Preparation method of 1,2-dimyristoyl-rac-glycerol-3-methoxypolyethylene glycol 2000

Abstract

The present invention belongs to the field of polymer synthesis technology, and the present invention discloses a kind of preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxy polyethylene glycol 2000. Comprise the following steps: using water as solvent, under the action of cation exchange resin, methoxy polyethylene glycol glycidyl ether is hydrolyzed into methoxy polyethylene glycol 2000 glycerol, then using tetradecanoic acid, dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), dichloromethane, 1,2-dimyristoyl-RAC-glycerol-3-methoxy polyethylene glycol 2000 is obtained by condensation. Preparation method of the present invention raw materials are easy to obtain, simple to operate, high conversion rate, mild conditions, and high product yield. For the development of a uniform protein modifier, stable chemical properties, no physiological toxicity, the preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxy polyethylene glycol 2000 with high yield provides a basis.

Description

Technical Field

[0001] The present invention relates to the technical field of polymer synthesis, and in particular to a preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000. Background Art

[0002] In recent years, polyethylene glycol (PEG) has been widely used to modify the structure of biomacromolecules and small molecule drugs. PEG modification can significantly improve their water solubility and stability, reduce renal filtration, and thus prolong the drug's circulation time in the body. Due to its excellent biocompatibility, a variety of PEG-based drugs have been used to treat diseases in recent years. For example, siRNA-based drugs have potential therapeutic effects for many diseases. However, due to the high molecular weight and polyanionic properties of siRNA, siRNA drugs typically require loading into complex delivery systems to reach the target and exert their therapeutic effects. 1,2-Dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 has been shown to play a crucial role in the delivery of siRNA drugs. It can self-assemble into large molecular nanoparticles through electrostatic interactions with polyanionic nucleic acids to encapsulate siRNA. The molecular structure of 1,2-Dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 is as follows:

[0003]

[0004] siRNA delivery vehicles are crucial for successful siRNA therapy, and cationic liposomes are a common delivery method for siRNA drugs. Studies have shown that the materials for these cationic liposomes require the addition of a PEGylated liposome material, with 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 being a key component. This material self-assembles into macromolecular nanoparticles through electrostatic interactions with polyanionic nucleic acids. This encapsulates siRNA, effectively delivering siRNA to the cytoplasm and releasing it, where it binds to its target site and triggers the degradation of the target mRNA. This type of liposome reduces liposome-cellular interactions and its ability to adsorb ApoE, resulting in superior gene silencing. The use of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 results in higher levels of gene silencing / expression and improved efficacy.

[0005] To form 1,2-dimyristoyl-RAC-glycerol-3-methoxy polyethylene glycol 2000, methoxy polyethylene glycol 2000 glycerol must first be formed. The methods for forming methoxy polyethylene glycol 2000 glycerol are:

[0006] 1. Hydrolyze methoxy polyethylene glycol 2000 glycerol ether with phosphoric acid to methoxy polyethylene glycol 2000 glycerol. This method has the disadvantage that the resulting 1,2-dimyristoyl-RAC-glycerol-3-methoxy polyethylene glycol 2000 has a broad molecular weight distribution, which is not conducive to the preparation of a uniform protein modifier. Furthermore, polyethylene glycol with a molecular weight less than 400 is physiologically toxic.

[0007] 2. Hydrolyze methoxy polyethylene glycol 2000 glycidyl ether with hydrochloric acid to methoxy polyethylene glycol 2000 glycerol. The disadvantage of this method is that the yield is low.

[0008] 3. Hydrolyze methoxy polyethylene glycol 2000 glycidyl ether to methoxy polyethylene glycol 2000 glycerol with sulfuric acid. The disadvantage of this method is that it causes the methoxy polyethylene glycol ether bond to break.

[0009] Based on this, it is urgently needed in this field to develop a preparation method for 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 that can prepare uniform protein modifiers, has stable chemical properties, is non-physiologically toxic, and has a high yield. Summary of the Invention

[0010] In view of this, the present invention provides a method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 to solve the problems of the existing preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, such as the uneven protein modifier prepared, unstable chemical properties, physiological toxicity, and low yield, which limit its application.

[0011] In order to achieve the above object, the present invention adopts the following technical solutions:

[0012] The present invention provides a preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, comprising the following steps:

[0013] (1) mixing methoxy polyethylene glycol 2000 glycidyl ether, a cation exchange resin, and a solvent, and hydrolyzing the mixture to obtain methoxy polyethylene glycol 2000 glycerol;

[0014] (2) Methoxypolyethylene glycol 2000 glycerol, tetradecanoic acid, dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), and a non-polar solvent are mixed and condensed to obtain 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000.

[0015] Preferably, in step (1), the molecular weight of methoxy polyethylene glycol 2000 glycidyl ether is 1800-2200; the solvent is one of water, methanol and ethanol; and the cation exchange resin is HND-12 cation exchange resin.

[0016] Preferably, in the step (1), the mass ratio of methoxy polyethylene glycol 2000 glycidyl ether to the cation exchange resin is 1:0.2-0.4; the mass volume ratio of methoxy polyethylene glycol 2000 glycidyl ether to the solvent is 1 g:8-12 mL.

[0017] Preferably, in step (1), the reaction temperature of the hydrolysis reaction is 20 to 30° C., and the reaction time is 10 to 20 hours.

[0018] Preferably, in the step (1), the methoxy polyethylene glycol 2000 glycerol reaction solution obtained by hydrolysis is post-treated to obtain pure methoxy polyethylene glycol 2000 glycerol;

[0019] The post-treatment comprises the following steps: filtering the obtained methoxy polyethylene glycol 2000 glycerol reaction solution to remove the cation exchange resin, adding dichloromethane for extraction, drying, and concentrating to obtain methoxy polyethylene glycol 2000 glycerol.

[0020] Preferably, in step (2), the non-polar solvent is one of dichloromethane, chloroform and ethyl acetate.

[0021] Preferably, in step (2), the molar ratio of methoxy polyethylene glycol 2000 glycerol, myristic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine is 1:1.9-3:1.9-3:0.1-1; and the mass volume ratio of methoxy polyethylene glycol 2000 glycerol to the non-polar solvent is 1 g:10-15 mL.

[0022] Preferably, in step (2), the reaction temperature of the condensation reaction is 20-30° C., and the reaction time is 10-20 h.

[0023] Preferably, in step (2), the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution obtained by condensation is post-treated to obtain pure 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000;

[0024] The post-treatment comprises the following steps: filtering the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution, concentrating, adding isopropyl alcohol, cooling to precipitate a white solid, filtering, and drying to obtain 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000.

[0025] It can be seen from the above technical solution that compared with the prior art, the present invention has the following beneficial effects:

[0026] The preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 of the present invention has readily available raw materials, simple operation, high conversion rate, and mild conditions. In the first step, the cation exchange resin is used to prevent the methoxypolyethylene glycol ether bond from breaking. The cation exchange resin is green, environmentally friendly, and recyclable, and can replace traditional inorganic acids while avoiding pollution. In the second step, a uniform and stable product can be obtained through recrystallization. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are merely embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on the provided drawings without paying any creative work.

[0028] Figure 1 Schematic diagram of the overall preparation process of the present invention;

[0029] Figure 2 This is the nuclear magnetic resonance of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 obtained in Example 4 of the present invention. 1 H NMR spectrum;

[0030] Figure 3 This is the nuclear magnetic resonance of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 obtained in Example 4 of the present invention. 13 C NMR spectrum;

[0031] Figure 4 This is the high-resolution mass spectrum of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 obtained in Example 4 of the present invention. DETAILED DESCRIPTION

[0032] The present invention provides a preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, comprising the following steps:

[0033] (1) mixing methoxy polyethylene glycol 2000 glycidyl ether, a cation exchange resin, and a solvent, and hydrolyzing the mixture to obtain methoxy polyethylene glycol 2000 glycerol;

[0034] (2) Methoxypolyethylene glycol 2000 glycerol, tetradecanoic acid, dicyclohexylcarbodiimide (DCC), 4-dimethylaminopyridine (DMAP), and a non-polar solvent are mixed and condensed to obtain 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000.

[0035] In the present invention, in step (1), the molecular weight of methoxy polyethylene glycol 2000 glycidyl ether is preferably 1800-2200, more preferably 1900-2100; the solvent is preferably one of water, methanol, and ethanol, more preferably water; and the cation exchange resin is preferably HND-12 cation exchange resin.

[0036] In the present invention, in the step (1), the mass ratio of methoxy polyethylene glycol 2000 glycidyl ether to the cation exchange resin is preferably 1:0.2-0.4, more preferably 1:0.25-0.35; the mass volume ratio of methoxy polyethylene glycol 2000 glycidyl ether to the solvent is preferably 1 g:8-12 mL, more preferably 1 g:9-11 mL.

[0037] In the present invention, in step (1), the reaction temperature of the hydrolysis reaction is preferably 20 to 30° C., more preferably 23 to 27° C.; the reaction time is preferably 10 to 20 h, more preferably 13 to 18 h.

[0038] In the present invention, the time when the hydrolysis reaction ends is determined by the following method: the reaction ends when methoxy polyethylene glycol 2000 glycidyl ether completely disappears as monitored by TLC.

[0039] In the present invention, in step (1), the methoxy polyethylene glycol 2000 glycerol reaction solution obtained by hydrolysis is post-treated to obtain pure methoxy polyethylene glycol 2000 glycerol;

[0040] The post-treatment comprises the following steps: filtering the obtained methoxy polyethylene glycol 2000 glycerol reaction solution to remove the cation exchange resin, adding dichloromethane for extraction, drying, and concentrating to obtain methoxy polyethylene glycol 2000 glycerol;

[0041] Alternatively, the obtained methoxy polyethylene glycol 2000 glycerol reaction solution is filtered to remove the cation exchange resin, dried, and concentrated to obtain methoxy polyethylene glycol 2000 glycerol.

[0042] In the present invention, the specific steps of adding dichloromethane for extraction are: adding dichloromethane and stirring for 5 to 15 minutes, standing and separating the liquids, discarding the aqueous phase, and retaining the organic phase;

[0043] The drying is carried out using anhydrous sodium sulfate.

[0044] In the present invention, in step (2), the non-polar solvent is preferably one of dichloromethane, chloroform, and ethyl acetate, and more preferably dichloromethane.

[0045] In the present invention, in the step (2), the molar ratio of methoxy polyethylene glycol 2000 glycerol, myristic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine is preferably 1:1.9-3:1.9-3:0.1-1, and more preferably 1:2.3-2.6:2.4-2.8:0.3-0.8; the mass volume ratio of methoxy polyethylene glycol 2000 glycerol to the non-polar solvent is preferably 1 g:10-15 mL, and more preferably 1 g:12-14 mL.

[0046] In the present invention, in step (2), the reaction temperature of the condensation reaction is preferably 20 to 30° C., more preferably 23 to 28° C.; the reaction time is preferably 10 to 20 h, more preferably 13 to 18 h.

[0047] In the present invention, the time when the condensation reaction ends is determined by the following method: the reaction ends when the methoxy polyethylene glycol 2000 glycerol completely disappears as monitored by HPLC.

[0048] In the present invention, in step (2), the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution obtained by condensation is post-treated to obtain pure 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000;

[0049] The post-treatment comprises the following steps: filtering the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution, concentrating, adding isopropyl alcohol, cooling to precipitate a white solid, filtering, and drying to obtain 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000.

[0050] In the present invention, the specific step of filtering the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution is: filtering the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution to remove insoluble matter, and then rinsing with dichloromethane.

[0051] The technical solutions provided by the present invention are described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0052] Example 1

[0053] Preparation of methoxy polyethylene glycol 2000 glycerol:

[0054] Add 15g of methoxy polyethylene glycol 2000 glycidyl ether (PEG, molecular weight 2000) and 5.0g of cation exchange resin to 150ml of purified water and stir at 25°C for 10 hours. The reaction is complete when the methoxy polyethylene glycol 2000 glycidyl ether disappears as monitored by TLC. Remove the cation exchange resin by filtration, add dichloromethane, and stir for 10 minutes. Allow to stand for separation, discard the aqueous phase, and dry the organic phase over anhydrous sodium sulfate and concentrate to yield 15g of methoxy polyethylene glycol 2000 glycerol, 99.3%.

[0055] Example 2

[0056] Preparation of methoxy polyethylene glycol 2000 glycerol:

[0057] Add 15 g of methoxy polyethylene glycol 2000 glycidyl ether (PEG, molecular weight 2000) and 5.0 g of cation exchange resin to 150 ml of methanol. Stir at 30°C for 10 hours. The reaction is complete when the methoxy polyethylene glycol 2000 glycidyl ether disappears as monitored by TLC. Remove the cation exchange resin by filtration and concentrate to obtain 13 g of methoxy polyethylene glycol 2000 glycerol (yield 86.1%).

[0058] Example 3

[0059] Preparation of methoxy polyethylene glycol 2000 glycerol:

[0060] Add 15 g of methoxy polyethylene glycol 2000 glycidyl ether (PEG, molecular weight 2000) and 5.0 g of cation exchange resin to 150 ml of ethanol and stir at 30°C for 10 hours. The reaction is complete when the methoxy polyethylene glycol 2000 glycidyl ether disappears as monitored by TLC. Filter to remove the cation exchange resin and concentrate to obtain 13 g of methoxy polyethylene glycol 2000 glycerol (yield 86.1%).

[0061] Example 4

[0062] Preparation of 1,2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol 2000:

[0063] 15g of methoxypolyethylene glycol 2000 glycerol (PEG, molecular weight 2000) obtained in Example 1 was added to dichloromethane (150mL), and the raw materials myristic acid (3.6g), DMAP (0.44g) and DCC (3.4g) were added in sequence. The temperature was raised to 30°C and the reaction was stirred for 15h. The reaction was terminated after the complete disappearance of methoxypolyethylene glycol 2000 glycerol as monitored by HPLC. The insoluble matter was removed by filtration, rinsed with dichloromethane, and the filtrate was concentrated. The residue was poured into cold isopropanol and cooled to precipitate a white solid, which was filtered and dried to obtain (12g) 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, with a yield of 66.7%.

[0064] Example 5

[0065] Preparation of 1,2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol 2000:

[0066] 15 g of methoxypolyethylene glycol 2000 glycerol (PEG, molecular weight 2000) obtained in Example 2 was added to chloroform (150 mL), followed by the addition of myristic acid (3.6 g), DMAP (0.44 g), and DCC (3.4 g). The reaction was stirred at 20° C. for 15 h. The reaction was terminated after the complete disappearance of methoxypolyethylene glycol 2000 glycerol as monitored by HPLC. The insoluble matter was removed by filtration, rinsed with dichloromethane, and the filtrate was concentrated. The residue was poured into cold isopropanol and cooled to precipitate a white solid, which was filtered and dried to obtain (10 g) of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 in a yield of 55.6%.

[0067] Example 6

[0068] Preparation of 1,2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol 2000:

[0069] 15g of methoxypolyethylene glycol 2000 glycerol (PEG, molecular weight 2000) obtained in Example 3 was added to ethyl acetate (150mL), followed by the addition of raw materials myristic acid (3.6g), DMAP (0.44g) and DCC (3.4g). The temperature was raised to 30°C and stirred for 20h. The reaction was terminated after the complete disappearance of methoxypolyethylene glycol 2000 glycerol as monitored by HPLC. The insoluble matter was removed by filtration, rinsed with dichloromethane, and the filtrate was concentrated. The residue was poured into cold isopropanol and cooled to precipitate a white solid, which was filtered and dried to obtain (10g) 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, with a yield of 55.6%.

[0070] Example 7

[0071] Preparation of 1,2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol 2000:

[0072] 15g of methoxypolyethylene glycol 2000 glycerol (PEG, molecular weight 2000) obtained in Example 1 was added to ethyl acetate (150mL), followed by the addition of raw materials myristic acid (3.3g), DMAP (0.1g) and DCC (3.0g). The temperature was raised to 30°C and stirred for 20h. The reaction was terminated after the complete disappearance of methoxypolyethylene glycol 2000 glycerol as monitored by HPLC. The insoluble matter was removed by filtration, rinsed with dichloromethane, and the filtrate was concentrated. The residue was poured into cold isopropanol and cooled to precipitate a white solid, which was filtered and dried to obtain (10g) 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, with a yield of 55.6%.

[0073] Example 8

[0074] Preparation of 1,2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol 2000:

[0075] 15g of methoxypolyethylene glycol 2000 glycerol (PEG, molecular weight 2000) obtained in Example 2 was added to dichloromethane (150mL), and the raw materials myristic acid (4.9g), DMAP (0.88g) and DCC (4.4g) were added in sequence. The temperature was raised to 30°C and stirred for 15h. The reaction was terminated after the complete disappearance of methoxypolyethylene glycol 2000 glycerol as monitored by HPLC. The insoluble matter was removed by filtration, rinsed with dichloromethane, and the filtrate was concentrated. The residue was poured into cold isopropanol and cooled to precipitate a white solid, which was filtered and dried to obtain (10g) 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, with a yield of 55.6%.

[0076] Example 9

[0077] Preparation of 1,2-dimyristoyl-RAC-glycero-3-methoxypolyethylene glycol 2000:

[0078] 15g of methoxypolyethylene glycol 2000 glycerol (PEG, molecular weight 2000) obtained in Example 1 was added to dichloromethane (150mL), and the raw materials myristic acid (4.9g), DMAP (0.88g) and DCC (4.4g) were added in sequence. The temperature was raised to 30°C and stirred for 15h. The reaction was terminated after the complete disappearance of methoxypolyethylene glycol 2000 glycerol as monitored by HPLC. The insoluble matter was removed by filtration, rinsed with dichloromethane, and the filtrate was concentrated. The residue was poured into cold isopropanol and cooled to precipitate a white solid, which was filtered and dried to obtain (10g) 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, with a yield of 55.6%.

[0079] Comparative Example 1

[0080] Preparation of methoxy polyethylene glycol 2000 glycerol:

[0081] Add 15g of methoxy polyethylene glycol 2000 glycidyl ether (PEG, molecular weight 2000) and 10mL of hydrochloric acid to 150mL of purified water. Stir at 20°C for 10 hours. The reaction is complete when the methoxy polyethylene glycol 2000 glycidyl ether disappears as monitored by TLC. Add dichloromethane and stir for 10 minutes. Allow to stand for separation, discard the aqueous phase, and dry the organic phase over anhydrous sodium sulfate and concentrate to obtain 5g of methoxy polyethylene glycol 2000 glycerol (33.1% yield).

[0082] From the comparison of Examples 1 to 3 and Comparative Example 1, it can be seen that the methoxy polyethylene glycol 2000 glycerol yield obtained by the technical scheme of the present invention reaches 86.1 to 99.3%, which is significantly higher than 33.1% obtained in Comparative Example 1. The methoxy polyethylene glycol 2000 glycerol yield obtained by the technical scheme of the present invention is high, which is more conducive to the preparation of 1,2-dimyristoyl-RAC-glycerol-3-methoxy polyethylene glycol 2000.

[0083] The preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 of the present invention has readily available raw materials, simple operation, high conversion rate, mild conditions, and both steps of the reaction achieve very high yields, further improving the yield of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000.

[0084] Depend on Figures 2-3 It can be seen that the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 obtained in the present invention has high purity and can be used to prepare a uniform protein modifying agent.

[0085] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000, characterized in that: The steps include: (1) Mixing methoxy polyethylene glycol 2000 glycidyl ether, a cation exchange resin, and a solvent, and hydrolyzing the mixture to obtain methoxy polyethylene glycol 2000 glycerol; (2) Methoxypolyethylene glycol 2000 glycerol, tetradecanoic acid, dicyclohexylcarbodiimide, 4-dimethylaminopyridine, and a non-polar solvent are mixed and condensed to obtain 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000; In the step (1), the molecular weight of methoxy polyethylene glycol 2000 glycidyl ether is 1800-2200; the solvent is one of water, methanol, and ethanol; and the cation exchange resin is HND-12 cation exchange resin.

2. The method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to claim 1, characterized in that: In the step (1), the mass ratio of methoxy polyethylene glycol 2000 glycidyl ether to the cation exchange resin is 1:0.2-0.4; the mass volume ratio of methoxy polyethylene glycol 2000 glycidyl ether to the solvent is 1 g:8-12 mL.

3. The preparation method of 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to claim 2, characterized in that: In the step (1), the reaction temperature of the hydrolysis reaction is 20-30° C., and the reaction time is 10-20 h.

4. The method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to any one of claims 1 to 3, wherein: In the step (1), the methoxy polyethylene glycol 2000 glycerol reaction solution obtained by hydrolysis is post-treated to obtain pure methoxy polyethylene glycol 2000 glycerol; The post-treatment comprises the following steps: filtering the obtained methoxy polyethylene glycol 2000 glycerol reaction solution to remove the cation exchange resin, adding dichloromethane for extraction, drying, and concentrating to obtain methoxy polyethylene glycol 2000 glycerol.

5. The method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to claim 1, characterized in that: In the step (2), the non-polar solvent is one of dichloromethane, chloroform and ethyl acetate.

6. The method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to claim 5, characterized in that: In the step (2), the molar ratio of methoxy polyethylene glycol 2000 glycerol, tetradecanoic acid, dicyclohexylcarbodiimide and 4-dimethylaminopyridine is 1:1.9~3:1.9~3:0.1~1; the mass volume ratio of methoxy polyethylene glycol 2000 glycerol to the non-polar solvent is 1 g:10~15 mL.

7. The method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to claim 6, characterized in that: In the step (2), the reaction temperature of the condensation reaction is 20-30° C., and the reaction time is 10-20 h.

8. The method for preparing 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 according to claim 5, 6 or 7, wherein: In the step (2), the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution obtained by condensation is post-treated to obtain pure 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000; The post-treatment comprises the following steps: filtering the 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000 reaction solution, concentrating, adding isopropyl alcohol, cooling to precipitate a white solid, filtering, and drying to obtain 1,2-dimyristoyl-RAC-glycerol-3-methoxypolyethylene glycol 2000.

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