Preparation method of lysophosphatidylcholine

Abstract

The invention provides a preparation method of lysophosphatidylcholine, which comprises the following step: reacting glycerophosphorylcholine with fatty acid acyl chloride under the action of an activating agent to generate lysophosphatidylcholine. The preparation method provided by the embodiment of the invention is short in synthetic route, high in total yield, less in generated three wastes, higher in feasibility of the route and suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of compound preparation, and more specifically, relates to a method for preparing lysophosphatidylcholine. Background Art

[0002] Lysophospholipids (lysolecithin) are compounds generated by the hydrolysis of phospholipids by phospholipase A1, phospholipase A2, phospholipase B, etc. Lysophospholipids can be divided into lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), lysophosphatidylinositol (LPI), and lysophosphatidic acid (LPA) according to their substrate sources. Lysophospholipids are considered to be second messenger molecules that regulate intracellular signaling pathways and are involved in many physiological and pathological processes, such as inflammation, reproduction, angiogenesis, tumorigenesis, atherosclerosis, and nervous system regulation.

[0003] The development of new synthetic methods for preparing bioactive phospholipid derivatives is a challenging problem in membrane chemistry and biochemistry today. In fact, in order to establish the structure and dynamics of biological membranes, phospholipid-protein interactions, and the structure-activity relationship and mechanism of action of phospholipid metabolic enzymes, a large number of phospholipid derivatives need to be prepared as a key step in advancing membrane biochemistry.

[0004] To date, there are relatively few methods for the synthesis of lysophosphatidylcholine, mainly due to the poor selectivity of glycerol derivatives when adding protecting groups, and the migration of acyl and phosphate groups during the synthesis process, resulting in the product being a mixture of isomers.

[0005] Currently, the existing synthetic routes include:

[0006] Route 1: Synthesis of 2-LPC using (S) glycol

[0007] The specific synthesis route is shown in the following formula (1):

[0008]

[0009] Although the synthetic route for preparing 2-LPC is shorter, the (S) glycol used is expensive and easily deteriorates, making it unsuitable for large-scale production.

[0010] Route 2: Synthesis of 2-LPC using glyceric acid

[0011] The specific synthesis route is shown in the following formula (2):

[0012]

[0013] However, this route has a long synthetic route, poor selectivity when adding protecting groups, and the protecting groups must be removed after addition, resulting in poor atom economy.

[0014] Route 3: Synthesis of 2-LPC using p-toluenesulfonylglycerol

[0015] The specific synthesis route is shown in the following formula (3):

[0016]

[0017] However, this route also involves the problem of poor selectivity when adding protecting groups. After adding the protecting groups, they have to be removed later, which leads to poor atom economy. Summary of the invention

[0018] In view of this, the object of the present invention is to provide a method for preparing lysophosphatidylcholine which is simple to operate, has good selectivity, a short route, a high total yield and is suitable for industrial production.

[0019] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0020] The method for preparing lysophosphatidylcholine according to an embodiment of the present invention comprises the following steps:

[0021] The above technical solution of the present invention has at least one of the following beneficial effects:

[0022] According to the preparation method of the embodiment of the present invention, the synthesis route is short, the total yield is high, less three wastes are generated, the route is more feasible, and it is suitable for industrial production. DETAILED DESCRIPTION

[0023] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution of the present invention will be clearly and completely described in combination with the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the described embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field belong to the scope of protection of the present invention.

[0024] The following first describes in detail the preparation method of lysophosphatidylcholine according to an embodiment of the present invention.

[0025] The method for preparing lysophosphatidylcholine according to an embodiment of the present invention comprises:

[0026] Glycerophosphocholine is reacted with fatty acid chloride under the action of dimethyltin dichloride to generate lysophosphatidylcholine.

[0027] That is, according to the preparation method of the present invention, glycerophosphocholine is used as the starting material, and first reacts with dimethyltin dichloride to form a five-membered ring intermediate (as shown in the following formula (4)), and the fatty acid chloride preferentially attacks the side with less steric hindrance, that is, first reacts with the primary alcohol end, and then selectively generates lysophosphatidylcholine.

[0028] According to the preparation method of the embodiment of the present invention, the synthesis route is short, the total yield is high, less three wastes are generated, the route is more feasible, and it is suitable for industrial production.

[0029] In some embodiments of the present invention, the activator is dimethyltin dichloride. The molar ratio of the glycerophosphocholine to the dimethyltin dichloride is 1:(1.0-1.2). Preferably, the molar ratio of glycerophosphocholine to the dimethyltin dichloride is 1:1.1. Dimethyltin dichloride is an activator, and the amount should not be too small, but should be excessive, so that it can better form an intermediate with glycerophosphocholine and avoid excess glycerophosphocholine.

[0030] In some embodiments of the present invention, the following steps are specifically included:

[0031] Step S1, dissolving glycerophosphocholine in an ether organic solvent, and adding the dimethyltin dichloride therein;

[0032] Step S2, continue to dropwise add fatty acid chloride to generate the lysophosphatidylcholine.

[0033] That is, glycerophosphocholine is first reacted with dimethyltin dichloride to generate an intermediate, and then the intermediate reacts with fatty acid chloride to generate the target product lysophosphatidylcholine.

[0034] Specifically, the synthesis route is shown in the following formula (4):

[0035]

[0036] In some embodiments of the present invention, the fatty acid chloride is selected from any one or more of oleic acid chloride, stearic acid chloride, palmitic acid chloride, and lauric acid chloride, and the molar ratio of glycerophosphocholine to fatty acid chloride is 1:(1.0-1.5). Preferably, the molar ratio of glycerophosphocholine to fatty acid chloride is 1:1.1, and a slight excess of fatty acid chloride can improve the reaction selectivity and avoid the reaction above the secondary alcohol.

[0037] In some embodiments of the present invention, the ether organic solvent is selected from any one or more of tetrahydrofuran, 2-methyltetrahydrofuran, and dioxane. Preferably, tetrahydrofuran is selected, because glycerophosphocholine has good solubility in tetrahydrofuran and has a low boiling point, which is conducive to the reaction and convenient for post-processing.

[0038] In some embodiments of the present invention, in step S1, an inorganic base is further added to the ether organic solvent, and the inorganic base is selected from any one or more of potassium carbonate, sodium carbonate, and cesium carbonate. Adding an inorganic base helps to free the hydrogen in the hydroxyl group at the end of glycerophosphocholine, which is beneficial to promote the reaction between glycerophosphocholine and dimethyltin dichloride. Among them, potassium carbonate is preferred, which has a strong alkalinity, is conducive to the reaction, and is cheaper than cesium carbonate.

[0039] Furthermore, the molar ratio of glycerophosphocholine to the inorganic base is 1:(3.0-4.0). Preferably, the molar ratio of glycerophosphocholine to the inorganic base is 1:3.5, and a slight excess of the inorganic base increases the reaction rate and keeps the reaction environment alkaline.

[0040] Furthermore, the reaction temperature in the whole process is 0-40°C; the reaction time is 5-8h. The reaction temperature is preferably 40°C, at which the yield is higher. The reaction time is preferably 6h. Too long a reaction time has poor economic efficiency, while too short a reaction time makes the reaction difficult to be complete.

[0041] In some embodiments of the present invention, the preparation method further comprises:

[0042] After the reaction is completed, water is added to quench the reaction, the filtrate is filtered and then spin-dried, slurried with acetonitrile and evaporated to dryness to obtain the lysophosphatidylcholine.

[0043] The post-processing process is simple and easy to operate, and is suitable for industrial production.

[0044] The preparation method of the lysophosphatidylcholine of the present invention is further described in detail below through specific examples.

[0045] Example 1 Preparation of 1-oleoyl-SN-glycerol-3-phosphorylcholine

[0046] In a 500 mL round-bottom flask, add 10.0 g (1.0 eq.) of glycerophosphocholine and 8.5 g (1.0 eq.) of dimethyltin dichloride to 100 mL of tetrahydrofuran, add 18.8 g (3.5 eq.) of potassium carbonate, raise the temperature to 40 °C and react for 2 h; then cool to about 4 °C, add dropwise 12.8 g (1.1 eq.) of oleic acid chloride; after addition, react at room temperature for 6 h.

[0047] 6 mL of water was added to the reaction solution to quench the reaction. The filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70 mL×2) at room temperature. The filter cake was dried to obtain 14.6 g of 1-oleoyl-SN-glycero-3-phosphorylcholine with a yield of 72%.

[0048] The NMR results of the product are shown below:

[0049] 1 H-NMR(400MHz,CD3OD-d4)δ(ppm)5.35(t,J=4.9Hz,2H),4.34–4.28(m,2H),4.18(dd, J=11.3,4.5Hz,1H),4.11(dd,J=11.4,6.0Hz,1H),4.02–3.95(m,1H),3.95–3.84(m,2 H),3.65(dd,J=6.0,3.3Hz,2H),3.23(s,9H),2.4(t,J=7.5Hz,2H),2.0(q,J=6.1Hz,4 H),1.6(q,J=7.3Hz,2H),1.4–1.2(m,20H),0.9(t,J=6.7Hz,3H); HRMS(ESI)m / z:[M+H] + calculated for C 26 H 53 NO7P 522.3554, found 522.3565.

[0050] The results showed that its structure was consistent with that of the target product 1-oleoyl-SN-glycero-3-phosphorylcholine.

[0051] Example 2 Preparation of 1-oleoyl-SN-glycerol-3-phosphorylcholine

[0052] In a 500 mL round-bottom flask, add 12.0 g (1.0 eq.) of glycerophosphocholine and 11.3 g (1.1 eq.) of dimethyltin dichloride to 120 mL of tetrahydrofuran, add 14.8 g (3.0 eq.) of sodium carbonate, heat to 40 °C and react for 2 h, then cool to about 4 °C and dropwise add 16.8 g (1.2 eq.) of oleic acid chloride; after the addition is complete, react at room temperature for 4 h.

[0053] 6.2 mL of water was added to the reaction solution to quench the reaction. The filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70 mL×2) at room temperature. The filter cake was dried to obtain 18.5 g of 1-oleoyl-SN-glycero-3-phosphorylcholine with a yield of 76%.

[0054] The product was subjected to a nuclear magnetic resonance experiment to confirm the product structure, and the result was consistent with the structure of 1-oleoyl-SN-glycero-3-phosphorylcholine. The detailed description is omitted here.

[0055] Example 3 Preparation of 1-oleoyl-SN-glycerol-3-phosphorylcholine

[0056] In a 500mL round-bottom flask, 11.0g (1.0eq.) glycerophosphocholine and 11.3g (1.2eq.) dimethyltin dichloride were added to 110mL tetrahydrofuran, and 44.6g (3.2eq.) cesium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 5°C, and 18.0g (1.4eq.) oleic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.4mL water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 9.0g of 1-oleoyl-SN-glycero-3-phosphocholine, with a yield of 70%.

[0057] The product was subjected to a nuclear magnetic resonance experiment to confirm the product structure, and the result was consistent with the structure of 1-oleoyl-SN-glycero-3-phosphorylcholine. The detailed description is omitted here.

[0058] Example 4 Preparation of 1-stearoyl-SN-glycerol-3-phosphorylcholine

[0059] In a 500mL round-bottom flask, 10.0g (1.0eq.) glycerophosphocholine and 8.5g (1.0eq.) dimethyltin dichloride were added to 100mL tetrahydrofuran, and 18.8g (3.5eq.) potassium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 4°C, and 12.9g (1.1eq.) stearic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 6h. 6mL of water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 14.4g of 1-stearoyl-SN-glycero-3-phosphocholine, with a yield of 71%.

[0060] The NMR results of the product are shown below:

[0061] 1 H-NMR(300MHz,CD3OD-d4)4.07–3.98(m,2H,Ha),3.96–3.83(m,2H,H-1),3.80–3.58(m,3H,H-2andH-3),3.403.33(m,2H,Hb),3.15(s,1H,-OH),2.9 9(s,9H,N(CH3)3),2.11(t,J7.6,2H,H-2a),1.44–1.31(m,2H,H-3a),1.11 –0.99(m,28H,H-4a–17a),0.64(t,J6.6,3H,H-18a); HRMS(ESI)m / z:[M+H] + calculated for C 26 H 55NO7P:524.3711,found524.3728.

[0062] The results were consistent with the structure of 1-stearoyl-SN-glycero-3-phosphorylcholine.

[0063] Example 5 Preparation of 1-stearoyl-SN-glycerol-3-phosphorylcholine

[0064] In a 500mL round-bottom flask, 12.0g (1.0eq.) glycerophosphocholine and 11.3g (1.1eq.) dimethyltin dichloride were added to 120mL tetrahydrofuran, and 14.8g (3.0eq.) sodium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 4°C, and 16.9g (1.2eq.) stearic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.2mL water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 18.1g of 1-stearoyl-SN-glycero-3-phosphocholine, with a yield of 74%.

[0065] The product was subjected to a nuclear magnetic resonance experiment to confirm the product structure, and the result was consistent with the structure of 1-stearoyl-SN-glycero-3-phosphorylcholine. The detailed description is omitted here.

[0066] Example 6 Preparation of 1-stearoyl-SN-glycerol-3-phosphorylcholine

[0067] In a 500mL round-bottom flask, 11.0g (1.0eq.) glycerophosphocholine and 11.3g (1.2eq.) dimethyltin dichloride were added to 110mL tetrahydrofuran, and 44.6g (3.2eq.) cesium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 5°C, and 18.1g (1.4eq.) stearic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.4mL water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 16.3g of 1-stearoyl-SN-glycero-3-phosphocholine, with a yield of 73%.

[0068] The product was subjected to a nuclear magnetic resonance experiment to confirm the product structure, and the result was consistent with the structure of 1-stearoyl-SN-glycero-3-phosphorylcholine. The detailed description is omitted here.

[0069] Example 7 Preparation of 1-palmitoyl-SN-glycerol-3-phosphorylcholine

[0070] In a 500mL round-bottom flask, 10.0g (1.0eq.) glycerophosphocholine and 8.5g (1.0eq.) dimethyltin dichloride were added to 100mL tetrahydrofuran, and 18.8g (3.5eq.) potassium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 4°C, and 11.7g (1.1eq.) palmitic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 6h. 6mL of water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 14.6g of 1-palmitoyl-SN-glycero-3-phosphocholine, with a yield of 76%.

[0071] The NMR results of the product are shown below:

[0072] 1 H-NMR (600MHz, CD3OD-d4) δ4.44(s,1H),4.20–4.15(m,2H),4.06(dd,J=11.4,4.5Hz,1H),3.99(dd,J=11.4,6.3Hz,1H),3.88–3.83(m,1H),3.82–3. 74(m,2H),3.54–3.50(m,2H),3.11(s,9H),2.24(t,J=7.5Hz,2H),1.50(p ,J=7.3Hz,2H),1.17(s,24H),0.78(t,J=7.0Hz,3H); HRMS(ESI)m / z:[M+H] + calculated for C 24 H 51 NO7P:496.3398,found496.3399.

[0073] The results were consistent with the structure of 1-palmitoyl-SN-glycero-3-phosphocholine.

[0074] Example 8 Preparation of 1-palmitoyl-SN-glycerol-3-phosphorylcholine

[0075] In a 500mL round-bottom flask, 12.0g (1.0eq.) glycerophosphocholine and 11.3g (1.1eq.) dimethyltin dichloride were added to 120mL tetrahydrofuran, and 14.8g (3.0eq.) sodium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 4°C, and 15.4g (1.2eq.) palmitic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.2mL water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 16.6g of 1-palmitoyl-SN-glycero-3-phosphocholine, with a yield of 72%.

[0076] The product was subjected to a nuclear magnetic resonance experiment to confirm the product structure, and the result was consistent with the structure of 1-palmitoyl-SN-glycero-3-phosphorylcholine. The detailed description is omitted here.

[0077] Example 9 Preparation of 1-palmitoyl-SN-glycerol-3-phosphorylcholine

[0078] In a 500mL round-bottom flask, 11.0g (1.0eq.) glycerophosphocholine and 11.3g (1.2eq.) dimethyltin dichloride were added to 110mL tetrahydrofuran, and 44.6g (3.2eq.) cesium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 5°C, and 16.4g (1.4eq.) palmitic acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.4mL water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 14.8g of 1-palmitoyl-SN-glycero-3-phosphocholine, with a yield of 70%.

[0079] The product was subjected to a nuclear magnetic resonance experiment to confirm the product structure, and the result was consistent with the structure of 1-palmitoyl-SN-glycero-3-phosphorylcholine. The detailed description is omitted here.

[0080] Example 10 Preparation of 1-lauroyl-SN-glycerol-3-phosphorylcholine

[0081] In a 500mL round-bottom flask, 10.0g (1.0eq.) glycerophosphocholine and 8.5g (1.0eq.) dimethyltin dichloride were added to 100mL tetrahydrofuran, and 18.8g (3.5eq.) potassium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 4°C, and 9.3g (1.1eq.) lauric acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 6h. 6mL of water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 13.8g of 1-lauroyl-SN-glycero-3-phosphocholine, with a yield of 75%.

[0082] The NMR results of the product are shown below:

[0083] 1H-NMR (600MHz, CD3OD-d4) δ4.44(s,1H),4.20–4.15(m,2H),4.06(dd,J=11.4,4.5Hz,1H),3.99(dd,J=11.4,6.3Hz,1H),3.88–3.83(m,1H),3.82–3. 74(m,2H),3.54–3.50(m,2H),3.11(s,9H),2.24(t,J=7.5Hz,2H),1.50(p ,J=7.3Hz,2H),1.17(s,16H),0.78(t,J=7.0Hz,3H); HRMS(ESI)m / z:[M+H] + calculated for C 20 H 43 NO7P:440.2698,found440.2699.

[0084] The results were consistent with the structure of 1-lauroyl-SN-glycero-3-phosphorylcholine.

[0085] Example 11 Preparation of 1-lauroyl-SN-glycerol-3-phosphorylcholine

[0086] In a 500mL round-bottom flask, 12.0g (1.0eq.) glycerophosphocholine and 11.3g (1.1eq.) dimethyltin dichloride were added to 120mL tetrahydrofuran, and 14.8g (3.0eq.) sodium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 4°C, and 12.2g (1.2eq.) lauric acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.2mL water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 16.2g of 1-lauroyl-SN-glycero-3-phosphocholine, with a yield of 73%.

[0087] The product was subjected to a nuclear magnetic resonance experiment to confirm the structure of the product, and the result was consistent with the structure of 1-lauroyl-SN-glycerol-3-phosphorylcholine. The detailed description is omitted here.

[0088] Example 12 Preparation of 1-lauroyl-SN-glycerol-3-phosphorylcholine

[0089] In a 500mL round-bottom flask, 11.0g (1.0eq.) glycerophosphocholine and 11.3g (1.2eq.) dimethyltin dichloride were added to 110mL tetrahydrofuran, and 44.6g (3.2eq.) cesium carbonate was added. After heating to 40°C for 2h, the temperature was lowered to about 5°C, and 13.1g (1.4eq.) lauric acid chloride was added dropwise; after the addition, the reaction was continued at room temperature for 4h. 6.4mL of water was added to the reaction solution to quench the reaction, and the filtrate was evaporated to dryness after suction filtration, dried with acetonitrile, and slurried with acetonitrile (70mL×2) at room temperature. The filter cake was dried to obtain 14.6g of 1-lauroyl-SN-glycero-3-phosphocholine, with a yield of 72%.

[0090] The product was subjected to a nuclear magnetic resonance experiment to confirm the structure of the product, and the result was consistent with the structure of 1-lauroyl-SN-glycerol-3-phosphorylcholine. The detailed description is omitted here.

[0091] In summary, the preparation method of lysophosphatidylcholine of the present invention has the advantages of good selectivity, short synthetic route, mild reaction conditions, high yield and strong route feasibility, and is suitable for industrial production.

[0092] The above is 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 the scope of protection of the present invention.

Claims

1. A method for preparing lysophosphatidylcholine, characterized in that: include: Glycerolphosphocholine is reacted with fatty acid chloride under the action of an activator to generate lysophosphatidylcholine.

2. The preparation method according to claim 1, characterized in that: The activator is dimethyltin dichloride, and the molar ratio of the glycerophosphocholine to the dimethyltin dichloride is 1:(1.0-1.2).

3. The preparation method according to claim 1, characterized in that: The fatty acid chloride is selected from any one or more of oleic acid chloride, stearic acid chloride, palmitic acid chloride, and lauric acid chloride, and the molar ratio of the glycerophosphocholine to the fatty acid chloride is 1:(1.0-1.5).

4. The preparation method according to claim 2, characterized in that: The specific steps include: Step S1, dissolving glycerophosphocholine in an ether organic solvent, and adding the dimethyltin dichloride therein; Step S2, continue to dropwise add fatty acid chloride to generate the lysophosphatidylcholine.

5. The preparation method according to claim 4, characterized in that: The ether organic solvent is selected from any one or more of tetrahydrofuran, 2-methyltetrahydrofuran and dioxane.

6. The preparation method according to claim 4, characterized in that: In the step S1, an inorganic base is further added to the ether organic solvent, and the inorganic base is selected from any one or more of potassium carbonate, sodium carbonate, and cesium carbonate.

7. The preparation method according to claim 6, characterized in that: The molar ratio of the glycerophosphocholine to the inorganic base is 1:(3.0-4.0).

8. The preparation method according to claim 4, characterized in that: The reaction temperature is 0-40°C; the reaction time is 5-8h.

9. The preparation method according to claim 4, characterized in that: Also includes: After the reaction is completed, water is added to quench the reaction, the filtrate is filtered and then spin-dried, slurried with acetonitrile and evaporated to dryness to obtain the lysophosphatidylcholine.

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