A controllable synthesis method of polyglutamic acid
By using low-polymerization-degree polyglutamic acid benzyl ester as an initiator under crown ether catalysis and combined with a buffer solution, a rapid and controllable synthesis of polyglutamic acid was achieved, solving the problems of harsh reaction conditions and polydispersity in traditional methods. Polyglutamic acid with consistent molecular weight was obtained, exhibiting excellent scale inhibition performance.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-07-10
- Publication Date
- 2026-03-20
AI Technical Summary
Traditional ring-opening polymerization methods for polyglutamic acid require stringent anhydrous and oxygen-free conditions and have a wide polydispersity, making it difficult to achieve rapid and controllable synthesis.
First, low-polymerization-degree polyglutamic acid benzyl ester was synthesized and used as an initiator to react with a buffer solution under crown ether catalysis to rapidly and controllably synthesize high-polymerization-degree polyglutamic acid benzyl ester, which was then hydrolyzed to obtain polyglutamic acid.
The reaction conditions were made less stringent, the reaction time was shortened, and the resulting polyglutamic acid had a narrow polydispersity and excellent scale inhibition properties.
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Abstract
Description
TECHNICAL FIELD
[0001] The application belongs to the technical field of corrosion and scale inhibition, and relates to a controllable synthesis method of polyglutamic acid. BACKGROUND
[0002] Industrial circulating cooling water accounts for a large proportion in industrial water. However, industrial circulating water contains a large amount of scale-forming ions such as calcium ions and barium ions. Long-term circulation use will cause deposition on the heat exchange surface, resulting in reduced heat exchange rate, corroded equipment and even endangering safety production. After the introduction of water treatment agents, there is a significant improvement, but there are still problems of environmental pollution and unsatisfactory efficiency. The polyaspartic acid scale inhibitor, which is most likely to replace the phosphorus-containing scale inhibitor, has attracted much attention due to its environmental-friendly and biodegradable properties. New scale inhibitors developed on the basis of the polyaspartic acid scale inhibitor have also made good progress.
[0003] Polyglutamic acid, also known as poly-γ-glutamic acid (PGA) for short, has excellent water solubility, super adsorbability and biodegradability. The structure of polyglutamic acid is a high molecular polymer formed by the peptide bond between the α-amino group and the γ-carboxyl group of glutamic acid units. Like polyaspartic acid, polyglutamic acid is also an environmentally friendly polymer, so polyglutamic acid is also expected to replace the phosphorus-containing scale inhibitor. The relative molecular mass of natural polyglutamic acid is widely distributed, which can be 100,000 to 2,000,000, and the molecular weight is an important factor affecting the properties of scale inhibitors, which is crucial to the development and application of polyglutamic acid. Therefore, controlling the molecular weight of polyglutamic acid is the key. Polyglutamic acid is usually obtained by alkaline hydrolysis of polyglutamic acid benzyl ester, and polyglutamic acid benzyl ester is generally prepared by ring-opening polymerization of L-glutamic acid benzyl ester-cyclohexane acid anhydride (BLG-NCA). However, in order to obtain polyglutamic acid with narrow polydispersity, the traditional ring-opening polymerization method requires strict polymerization conditions (water-free and oxygen-free conditions throughout the reaction) and a long reaction time, so it is necessary to explore a new fast and controllable method for synthesizing polyglutamic acid, so as to make it have better application and development as a scale inhibitor. SUMMARY
[0004] The present application provides a controllable synthesis method of polyglutamic acid, which synthesizes polyglutamic acid benzyl ester with low polymerization degree first, then uses polyglutamic acid benzyl ester with low polymerization degree as an initiator, introduces a buffer solution, and quickly and controllably synthesizes polyglutamic acid benzyl ester with high polymerization degree under the catalysis of crown ether, thereby reducing the reaction conditions required by the traditional ring-opening polymerization method, i.e. water-free and oxygen-free conditions throughout the reaction, and the polydispersity of the obtained polyglutamic acid is narrow.
[0005] To achieve the above object, the present application adopts the following technical scheme:
[0006] The application provides a controllable synthesis method of polyglutamic acid, which comprises the following steps:
[0007] a. Preparation of polyglutamic acid benzyl ester
[0008] The purified L-glutamic acid benzyl ester-cyclic anhydride (BLG-NCA) is dissolved in dimethylformamide (DMF), an initiator n-butylamine is added, and the reaction is carried out for 48 h under anhydrous and anaerobic conditions; after the reaction is completed, the product is dissolved in dichloromethane, washed with water for three times, and the organic phase is dried and spin-dried to obtain polyglutamic acid benzyl ester with low polymerization degree, which is stored at-10 ℃;
[0009] The unpurified L-glutamic acid benzyl ester-cyclic anhydride is dissolved in dichloromethane, a hydrochloric acid-borax buffer solution is added, then polyglutamic acid benzyl ester with low polymerization degree is added, and a controllable polymerization reaction is carried out for 2 h under the catalysis of a crown ether; the organic phase is dried and spin-dried to obtain polyglutamic acid benzyl ester (PBLG) with high polymerization degree.
[0010] b. Preparation of polyglutamic acid
[0011] The polyglutamic acid benzyl ester with high polymerization degree obtained in step a is dissolved in THF, and a NaOH solution is added dropwise into the mixed solution, and the reaction is carried out at 25 ℃ for 24 h; after the reaction is completed, the product is purified by dialysis and vacuum dried to obtain polyglutamic acid (PGA).
[0012] The reaction route of the above method is as follows:
[0013]
[0014] In one technical solution, the molar ratio of the L-glutamic acid benzyl ester-cyclic anhydride to the n-butylamine is not less than 3:1.
[0015] In one technical solution, the pH of the buffer solution is 7-9, and the addition amount is 5%-10% of the total volume of the reaction.
[0016] In one technical solution, the crown ether is selected from one of 18-crown-6, dibenzo-18-crown-6 and 15-crown-5.
[0017] In one technical solution, the molar ratio of the polyglutamic acid benzyl ester with low polymerization degree to the unpurified L-glutamic acid benzyl ester-cyclic anhydride is 0.01-0.1:1.
[0018] In one technical solution, the molar ratio of the crown ether to the unpurified L-glutamic acid benzyl ester-cyclic anhydride is 0.05-0.2:1.
[0019] Compared with the prior art, the application has the following beneficial effects:
[0020] The application first synthesizes polybenzyl glutamate with low polymerization degree (polymerization degree n is less than 10), then introduces a buffer solution under the catalysis of crown ether, and rapidly and controllably synthesizes polybenzyl glutamate with high polymerization degree by taking polybenzyl glutamate with low polymerization degree as an initiator, so that polyglutamic acid with high polymerization degree is obtained by hydrolysis, the harsh reaction conditions of traditional ring-opening polymerization requiring no water and no oxygen throughout the process are reduced, the reaction time is relatively short, the molecular weight of the obtained polyglutamic acid is relatively uniform, that is, the polydispersity of the polyglutamic acid is relatively narrow. Different polymerization degrees of polyglutamic acid all exhibit excellent scale inhibition performance at the same concentration, which also verifies that the polydispersity of the polyglutamic acid is relatively narrow.
[0021] When the polybenzyl glutamate with low polymerization degree is taken as an initiator to perform the polymerization reaction, there are both inorganic phases and organic phases in the reaction system, crown ether is selected as a phase transfer catalyst, the reaction time can be shortened, and the polydispersity of the polyglutamic acid is reduced; meanwhile, the buffer solution is introduced to dissolve by-products, and the polydispersity of the polyglutamic acid is further reduced. BRIEF DESCRIPTION OF DRAWINGS
[0022] Figure 1 The scale inhibition performance curve of polyglutamic acid synthesized for example 3.
[0023] Figure 2 The scale inhibition performance curve of polyglutamic acid synthesized for example 3. DETAILED DESCRIPTION
[0024] The following examples are used to illustrate the application, but are not used to limit the protection scope of the application. If not specifically indicated, the technical means used in the examples is a conventional means familiar to those skilled in the art. The test method in the following examples is a conventional method, unless otherwise specified.
[0025] The L-benzyl glutamate-cycloin anhydride (BLG-NCA) used in the examples of the application can be prepared according to the method in the literature (T.M.Fan, J.Cheng, Biomacromolecules 14 (2013) 920-929; 2) Tian, ZY., Zhang, Z., Wang, S. et al. Nat. Commun. 12 (2021) 5810.).
[0026] Example 1 synthesis of PBLG-1
[0027] BLG-NCA was first purified by recrystallization using THF as solvent. 523 mg (2.10 mmol) of recrystallized and purified BLG-NCA was dissolved in 3 mL of DMF, then 51 mg (0.70 mmol) of initiator n-butylamine was added, the reaction was stirred for 48 h under anhydrous and anaerobic conditions. After the reaction was completed, the product was dissolved in CH2Cl2, washed with water three times, the organic phase was dried and rotary evaporated to obtain 440 mg of PBLG-1, with a yield of 91%. The polymerization degree n of PBLG-1 was calculated by H NMR to be 3. PBLG-1 was dissolved in CH2Cl2to prepare a 10 mg / mL solution for use, and was stored at -10°C. 1 H NMR calculated the polymerization degree n of PBLG-1 to be 3. PBLG-1 was dissolved in CH2Cl2to prepare a 10 mg / mL solution for use, and was stored at -10°C.
[0028] Example 2 Synthesis of PBLG-2
[0029] BLG-NCA was first purified by recrystallization using THF as solvent. 523 mg (2.10 mmol) of recrystallized and purified BLG-NCA was dissolved in 3 mL of DMF, then 51 mg (0.70 mmol) of initiator n-butylamine was added, the reaction was stirred for 48 h under anhydrous and anaerobic conditions. After the reaction was completed, the product was dissolved in CH2Cl2, washed with water three times, the organic phase was dried and rotary evaporated to obtain 440 mg of PBLG-1, with a yield of 91%. The polymerization degree n of PBLG-1 was calculated by H NMR to be 3. PBLG-1 was dissolved in CH2Cl2to prepare a 10 mg / mL solution for use, and was stored at -10°C. 1 H NMR calculated the polymerization degree n of PBLG-1 to be 3. PBLG-1 was dissolved in CH2Cl2to prepare a 10 mg / mL solution for use, and was stored at -10°C.
[0030] Example 3 Synthesis of PGA
[0031] 183 mg (0.7 mmol) of unpurified BLG-NCA was dissolved in 5 mL of CH2Cl2, and 26 mg (0.07 mmol) of dibenzo-18-crown-6 ether-6 and 0.35 mL of pH = 7 hydrochloric acid-borax buffer solution were added, and stirred well, then 22 mg (0.1 mmol, 1 / 7 eq) of PBLG-1 was added, and the reaction was stirred at 25°C for 2 h.
[0032] After the organic phase was vacuum dried and rotary evaporated, the product was dissolved in 5 mL of THF, 60 mg (1.5 mmol, 1.5 eq) of NaOH was dissolved in 2 mL of H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. The product polyglutamic acid PGA 110 mg was obtained by dialysis purification and vacuum drying, with a yield of 88%.
[0033] The polymerization degree n of PGA was calculated by H NMR to be 10, and its polydispersity D was calculated by GPC to be 1.10. 1 The polymerization degree n of PGA was calculated by H NMR to be 10, and its polydispersity D was calculated by GPC to be 1.10.
[0034] Calcium sulfate scale inhibition performance test (refer to GB / T 39221-2020): 250 mL simulated water was prepared by using CaCl2 and Na2SO4, and the Ca 2+ concentration was 2000 mg / L, and the SO4 2- concentration was 4800 mg / L, and the polyglutamic acid concentration was 1 mg / L, and 25 mL of 0.025 mol / L borax buffer solution was added. The mixture was water-bathed at 70°C for 6 h in a constant temperature water bath, cooled to room temperature 25°C, and the Ca 2+ content in the supernatant was calibrated by using 0.025 mol / L ethylenediaminetetraacetic acid disodium salt standard solution. Parallel tests were also conducted with polyglutamic acid concentrations of 2 mg / L, 3 mg / L, 4 mg / L, 5 mg / L, and 6 mg / L. The results are shown in Figure 1 Figure 1 It can be seen that when the polyglutamic acid PGA concentration is 6 mg / L, the calcium sulfate scale inhibition efficiency is 99.8%.
[0035] Calcium carbonate scale inhibition performance test (refer to GB / T 39221-2020): 250 mL simulated water was prepared by using CaCl2 and NaHCO3, and the Ca 2+ concentration was 240 mg / L, and the SO4 2- concentration was 720 mg / L, and the polyglutamic acid concentration was 5 mg / L, and 10 mL of 0.01 mol / L borax buffer solution was added. The mixture was water-bathed at 80°C for 10 h in a constant temperature water bath, cooled to room temperature 25°C, and the Ca 2+ content in the supernatant was calibrated by using 0.01 mol / L ethylenediaminetetraacetic acid disodium salt standard solution. Parallel tests were also conducted with polyglutamic acid concentrations of 10 mg / L, 20 mg / L, 30 mg / L, and 50 mg / L. The results are shown in Figure 2 Figure 2 It can be seen that when the polyglutamic acid PGA concentration is 50 mg / L, the calcium carbonate scale inhibition efficiency is 43.3%.
[0036] Example 4
[0037] 260 mg (1.2 mmol) of unpurified BLG-NCA was dissolved in 5 mL of CH2Cl2, and 44 mg (0.12 mmol) of dibenzo-18-crown-6 ether-6 and 0.7 mL of pH = 8 hydrochloric acid-borax buffer solution were added, and the mixture was stirred, and then 22 mg (0.1 mmol, 1 / 12 eq) of PBLG-1 was added, and the reaction was stirred at 25°C for 2 h.
[0038] The product was dissolved in 5 mL THF after vacuum drying and rotary evaporation of the organic phase, 90 mg (2.3 mmol, 1.5 eq) NaOH was dissolved in 2 mL H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. The product polyglutamic acid PGA 159 mg was obtained by dialysis purification and vacuum drying, with a yield of 85%.
[0039] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and its polydispersity D can be obtained by GPC.
[0040] The scale inhibition test process was the same as that of Example 3, and the results were as follows: when the concentration of polyglutamic acid PGA was 6 mg / L, the inhibition efficiency of calcium sulfate scale was 99.3%; when the concentration of polyglutamic acid PGA was 50 mg / L, the inhibition efficiency of calcium carbonate scale was 43.9%.
[0041] Example 5
[0042] 370 mg (1.7 mmol) of unpurified BLG-NCA was dissolved in 10 mL CH2Cl2, and 62 mg (0.7 mmol) of dibenzo-18-crown-6 and 1.0 mL of pH = 9 hydrochloric acid-borax buffer solution were added, and the mixture was stirred, then 22 mg (0.1 mmol, 1 / 17 eq) of PBLG-1 was added, and the reaction was stirred at 25°C for 2 h.
[0043] The product was dissolved in 10 mL THF after vacuum drying and rotary evaporation of the organic phase, 120 mg (3 mmol, 1.5 eq) NaOH was dissolved in 3 mL H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. The product polyglutamic acid PGA 215 mg was obtained by dialysis purification and vacuum drying, with a yield of 86%.
[0044] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and its polydispersity D can be obtained by GPC.
[0045] The scale inhibition test process was the same as that of Example 3, and the results were as follows: when the concentration of polyglutamic acid PGA was 6 mg / L, the inhibition efficiency of calcium sulfate scale was 99.3%; when the concentration of polyglutamic acid PGA was 50 mg / L, the inhibition efficiency of calcium carbonate scale was 44.0%.
[0046] Example 6
[0047] PBLG-1 22 mg (0.1 mmol, 1 / 22 eq) was added and the reaction was stirred at 25 °C for 2 h.
[0048] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 10 mL THF, 150 mg (3.75 mmol, 1.5 eq) NaOH was dissolved in 3 mL H2O and added dropwise to the mixed solution, and the reaction was carried out at 25 °C for 24 h. Dialysis purification and vacuum drying gave the product polyglutamic acid PGA 277 mg, with a yield of 89%.
[0049] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and its polydispersity D can be obtained by GPC.
[0050] The scale inhibition test process was the same as Example 3, and the results were as follows: when the concentration of polyglutamic acid PGA was 6 mg / L, the inhibition efficiency of calcium sulfate scale was 99.1%; when the concentration of polyglutamic acid PGA was 50 mg / L, the inhibition efficiency of calcium carbonate scale was 43.6%.
[0051] Example 7
[0052] PBLG-1 22 mg (0.1 mmol, 1 / 22 eq) was added and the reaction was stirred at 25 °C for 2 h.
[0053] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 10 mL THF, 150 mg (3.75 mmol, 1.5 eq) NaOH was dissolved in 3 mL H2O and added dropwise to the mixed solution, and the reaction was carried out at 25 °C for 24 h. Dialysis purification and vacuum drying gave the product polyglutamic acid PGA 277 mg, with a yield of 89%.
[0054] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and its polydispersity D can be obtained by GPC.
[0055] The anti-scaling test process is the same as Example 3, and the results are as follows: when the concentration of polyglutamic acid PGA is 6 mg / L, the calcium sulfate scale inhibition efficiency is 99.2%; when the concentration of polyglutamic acid PGA is 50 mg / L, the calcium carbonate scale inhibition efficiency is 43.4%.
[0056] Example 8
[0057] 695 mg (3.2 mmol) of unpurified BLG-NCA was dissolved in 15 mL of CH2Cl2, 108 mg (0.3 mmol) of dibenzo-18-crown-6 ether-6 and 1.5 mL of a hydrochloric acid-borax buffer solution with pH = 7 were added, and the mixture was stirred, and then 222 mg (0.1 mmol, 1 / 32 eq) of PBLG was added, and the reaction was stirred at 25°C for 2 h.
[0058] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 15 mL of THF, 210 mg (5.3 mmol, 1.5 eq) of NaOH was dissolved in 5 mL of H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. Dialysis purification and vacuum drying gave the product polyglutamic acid PGA 394 mg, with a yield of 90%.
[0059] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and the polydispersity D thereof can be obtained by GPC.
[0060] The anti-scaling test process is the same as Example 3, and the results are as follows: when the concentration of polyglutamic acid PGA is 6 mg / L, the calcium sulfate scale inhibition efficiency is 99.4%; when the concentration of polyglutamic acid PGA is 50 mg / L, the calcium carbonate scale inhibition efficiency is 43.3%.
[0061] Example 9
[0062] 803 mg (3.7 mmol) of unpurified BLG-NCA was dissolved in 20 mL of CH2Cl2, 108 mg (0.3 mmol) of dibenzo-18-crown-6 ether-6 and 2 mL of a hydrochloric acid-borax buffer solution with pH = 8 were added, and the mixture was stirred, and then 22 mg (0.1 mmol, 1 / 37 eq) of PBLG-2 was added, and the reaction was stirred at 25°C for 2 h.
[0063] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 20 mL of THF, 240 mg (6 mmol, 1.5 eq) of NaOH was dissolved in 5 mL of H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. Dialysis purification and vacuum drying gave the product polyglutamic acid PGA 450 mg, with a yield of 90%.
[0064] By 1H NMR can get the degree of polymerization n = 41 of PGA, and GPC can get its polydispersity D = 1.10.
[0065] The scale inhibition test process is the same as Example 3, and the results are as follows: when the concentration of polyglutamic acid PGA is 6 mg / L, the inhibition efficiency of calcium sulfate scale is 99.1%; when the concentration of polyglutamic acid PGA is 50 mg / L, the inhibition efficiency of calcium carbonate scale is 43.4%.
[0066] Example 10
[0067] 911 mg (4.2 mmol) of unpurified BLG-NCA was dissolved in 20 mL of CH2Cl2, 140 mg (0.4 mmol) of dibenzo-18-crown-6 and 2 mL of pH = 9 hydrochloric acid-borax buffer solution were added, and the mixture was stirred, then 22 mg (0.1 mmol, 1 / 42 eq) of PBLG-2 was added, and the reaction was stirred at 25°C for 2 h.
[0068] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 20 mL of THF, 270 mg (6.75 mmol, 1.5 eq) of NaOH was dissolved in 5 mL of H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. Dialysis purification and vacuum drying gave the product polyglutamic acid PGA 506 mg, with a yield of 90%.
[0069] By 1 H NMR can get the degree of polymerization n = 46 of PGA, and GPC can get its polydispersity D = 1.16.
[0070] The scale inhibition test process is the same as Example 3, and the results are as follows: when the concentration of polyglutamic acid PGA is 6 mg / L, the inhibition efficiency of calcium sulfate scale is 99.3%; when the concentration of polyglutamic acid PGA is 50 mg / L, the inhibition efficiency of calcium carbonate scale is 43.2%.
[0071] Example 11
[0072] 1020 mg (4.7 mmol) of unpurified BLG-NCA was dissolved in 25 mL of CH2Cl2, 105 mg (0.4 mmol) of 18-crown-6 and 3 mL of pH = 9 hydrochloric acid-borax buffer solution were added, and the mixture was stirred, then 22 mg (0.1 mmol, 1 / 47 eq) of PBLG-2 was added, and the reaction was stirred at 25°C for 2 h.
[0073] The product was dissolved in 25 mL THF after vacuum drying and rotary evaporation of the organic phase, 300 mg (7.5 mmol, 1.5 eq) NaOH was dissolved in 7 mL H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. The product polyglutamic acid PGA 563 mg was obtained by dialysis purification and vacuum drying, with a yield of 90%.
[0074] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and its polydispersity D can be obtained by GPC.
[0075] The scale inhibition test process is the same as Example 3, and the results are as follows: when the concentration of polyglutamic acid PGA is 6 mg / L, the inhibition efficiency of calcium sulfate scale is 99.2%; when the concentration of polyglutamic acid PGA is 50 mg / L, the inhibition efficiency of calcium carbonate scale is 43.3%.
[0076] Example 12
[0077] 1128 mg (5.2 mmol) of unpurified BLG-NCA was dissolved in 25 mL CH2Cl2, and 88 mg (0.4 mmol) of 15-crown-5 and 3 mL of pH = 9 hydrochloric acid-borax buffer solution were added, and the mixture was stirred well, then 22 mg (0.1 mmol, 1 / 52 eq) of PBLG-2 was added, and the reaction was stirred at 25°C for 2 h.
[0078] The product was dissolved in 25 mL THF after vacuum drying and rotary evaporation of the organic phase, 300 mg (7.5 mmol, 1.5 eq) NaOH was dissolved in 7 mL H2O and added dropwise to the mixed solution, and the reaction was carried out at 25°C for 24 h. The product polyglutamic acid PGA 563 mg was obtained by dialysis purification and vacuum drying, with a yield of 90%.
[0079] By 1 The degree of polymerization n of PGA can be obtained by H NMR, and its polydispersity D can be obtained by GPC.
[0080] The scale inhibition test process is the same as Example 3, and the results are as follows: when the concentration of polyglutamic acid PGA is 6 mg / L, the inhibition efficiency of calcium sulfate scale is 99.2%; when the concentration of polyglutamic acid PGA is 50 mg / L, the inhibition efficiency of calcium carbonate scale is 43.3%.
[0081] Example 13 Comparative synthesis without crown ether
[0082] 1128 mg (5.2 mmol) of unpurified BLG-NCA was dissolved in 25 mL of CH2Cl2, and 3 mL of hydrochloric acid-borax buffer solution with pH=9 was added and stirred thoroughly. Then, 22 mg (0.1 mmol, 1 / 52 eq) of PBLG-1 was added, and the mixture was stirred at 25 °C for 2 h.
[0083] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 25 mL of THF. 330 mg (8.25 mmol, 1.5 eq) of NaOH was dissolved in 7 mL of H₂O and added dropwise to the mixed solution. The reaction was carried out at 25 °C for 24 h. After dialysis purification and vacuum drying, 619 mg of polyglutamic acid (PGA) was obtained, with a yield of 70%.
[0084] pass 1 H NMR showed that the degree of polymerization of PGA was n=37, and GPC showed that its polydispersity was D=4.2.
[0085] Example 14 Synthesis without Buffer Solution
[0086] 1128 mg (5.2 mmol) of unpurified BLG-NCA was dissolved in 25 mL of CH2Cl2, and 105 mg (0.4 mmol) of 18-crown ether-6 was added and stirred thoroughly. Then 22 mg (0.1 mmol, 1 / 52 eq) of PBLG-2 was added, and the mixture was stirred at 25 °C for 2 h.
[0087] After vacuum drying and rotary evaporation of the organic phase, the product was dissolved in 25 mL of THF. 330 mg (8.25 mmol, 1.5 eq) of NaOH was dissolved in 7 mL of H₂O and added dropwise to the mixed solution. The reaction was carried out at 25 °C for 24 h. After dialysis purification and vacuum drying, 619 mg of polyglutamic acid (PGA) was obtained, with a yield of 89%.
[0088] pass 1 H NMR yielded a degree of polymerization of PGA n = 72, and GPC yielded a polydispersity of D = 3.7.
[0089] The embodiments described above are merely preferred embodiments of the present invention and are only used to explain the present invention. They are not intended to limit the scope of the present invention. For those skilled in the art, other implementation methods can be easily made by substitution or modification based on the technical content disclosed in this specification. Therefore, all changes and improvements made on the principle of the present invention should be included within the scope of the patent application of the present invention.
Claims
1. A controllable synthesis method for sodium polyglutamate, characterized in that, Includes the following steps: a. Preparation of polyglutamic acid benzyl ester The purified L-glutamic acid benzyl ester-cyclic anhydride was dissolved in dimethylformamide, and the initiator n-butylamine was added. The reaction was carried out under anhydrous and oxygen-free conditions for 48 h. After the reaction was completed, the product was dissolved in dichloromethane, washed three times with water, dried, and the organic phase was evaporated to obtain low-polymerization degree polyglutamic acid benzyl ester, which was stored at -10 °C. The degree of polymerization of the low-polymerization degree polyglutamic acid benzyl ester was less than 10. Unpurified L-glutamic acid benzyl ester-cyclic anhydride was dissolved in dichloromethane, and a hydrochloric acid-borax buffer solution was added. Then, low-polymerization-degree polyglutamic acid benzyl ester was added, and a controlled polymerization reaction was carried out for 2 hours under the catalysis of a crown ether. The organic phase was dried and evaporated to obtain high-polymerization-degree polyglutamic acid benzyl ester. The pH of the buffer solution was 7-9 and the amount added was 5%-10% of the total reaction volume. The crown ether was selected from 18-crown ether-6, dibenzo-18-crown ether-6, or 15-crown ether-5. The molar ratio of the low-polymerization-degree polyglutamic acid benzyl ester to the unpurified L-glutamic acid benzyl ester-cyclic anhydride was 0.01-0.1:
1. The molar ratio of the crown ether to the unpurified L-glutamic acid benzyl ester-cyclic anhydride was 0.05-0.2:
1. b. Preparation of sodium polyglutamate The highly polymerized polyglutamic acid benzyl ester obtained in step a was dissolved in THF, and NaOH solution was added dropwise to the mixed solution. The mixture was reacted at 25°C for 24 hours. After the reaction was completed, the mixture was purified by dialysis and dried under vacuum to obtain sodium polyglutamate.
2. The method for controlled synthesis of sodium polyglutamate according to claim 1, characterized in that, The molar ratio of L-glutamic acid benzyl ester-cyclic anhydride to n-butylamine is not less than 3:1.