Polymer and preparation method thereof

Abstract

The invention provides a polymer and a preparation method thereof. The invention discloses a polymer as shown in a formula V. The polymer is excellent in liquid drop stability. The invention also discloses a preparation method of the polymer as shown in the formula V. The preparation method comprises the following step: in a solvent and in an inert atmosphere, carrying out an addition reaction as shown in the specification on the polymer as shown in the formula Z8 and the polymer as shown in the formula S4 under the action of a catalyst to prepare the polymer as shown in the formula V. When the polymer shown in the formula V is prepared by using the method, the synthesis steps are few, the reaction condition is mild, the yield is high, the polymer dispersity is low, the repeatability is good, and accurate molecular weight control and blocking group control are realized. # imgabs0 #

Description

Polymer and preparation method thereof Technical Field

[0001] The invention relates to a polymer and a preparation method thereof, and belongs to the field of polymers. Background Art

[0002] Self-assembly at the nanoscale is a key property that nature relies on to generate biological membranes. These membranes construct a functional molecular framework by embedding channels, receptors, and molecular pumps within a microenvironmental and functional framework. Leveraging hydrophobic-hydrophilic interactions, these membranes self-assemble into bilayers, vesicles, and other structures. Self-assembled membranes are a key component in mimicking the principles of natural nanostructures. In recent years, a range of polymer systems have been exploited for drug delivery, biopharmaceutical coatings, virus-assisted gene delivery, and nanoreactors through their self-assembly. These are amphiphilic diblock or triblock copolymers that self-assemble in suitable solvents into micelles, worm-like micelles, tubular structures, membranes, or vesicles.

[0003] While a wide variety of block copolymer structures exist, ABA triblock copolymers have garnered particular attention in recent years due to their inherent ability to self-assemble into vesicular structures, despite their highly hydrophobic and hydrophilic nature. From a biomedical perspective, polyoxazolines, which offer a pseudopolypeptide architecture, are particularly attractive and have been chosen as the hydrophilic block A. Polymethylsiloxane (PDMS), due to the ionic nature of its Si-CH3 bonds, exhibits a very low glass transition temperature and is generally liquid at room temperature. Furthermore, poly(siloxanes) have very low surface energy and are extremely hydrophobic; therefore, they have been chosen as the hydrophobic block B. This class of ABA triblock copolymer systems has been extensively studied and demonstrated to possess interesting biomedical and self-assembly properties.

[0004] Existing synthesis methods, through a core-first synthesis strategy, have constructed a series of ABA triblock backbone polymers, but they have disadvantages such as many synthesis steps, low yield, high polymer dispersibility, poor reproducibility, and difficulty in modifying the molecular structure.

[0005] Existing technologies offer a small number of triblock polymer preparation methods. For example, the following method, which involves four to five steps, achieves the preparation of a single hydroxyl-terminated triblock polymer, PMOXA-PDMS-PMOXA. However, the process is lengthy and involves reagents such as unstable metallic lithium and highly toxic pyridine, resulting in significant environmental pollution and making it unsuitable for large-scale industrial production.

[0006]

[0007] Summary of the Invention

[0008] The technical problem to be solved by the present invention is that existing methods for synthesizing block copolymers have multiple synthesis steps, involve reagents such as lithium metal, which is unstable, and pyridine, which is highly toxic. These methods also result in low yields, high polymer dispersibility, poor reproducibility, and difficulty in modifying the molecular structure. To address this issue, the present invention provides a polymer and a method for its preparation.

[0009] The present invention provides a polymer represented by formula V:

[0010]

[0011] in,

[0012] The R is -OR t1 、-NR t2 R t3 、-COOMe、-(CH2) n1 SH, 5-10 membered heteroaryl substituted by 1, 2 or 3 oxo groups, -O(CH2) n2 OH, -OP(O)(OMe), -OP(O)(OMe)(O(CH2) n3 N + (Et)3,

[0013] Among them, the R t1 、R t2 、R t3 are independently H, Ts, C1-C6 alkyl or -(CH2) n4 SH;

[0014] n1, n3 and n4 are independently 0, 1, 2, 3, 4, 5 or 6;

[0015] n2 is 2, 3, 4, 5, 6, 7, 8 or 9;

[0016] The L is

[0017] described In the R c is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, -CN or -NO2;

[0018] described In, n is 1, 2, 3, 4, 5 or 6;

[0019] described In, n is 3, 4, 5, 6, 7, 8 or 9;

[0020] described In the R a (CH2) n, n is 3, 4 or 5, said R b is hydrogen, C1-C6 alkyl or acetyl;

[0021] The 1 end and the connected;

[0022] described It is poly-2-methyloxazoline, polyphospholipid, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide, polymethyl methacrylate, poly(N,N-dimethylacrylamide), polyacylalkylene imine, polyhydroxyalkyl acrylate, poly-2-methyloxazoline polyethylene glycol or poly-2-methyloxazoline polyphospholipid;

[0023] The R 1 C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5;

[0024] The R 1’ C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5;

[0025] The Y is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5;

[0026] Said p is 20-50;

[0027] In the 5-10 membered heteroaryl group, the number of heteroatoms is independently 1, 2 or 3, and the heteroatoms are independently selected from one or more of N, O and S.

[0028] In some embodiments, the Preferably Among them, each R 2Each is independently a C1-C3 alkyl group, preferably a methyl group; each m is independently any value from 1 to 22; preferably any value from 1 to 6; more preferably 1, 1.1, 1.3, 3.6, 3.8 or 5.4; further preferably 1, 1.1, 1.3 or 3.6; each w is independently any value from 1 to 22; preferably any value from 1 to 6; more preferably 3.

[0029] In some embodiments, the Preferably

[0030] In some embodiments, the Preferably

[0031] In some embodiments, the Preferably

[0032] In some embodiments, the R 1 It is preferably a C1-C6 alkyl group, and more preferably a methyl group.

[0033] In some embodiments, the R 1’ It is preferably a C1-C6 alkyl group, and more preferably a methyl group.

[0034] In some embodiments, Y is preferably a C1-C6 alkyl group, more preferably a methyl group.

[0035] In some embodiments, the R is preferably hydroxy, methoxy, TsO- or More preferably, hydroxyl or

[0036] In some embodiments, the L is preferably Or -CH2-.

[0037] In some embodiments, the p is preferably any value between 20 and 47, more preferably 20 or 35.

[0038] In some embodiments, the R 1 Preferably methyl; said R 1’ Preferably methyl; Preferably The R 2 Preferably, it is methyl; R is preferably hydroxy; Y is preferably methyl; L is preferably The m is preferably 3.6; the p is preferably 35.

[0039] In some embodiments, the R 1 Preferably methyl; said R1’ Preferably methyl; Preferably The R 2 Preferably, it is methyl; said R is preferably The Y is preferably a methyl group; the L is preferably -CH2-; the m is preferably 3.6; and the p is preferably 35.

[0040] In some embodiments, the R 1 Preferably methyl; said R 1’ Preferably methyl; Preferably The R 2 It is preferably a methyl group; R is preferably a hydroxyl group; Y is preferably a methyl group; L is preferably -CH2-; m is preferably 1; w is preferably 3; and p is preferably 30.

[0041] In some embodiments, the R 1 Preferably methyl; said R 1’ Preferably methyl; Preferably The R 2 Preferably, it is methyl; R is preferably hydroxy; Y is preferably methyl; L is preferably The m is preferably 1.1; the w is preferably 3; and the p is preferably 20.

[0042] In some embodiments, the R 1 Preferably methyl; said R 1’ Preferably methyl; Preferably The R 2 Preferably, it is methyl; R is preferably hydroxy; Y is preferably methyl; L is preferably The m is preferably 1.3; the w is preferably 3; and the p is preferably 20.

[0043] In some embodiments, the polymer represented by formula V is

[0044] In some embodiments, the polymer represented by formula V is

[0045] In some embodiments, the polymer represented by formula V is

[0046] In some embodiments, the polymer represented by formula V is

[0047] In some embodiments, the polymer represented by formula V is

[0048] The present invention provides a method for preparing a polymer represented by formula V, comprising the following steps: in a solvent and in an inert atmosphere, subjecting a polymer represented by formula Z8 and a polymer represented by formula S4 to an addition reaction as shown below under the action of a catalyst to obtain a polymer represented by formula V.

[0049]

[0050] in,

[0051] R, L, R 1 、R 1’ , Y, and p are defined as above.

[0052] In some embodiments, in the method for preparing the polymer represented by Formula V, the catalyst may be any conventional catalyst in the art for such reactions. Preferably, it is H2PtCl2 or a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution. More preferably, the catalyst is a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution.

[0053] In some embodiments, in the method for preparing the polymer represented by Formula V, the solvent may be a commonly used solvent for such reactions in the art. The solvent is preferably one or more of a chlorinated hydrocarbon solvent, an ether solvent, an ester solvent, an aromatic hydrocarbon solvent, and a nitrile solvent. The chlorinated hydrocarbon solvent is preferably one or more of chloroform and dichloroethane. The ether solvent is preferably tetrahydrofuran. The ester solvent is preferably ethyl acetate. The aromatic hydrocarbon solvent is preferably toluene. The nitrile solvent is preferably one or more of benzonitrile and acetonitrile. The solvent is preferably a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, more preferably a mixed solvent of toluene and acetonitrile. In the mixed solvent of the aromatic hydrocarbon solvent and the nitrile solvent, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent is preferably 1:0.01-1:3; more preferably 1:1.

[0054] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar ratio of Z8 to S4 can be conventional in the art for such reactions, preferably 2.5-3, more preferably 2.5.

[0055] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar volume ratio of Z8 to the catalyst can be conventional in the art for such reactions, preferably 15-30 mol / L.

[0056] In some embodiments, in the method for preparing the polymer represented by Formula V, the platinum content in the catalyst may be conventional for such reactions in the art, preferably 1-4%, and more preferably 2%.

[0057] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar volume ratio of Z8 to the solvent can be conventional in the art for such reactions, preferably 0.05-0.2 mol / L, and more preferably 0.125 mol / L.

[0058] In some embodiments, in the method for preparing the polymer represented by Formula V, the reaction temperature may be conventional in the art for such reactions, preferably 60 to 80°C, more preferably 60°C or 80°C.

[0059] In some embodiments, in the method for preparing the polymer represented by Formula V, the reaction time can be conventional for such reactions in the art, preferably 24 to 48 hours, more preferably 24 hours or 48 hours.

[0060] In some embodiments, in the method for preparing the polymer represented by Formula V, the inert atmosphere may be any conventional inert atmosphere for such reactions in the art, preferably nitrogen atmosphere or argon atmosphere.

[0061] In some embodiments, in the preparation method of the polymer shown in Formula V, the reaction may further include post-treatment. The post-treatment step may be conventional in the art for such reactions. Preferably, ethanol and a regenerated cellulose membrane are used for diafiltration purification. More preferably, a regenerated cellulose membrane (Millipore, with a molecular weight cut-off of 1K) is used for diafiltration purification.

[0062] In some embodiments, in the method for preparing the polymer represented by Formula V, the molar volume ratio of the compound represented by Formula Z8 to ethanol in the post-treatment can be conventional in the art for such reactions, preferably 1:40 mol / L.

[0063] In some embodiments, in the method for preparing the polymer of Formula V, the order of adding the materials for the reaction can be conventional in the art for such reactions. Preferably, Z8 is first dissolved in the solvent, S4 is added, and then the catalyst is added. More preferably, the order of adding the materials for the reaction is first dissolved in the solvent, and after it is completely dissolved or mostly dissolved, S4 is added, and after it is completely dissolved, the catalyst is added.

[0064] In some embodiments, in the method for preparing the polymer represented by Formula V, the specific reaction operations may be conventional in the art for such reactions. Preferably, a) Z8 is first dissolved in a solvent and stirred thoroughly until completely or mostly dissolved; b) S4 is added, allowed to dissolve, and stirred thoroughly for 5 minutes; c) a catalyst is added and stirred thoroughly for 5-10 minutes; and d) the temperature is increased with stirring.

[0065] In some embodiments, in the method for preparing the polymer represented by formula V, the polymer represented by formula Z8 is The polymer represented by formula S4 is The polymer represented by formula V is The catalyst is a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; the solvent is a mixed solvent of toluene and acetonitrile; the volume ratio of toluene and acetonitrile is 1:1; the inert atmosphere is an argon atmosphere; the molar ratio of Z8 to S4 is preferably 2.5; the molar volume ratio of Z8 to the catalyst is preferably 125:6 mol / L; the platinum content in the catalyst is preferably 2%; the molar volume ratio of Z8 to the solvent is preferably 0.125 mol / L; the reaction temperature is 80°C; and the reaction time is 24 hours.

[0066] In some embodiments, in the method for preparing the polymer represented by formula V, the polymer represented by formula Z8 is The polymer represented by formula S4 is The polymer represented by formula V is The catalyst is a platinum (0)-1,3-diethene-1,1,3,3-tetramethyldisiloxane complex solution; the solvent is a mixed solvent of toluene and acetonitrile; the volume ratio of toluene and acetonitrile is 1:1; the inert atmosphere is argon; the molar ratio of Z8 to S4 is preferably 2.5; the molar volume ratio of Z8 to the catalyst is preferably 125:6 mol / L; the platinum content in the catalyst is preferably 2%; the molar volume ratio of Z8 to the solvent is preferably 0.125 mol / L; the reaction temperature is 80°C; and the reaction time is 48 hours.

[0067] In some embodiments, in the method for preparing the polymer represented by formula V, the polymer represented by formula Z8 is The polymer represented by formula S4 is The polymer represented by formula V is The catalyst is a platinum (0)-1,3-diethene-1,1,3,3-tetramethyldisiloxane complex solution; the solvent is a mixed solvent of toluene and acetonitrile; the volume ratio of toluene and acetonitrile is 1:1; the inert atmosphere is argon; the molar ratio of Z8 to S4 is preferably 2.5; the molar volume ratio of Z8 to the catalyst is preferably 125:6 mol / L; the platinum content in the catalyst is preferably 2%; the molar volume ratio of Z8 to the solvent is preferably 0.125 mol / L; the reaction temperature is 80°C; and the reaction time is 48 hours.

[0068] In some embodiments, in the method for preparing the polymer represented by formula V, the polymer represented by formula Z8 is The polymer represented by formula S4 is The polymer represented by formula V is The catalyst is a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; the solvent is a mixed solvent of toluene and acetonitrile; the volume ratio of toluene and acetonitrile is 1:1; the inert atmosphere is an argon atmosphere; the molar ratio of Z8 to S4 is preferably 2.5; the molar volume ratio of Z8 to the catalyst is preferably 125:6 mol / L; the platinum content in the catalyst is preferably 2%; the molar volume ratio of Z8 to the solvent is preferably 0.125 mol / L; the reaction temperature is 80°C; and the reaction time is 48 hours.

[0069] In some embodiments, in the method for preparing the polymer represented by formula V, the polymer represented by formula Z8 is The polymer represented by formula S4 is The polymer represented by formula V is The catalyst is a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; the solvent is a mixed solvent of toluene and acetonitrile; the volume ratio of toluene and acetonitrile is 1:1; the inert atmosphere is an argon atmosphere; the molar ratio of Z8 to S4 is preferably 2.5; the molar volume ratio of Z8 to the catalyst is preferably 125:6 mol / L; the platinum content in the catalyst is preferably 2%; the molar volume ratio of Z8 to the solvent is preferably 0.125 mol / L; the reaction temperature is 80°C; and the reaction time is 48 hours.

[0070] In some embodiments, the method for preparing the polymer of formula V further includes a method for preparing the polymer of formula Z8, which comprises the following steps: in a solvent, in an inert atmosphere, reacting the compound of formula S5, the compound of formula Z6, and the quenching reagent S7 as shown below to obtain the polymer of formula Z8.

[0071]

[0072] Among them, R, L and The definitions are the same as above;

[0073] X is halogen, OTf or OTs;

[0074] The quenching reagent S7 is an inorganic base (such as KOH) or RH, and R is defined as above;

[0075] described For polymer The corresponding monomer.

[0076] In some embodiments, in the method for preparing the polymer represented by Formula Z8, the solvent can be a commonly used solvent for such reactions in the art. The solvent is preferably a nitrile solvent. More preferably, the solvent is acetonitrile.

[0077] In some embodiments, in the method for preparing the polymer represented by formula Z8, the L is preferably Or -CH2-, the 1 end is connected to X.

[0078] In some embodiments, in the method for preparing the polymer represented by formula Z8, the 2-Methyloxazoline is preferred.

[0079] In some embodiments, in the method for preparing the polymer represented by formula Z8, X is preferably Br, Cl or OTs.

[0080] In some embodiments, in the method for preparing the polymer represented by formula Z8, X is preferably Br.

[0081] In some embodiments, in the method for preparing the polymer represented by formula Z8, X is preferably Cl.

[0082] In some embodiments, in the method for preparing the polymer represented by formula Z8, X is preferably OTs.

[0083] In some embodiments, in the method for preparing the polymer represented by formula Z8, the quenching reagent S7 is preferably a methanol solution of potassium hydroxide,

[0084] In some embodiments, in the method for preparing the polymer represented by formula Z8, the quenching reagent S7 is preferably a methanol solution of potassium hydroxide, more preferably a methanol solution with a potassium hydroxide concentration of 0.5 M.

[0085] In some embodiments, in the method for preparing the polymer represented by formula Z8, the quenching reagent S7 is preferably

[0086] In some embodiments, in the method for preparing the polymer represented by formula Z8, the quenching reagent S7 is preferably

[0087] In some embodiments, in the method for preparing the polymer of Formula Z8, the molar ratio of the compound of Formula S5 to the compound of Formula Z6 can be conventional in the art for such reactions, preferably 2:1 to 1:8, more preferably 1:1 or 1:4.

[0088] In some embodiments, in the method for preparing the polymer of Formula Z8, when the quenching agent S7 is a methanol solution of potassium hydroxide, the molar volume ratio of the compound of Formula S5 to the quenching agent S7 can be conventional in the art for such reactions, preferably 5-20 mol / L, more preferably 10 mol / L.

[0089] In some embodiments, in the method for preparing the polymer represented by formula Z8, when the quenching reagent S7 is When the molar ratio of the compound represented by formula S5 to the quenching reagent S7 is conventional in the art for such reactions, preferably 1:2 to 2:1, and more preferably 1:1.

[0090] In some embodiments, in the method for preparing the polymer represented by formula Z8, when the quenching reagent S7 is When the molar ratio of the compound represented by formula S5 to the quenching reagent S7 is conventional in the art for such reactions, preferably 1:2 to 2:1, and more preferably 1:1.

[0091] In some embodiments, in the method for preparing the polymer of Formula Z8, the molar volume ratio of the compound of Formula S5 to the solvent can be conventional in the art for such reactions, preferably 1:1.5 mol / L to 1:3 mol / L, and more preferably 50:120 mol / L.

[0092] In some embodiments, in the method for preparing the polymer represented by formula Z8, the reaction temperature may be conventional for such reactions in the art, preferably 40-120°C, more preferably 80°C.

[0093] In some embodiments, in the method for preparing the polymer represented by Formula Z8, the reaction time may be conventional for such reactions in the art, preferably 12-48 hours, more preferably 24 hours.

[0094] In some embodiments, in the method for preparing the polymer represented by formula Z8, the inert atmosphere can be conventional in the art for such reactions, preferably a nitrogen atmosphere or an argon atmosphere.

[0095] In some embodiments, in the method for preparing the polymer of Formula Z8, the quenching reagent S7 may be added at a time conventional in the art for such reactions. Preferably, it is added after the reaction has cooled to room temperature. More preferably, it is added after the reaction has cooled to room temperature and stirred for 3 hours.

[0096] In some embodiments, in the preparation method of the polymer represented by formula Z8, the reaction may further include post-processing. The post-processing step may be conventional in the art for such reactions. Preferably, ethanol and a regenerated cellulose membrane are used for diafiltration purification. More preferably, a regenerated cellulose membrane (Millipore, molecular weight cut-off is 1K) is used for diafiltration purification.

[0097] In some embodiments, in the method for preparing the polymer represented by formula Z8, the molar volume ratio of the compound represented by formula S5 to ethanol in the post-treatment can be conventional in the art for such reactions, preferably 5:70 mol / L.

[0098] In some embodiments, in the method for preparing the polymer represented by formula Z8, the solvent is acetonitrile; the compound represented by S5 is The quenching reagent S7 is a methanol solution with a potassium hydroxide concentration of 0.5M; the polymer represented by formula Z8 is The compound represented by Z6 is 2-methyloxazoline; the compound represented by formula S5 and the compound represented by formula Z6 The molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:4; the molar volume ratio of the compound represented by formula S5 to the quenching reagent S7 is 10 mol / L; the molar volume ratio of the compound represented by formula S5 to the solvent is 50:120 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the inert atmosphere is argon; the quenching reagent S7 is added after the reaction is cooled to room temperature and stirred for 3 hours after addition.

[0099] In some embodiments, in the method for preparing the polymer represented by formula Z8, the solvent is acetonitrile; the compound represented by S5 is The quenching reagent S7 is The polymer represented by formula Z8 is The compound represented by Z6 is 2-methyloxazoline; the compound represented by formula S5 and the compound represented by formula Z6 The molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:4; the molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:1; the molar volume ratio of the compound represented by formula S5 to the solvent is 50:120 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the inert atmosphere is argon; the quenching reagent S7 is added after the reaction is cooled to room temperature and stirred for 3 hours after addition.

[0100] In some embodiments, in the method for preparing the polymer represented by formula Z8, the solvent is acetonitrile; the compound represented by S5 is The quenching reagent S7 is The polymer represented by formula Z8 is The compound represented by Z6 is 2-methyloxazoline; the compound represented by formula S5 and the compound represented by formula Z6 The molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:4; the molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:1; the molar volume ratio of the compound represented by formula S5 to the solvent is 50:120 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the inert atmosphere is argon; the quenching reagent S7 is added after the reaction is cooled to room temperature and stirred for 3 hours after addition.

[0101] In some embodiments, in the method for preparing the polymer represented by formula Z8, the solvent is acetonitrile; the compound represented by S5 is The quenching reagent S7 is The polymer represented by formula Z8 is The compound represented by Z6 is 2-methyloxazoline; the compound represented by formula S5 and the compound represented by formula Z6 The molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:1; the molar volume ratio of the compound represented by formula S5 to the solvent is 50:120 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the inert atmosphere is argon; the quenching reagent S7 is added after the reaction is cooled to room temperature and stirred for 3 hours after addition.

[0102] In some embodiments, in the method for preparing the polymer represented by formula Z8, the solvent is acetonitrile; the compound represented by S5 is The quenching reagent S7 is a methanol solution with a potassium hydroxide concentration of 0.5M; the polymer represented by formula Z8 is The compound represented by Z6 is 2-methyloxazoline; the compound represented by formula S5 and formula Z6 The molar ratio of the compounds shown is 1:1; the molar volume ratio of the compound shown in formula S5 to the quenching reagent S7 is 2.5 mol / L; the molar volume ratio of the compound shown in formula S5 to the solvent is 12.5:120 mol / L; the reaction is carried out at a reaction temperature of 80°C; the reaction time is 24 hours; the inert atmosphere is argon; the quenching reagent S7 is added after the reaction is cooled to room temperature and stirred for 3 hours after addition.

[0103] The present invention provides a polymer represented by formula Z8:

[0104]

[0105] Among them, R, L and The definitions are the same as above.

[0106] In some embodiments, the polymer represented by formula Z8 is

[0107] In some embodiments, the polymer represented by formula Z8 is

[0108] In some embodiments, the polymer represented by formula Z8 is

[0109] In some embodiments, the polymer represented by formula Z8 is

[0110] In some embodiments, the polymer represented by formula Z8 is

[0111] In some embodiments, the polymer represented by formula Z8 is

[0112] In some embodiments, the polymer represented by formula Z8 is

[0113] The present invention provides a method for preparing a polymer represented by formula Z8, comprising the following steps: in a solvent and in an inert atmosphere, reacting a compound represented by formula S5, a compound represented by formula Z6, and a quenching reagent S7 as shown below to obtain a polymer represented by formula Z8.

[0114]

[0115] Among them, R, X, quenching reagent S7, L and Definitions and reaction conditions such as reaction temperature, reaction time, molar ratio of reactants, reaction operation, etc. are the same as described above.

[0116] Unless otherwise specified, the terms used in this invention have the following meanings:

[0117] A "-" at the end of a group indicates that the group is attached to the rest of the molecule through that site. For example, -CN refers to a cyano group.

[0118] The term "alkyl" refers to a linear or branched, saturated, monovalent hydrocarbon radical having a specified number of carbon atoms. For example, C1-C6 alkyl includes, but is not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, n-hexyl, and the like.

[0119] The term "alkoxy" refers to a group R X -O-, R X The same definition as the term "alkyl". Alkoxy includes, but is not limited to, methoxy, ethoxy, n-propoxy, isopropoxy, and the like.

[0120] The term "alkylthio" refers to a group R X -S-, R X The same definition as the term "alkyl". Alkylthio includes, but is not limited to, methylthio, ethylthio, n-propylthio, isopropylthio, and the like.

[0121] The term "aryl" refers to a group having the specified number of carbon atoms (e.g., C6-C 10 ) cyclic, unsaturated monovalent hydrocarbon group, which is monocyclic or polycyclic (for example, 2 or 3), in the case of polycyclic, the monocyclics share two atoms and one bond, and at least one ring is aromatic. The aryl group is connected to the rest of the molecule through an aromatic ring or a non-aromatic ring. Aryl groups include but are not limited to: phenyl, naphthyl, wait.

[0122] The term "heteroaryl" refers to a cyclic, unsaturated, monovalent group having a specified number of ring atoms (e.g., 5-10 members), a specified number of heteroatoms (e.g., 1, 2, or 3), a specified type of heteroatom (one or more of N, O, and S), which is monocyclic or polycyclic, with two atoms and one bond shared between the rings, and at least one ring being aromatic. A heteroaryl group is attached to the rest of the molecule through a carbon atom or a heteroatom; a heteroaryl group is attached to the rest of the molecule through a ring that has heteroatoms or a ring that does not have heteroatoms; a heteroaryl group is attached to the rest of the molecule through a ring that is aromatic or a ring that is not aromatic. Heteroaryl groups include, but are not limited to: wait.

[0123] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain preferred embodiments of the present invention.

[0124] The reagents and raw materials used in the present invention are commercially available.

[0125] The positive advances of the present invention include: the polymer can self-assemble into vesicle structures in solution, and the vesicles have good stability. The preparation method of the present invention has advantages such as fewer synthetic steps, mild reaction conditions, high yield, low polymer dispersibility, and good reproducibility. It also enables precise molecular weight control and diversified modification of the end-capping groups and the linking groups between the hydrophobic and hydrophilic blocks of the polymer. DETAILED DESCRIPTION

[0126] The purity and manufacturer information of each reagent in the examples are as follows:

[0127]

[0128] Example 1 Synthesis of triblock polymer P1

[0129] The synthesis route of triblock polymer P1 is as follows:

[0130]

[0131] Step 1, Synthesis of Prepolymer S4-1: Under nitrogen, pipette 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) into a Schlenk flask. Seal the top with a rubber stopper. Then, add 1.5 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 8.49 mmol) via syringe. The molar ratio of S1 to S2 is 8:1. A slight excess of S1 is acceptable. Deoxygenate with argon three times. Raise the temperature to 55°C, then add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) via microinjector. Reaction at 55°C for 72 h. After the reaction is complete, cool to room temperature and dissolve the product in 200 ml of ether. Extract the trifluoromethanesulfonic acid in the system with deionized water several times in a separatory funnel. Add anhydrous magnesium sulfate and stir for approximately 1 hour to remove moisture. Filter. Remove the ether by rotary evaporation. Dry under vacuum at 120°C for approximately 8 hours to obtain Si-H bond-terminated PDMS prepolymer S4 (19.7 g, 93%). Its structure and degree of polymerization (DP) were confirmed to be 35 by H NMR spectrum integration.

[0132] 1 H NMR (500MHz, CDCl3) δ4.71-4.70 (m, 1H), 0.19-0.07 (m, 111.77H); 1 / 111.77=2 / (6n+12), n=35, Mn=3200g / mol.

[0133] GPC(DMF):PDI 1.101.

[0134] Step 2, Synthesis of Prepolymer Z8-1: Dry vinyl compound S5-1 (7.6 g, 152.62 g / mol, 50 mmol) and starting material Z6-1 (17 g, 85.1 g / mol, 200 mmol) were mixed and dissolved in dry acetonitrile (120 mL) under argon. The mixture was reacted at 80°C for 24 h. H-NMR spectroscopy confirmed the completion of the reaction. After completion, the mixture was cooled to room temperature. 5 mL of a 0.5 M methanol solution containing potassium hydroxide S7-1 (0.48 g) was added to the mixture to terminate the reaction. The mixture was stirred for 3 hours. After removing the solvent under reduced pressure, the product was dissolved in 100 mL of dichloromethane and filtered to remove residual inorganic salts and excess potassium hydroxide. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to yield vinyl-terminated PMOXA prepolymer Z8-1 (20.0 g, 91% yield). Its structure and degree of polymerization were confirmed by integration of the H-NMR spectrum.

[0135] 1 H NMR (500MHz, CDCl3) δ7.45-7.32(m,2H),7.25-7.10(m,2H),6.75-6.62(m,1H),5.82-5.63(m, 1H),5.35-5.16(m,1H),4.70-4.45(m,2H),3.85-3.65(m,15.67H),2.25-2.00(m,10.82H),1 / 3m=1 / 10.82,m=3.6.Mn=440g / mol

[0136] GPC(DMF):PDI 1.197.

[0137] Step 3, Synthesis of Triblock P1: Under argon, the reaction material S4-1 (3.2 g, 3200 g / mol, 1 mmol) and the dried reaction material Z8-1 (1.1 g, 440 g / mol, 2.5 mmol) were dissolved in 20 mL of a 1 / 1 dry toluene-acetonitrile mixture. Once fully dissolved, 120 μL of Karstedt Catalyst (in xylene, Pt~2%) was added. The mixture was then heated to 80°C and stirred at 80°C for 24 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The solid was washed three times with 10 mL of diethyl ether. The product was dissolved in 100 mL of ethanol and purified by diafiltration through a regenerated cellulose membrane (Millipore, 1 kDa molecular weight cutoff) with more than 600 mL of ethanol. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain the triblock HO-PMOXA-PDMS-PMOXA-OH polymer P1 (1.5 g, 42% yield).

[0138] 1H NMR (500MHz, CDCl3) δ7.20-7.07(m,2H),3.57-3.17(m,1H),2.23-1.92(m,1H),0.03-0.00(m,8.3H).Mn=3604g / mol

[0139] GPC(DMF):1.129.

[0140] Example 2 Synthesis of triblock polymer P2

[0141] The synthesis route of triblock polymer P2 is as follows:

[0142]

[0143] Step 1, Synthesis of Prepolymer S4-1: Under nitrogen, pipette 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) into a Schlenk flask. Seal the top with a rubber stopper. Then, add 1.5 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 8.49 mmol) via syringe. The molar ratio of S1 to S2 is 8:1. A slight excess of S1 is acceptable. Deoxygenate three times. Raise the temperature to 55°C, then add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) via microinjector. React at 55°C for 72 h. After the reaction is complete, cool to room temperature and dissolve the product in 200 mL of ether. Extract the trifluoromethanesulfonic acid in the system with deionized water several times in a separatory funnel. Add anhydrous magnesium sulfate and stir for approximately 1 hour to remove moisture. Filter. Remove the ether by rotary evaporation. Dry under vacuum at 120°C for approximately 8 hours to obtain Si-H bond-terminated PDMS prepolymer S4 (19.7 g, 93%). Its structure and degree of polymerization (DP) were determined to be 35 by H NMR spectrum integration.

[0144] 1 H NMR (500MHz, CDCl3) δ4.71-4.70 (m, 1H), 0.19-0.07 (m, 111.77H); 1 / 111.77=2 / (6n+12), n=35, Mn=3200g / mol.

[0145] GPC(DMF):PDI 1.101.

[0146] Step 2, Synthesis of Prepolymer Z8-2: Dry vinyl compound S5-2 (50 mmol) (6.1 g, 120.99 g / mol, 50 mmol) and starting material Z6-1 (17 g, 85.1 g / mol, 200 mmol) were mixed and dissolved in dry acetonitrile (120 mL) under argon. The mixture was reacted at 80°C for 24 h. H-NMR spectroscopy confirmed the completion of the reaction. After the reaction was complete, the mixture was cooled to room temperature and terminated by the addition of S7-2 (14.7 g, 147.1 g / mol, 50 mmol). The mixture was stirred for 3 h. After removing the solvent under reduced pressure, the product was dissolved in 100 mL of deionized water and the residual S7-2 was removed by filtration. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain vinyl-terminated PMOXA prepolymer Z8-2 (19.0 g, 79.2%). Its structure and degree of polymerization were confirmed by H-NMR spectroscopy integration.

[0147] 1 H NMR (500MHz, CDCl3) δ7.86-7.78(m,1.19H),7.78-7.64(m,1.35H),7.45-7.30(m,2.04H),7.25-7.00(m,1.82H),6.75-6.58(m,1.00 H),5.81-5.63(m,1H),5.33-5.15(m,1H),4.78-4.45(m,2.22H),4.00-3.20(m,14.49H),2.30-1.90(m,11.00).m=3.6.Mn=493g / mol

[0148] GPC (DMF): PDI = 1.056.

[0149] Step 3, Synthesis of Triblock P2: Under argon, the reaction material S4-1 (3.2 g, 3200 g / mol, 1 mmol) and the dried reaction material Z8-2 (1.2 g, 493 g / mol, 2.5 mmol) were dissolved in 20 ml of a 1 / 1 dry toluene / acetonitrile mixture. After the materials were fully dissolved at room temperature, 120 μL of Karstedt catalyst (in xylene, Pt~2%) was added. The temperature was raised to 80°C and stirred at 80°C for 48 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The solid was washed three times with ether (10 mL). The product was dissolved in 100 ml of ethanol and purified by diafiltration through a regenerated cellulose membrane (Millipore, molecular weight cutoff, 1K) with more than 600 ml of ethanol. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain the triblock PMOXA-PDMS-PMOXA polymer P2 (1.2 g, yield 32.4%).

[0150] 1 H NMR (500MHz, CDCl3) δ7.86-7.75(m,4H),7.75-7.63(m,4H),3.65-3.15(m,8H),2.22-1.82 (m,6.70H),0.15-0.00(m,42.65H).Mn=3710g / mol

[0151] GPC(DMF):PDI 1.131.

[0152] Example 3 Synthesis of Pentablock Polymer P3

[0153] The synthetic route of the pentablock polymer P3 is as follows:

[0154]

[0155] Step 1, Synthesis of Prepolymer S4-2: Under nitrogen, pipette 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) into a Schlenk flask. Seal the top with a rubber stopper. Then, syringe-dose 1.7 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 9.67 mmol) at a molar ratio of 7:1. A slight excess of S1 is acceptable. Deoxygenate with argon three times. Heat to 55°C, then add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) via microinjector. Reaction at 55°C for 72 h. After the reaction is complete, cool to room temperature and dissolve the product in 200 ml of ether. Extract the trifluoromethanesulfonic acid in the system with deionized water several times in a separatory funnel. Add anhydrous magnesium sulfate and stir for approximately 1 hour to remove moisture. Filter. Remove the ether by rotary evaporation. Dry under vacuum at 120°C for approximately 8 hours to obtain Si-H bond-terminated PDMS prepolymer S4 (18.7 g, 89% yield). Its structure and degree of polymerization (DP) were determined to be 30.0 by integrating the H-NMR spectrum, as shown below.

[0156] 1 H NMR (500 MHz, CDCl3) δ 4.71-4.70 (m, 1H), 0.19-0.07 (m, 89.58H). The degree of polymerization of PDMS was calculated based on H-NMR integration: 1 / 89.58 = 2 / (6n+12)n = 29.94, Mn = 2354 g / mol;

[0157] GPC(DMF):PDI 1.190.

[0158] Step 2 Synthesis of prepolymer Z8-3: Dry vinyl compound S5-2 (6.1 g, 120.99 g / mol, 50 mmol) and reaction raw material Z6-1 (17 g, 85.1 g / mol, 200 mmol) were mixed and dissolved in dry acetonitrile (120 mL) under argon. React at 80°C for 24 h. Nuclear magnetic hydrogen spectrum confirmed that the reaction was complete. After the reaction was complete, the mixture was cooled to room temperature, and then the reaction was terminated by adding S7-3 (7.5 g, 150.2 g / mol, 50 mmol) and stirred for 3 hours. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain vinyl-terminated PMOXA prepolymer Z8-3 (19.0 g, 79.2%). Its structure and degree of polymerization were determined by nuclear magnetic hydrogen spectrum integration.

[0159] 1 H NMR (500 MHz, CDCl3) δ 6.10-4.88 (m, 3H), 4.53-3.80 (m, 5.87H), 3.70-3.16 (m, 24.98H), 2.49-2.46 (m, 1.13H), 2.00-1.84 (m, 3.06H). PMOXA degree of polymerization calculated from H-NMR integration: 3.06 / 1 = 3 m / 1m = 1.0 Mn = 289 g / mol

[0160] GPC(DMF):PDI 1.10.

[0161] Step 3, triblock P3 synthesis: The reaction raw material S4-2 (2.3 g, 2354 g / mol, 1 mmol) and the dried reaction raw material Z8-3 (0.7 g, 289 g / mol, 2.5 mmol) were dissolved in 20 ml of dry toluene / acetonitrile mixed solvent (1 / 1) under argon. After the raw materials were fully dissolved at room temperature, 120 uL of Karstedt catalyst (in xylene, Pt ~ 2%) was added, the temperature was raised to 80 ° C, and stirred at 80 ° C for 48 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The solid was washed three times with ether (10 mL), and the product was dissolved in 100 ml of ethanol and purified by filtration through a regenerated cellulose membrane (Millipore, molecular weight cutoff of 1K) with more than 600 ml of ethanol. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to afford pentablock PEG-PMOXA-PDMS-PMOXA-PEG(3-1-30-1-3) polymer P3 (1.1 g, 38% yield).

[0162] 1H NMR (500MHz, CDCl3) δ3.82-3.47(m,17.23H),2.35-2.08(m,3.00H),0.45(m,0.89H),0.07(198.0H).Mn=2932g / mol;

[0163] GPC(DMF):PDI 1.21

[0164] Example 4 Synthesis of Pentablock Polymer P4

[0165] The synthetic route of the pentablock polymer P4 is as follows:

[0166]

[0167] Step 1, Synthesis of Prepolymer S4-3: Under nitrogen, pipette 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) into a Schlenk flask. Seal the top with a rubber stopper. Then, add 2.4 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 13.54 mmol) via syringe. The molar ratio of S1 to S2 is 5:1. A slight excess of S1 is acceptable. Deoxygenate with argon three times. Raise the temperature to 55°C, and add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) via microinjector. React at 55°C for 72 h. After the reaction is complete, cool to room temperature and dissolve the product in 200 ml of ether. Extract the trifluoromethanesulfonic acid in the system with deionized water several times in a separatory funnel. Add anhydrous magnesium sulfate and stir for approximately 1 hour to remove moisture. Filter. Remove the ether by rotary evaporation. Dry under vacuum at 120°C for approximately 8 hours to obtain Si-terminated PDMS prepolymer S4-3 (19.7 g, 90% yield). Its structure and degree of polymerization (DP) were confirmed to be 20 by H NMR spectrum integration.

[0168] 1 H NMR (500MHz, CDCl3) δ4.72-4.69 (m, 2H), 0.19-0.07 (m, 131.24H); 2 / 131.24=2 / (6n+12), n=20, Mn=1628g / mol.

[0169] GPC(DMF):PDI 1.181.

[0170] Step 2, Synthesis of Prepolymer Z8-4: Dry vinyl compound S5-1 (7.6 g, 152.62 g / mol, 50 mmol) and starting material Z6-1 (4.3 g, 85.1 g / mol, 50 mmol) were mixed and dissolved in dry acetonitrile (120 mL) under argon. The mixture was reacted at 80°C for 24 h. H-NMR spectroscopy confirmed the completion of the reaction. After completion, the mixture was cooled to room temperature and terminated by the addition of S7-3 (7.5 g, 150.2 g / mol, 50 mmol). The mixture was stirred for 3 h. After removing the solvent under reduced pressure, the product was dissolved in 100 mL of dichloromethane and filtered to remove residual inorganic salts and excess potassium hydroxide. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain vinyl-terminated PMOXA prepolymer Z8-4 (16.1 g, 88% yield). Its structure and degree of polymerization were confirmed by integration of the H-NMR spectrum.

[0171] 1 H NMR (500MHz, CDCl3) δ7.60-7.20(m,4H),6.69-6.59(m,1H),5.73-5.69(m,1H),5.25-5.17(m,1H ),4.06(s,2H),3.66-3.40(m,19.63H),2.20-1.95(m,3.44H),1 / 3m=1 / 3.44,m=1.1.Mn=366g / mol

[0172] GPC(DMF):PDI 1.197.

[0173] Step 3, synthesis of triblock P4: The reaction raw material S4-3 (1.6 g, 1628 g / mol, 1 mmol) and the dried reaction raw material Z8-4 (0.92 g, 366 g / mol, 2.5 mmol) were dissolved in 20 ml of dry toluene / acetonitrile mixed solvent (1 / 1) under argon. After the raw materials were fully dissolved at room temperature, 120 uL of Karstedt catalyst (in xylene, Pt~2%) was added, the temperature was raised to 80 ° C, and stirred at 80 ° C for 48 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The solid was washed three times with ether (10 mL), and the product was dissolved in 100 ml of ethanol and purified by filtration through a regenerated cellulose membrane (Millipore, molecular weight cutoff of 1K) with more than 600 ml of ethanol. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain pentablock PEG-PMOXA-PDMS-PMOXA-PEG (3-1.1-20-1.1-3) polymer P4 (0.9 g, yield 39%).

[0174] 1H NMR(500MHz, CDCl3)δ7.50-7.00(m,1H),4.70-4.40(m,0.29H),3.80-3.40( m,19.70H),2.70-2.20(m,6.00H),0.07-0.00(m,121.10H).Mn=2316g / mol;

[0175] GPC(DMF):PDI 1.218.

[0176] Example 5 Synthesis of Pentablock Polymer P5

[0177] The synthetic route of the pentablock polymer P5 is as follows:

[0178]

[0179] Step 1, Synthesis of Prepolymer S4-3: Under nitrogen, pipette 21 mL of S1 (0.956 g / mL, 296.62 g / mol, 67.68 mmol) into a Schlenk flask. Seal the top with a rubber stopper. Then, add 2.4 mL of 1,1,3,3-tetramethyldisiloxane S2 (0.76 g / mL, 134.33 g / mol, 13.54 mmol) via syringe. The molar ratio of S1 to S2 is 5:1. A slight excess of S1 is acceptable. Deoxygenate with argon three times. Raise the temperature to 55°C, and add 76.5 μL of trifluoromethanesulfonic acid S3 (1.696 g / mL, 150.08 g / mol, 0.86 mmol) via microinjector. React at 55°C for 72 h. After the reaction is complete, cool to room temperature and dissolve the product in 200 ml of ether. Extract the trifluoromethanesulfonic acid in the system with deionized water several times in a separatory funnel. Add anhydrous magnesium sulfate and stir for approximately 1 hour to remove moisture. Filter. Remove the ether by rotary evaporation. Dry under vacuum at 120°C for approximately 8 hours to obtain Si-terminated PDMS prepolymer S4-3 (19.7 g, 90% yield). Its structure and degree of polymerization (DP) were confirmed to be 20 by H NMR spectrum integration.

[0180] 1 H NMR (500MHz, CDCl3) δ4.72-4.69 (m, 2H), 0.19-0.07 (m, 131.24H); 2 / 131.24=2 / (6n+12), n=20, Mn=1628g / mol.

[0181] GPC(DMF):PDI 1.181.

[0182] Step 2: Synthesis of Prepolymer Z8-9-1: Dry vinyl compound S5-1 (7.6 g, 152.62 g / mol, 50 mmol) was mixed with the starting material S7-3 (15.0 g, 150.2 g / mol, 100 mmol) and dissolved in dry 1,4-dioxane (120 mL) under a nitrogen atmosphere. Solid potassium hydroxide (5.6 g, 56.10 g / mol, 100 mmol) was added, and the mixture was reacted at 50°C for 48 h. H-NMR spectroscopy confirmed the completion of the reaction. After the reaction was complete, the mixture was cooled to room temperature, the solvent was removed under reduced pressure, and the mixture was purified by silica gel column chromatography (n-hexane / ethyl acetate = 1 / 1) to obtain prepolymer Z8-9-1 (7.9 g, 57% yield).

[0183] 1 H NMR(500MHz, CDCl3)δ7.38(d,J=10.0Hz,2H),7.30(d,J=10.0Hz,2H),6.70(dd,J=15& 10Hz, 1H), 5.73 (d, J = 20.0Hz, 1H), 5.23 (d, J = 15Hz), 4.54 (s, 2H), 3.80-3.55 (m, 12H).

[0184] Step 3 Synthesis of prepolymer Z8-5-3: In a nitrogen atmosphere, the dried vinyl compound Z8-9-1 (7.9 g, 270 g / mol, 29.2 mmol) and the reaction raw material S11 triethylamine (3.5 g, 101.2 g / mol, 35.0 mmol) were mixed and dissolved in dry dichloromethane (120 mL), and cooled and stirred in an ice bath for 15 minutes. The reaction raw material S10 p-toluenesulfonyl chloride (5.4 g, 154.6 g / mol, 35.0 mmol) was added in three portions. The temperature was restored to 25 ° C and stirred for 24 hours. After the reaction was complete, the salt was removed by filtration under reduced pressure, the filtrate was decompressed to remove the solvent, and the prepolymer Z8-5-3 (6.4 g, yield 52.4%) was obtained by silica gel column chromatography (n-hexane / ethyl acetate = 3 / 1).

[0185] 1 H NMR(500MHz, CDCl3)δ7.75(d,J=10.0Hz,2H),7.40-7.20(m,6H),6.66(dd,J=15&5Hz,1H),5.70(d,J=25Hz ,1H),5.25-5.18(m,1H),4.50(s,2H),4.20-4.00(m,2H),3.70-3.50(m,10H),2.38(s,3H).Mn=420.5g / mol

[0186] Step 4, Synthesis of Prepolymer Z8-5: Dry vinyl compound Z8-5-3 (5.3 g, 420.5 g / mol, 12.5 mmol) and starting material Z6-1 (1.1 g, 85.1 g / mol, 12.5 mmol) were mixed and dissolved in dry acetonitrile (120 mL) under argon. The mixture was reacted at 80°C for 24 h. H-NMR spectroscopy confirmed the completion of the reaction. After completion, the mixture was cooled to room temperature. 5 mL of a 0.5 M methanol solution containing potassium hydroxide S7-1 (0.48 g) was added to terminate the reaction, and the mixture was stirred for 3 hours. After removing the solvent under reduced pressure, the product was dissolved in 100 mL of dichloromethane and filtered to remove residual inorganic salts and excess potassium hydroxide. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to yield vinyl-terminated PMOXA prepolymer Z8-5 (3.9 g, 89% yield). Its structure and degree of polymerization were confirmed by integration of the H-NMR spectrum.

[0187] 1 H NMR (500MHz, CDCl3) δ7.86-7.70(m,1.49H),7.45-7.28(m,4.72H),6.80-6.65(m,1H),5.77-5.72(m,1H),5.30-5.23(m,1 H),4.54(s,2H),4.17-4.15(m,1.85H),3.70-3.40(m,15.71H),2.20-1.95(m,4.12H),1 / 3m=1 / 4.12,m=1.4.Mn=385g / mol

[0188] GPC(DMF):PDI 1.197.

[0189] Step 5, synthesis of triblock P5: The reaction raw material S4-3 (1.6 g, 1628 g / mol, 1 mmol) and the dried reaction raw material Z8-5 (0.96 g, 385 g / mol, 2.5 mmol) were dissolved in 20 ml of dry toluene / acetonitrile mixed solvent (1 / 1) under argon. After the raw materials were fully dissolved at room temperature, 120 uL of Karstedt catalyst (in xylene, Pt~2%) was added, the temperature was raised to 80 ° C, and stirred at 80 ° C for 48 h. After the reaction was complete, the mixture was cooled to room temperature and filtered. The solid was washed three times with ether (10 mL), and the product was dissolved in 100 ml of ethanol and purified by filtration through a regenerated cellulose membrane (Millipore, molecular weight cutoff of 1K) with more than 600 ml of ethanol. The solvent was removed under reduced pressure, and the resulting polymer was dried under vacuum to obtain pentablock PMOXA-PEG-PDMS-PEG-PMOXA (1.3-3-20-3-1.3) polymer P5 (1.0 g, yield 42%).

[0190] 1 H NMR (500MHz, CDCl3) δ7.80-7.77(m,1H),7.40-7.10(m,3.9H),4.54-4.49(m,1.28H),4.20- 4.10(m,1.00H),3.75-3.50(m,8.19H),2.70-2.50(m,0.99H),2.35-1.90(m,1.98H),0.9 0-0.82(m,0.82H),0.07-0.00(m,65.47H).1.98 / 65.47=3m / 132, m=1.34, Mn=2398g / mol;

[0191] GPC(DMF):PDI 1.230.

[0192] Example 6 Preparation and Testing of Droplet Microfluidics of Triblock Polymer P5

[0193] According to the droplet microfluidics reference:

[0194] 1)Janelle R.Anderson et al.Fabrication of Topologically Complex Three-Dimensional Microfluidic Systems in PDMS by Rapid Prototyping.Anal.Chem.2000,72,3158-3164;

[0195] 2) George M. Whitesides. The origins and the future of microfluidics. Nature, 2006, 442, 368-373.

[0196] It was measured that the droplets of the polymer P5 of the present application could exist stably for more than 30 minutes, had good uniformity, and had no obvious fusion between the droplets.

Claims

1. A polymer represented by formula V: in, The R is -OR t1 、-NR t2 R t3 、-COOMe、-(CH2) n1 SH, 5-10 membered heteroaryl substituted by 1, 2 or 3 oxo groups, -O(CH2) n2 OH, -OP(O)(OMe), -OP(O)(OMe)(O(CH2) n3 N + (Et)3, The R t1 、R t2 、R t3 are independently H, Ts, C1-C6 alkyl or -(CH2) n4 SH; n1, n3 and n4 are independently 0, 1, 2, 3, 4, 5 or 6; n2 is 2, 3, 4, 5, 6, 7, 8 or 9; The L is described In the R c is hydrogen, C1-C6 alkyl, C1-C6 alkoxy, -CN or -NO2; described In, n is 1, 2, 3, 4, 5 or 6; described In, n is 3, 4, 5, 6, 7, 8 or 9; described In the R a (CH2) n , n is 3, 4 or 5, said R b is hydrogen, C1-C6 alkyl or acetyl; The 1 end and the connected; described It is poly-2-methyloxazoline, polyphospholipid, polyethylene glycol, polyvinyl alcohol, polyvinyl pyrrolidone, polyacrylamide, polymethyl methacrylate, poly(N,N-dimethylacrylamide), polyacylalkylene imine, polyhydroxyalkyl acrylate, poly-2-methyloxazoline polyethylene glycol or poly-2-methyloxazoline polyphospholipid; The R 1 C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5; The R 1’ C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C1-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5; The Y is C1-C6 alkyl, C1-C6 alkoxy, C1-C6 alkylthio, C6-C 12 Aryl, -(CH2) n OH, or -(CH2) n -CH=CH2, wherein n is 3, 4 or 5; Said p is 20-50; In the 5-10 membered heteroaryl group, the number of heteroatoms is independently 1, 2 or 3, and the heteroatoms are independently selected from one or more of N, O and S.

2. The polymer of formula V according to claim 1, wherein The polymer represented by formula V satisfies one or more of the following conditions: a) the R 1 is a C1-C6 alkyl group; preferably a methyl group; b) the R 1’ is a C1-C6 alkyl group; preferably a methyl group; c) Y is a C1-C6 alkyl group, preferably a methyl group; d) L is or -CH2-; e) p is 20-47; preferably 20 or 35.

3. The polymer of formula V according to claim 2, wherein The polymer represented by formula V satisfies one or more of the following conditions: a) for Among them, each R 2 Each is independently a C1-C3 alkyl group, preferably a methyl group; each m is independently any number from 1 to 22; preferably any number from 1 to 6; more preferably 1, 1.1, 1.3, 3.6, 3.8 or 5.4; further preferably 1, 1.1, 1.3 or 3.6; each w is independently any number from 1 to 22; preferably any number from 1 to 6; more preferably 3; b) R is hydroxy, methoxy, TsO- or More preferably, hydroxyl or c) The polyoxazoline polymer is preferably poly-2-methyloxazoline.

4. The polymer of formula V according to claim 1, wherein The polymer represented by formula V is any of the following polymers:

5. A method for preparing a polymer of formula V according to any one of claims 1 to 4, comprising the steps of: subjecting a polymer of formula Z8 and a polymer of formula S4 to an addition reaction as shown below in a solvent under an inert atmosphere in the presence of a catalyst to obtain a polymer of formula V. in, R、L、 R 1 、R 1’ , Y, and p are defined as described in any one of claims 1-4.

6. The method for preparing the polymer of formula V according to claim 5, wherein: The preparation method satisfies one or more of the following conditions: a) The catalyst is H2PtCl2 or a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; preferably a platinum (0)-1,3-diethylene-1,1,3,3-tetramethyldisiloxane complex solution; b) the solvent is one or more of a chlorinated hydrocarbon solvent, an ether solvent, an ester solvent, an aromatic hydrocarbon solvent and a nitrile solvent; the chlorinated hydrocarbon solvent is preferably one or more of chloroform and dichloroethane; the ether solvent is preferably tetrahydrofuran; the ester solvent is preferably ethyl acetate; the aromatic hydrocarbon solvent is preferably toluene; the nitrile solvent is preferably one or more of benzonitrile and acetonitrile; the solvent is more preferably a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, and further preferably a mixed solvent of toluene and acetonitrile; c) the molar ratio of Z8 to S4 is 2.5-3; preferably 2.5; d) the molar volume ratio of the Z8 to the catalyst is 15-30 mol / L; e) the molar volume ratio of Z8 to the solvent is 0.05-0.2 mol / L, preferably 0.125 mol / L; f) the reaction temperature is 60-80°C; preferably 60°C or 80°C; g) the reaction time of the reaction is 24 to 48 hours; preferably 24 hours or 48 hours; h) the inert atmosphere is a nitrogen atmosphere or an argon atmosphere; i) the reaction includes post-treatment; the post-treatment step is diafiltration purification using ethanol and a regenerated cellulose membrane; preferably, the diafiltration purification is performed using a regenerated cellulose membrane with a molecular weight cut-off of 1K; j) The order of adding materials for the reaction is to first dissolve Z8 in the solvent, then add S4, and then add the catalyst; the order of adding materials for the reaction is preferably to first dissolve Z8 in the solvent, wait for it to be completely dissolved or mostly dissolved, then add S4, wait for it to be completely dissolved, and then add the catalyst.

7. The method for preparing the polymer of formula V according to claim 6, wherein: The preparation method satisfies one or more of the following conditions: a) when the solvent is a mixed solvent of an aromatic hydrocarbon solvent and a nitrile solvent, the volume ratio of the aromatic hydrocarbon solvent to the nitrile solvent in the mixed solvent is 1:0.01-1:3; preferably 1:1; b) the platinum content of the catalyst is 1-4%, preferably 2%; c) when the reaction includes post-treatment, in the post-treatment, the molar volume ratio of the compound represented by formula Z8 to ethanol is 1:40 mol / L; d) The specific operation of the reaction is as follows: a) dissolving Z8 in a solvent and stirring thoroughly until it is completely dissolved or mostly dissolved; b) adding S4, waiting for it to dissolve, and stirring thoroughly for 5 minutes; c) adding a catalyst and stirring thoroughly for 5-10 minutes; d) Heat and stir.

8. The method for preparing a polymer of formula V according to any one of claims 5 to 7, wherein: The preparation method also includes a preparation method of a polymer represented by formula Z8, which comprises the following steps: in a solvent, in an inert atmosphere, reacting a compound represented by formula S5, a compound represented by formula Z6, and a quenching reagent S7 as shown below to obtain a polymer represented by formula Z8. Among them, R, L and As defined in any one of claims 1 to 4; X is halogen, OTf or OTs; The quenching reagent S7 is an inorganic base (such as KOH) or RH, and R is defined as described in any one of claims 1 to 4; described For polymer The corresponding monomer.

9. The method for preparing the polymer of formula V according to claim 8, wherein: The preparation method of the polymer represented by formula Z8 satisfies one or more of the following conditions: a) the solvent is a nitrile solvent; preferably acetonitrile; b) It is 2-methyloxazoline; c) X is Br, Cl or OTs; d) the quenching reagent S7 is a methanol solution of potassium hydroxide, Preferably, the potassium hydroxide concentration is 0.5M methanol solution; e) the molar ratio of the compound represented by formula S5 to the compound represented by formula Z6 is 2:1-1:8; preferably 1:1 or 1:4; f) the molar volume ratio of the compound represented by formula S5 to the solvent is 1:1.5 mol / L-1:3 mol / L; preferably 50:120 mol / L; g) the reaction temperature is 40-120° C., preferably 80° C.; h) the reaction time is 12-48 hours; preferably 24 hours; i) the inert atmosphere is a nitrogen atmosphere or an argon atmosphere; j) adding the quenching reagent S7 after the reaction is cooled to room temperature; preferably, adding the quenching reagent S7 after the reaction is cooled to room temperature and stirring for 3 hours; k) The reaction includes post-treatment; the post-treatment step is to perform diafiltration purification using ethanol and a regenerated cellulose membrane; preferably, the diafiltration purification is performed using a regenerated cellulose membrane with a molecular weight cut-off of 1K.

10. The method for preparing the polymer of formula V according to claim 9, wherein: The preparation method of the polymer represented by formula Z8 satisfies one or more of the following conditions: a) when the quenching agent S7 is a methanol solution of potassium hydroxide, the molar volume ratio of the compound represented by formula S5 to the quenching agent S7 is 5-20 mol / L, preferably 10 mol / L; b) When the quenching reagent S7 is When the molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:2-2:1; preferably 1:1; c) When the quenching reagent S7 is When the molar ratio of the compound represented by formula S5 to the quenching reagent S7 is 1:2-2:1; preferably 1:1; d) When the reaction includes post-treatment, in the post-treatment, the molar volume ratio of the compound represented by formula S5 to ethanol is 5:70 mol / L.

11. A polymer represented by formula Z8: in, R, L and As defined in any one of claims 1 to 4; The polymer represented by formula Z8 is preferably any of the following polymers:

12. A method for preparing a polymer of formula Z8 according to claim 11, comprising the steps of: reacting a compound of formula S5, a compound of formula Z6, and a quenching agent S7 in a solvent under an inert atmosphere to obtain a polymer of formula Z8. in, R, X, quenching reagent S7, L and The definition is as described in claim 11, and the reaction conditions are as described in claim 9 or 10.

Images