexylcarbodiimide (DCC), the molar ratio of the pentynoic acid to the DCC to the DMAP is 1: 1.05, reacting at room temperature for 6-24 hours after adding the catalyst, filtering and precipitating the obtained product, and drying the obtained product in a vacuum oven to constant weight to obtain a product B, namely end alkyne modified ethyl cellulose grafted poly-caprolactone;

3. suspending beta-cyclodextrin beta-CD in water, dropwise adding a sodium hydroxide aqueous solution to enable the suspension to become a homogeneous phase, enabling the molar ratio of the beta-cyclodextrin beta-CD to the sodium hydroxide to be 1: 4, dropwise adding an acetonitrile solution of p-methylbenzenesulfonyl chloride in an ice water bath, enabling TsCl to be more than 1.5 times (mol) of the beta-CD, reacting for more than 1 hour at room temperature, performing suction filtration to collect white precipitates, refrigerating the filtrate overnight, collecting the precipitates again, and obtaining 6-p-methylbenzenesulfonic acid-beta-cyclodextrin (beta-CD-6-OTs) after two precipitates;

4. suspending beta-CD-6-OTs in N, N-Dimethylformamide (DMF), adding potassium iodide and sodium azide (NaN3), wherein the molar ratio of the beta-CD-6-OTs to the potassium iodide to the sodium azide is 2: 1: 20, the reaction temperature is 60-65 ℃, the reaction time is 12-24 hours, and purifying to obtain azido cyclodextrin;

5. dissolving the product B and azido cyclodextrin in N, N-Dimethylformamide (DMF), adding catalysts of cuprous bromide (CuBr) and Pentamethyldiethylenetriamine (PMDETA), wherein the molar ratio of the product B to the azido cyclodextrin is 1: 35-1: 100, the molar ratio of a branched chain unit of the product B to the CuBr to the PMDETA is 1: 1.1, reacting for 10-48 hours in the dark under the protection of inert gas, reacting at normal temperature, wherein the inert gas is nitrogen or argon, passing the product obtained by the reaction through a neutral alumina column, dialyzing, and freeze-drying by using a freeze dryer to obtain the product C biological polyester.

The invention has the beneficial effects that:

1. has good biocompatibility and degradability;

2. the cyclodextrin is connected with the copolymer through a covalent bond, so that the assembly is more stable;

3. the cyclodextrin positioned on the outer layer of the assembly can be further subjected to inclusion complexation with other molecules, and ferrocene is selected as a guest molecule, so that controllable release can be realized in electrode reaction, the assembly is more functional, and the cyclodextrin can be used as a carrier for drug release.

The specific implementation mode is as follows:

example (b):

(1) ethyl cellulose EC (2.392g, 0.104mmol) was dissolved in 45mL of anhydrous xylene, and after dissolution, caprolactone monomer CL (6.08g, 53.3mmol) and catalyst stannous octoate Sn (Oct)2(60 μ L, 1mol/L) were added, and after three vacuums-inert gas introduction, the reaction was carried out for 24 hours in a 120 ℃ oil bath. After the reaction had ceased to cool to room temperature, it was then precipitated in petroleum ether at a ratio of petroleum ether to solvent of 10: 1, approximately 500mL, and so dissolved-after precipitation twice, the product was dried in a vacuum oven to constant weight and number average molecular weight of 68500.

(2) The product of (1) (1.968g, 2.04mmol of the number of copolymer branches) was dissolved in 20mL of chloroform, after dissolution, pentynoic acid (4-penynoid acid, 0.4g, 4.08mmol) and 4-dimethylaminopyridine (DMAP, 49.82mg, 4.08mmol) were added to the chloroform solution, and DCC (0.8416g, 5.1mmol) was dissolved in 5mL of chloroform and then added dropwise to the flask over 5 minutes in an ice-water bath, gradually developing a milky precipitate, and reacted at 25 ℃ for 24 hours. After the reaction is stopped, filtering out a by-product N, N' -Dicyclohexylurea (DCU), precipitating for 2 times in methanol to remove excessive acid, precipitating for 2 times in normal hexane or normal heptane to remove excessive DCC and DCU, wherein the volume ratio of a precipitator to a solvent is 10: 1, the volume ratio of the precipitator to the solvent is about 250mL, and finally drying in a vacuum oven to a constant temperature;

(3) beta-cyclodextrin (. beta. -CD, 6g, 5.29mmol) was suspended in 50mL of water, sodium hydroxide (NaOH, 0.674g, 16.4mmol) was dissolved in 2mL of water, and then added dropwise to the aqueous cyclodextrin solution over 5 minutes with magnetic stirring, at which time the suspension was gradually found to be homogeneous. P-methylbenzenesulfonyl chloride (TsCl, 1.5g, 7.87mmol) was dissolved in 3mL of acetonitrile and added dropwise to the above solution over 5 minutes in an ice-water bath, whereupon a white precipitate precipitated out. After which it was stirred at 25 ℃ for 2 hours. After the reaction was stopped, the white precipitate was collected by suction filtration, and the filtrate was refrigerated overnight at 4 ℃. The two precipitates are the reaction product beta-CD-6-OTs. The precipitate was recrystallized and dried in a vacuum oven.

(4) beta-CD-6-OTs (1g, 0.776mmol) were suspended in dry 3mL DMF and became homogeneous at 63 deg.C, then potassium iodide (KI, 0.064g, 0.388mmol) and sodium azide (NaN3, 0.504g, 7.6mmol) were added and the reaction was carried out at 60-65 deg.C for 24 hours. After the reaction had stopped, the DMF was drained and washed several times with acetone. The azide cyclodextrin then needs to be purified using a sephadex column.

(5) The product EC-g-PCL-alkyne (0.1g, 0.104mmol of copolymer branched units) of (2) is taken and added into 10mL of DMF, after dissolution, azido cyclodextrin (55.4mg, 0.048mmol), CuBr (16mg, 0.112mmol) and PMDETA (27 μ L, 0.112mmol) are added, reaction is carried out for 30 hours at 35 ℃ under the protection of inert gas, and light is intentionally avoided during the reaction. After the reaction was stopped, 15mL of a chloroform diluent was added, and the catalyst was removed by passing through a neutral alumina column. Then the chloroform is evaporated in a rotary way, the residual DMF solution is dialyzed in DMF for 2 days to remove unreacted cyclodextrin, then is dialyzed in water for 3 days to complete the exchange of the solvent, and then is freeze-dried by a freeze dryer to obtain a product C, namely comb-shaped copolymer (EC-g-PCL-beta-CD).

Claims (1)

1. A method for producing a bio-polyester, comprising: the preparation method comprises the following steps:

1. dissolving ethyl cellulose EC in anhydrous xylene, adding caprolactone monomer CL and a catalyst, wherein the molar ratio of CL to EC is 140: 1-5000: 1, the catalyst is stannous octoate, the molar ratio of the stannous octoate to CL is 1: 1100-1: 600, vacuumizing, introducing inert gas, reacting at 90-140 ℃ for 1-24 hours to obtain a reaction solution, precipitating in petroleum ether, wherein the volume ratio of the petroleum ether to the reaction solution is more than 11: 1, performing suction filtration, and drying in vacuum to constant weight to obtain a product A, namely ethyl cellulose grafted poly-caprolactone;

2. dissolving the product A in trichloromethane, adding pentynoic acid, wherein the molar ratio of the product A to the pentynoic acid is 1: 133, the catalyst is 4-dimethylaminopyridine and 1, 3-Dicyclohexylcarbodiimide (DCC), the molar ratio of the pentynoic acid to the DCC to the DMAP is 1: 1.05, reacting at room temperature for 6-24 hours after adding the catalyst, filtering and precipitating the obtained product, and drying the obtained product in a vacuum oven to constant weight to obtain a product B, namely end alkyne modified ethyl cellulose grafted poly-caprolactone;

3. suspending beta-cyclodextrin beta-CD in water, dropwise adding a sodium hydroxide aqueous solution to enable the suspension to become a homogeneous phase, enabling the molar ratio of the beta-cyclodextrin beta-CD to the sodium hydroxide to be 1: 4, dropwise adding an acetonitrile solution of p-methylbenzenesulfonyl chloride in an ice water bath, enabling TsCl to be more than 1.5 times (mol) of the beta-CD, reacting for more than 1 hour at room temperature, performing suction filtration to collect white precipitates, refrigerating the filtrate overnight, collecting the precipitates again, and obtaining 6-p-methylbenzenesulfonic acid-beta-cyclodextrin (beta-CD-6-OTs) after two precipitates;

4. suspending beta-CD-6-OTs in N, N-Dimethylformamide (DMF), adding potassium iodide and sodium azide (NaN3), wherein the molar ratio of the beta-CD-6-OTs to the potassium iodide to the sodium azide is 2: 1: 20, the reaction temperature is 60-65 ℃, the reaction time is 12-24 hours, and purifying to obtain azido cyclodextrin;

5. dissolving the product B and azido cyclodextrin in N, N-Dimethylformamide (DMF), adding catalysts of cuprous bromide (CuBr) and Pentamethyldiethylenetriamine (PMDETA), wherein the molar ratio of the product B to the azido cyclodextrin is 1: 35-1: 100, the molar ratio of a branched chain unit of the product B to the CuBr to the PMDETA is 1: 1.1, reacting for 10-48 hours in the dark under the protection of inert gas, reacting at normal temperature, wherein the inert gas is nitrogen or argon, passing the product obtained by the reaction through a neutral alumina column, dialyzing, and freeze-drying by using a freeze dryer to obtain the product C biological polyester.