A single fatty chain choline phospholipid, its preparation method and application

Abstract

The present application relates to a kind of single fatty chain choline phospholipid and its preparation method and application, belong to the field of biomedical materials.The single fatty chain choline phospholipid of the present application, structural formula is as shown in formula (I) or formula (II).Single fatty chain choline phospholipid can be applied in preparation of the medicament for reducing the content of lysophospholipid in human body.The single fatty chain choline phospholipid of the present application can produce strong charge interaction with lysophospholipid, and then combine with lysophospholipid in vivo, so that lysophospholipid loses lysolabine toxicity, weaken the hemolysis harm caused to red blood cell due to high concentration of lysophospholipid in vivo, thereby reduce the harm of lysophospholipid to liver disease patient lacking lysophospholipase.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of single fatty chain choline phospholipid and its preparation method and application, especially to the single fatty chain choline phospholipid in preparation reduce the application of lyso-phospholipid content in human body medicament, belong to the field of biomedical materials. BACKGROUND

[0002] Lyso-phospholipid is one of the metabolic products of phospholipid, which is formed by removing one fatty acid chain from phosphatidylcholine.

[0003] Lyso-phospholipid is a kind of phospholipid with strong surface activity, which can cause hemolysis or cell necrosis by rupturing red blood cell and other cell membranes. When the fatty acid is removed by phospholipase B, it is converted into glycerophosphocholine or glycerophosphoethanolamine, which loses the ability to dissolve cell membranes.

[0004] Lyso-phospholipid can better regulate fat metabolism, and has obvious effect in preventing overweight and obesity. It plays an important role in fat absorption, transport and storage. It can also maintain the normal structure of cell membranes and maintain various cell functions. In addition, it can prevent cholesterol accumulation in blood vessels and reduce blood viscosity to promote physical health. Therefore, most of the existing technologies focus on how to synthesize and apply lyso-phospholipid.

[0005] However, in the human body, lyso-phospholipid is mainly metabolized in the liver, and it is hydrolyzed by lyso-phospholipase in the liver to produce fatty acid and glycerophosphatidylcholine. Therefore, the content of lyso-phospholipid in patients with liver disease and hepatotoxicity is significantly higher than that of normal people, which causes great harm to the health of patients.

[0006] Therefore, it is urgent to develop a medicament that can reduce the content of lyso-phospholipid in the body, so that lyso-phospholipid does not harm patients with liver disease who lack lyso-phospholipase. SUMMARY

[0007] Therefore, the purpose of the present application is to provide a single fatty chain choline phospholipid and its preparation method and application, which can combine with lyso-phospholipid in the human body through strong charge interaction, so that lyso-phospholipid loses hemolytic toxicity.

[0008] The single fatty chain choline phospholipid provided by the present application has the structural formula as shown in formula (I) or formula (II):

[0009]

[0010] In the formula, R1 is selected from C x H 2x+y O z or C x F2x+y ; x is an integer from 1 to 21, y is an odd integer from 1 1 to 1, and z is 0 or 1;

[0011] R2is selected from one of C1to C18alkyl, C3to C18monoalkenyl, C5to C18conjugated dialkenyl, C3to C18monoalkynyl, fluorine substituted C1to C12alkyl, fluorine substituted C3to C12alkenyl, fluorine substituted C3to C12alkynyl, fluorine substituted C7to C12aryl, hydroxy substituted C2to C4alkyl, hydroxy substituted C2to C4fluoroalkyl, azido substituted C2to C4alkyl, azido substituted C2to C4fluoroalkyl, amino substituted C2to C4alkyl, amino substituted C2to C4fluoroalkyl, mercapto substituted C2to C4alkyl, mercapto substituted C2to C4fluoroalkyl.

[0012] Preferably, R1is selected from one of the following structures:

[0013] CH3-, CH3CH2-, CH3(CH2)2-, CH3(CH2)3-, CH3(CH2)4-, CH3(CH2)5-, CH3(CH2)6-, CH3(CH2)7-, CH3(CH2)8-, CH3(CH2)9-, CH3(CH2) 10 -, CH3(CH2) 11 -, CH3(CH2) 12 -, CH3(CH2) 13 -, CH3(CH2) 14 -, CH3(CH2) 15 -, CH3(CH2) 16 -, CH3(CH2) 17 -, CH3(CH2) 18 -, CH3(CH2) 19 -, CH3(CH2) 20 -, CF3-, CF3CF2-, CF3(CF2)2-, CF3(CF2)3-, CF3(CF2)4-, CF3(CF2)5-, CF3(CF2)6-, CF3(CF2)7-, CF3(CF2)8-, CF3(CF2)9-, CF3(CF2) 10 -, CF3(CF2) 11 -, CF3(CF2) 12 -, CF3(CF2) 13 -, CF3(CF2) 14 -, CF3(CF2) 15 -, CF3(CF2) 16 -, CF3(CF2) 17 -, CF3(CF2)18 -, CH3(CH2)5CH=CH(CH2)7-, CH3(CH2)5CH=CH(CH2)9-, CH3(CH2)7CH=CH(CH2)7-, CH3(CH2)5CH=CH(CH2) 11 -, CH3(CH2)7CH=CH(CH2) 11 -, CH3(CH2)7CH=CH(CH2) 13 -, CH3(CH2)3(CH2CH=CH)2(CH2)4-, CH3(CH2)3(CH2CH=CH)2(CH2)7-, CH3(CH2)4CH=CHCH=CH-, CH3(CH2)4(CH=CH)2(CH2)8-, CH3(CH2)5(CH=CH)2(CH2)7-, CH3(CH2CH=CH)3(CH2)7-, CH3(CH2)3(CH=CH)3(CH2)7-, CH3(CH2)3(CH2CH=CH)3(CH2)6-, CH3(CH2CH=CH)4(CH2)4-, CH3(CH2)3(CH2CH=CH)4(CH2)3-, CH3(CH2)3(CH2CH=CH)4(CH2)4-, CH3(CH2)3(CH2CH=CH)4(CH2)5-, CH3(CH2CH=CH)5(CH2)3-, CH3(CH2CH=CH)6(CH2)2-, CH3(CH2)7CH2(OH)CH2CH=CH(CH2)7-.

[0014] Preferably,

[0015] the C1-C18 alkyl group is one of the following structures: CH3-, CH3CH2-, CH3(CH2)2-, (CH3)2CH-, (CH3)2CHCH2-, (CH3)3C-, CH3(CH2)3-, CH3(CH2)4-, (CH3)2CH(CH2)2-, (CH3)3CCH2-, CH3(CH2)5-, (CH3)2CH(CH2)3-, CH3CH2CH(CH3)CH2CH2-, CH3CH2CH2CH(CH3)CH2-, CH3(CH2)6-, (CH3)2CH(CH2)4-, CH3CH2CH2CH(CH3)CH2CH2-, CH3(CH2)7-, CH3(CH2)3CH(C2H5)CH2-, CH3(CH2)8-, CH3(CH2)9-, CH3(CH2) 10 -, CH3(CH2) 11 -, CH3(CH2) 12 -, CH3(CH2)13 -, CH3(CH2) 14 -, CH3(CH2) 15 -, CH3(CH2) 16 -, CH3(CH2) 17 -;

[0016] The C3-C18 monoalkenyl group is one of the following structures: CH2=CH(CH2)-, CH2=CH(CH2)2-, CH2=CH(CH2)3-, CH2=CH(CH2)4-, CH2=CH(CH2)5-, CH2=CH(CH2)6-, CH2=CH(CH2)7-, CH2=CH(CH2)8-, CH2=CH(CH2)9-, CH2=CH(CH2) 10 - CH2=CH(CH2) 11 - CH2=CH(CH2) 12 - CH2=CH(CH2) 13 - CH2=CH(CH2) 14 - CH2=CH(CH2) 15 - CH2=CH(CH2) 16 -, CH3(CH2)3CH=CH(CH2)7CH2-, CH3(CH2)5CH=CH(CH2)7CH2-, CH3(CH2)7CH=CH(CH2)7CH2-;

[0017] The C5-C18 conjugated diene group is one of the following structures: CH2=CH-CH=CH2(CH2)-, CH2=CH-CH=CH(CH2)2-, CH2=CH-CH=CH(CH2)3-, CH2=CH-CH=CH(CH2)4-, CH2=CH-CH=CH(CH2)5-, CH2=CH-CH=CH(CH2)6-, CH2=CH-CH=CH(CH2)7-, CH2=CH-CH=CH(CH2)8-, CH2=CH-CH=CH(CH2)9-, CH2=CH-CH=CH(CH2) 10 - CH2=CH-CH=CH(CH2) 11 - CH2=CH-CH=CH(CH2) 17 - CH2=CH-CH=CH(CH2) 13 - CH2=CH-CH=CH(CH2) 14 -;

[0018] The C3-C18 monoyne group is one of the following structures: CH≡C(CH2)-, CH≡C(CH2)2-, CH≡C(CH2)3-, CH≡C(CH2)4-, CH≡C(CH2)5-, CH≡C(CH2)6-, CH≡C(CH2)7-, CH≡C(CH2)8-, CH≡C(CH2)9-, CH≡C(CH2) 10 -、CH≡C(CH2) 11 -、CH≡C(CH2) 12 -、CH≡C(CH2) 13 -、CH≡C(CH2) 14 -、CH≡C(CH2) 15 -、CH≡C(CH2) 16 -;

[0019] The fluorine-substituted C1-C12 alkyl group is one of the following structures: CF3-, CF3CF2-, CF3CH2-, CHF2CH2-, CF3(CF2)2-, (CF3)2CHCF2-, (CF3)3CCH2-, (CF3)2CHCH2-, CF3(CF2)3-, CF3(CF2)4-, CF3(CF2)5-, CF3(CF2)6-, CF3(CF2)7-, CF3(CF2)8-, CF3(CF2)9-, CF3(CF2) 10 - CF3 (CF2) 11 -;

[0020] The fluorine-substituted C3-C12 alkenyl group is one of the following structures: CF2=CFCF2-, CF2=CF(CF2)2-, CF2=CF(CF2)3-, CF2=CF(CF2)4-, CF2=CF(CF2)5-, CF2=CF(CF2)6-, CF2=CF(CF2)7-, CF2=CF(CF2)8-, CF2=CF(CF2)9-, CF2=CF(CF2) 10 -;

[0021] The fluorine-substituted C3-C12 alkynyl group is one of the following structures: CF≡CCF2-, CF≡C(CF2)2-, CF≡C(CF2)3-, CF≡C(CF2)4-, CF≡C(CF2)5-, CF≡C(CF2)6-, CF≡C(CF2)7-, CF≡C(CF2)8-, CF≡C(CF2)9-, CF≡C(CF2) 10 -;

[0022] said fluorine-substituted C7-C12 aryl is one of the following structures: C6F5-CH2-, C6F5-(CH2)2-, C6F5-(CH2)3-, C6F5-(CH2)4-, C6F5-(CH2)5-, C6F5-(CH2)6-, o-CF3-C6H4-, o-CF3-C6H4-CH2-, o-CF3-C6H4-(CH2)2-, o-CF3-C6H4-(CH2)3-, o-CF3-C6H4-(CH2)4-, o-CF3-C6H4-(CH2)5-, m-CF3-C6H4-, m-CF3-C6H4-CH2-, m-CF3-C6H4-(CH2)2-, m-CF3-C6H4-(CH2)3-, m-CF3-C6H4-(CH2)4-, m-CF3-C6H4-(CH2)5-, p-CF3-C6H4-, p-CF3-C6H4-CH2-, p-CF3-C6H4-(CH2)2-, p-CF3-C6H4-(CH2)3-, p-CF3-C6H4-(CH2)4-, p-CF3-C6H4-(CH2)5-;

[0023] said hydroxy-substituted C2-C4 alkyl is one of HO-(CH2)2-, HO-(CH2)3-, HO-(CH2)4-;

[0024] said hydroxy-substituted C2-C4 fluoroalkyl is one of HO-(CF2)2-, HO-(CF2)3-, HO-(CF2)4-;

[0025] said azido-substituted C2-C4 alkyl is one of N3-(CH2)2-, N3-(CH2)3-, N3-(CH2)4-, N3-(CF2)2-, N3-(CF2)3-, N3-(CF2)4-;

[0026] said azido-substituted C2-C4 fluoroalkyl is one of N3-(CF2)2-, N3-(CF2)3-, N3-(CF2)4-;

[0027] said amino-substituted C2-C4 alkyl is one of NH2(CH2)2-, NH2(CH2)3-, NH2(CH2)4-, NH2CF2-, NH2(CF2)2-, NH2(CF2)3-, NH2(CF2)4-;

[0028] said amino-substituted C2-C4 fluoroalkyl is one of NH2CF2-, NH2(CF2)2-, NH2(CF2)3-, NH2(CF2)4-;

[0029] The thiol-substituted C2-C4 alkyl is one of SH(CH2)2-, SH(CH2)3-, SH(CH2)4-.

[0030] The thiol-substituted C2-C4 fluoroalkyl is one of SHCF2-, SH(CF2)2-, SH(CF2)3-, SH(CF2)4-.

[0031] The preparation method of the single fatty chain choline phospholipid with the structure of formula (I) in the application, when R2 is one of C1-C18 alkyl, C3-C18 monoalkenyl, C5-C18 conjugated dienyl, C3-C18 monoalkynyl, fluorine-substituted C1-C12 alkyl, fluorine-substituted C3-C12 alkenyl, fluorine-substituted C3-C12 alkynyl, fluorine-substituted C7-C12 aryl, hydroxyl-substituted C2-C4 alkyl, hydroxyl-substituted C2-C4 fluoroalkyl, azido-substituted C2-C4 alkyl, azido-substituted C2-C4 fluoroalkyl, thiol-substituted C2-C4 alkyl, thiol-substituted C2-C4 fluoroalkyl, is as follows:

[0032] a) reacting the organic base, the compound X-1 and the compound R2-OH to obtain the compound X-2;

[0033] b) performing ring-opening reaction on the compound X-3 and the compound X-2 in the organic solvent A, and after precipitation in the organic solvent B, the compound X-4 is obtained;

[0034] c) performing esterification reaction on the compound X-4 and the compound R1-COOH in the organic solvent C under the action of the hydroxyl protection agent, the dehydrating agent and the catalyst to obtain the single fatty chain choline phospholipid;

[0035] The structural formulae of the compound X-1, the compound X-2, the compound X-3 and the compound X-4 are as follows respectively:

[0036]

[0037] When R2 is one of amino-substituted C2-C4 alkyl and amino-substituted C2-C4 fluoroalkyl, the steps are as follows: reducing the azido group of the single fatty chain choline phospholipid with the corresponding R2 being one of azido-substituted C2-C4 alkyl and azido-substituted C2-C4 fluoroalkyl into amino group.

[0038] Preferably, the process of step a) is as follows: under the protection of inert atmosphere, an organic base and compound R2-OH are added into anhydrous tetrahydrofuran, after stirring in an ice water bath for 20-40 min, 1.0-2.0 times of compound R2-OH equivalent of compound X-1 is added dropwise, which is completed within 1 h, after keeping the ice water bath for 2-4 h, it is raised to room temperature within 1 h, and the reaction is continued for 1-3 h, then filtered, and the filtrate is concentrated and distilled to obtain compound X-2; more preferably, the ratio of anhydrous tetrahydrofuran to compound R2-OH is 1 mL:(0.6-1) mmol; the molar ratio of compound X-1 to compound R2-OH is 1:(1-1.5); the molar ratio of the organic base to compound R2-OH is (1-1.5):1; the organic base is triethylamine, pyridine, pyrrole, dimethylaminopyridine, diethylamine, diisopropylethylamine, morpholine or 3-methylpyridine.

[0039] Preferably, in step b), the molar ratio of compound X-3 to compound X-2 is (1-2):1.

[0040] Preferably, in step b), the organic solvent A is anhydrous acetonitrile, and the molar ratio of organic solvent A to compound X-3 is (20-40):1.

[0041] Preferably, in step b), the ring-opening reaction temperature is 60-80°C, and the reaction time is 48-56 h.

[0042] Preferably, in step b), the organic solvent B is tetrahydrofuran or ethyl acetate.

[0043] Preferably, in step c), the organic solvent C is dichloromethane.

[0044] Preferably, in step c), the hydroxyl protecting agent is dibutyl tin oxide.

[0045] Preferably, in step c), the catalyst is 4-dimethylaminopyridine (DMAP) or concentrated sulfuric acid.

[0046] Preferably, in step c), the dehydrating agent is N,N’-dicyclohexyl carbodiimide (DCC), N,N’-diisopropyl carbodiimide (DIC), N-(3-dimethylaminopropyl)-N’-ethyl carbodiimide (EDC), N-tert-butyl-N’-ethyl carbodiimide, N,N’-di-tert-butyl carbodiimide, N-(3-dimethylaminopropyl)-N’-ethyl carbodiimide hydrochloride, N-cyclohexyl-N’-[β-(N-methylmorpholine)ethyl] carbodiimide, N,N’-di(2,6-diisopropylphenyl) carbodiimide, bis(trimethylsilyl) carbodiimide or 1,3-di-p-tolyl carbodiimide.

[0047] Preferably, in step c), after the esterification reaction, the filtrate is filtered, concentrated and purified by recrystallization for multiple times to obtain the choline phospholipid.

[0048] Preferably, in step c), the esterification reaction temperature is 0-150°C, and the esterification reaction time is 4-48 hours.

[0049] Preferably, in step c), the molar ratio of compound X-4 to compound R1-COOH is 1:(1-2).

[0050] The preparation method of the single fatty chain choline phospholipid with the structure of formula (II) of the present application, when R2 is selected from one of C1-C18 alkyl, C3-C18 monoalkenyl, C5-C18 conjugated dienyl, C3-C18 monoalkynyl, fluorine-substituted C1-C12 alkyl, fluorine-substituted C3-C12 alkenyl, fluorine-substituted C3-C12 alkynyl, fluorine-substituted C7-C12 aryl, hydroxyl-substituted C2-C4 alkyl, hydroxyl-substituted C2-C4 fluoralkyl, azido-substituted C2-C4 alkyl, azido-substituted C2-C4 fluoralkyl, mercapto-substituted C2-C4 alkyl, and mercapto-substituted C2-C4 fluoralkyl, the steps are as follows

[0051] d) Compound X-5 and compound X-2 are subjected to ring-opening reaction in organic solvent A, and after precipitation in organic solvent B, compound X-6 is obtained;

[0052] e) Compound X-6 and R1-COOH are subjected to esterification reaction in organic solvent C in the presence of a dehydrating agent and a catalyst to obtain the single fatty chain choline phospholipid;

[0053] The structural formulae of the compound X-5 and the compound X-6 are as follows, respectively:

[0054]

[0055] When R2 is selected from one of amino-substituted C2-C4 alkyl and amino-substituted C2-C4 fluoralkyl, the steps are as follows: the azido group of the single fatty chain choline phospholipid corresponding to one of azido-substituted C2-C4 alkyl and azido-substituted C2-C4 fluoralkyl is reduced to an amino group.

[0056] Preferably, in step d), the molar ratio of compound X-5 to compound X-2 is (1-2):1.

[0057] Preferably, in step d), the organic solvent A is anhydrous acetonitrile, and the molar ratio of the organic solvent A to compound X-5 is (20-40):1.

[0058] Preferably, in step d), the ring-opening reaction temperature is 60℃~80℃, and the reaction time is 48h~56h.

[0059] Preferably, in step d), the organic solvent B is tetrahydrofuran or ethyl acetate.

[0060] Preferably, in step e), the organic solvent C is dichloromethane; the dehydrating agent is N,N'-dicyclohexylcarbodiimide (DCC), N,N'-diisopropylcarbodiimide (DIC), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC), N-tert-butyl-N'-ethylcarbodiimide, N,N'-ditert-butylcarbodiimide, N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, N-cyclohexyl-N'-[β-(N-methylmorpholine)ethyl]carbodiimide, N,N'-bis(2,6-diisopropylphenyl)carbodiimide, bis(trimethylsilyl)carbodiimide, or 1,3-di-p-tolylcarbodiimide.

[0061] Preferably, in step e), after the esterification reaction, the solution is filtered, and the filtrate is concentrated and recrystallized multiple times to obtain choline phospholipids.

[0062] Preferably, in step e), the esterification reaction temperature is 0–150°C and the esterification reaction time is 4–48 hours.

[0063] Preferably, in step e), the molar ratio of compound X-6 to R1-COOH is 1:(1-2).

[0064] The present invention also provides the application of the above-mentioned monofatty chain choline phosphate lipid and the monofatty chain choline phosphate lipid prepared by the above preparation method in the preparation of pharmaceutical agents that reduce the content of lysophospholipids in the human body.

[0065] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0066] The monofatty chain choline phospholipid of the present invention can generate a strong charge interaction with lysophospholipids (also known as lysophosphatidylcholine), thereby binding with lysophospholipids in the body, causing lysophospholipids to lose their hemolytic toxicity, reducing the hemolytic harm to red blood cells caused by high concentrations of lysophospholipids in the body, and thus reducing the harm caused by lysophospholipids to liver disease patients lacking lysophospholipase. Attached Figure Description

[0067] To more clearly illustrate the technical solutions in the embodiments of the present invention, the accompanying drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0068] Figure 1 The nuclear magnetic resonance hydrogen spectrum of the single fatty chain choline phosphatide lipid with the structure of formula (I) prepared in Example 1 of the present application;

[0069] Figure 2 The nuclear magnetic resonance phosphorus spectrum of the single fatty chain choline phosphatide lipid with the structure of formula (I) prepared in Example 1 of the present application;

[0070] Figure 3 The nuclear magnetic resonance hydrogen spectrum of the single fatty chain choline phosphatide lipid with the structure of formula (II) prepared in Example 2 of the present application;

[0071] Figure 4 The nuclear magnetic resonance phosphorus spectrum of the single fatty chain choline phosphatide lipid with the structure of formula (II) prepared in Example 2 of the present application;

[0072] Figure 5 The binding force test of the single fatty chain choline phosphatide lipid with lysophospholipid in Example 3 of the present application;

[0073] Figure 6 The hemolytic rate test of the single fatty chain choline phosphatide lipid, lysophospholipid and their combination in Example 4 of the present application. DETAILED DESCRIPTION

[0074] In order to further understand the present application, the preferred embodiments of the present application are described below, but it should be understood that these descriptions are only for further illustrating the features and advantages of the present application, but not for limiting the claims of the present application.

[0075] The single fatty chain choline phosphatide lipid of the present application has the structure as shown in formula (I) or (II) (formula (I) has one more hydroxyl group at the β position of the ester bond than formula (II)):

[0076]

[0077] In the formula, R1 is selected from C x H 2x+y O z or a fluorine-substituted hydrocarbon group C x F 2x+y ; x is an integer of 1-21, y is an odd number of -11-1, and z is 0 or 1;

[0078] R2is selected from one of the following: C1-C18alkyl, C3-C18monoalkenyl, C5-C18conjugated dialkenyl, C3-C18monoalkynyl, fluorine substituted C1-C12alkyl, fluorine substituted C3-C12alkenyl, fluorine substituted C3-C12alkynyl, fluorine substituted C7-C12aryl, hydroxyl substituted C2-C4alkyl, hydroxyl substituted C2-C4fluoroalkyl, azido substituted C2-C4alkyl, azido substituted C2-C4fluoroalkyl, amino substituted C2-C4alkyl, amino substituted C2-C4fluoroalkyl, mercapto substituted C2-C4alkyl, mercapto substituted C2-C4fluoroalkyl.

[0079] In the above technical solution, R1is selected from one of the following structures:

[0080] (1) when z = 0,

[0081] a) y = 1, R1is selected from hydrocarbyl groups, specifically as follows: CH3-, CH3CH2-, CH3(CH2)2-, CH3(CH2)3-, CH3(CH2)4-, CH3(CH2)5-, CH3(CH2)6-, CH3(CH2)7-, CH3(CH2)8-, CH3(CH2)9-, CH3(CH2) 10 -, CH3(CH2) 11 -, CH3(CH2) 12 -, CH3(CH2) 13 -, CH3(CH2) 14 -, CH3(CH2) 15 -, CH3(CH2) 16 -, CH3(CH2) 17 -, CH3(CH2) 18 -, CH3(CH2) 19 -, CH3(CH2) 20 -;

[0082] or independently selected from fluorine substituted hydrocarbyl groups, specifically as follows: CF3-, CF3CF2-, CF3(CF2)2-, CF3(CF2)3-, CF3(CF2)4-, CF3(CF2)5-, CF3(CF2)6-, CF3(CF2)7-, CF3(CF2)8-, CF3(CF2)9-, CF3(CF2) 10 -, CF3(CF2) 11 -, CF3(CF2) 12 -, CF3(CF2) 13 -, CF3(CF2) 14 -, CF3(CF2) 15 -, CF3(CF2) 16-, CF3(CF2) 17 -, CF3(CF2) 18 - ;

[0083] b) y = -1, R1is selected from monoalkenyl, in particular: CH3(CH2)5CH=CH(CH2)7-, CH3(CH2)5CH=CH(CH2)9-, CH3(CH2)7CH=CH(CH2)7-, CH3(CH2)5CH=CH(CH2) 11 -, CH3(CH2)7CH=CH(CH2) 11 -, CH3(CH2)7CH=CH(CH2) 13 - ;

[0084] c) y = -3, R1is selected from dialkenyl, in particular: CH3(CH2)3(CH2CH=CH)2(CH2)4-, CH3(CH2)3(CH2CH=CH)2(CH2)7-, CH3(CH2)4CH=CHCH=CH-, CH3(CH2)4(CH=CH)2(CH2)8-, CH3(CH2)5(CH=CH)2(CH2)7-;

[0085] d) y = -5, R1is selected from trialkenyl, in particular: CH3(CH2CH=CH)3(CH2)7-, CH3(CH2)3(CH=CH)3(CH2)7-, CH3(CH2)3(CH2CH=CH)3(CH2)6-;

[0086] e) y = -7, R1is selected from tetraalkenyl, in particular: CH3(CH2CH=CH)4(CH2)4-, CH3(CH2)3(CH2CH=CH)4(CH2)3-, CH3(CH2)3(CH2CH=CH)4(CH2)4-, CH3(CH2)3(CH2CH=CH)4(CH2)5-;

[0087] f) y = -9, R1is selected from pentaalkenyl, in particular: CH3(CH2CH=CH)5(CH2)3-;

[0088] g) y = -11, z = 0, R1is selected from hexaalkenyl, in particular: CH3(CH2CH=CH)6(CH2)2-;

[0089] (2) when z = 1,

[0090] h) y = -1, R1is selected from: CH3(CH2)7CH2(OH)CH2CH=CH(CH2)7-.

[0091] In the above technical solution, R2is selected from one of the following structures:

[0092] a) C1-C18alkyl, CH3-, CH3CH2-, CH3(CH2)2-, (CH3)2CH-, (CH3)2CHCH2-, (CH3)3C-, CH3(CH2)3-, CH3(CH2)4-, (CH3)2CH(CH2)2-, (CH3)3CCH2-, CH3(CH2)5-, (CH3)2CH(CH2)3-, CH3CH2CH(CH3)CH2CH2-, CH3CH2CH2CH(CH3)CH2-, CH3(CH2)6-, (CH3)2CH(CH2)4-, CH3CH2CH2CH(CH3)CH2CH2-, CH3(CH2)7-, CH3(CH2)3CH(C2H5)CH2-, CH3(CH2)8-, CH3(CH2)9-, CH3(CH2) 10 11 12 13 14 15 16 17

[0093] b) C3-C18monoalkenyl, CH2=CH(CH2)-, CH2=CH(CH2)2-, CH2=CH(CH2)3-, CH2=CH(CH2)4-, CH2=CH(CH2)5-, CH2=CH(CH2)6-, CH2=CH(CH2)7-, CH2=CH(CH2)8-, CH2=CH(CH2)9-, CH2=CH(CH2) 10 11 12 13 14 15 16

[0094] ​​​​​​​​​​​​​​​c) C5~C18 conjugated dienyl group, CH2=CH-CH=CH2(CH2)-, CH2=CH-CH=CH(CH2)2-, CH2=CH-CH=CH(CH2)3-, CH2=CH-CH=CH(CH2)4-, CH2=CH-CH=C H(CH2)5-, CH2=CH-CH=CH(CH2)6-, CH2=CH-CH=CH(CH2)7-, CH2=CH-CH=CH(CH2)8-, CH2=CH-CH=CH(CH2)9-, CH2=CH-CH=CH(CH2) 10 - CH2=CH-CH=CH(CH2) 11 - CH2=CH-CH=CH(CH2) 17 - CH2=CH-CH=CH(CH2) 13 - CH2=CH-CH=CH(CH2) 14 -;

[0095] d) C3~C18 monoalkynyl group, CH≡C(CH2)-, CH≡C(CH2)2-, CH≡C(CH2)3-, CH≡C(CH2)4-, CH≡C( CH2)5-, CH≡C(CH2)6-, CH≡C(CH2)7-, CH≡C(CH2)8-, CH≡C(CH2)9-, CH≡C(CH2) 10 -、CH≡C(CH2) 11 -、CH≡C(CH2) 12 -、CH≡C(CH2) 13 -、CH≡C(CH2) 14 -、CH≡C(CH2) 15 -、CH≡C(CH2) 16 -;

[0096] e) Fluorine-substituted C1-C12 alkyl, fluorine-substituted C3-C12 alkenyl, fluorine-substituted C3-C12 alkynyl, and fluorine-substituted C7-C12 aryl, namely: CF3-, CF3CF2-, CF3CH2-, CHF2CH2-, CF3(CF2)2-, (CF3)2CHCF2-, (CF3)3CCH2-, (CF3)2CHCH2-, CF3(CF2)3-, CF3(CF2)4-, CF3(CF2)5-, CF3(CF2)6-, CF3(CF2)7-, CF3(CF2)8-, CF3(CF2)9-, CF3(CF2) 10 - CF3 (CF2) 11-, CF2=CFCF2-, CF2=CF(CF2)2-, CF2=CF(CF2)3-, CF2=CF(CF2)4-, CF2=CF(CF2)5-, CF2=CF(CF2)6-, CF2=CF(CF2)7-, CF2=CF(CF2)8-, CF2=CF(CF2)9-, CF2=CF(CF2) 10 -, CF≡CCF2-, CF≡C(CF2)2-, CF≡C(CF2)3-, CF≡C(CF2)4-, CF≡C(CF2)5-, CF≡C(CF2)6-, CF≡C(CF2)7-, CF≡C(CF2)8-, CF≡C(CF2)9-, CF≡C(CF2) 10 -, C6F5-CH2-, C6F5-(CH2)2-, C6F5-(CH2)3-, C6F5-(CH2)4-, C6F5-(CH2)5-, C6F5-(CH2)6-, o-CF3-C6H5-, o-CF3- C6H4-CH2-, o-CF3-C6H4-(CH2)2, o-CF3-C6H4-(CH2)3, o-CF3-C6H4-(CH2)4, o-CF3-C6H4-(CH2)5-, m-CF3-C6H5-, m-CF3-C6H4-CH2-, m-CF3-C6H4-(CH2)2, m-CF3-C6H4-(CH2)3, m-CF3-C6H4-(CH2)4, m-CF3-C6H4-(CH2)5-, p-CF3- C6H5-, p-CF3-C6H4-CH2-, p-CF3-C6H4-(CH2)2, p-CF3-C6H4-(CH2)3, p-CF3-C6H4-(CH2)4, p-CF3-C6H4-(CH2)5-;

[0097] f) The hydroxyl-substituted C2- to C4 alkyl group is one of HO-(CH2)2-, HO-(CH2)3-, or HO-(CH2)4-.

[0098] g) The hydroxyl-substituted C2- to C4 fluoroalkyl group is one of HO-(CF2)2-, HO-(CF2)3-, or HO-(CF2)4-.

[0099] h) The C2-C4 alkyl group substituted with azide is one of N3-(CH2)2-, N3-(CH2)3-, N3-(CH2)4-, N3-(CF2)2-, N3-(CF2)3-, and N3-(CF2)4-;

[0100] i) azido-substituted C2-C4 fluoroalkyl is one of N3-(CF2)2-, N3-(CF2)3-, N3-(CF2)4-;

[0101] j) amino-substituted C2-C4 alkyl is one of NH2(CH2)2-, NH2(CH2)3-, NH2(CH2)4-, NH2CF2-, NH2(CF2)2-, NH2(CF2)3-, NH2(CF2)4-;

[0102] k) amino-substituted C2-C4 fluoroalkyl is one of NH2CF2-, NH2(CF2)2-, NH2(CF2)3-, NH2(CF2)4-;

[0103] l) mercapto-substituted C2-C4 alkyl is one of SH(CH2)2-, SH(CH2)3-, SH(CH2)4-;

[0104] m) mercapto-substituted C2-C4 fluoroalkyl is one of SHCF2-, SH(CF2)2-, SH(CF2)3-, SH(CF2)4-.

[0105] The preparation method of the single fatty chain choline phospholipid with the structure of formula (I) in the application, when R2 is one of C1-C18 alkyl, C3-C18 monoalkenyl, C5-C18 conjugated dienyl, C3-C18 monoalkynyl, fluorine-substituted C1-C12 alkyl, fluorine-substituted C3-C12 alkenyl, fluorine-substituted C3-C12 alkynyl, fluorine-substituted C7-C12 aryl, hydroxyl-substituted C2-C4 alkyl, hydroxyl-substituted C2-C4 fluoroalkyl, azido-substituted C2-C4 alkyl, azido-substituted C2-C4 fluoroalkyl, mercapto-substituted C2-C4 alkyl, and mercapto-substituted C2-C4 fluoroalkyl, the steps are as follows:

[0106] a) under the protection of inert atmosphere, an organic base and a compound R2-OH are added to anhydrous tetrahydrofuran, after stirring in an ice water bath for 20-40 min, 1.0-2.0 times the equivalent of the compound R2-OH is added dropwise to the compound X-1, and the dropwise addition is completed within 1 h, the reaction is kept in the ice water bath for 2-4 h, then it is raised to room temperature within 1 h, and the reaction is continued for 1-3 h, then it is filtered, and the filtrate is concentrated and distilled to obtain the compound X-2;

[0107] b) the compound X-3 is subjected to ring-opening reaction with the compound X-2 in an organic solvent A, and after precipitation in an organic solvent B, the compound X-4 is obtained;

[0108] c) the compound X-4 is subjected to esterification reaction with the compound R1-COOH in an organic solvent C in the presence of a hydroxyl protecting agent, a dehydrating agent and a catalyst, and the single fatty chain choline phospholipid is obtained.

[0109] wherein the structural formula of compound X-1, compound X-2, compound X-3, compound X-4 are as follows respectively:

[0110]

[0111] When R2 is selected from one of amino-substituted C2-C4 alkyl, amino-substituted C2-C4 fluoroalkyl, the step is as follows: reducing the azido group of the corresponding single fatty chain choline phosphatidyl lipid with R2 being one of azido-substituted C2-C4 alkyl, azido-substituted C2-C4 fluoroalkyl into amino group.

[0112] In the step a), the ratio of anhydrous tetrahydrofuran and compound R2-OH is preferably 1 mL:(0.6-1) mmol; the molar ratio of organic base to compound R2-OH is (1-1.5):1; the organic base is triethylamine, pyridine, pyrrole, dimethylaminopyridine, diethylamine, diisopropylethylamine, morpholine or 3-methylpyridine.

[0113] In the step b), the molar ratio of compound X-3 and compound X-2 is preferably (1-2):1; the organic solvent A is anhydrous acetonitrile, and the molar ratio of organic solvent A and compound X-3 is (20-40):1; the ring-opening reaction temperature is 60-80℃, and the reaction time is 48-56 h; the organic solvent B is tetrahydrofuran or ethyl acetate.

[0114] In the step c), the organic solvent C is preferably dichloromethane; the hydroxyl protecting agent is dibutyl tin oxide; the catalyst is 4-dimethylaminopyridine (DMAP) or concentrated sulfuric acid; the dehydrating agent is N,N’-dicyclohexyl carbodiimide (DCC), N,N’-diisopropyl carbodiimide (DIC), N-(3-dimethylaminopropyl)-N’-ethyl carbodiimide (EDC), N-tert-butyl-N’-ethyl carbodiimide, N,N’-di-tert-butyl carbodiimide, N-(3-dimethylaminopropyl)-N’-ethyl carbodiimide hydrochloride, N-cyclohexyl-N’-[β-(N-methylmorpholine) ethyl] carbodiimide, N,N’-di(2,6-diisopropylphenyl) carbodiimide, bis(trimethylsilyl) carbodiimide or 1,3-di-p-tolyl carbodiimide; after the esterification reaction, the filtrate is concentrated and purified by recrystallization for multiple times to obtain the choline phosphatidyl lipid; the esterification reaction temperature is 0-150℃, and the esterification reaction time is 4-48 hours; the molar ratio of compound X-4 and compound R1-COOH is 1:(1-2).

[0115] The preparation method of the single fatty chain choline phospholipid with the structure of formula (II) in the application, when R2 is selected from one of C1-C18 alkyl, C3-C18 monoalkenyl, C5-C18 conjugated dienyl, C3-C18 monoalkynyl, fluorine-substituted C1-C12 alkyl, fluorine-substituted C3-C12 alkenyl, fluorine-substituted C3-C12 alkynyl, fluorine-substituted C7-C12 aryl, hydroxyl-substituted C2-C4 alkyl, hydroxyl-substituted C2-C4 fluoralkyl, azido-substituted C2-C4 alkyl, azido-substituted C2-C4 fluoralkyl, mercapto-substituted C2-C4 alkyl, and mercapto-substituted C2-C4 fluoralkyl, the steps are as follows:

[0116] d) performing ring-opening reaction on compound X-5 and compound X-2 in organic solvent A, and precipitating after organic solvent B to obtain compound X-6;

[0117] e) performing esterification reaction on compound X-6 and R1-COOH in organic solvent C under the action of a dehydrating agent and a catalyst to obtain the single fatty chain choline phospholipid;

[0118] wherein, the structural formulae of compound X-5 and compound X-6 are as follows:

[0119]

[0120] when R2 is selected from one of amino-substituted C2-C4 alkyl and amino-substituted C2-C4 fluoralkyl, the steps are as follows: reducing the azido group of the single fatty chain choline phospholipid with R2 being one of azido-substituted C2-C4 alkyl and azido-substituted C2-C4 fluoralkyl into an amino group.

[0121] In the above technical solution, in step d), the molar ratio of compound X-5 and compound X-2 is preferably (1-2):1; the organic solvent A is anhydrous acetonitrile, and the molar ratio of the organic solvent A and compound X-5 is (20-40):1; the ring-opening reaction temperature is 60-80℃, and the reaction time is 48-56h; the organic solvent B is tetrahydrofuran or ethyl acetate.

[0122] In step e), the organic solvent C is preferably dichloromethane; the catalyst is 4-dimethylaminopyridine (DMAP) or concentrated sulfuric acid; the dehydrating agent is N,N'-dicyclohexyl carbodiimide (DCC), N,N'-diisopropyl carbodiimide (DIC), N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide (EDC), N-tert-butyl-N'-ethyl carbodiimide, N,N'-di-tert-butyl carbodiimide, N-(3-dimethylaminopropyl)-N'-ethyl carbodiimide hydrochloride, N-cyclohexyl-N'-[beta-(N-methylmorpholine)ethyl] carbodiimide, N,N'-di(2,6-diisopropylphenyl) carbodiimide, bis(trimethylsilyl) carbodiimide, or 1,3-di-p-tolyl carbodiimide; after the esterification reaction, the filtrate is concentrated and purified by recrystallization multiple times to obtain the choline phosphatide lipid; the esterification reaction temperature is 0-150°C, and the esterification reaction time is 4-48 hours; and the molar ratio of compound X-6 to R1-COOH is 1:(1-2).

[0123] The single fatty chain choline phosphatide lipid of the present application can be used in the preparation of a medicament for reducing the content of lysophospholipids in the human body. The principle is that the single fatty chain choline phosphatide lipid interacts with lysophospholipids in the human body, so that the concentration of lysophospholipids in the body is reduced, thereby eliminating the toxicity of lysophospholipids in the body.

[0124] The terms used in the present application generally have the meanings commonly understood by those of ordinary skill in the art, unless otherwise defined. In order for those skilled in the art to better understand the technical solutions of the present application, the present application will be further described in detail below with reference to the embodiments.

[0125] In the following examples, various processes and methods that are not described in detail are conventional methods known in the art. The materials, reagents, devices, instruments, equipment, etc. used in the following examples, unless otherwise specified, can be obtained commercially.

[0126] The present application will be further described below with reference to the examples.

[0127] Example 1 Preparation of single fatty chain choline phosphatide lipid having the structure of formula (I)

[0128] Triethylamine (51 g, 0.51 mol), anhydrous ethanol (22 g, 0.5 mol) were added to a 300 mL flask with a side arm containing anhydrous tetrahydrofuran under nitrogen protection, magnetic stirring, and cooling in an ice water bath for 30 minutes. 2-chloro-2-oxo-dioxaphospholane (71 g, 0.5 mol) was added dropwise from a constant pressure dropping funnel. A large amount of white precipitate was generated during the addition. The addition was completed in 1 hour. The reaction was maintained in the ice water bath for 2 hours, then allowed to warm to room temperature over 1 hour. The reaction was continued for 2 hours. The reaction was filtered, and the filter cake was washed twice with anhydrous tetrahydrofuran. The filtrate was combined and the solvent was removed under reduced pressure to give a crude product. The crude product was distilled in a short path distillation apparatus to give pure 2-oxoethyl-2-oxo-dioxaphospholane (COP) 49.4 g in 65% yield. The structure of the product is as follows:

[0129]

[0130] COP (5.41 g, 30 mmol) and 2-methylaminoethanediol (3.92 g, 33 mmol) were added to a 100 mL flask containing 50 mL of anhydrous acetonitrile. The reaction was heated to 70°C for 24 hours. The reaction was then precipitated in 500 mL of tetrahydrofuran three times. The tetrahydrofuran was finally removed to give the product, 1,2-propanediol choline phosphate ethyl ester, 6.27 g in 70% yield. The structure of the product is as follows:

[0131]

[0132] Hydroxyl protecting agent dibutyltin oxide (2.99 g, 0.012 mol), octadecanoic acid (3.41 g, 0.012 mol), and 1,2-propanediol choline phosphate ethyl ester (2.7 g, 0.01 mol) were added to a 100 mL flask. 50 mL of dichloromethane was added. After stirring, N,N'-diisopropylcarbodiimide (DIC, 1.51 g, 0.012 mol) and 4-dimethylaminopyridine (DMAP, 0.061 g, 0.0005 mol) were added. The reaction was stirred at room temperature for 24 hours. The reaction was filtered, and the filtrate was concentrated and further purified by recrystallization three times to give the product, 5.32 g in 96% yield. The structure of the product is as follows:

[0133]

[0134] The product was tested and the proton nuclear magnetic resonance spectrum is shown in Figure 1 and the phosphorus nuclear magnetic resonance spectrum is shown in Figure 2

[0135] Example 2 Preparation of a single fatty chain choline phosphate lipid having the structure of Formula (II)

[0136] ​COP (obtained in Example 1, 5.41 g, 30 mmol), 2-methylaminoethanol (2.94 g, 33 mmol) were added to a 100 mL flask containing 50 mL of anhydrous acetonitrile, heated to 70 °C for 24 hours, after the reaction was completed, the solution was precipitated in 500 mL of a tetrahydrofuran solution for three times, and finally removed the tetrahydrofuran to obtain the product, 5.6 g of ethyl phosphonate of hydroxyethylcholine, the yield was 70%, the structure of the product is as follows:

[0137]

[0138] Octadecanoic acid (3.41 g, 0.012 mol), ethyl phosphonate of hydroxyethylcholine (2.41 g, 0.01 mol) were added to a 100 mL reaction flask, 50 mL of dichloromethane was added, after stirring, N,N'-diisopropyl carbodiimide (DIC, 1.51 g, 0.012 mol) and 4-dimethylamino pyridine (DMAP, 0.061 g, 0.0005 mol) were added, after stirring at room temperature for 24 h, filtration, the filtrate was concentrated and further purified by recrystallization three times to obtain the product, 5.0 g, the yield was 96%, the structure of the product is as follows:

[0139]

[0140] The product was detected, the nuclear magnetic resonance hydrogen spectrum is as shown in Figure 3 , and the nuclear magnetic resonance phosphorus spectrum is as shown in Figure 4 .

[0141] Example 3 Test of the interaction between single fatty chain choline phospholipid and lysophospholipid

[0142] 2.5 μL of single fatty chain choline phospholipid solution with a concentration of 13 mM was injected into a chamber (200 μL) containing 1.625 mM lysophospholipid solution for 17 times in succession. Before use, the syringe and the solution in the chamber were degassed under vacuum for 30 minutes. The injection was carried out at an interval of 300 seconds. A constant stirring speed of 400 rpm was maintained during the experiment to ensure sufficient mixing after each injection. In order to calculate the binding curve, the dilution heat was measured in a separate titration and subtracted as background. The obtained binding heat results of single fatty chain choline phospholipid and lysophospholipid are as shown in Figure 5 , it can be seen that they have strong binding force.

[0143] Example 4 Test of hemolysis rate of single fatty chain choline phospholipid after binding with lysophospholipid

[0144] Fresh mouse blood was collected from the heart and red blood cells (RBCs) were washed with PBS 3 times. After that, RBCs were diluted and suspended with 10 mL PBS. First, 0.3 mL RBCs suspension was mixed with 1.2 mL PBS as negative control group and with 1.2 mL water as positive control group. Different concentrations of monofatty chain choline phospholipid, lysophospholipid and their conjugates dissolved in 1.2 mL PBS were added to RBCs suspension (0.3 mL) and then incubated at 37°C for 2 hours. Finally, samples were centrifuged at 12000 r / min for 10 minutes, supernatant was collected and absorbance at 541 nm was measured with microplate spectrophotometer. Hemolysis percentage was calculated according to the following equation:

[0145] Hemolysis percentage (%) = (absorbance of sample) / (absorbance of positive control) x 100%

[0146] The results of hemolysis rate are shown in Table 1 Figure 6 As can be seen from Table 1, the hemolysis rate of conjugates is significantly less than that of lysophospholipid or monofatty chain choline phospholipid

[0147] Obviously, the above embodiments are only examples for clearly illustrating, but not limit to the embodiments. For those skilled in the art, other different forms of changes or variations can be made on the basis of the above description. Here, it is not necessary and also impossible to enumerate all the embodiments. The obvious changes or variations derived therefrom are still within the protection scope of the present application.

Claims

1. Mono-fatty chain choline phospholipid, characterized in that, The structural formula is shown in formula (I) or formula (II): In the formula, R1 is a heptadecyl group, and R2 is an ethyl group.

2. A process for the preparation of a monofatty chain choline phospholipid having the structure of formula (I) as claimed in claim 1, characterized in that, The steps are as follows: a) under the protection of an inert atmosphere, triethylamine and a compound R2-OH are added to anhydrous tetrahydrofuran, after stirring in an ice water bath for 20-40 min, the compound X-1 is added dropwise, and the addition is completed within 1 h, the reaction is maintained in an ice water bath for 2 h, then the temperature is raised to room temperature within 1 h, and the reaction is continued for 2 h, then filtration is performed, and the filtrate is concentrated and distilled to obtain a compound X-2; The molar ratio of the triethylamine, the compound R2-OH and the compound X-1 is 0.51:0.5:0.5; b) the compound X-3 is subjected to an open ring reaction with the compound X-2 in anhydrous acetonitrile, and after precipitation with tetrahydrofuran, a compound X-4 is obtained; The molar ratio of the compound X-3 and the compound X-2 is 33:30, the open ring reaction temperature is 70°C, and the reaction time is 24 h; c) the compound X-4 is subjected to an esterification reaction with a compound R1-COOH in dichloromethane in the presence of oxidized dibutyl tin, N,N'-diisopropyl carbodiimide and 4-dimethylamino pyridine, after the esterification reaction, filtration is performed, the filtrate is concentrated and recrystallized for multiple times to obtain a single fatty chain choline phosphatidic acid lipid; The esterification reaction temperature is room temperature, and the esterification reaction time is 24 h; The molar ratio of the compound X-4 and the compound R1-COOH is 0.01:0.012; The structural formulae of the compound X-1, the compound X-2, the compound X-3 and the compound X-4 are as follows:

3. A process for the preparation of a monofatty chain choline phospholipid having the structure of formula (II) as claimed in claim 1, characterized in that, The steps are as follows: d) the compound X-5 is subjected to an open ring reaction with the compound X-2 in anhydrous acetonitrile, and after precipitation with tetrahydrofuran, a compound X-6 is obtained; The molar ratio of the compound X-5 and the compound X-2 is 33 mmol:30 mmol; The open ring reaction temperature is 70°C, and the reaction time is 24 h; e) the compound X-6 is subjected to an esterification reaction with R1-COOH in dichloromethane in the presence of N,N'-diisopropyl carbodiimide and 4-dimethylamino pyridine, after the esterification reaction, filtration is performed, the filtrate is concentrated and recrystallized for multiple times to obtain a single fatty chain choline phosphatidic acid lipid; The esterification reaction temperature is room temperature, and the esterification reaction time is 24 h; The molar ratio of the compound X-6 and R1-COOH is 0.01:0.012; The structural formulae of the compound X-2, the compound X-5 and the compound X-6 are as follows:

4. Use of the single fatty chain choline phosphatidic acid lipid of claim 1 and the single fatty chain choline phosphatidic acid lipid prepared by the preparation method of any one of claims 2-3 in the preparation of a medicament for reducing the content of lysophospholipids in the human body.

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