A cyclic anhydride monomer, its preparation method and application

Abstract

This invention relates to an intracyclic anhydride monomer, its preparation method, and its applications. The monomer has a structure as shown in formula (I). The monomer (N-substituted α-amino acid N-carboxyl (thiocarbonyl) intracyclic anhydride monomer) can be used to prepare a multifunctional polymer. The polymer can be used in fields such as antibacterial, antifungal, antiviral, antimite, antitumor, cell adhesion promotion, tissue engineering, drug modification, protein modification, protein protection, cell protection, tissue and organ cryoprotection, drug modification, drug synergy, drug delivery, gene delivery and self-assembly materials, surface antifouling (including antiprotein adsorption, anti-cell, antibacterial, antifungal, and antiplatelet adhesion), surface antibacterial, and surface modification. It can also be used to modify medical material substrates (such as PU, PTFE, PVP, PVC, PDMS, PEEK, titanium, and titanium alloys) and other possible surfaces.

Description

Technical Field

[0001] This invention belongs to the field of polymer technology, and particularly relates to an intracyclic anhydride monomer, its preparation method, and its application. Background Technology

[0002] Peptides are a class of molecules formed by the condensation of N-substituted amino acids. Based on their amino acid structure, peptides are generally classified into α-peptides, β-peptides, and γ-peptides. Peptides possess excellent biocompatibility and are resistant to protease hydrolysis, showing broad application prospects in the field of biomedical materials, such as protein mimicry, antibacterial materials, drug and gene delivery, stimulus-responsive peptides, tissue engineering, and self-assembled materials. However, the main synthetic method for functional peptides currently involves solid-phase synthesis of amino-containing peptide compounds with side chains.

[0003] While the preparation of peptide-like polymers and their derived materials from the ring-opening polymerization of N-substituted amino acid monomers (α-NNCA, α-NNTA, and β-NNCA) has been reported, only a few studies have reported the synthesis of hydrophobic α-NNCA, α-NNTA, and β-NNCA monomers and their limited functions in the biomedical field. Furthermore, the synthesis and polymerization of N-substituted α-amino acid monomers (α-NNCA or α-NNTA) and N-substituted β-amino acid monomers (β-NNCA) with amino groups in their side chains have never been reported. However, the polymers of these monomers have significant applications in numerous biomedical fields, including drug delivery, antibacterial materials, and protein mimicry. Additionally, some reported β-NNCA monomers require polymerization under inert gas protection and ultra-dry solvent conditions, which limit the synthesis and application of these polymers. Therefore, there is an urgent need in this field to develop functional and applicable N-substituted amino acid polymers with amino groups in their side chains for biomedical use, and to develop a mild polymerization method for synthesizing β-peptides under open conditions.

[0004] Meanwhile, peptides / peptide-like hybrid peptides are molecules formed by the condensation of amino acids and N-substituted amino acids. They are widely used in important fields such as protein mimicry and modification, regulation of peptide secondary structure and degradation, and antibacterial applications. However, the main synthetic methods currently used are solid-phase synthesis, which is time-consuming, cumbersome, and not suitable for preparing peptides / peptide-like hybrid peptides with long amino acid repeating units. Therefore, there is an urgent need to develop a simple polymerization method to synthesize peptides / peptide-like hybrid polymers. Summary of the Invention

[0005] The purpose of this invention is to provide an intracyclic anhydride monomer, its preparation method, and its applications, which can conveniently synthesize peptide-like polymers and peptide / peptide-like hybrid polymers. The resulting polymers can be used as antibacterial, antifungal, antiviral, anti-mite, antitumor, cell adhesion promoters, tissue engineering agents, drug modifiers, protein modifiers, protein protectants, cell protectants, tissue and organ cryoprotectants, drug synergists, drug delivery agents, gene delivery and self-assembly agents, surface antifouling agents, surface antibacterial agents, surface modification materials, and for modifying medical material substrates.

[0006] In a first aspect, the present invention provides an intracyclic anhydride monomer, wherein the monomer has a structure as shown in formula (I).

[0007]

[0008] in,

[0009] X is either S or O;

[0010] n is 1, 2, 3 or 4;

[0011] R is independently selected from the following group: C1-C, whether substituted or unsubstituted. 12 Alkyl, C1-C 12 Haloalkyl, C1-C 12 Alkyl hydroxyl, C1-C 12 Alkoxy, 2-12 heteroalkyl, C1-C 12 Alkyl sulfonyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 3-12 membered heterocyclic, C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester, Wherein, the substitution refers to being replaced by one or more R m replace;

[0012] Each R1 and R2 is independently selected from the following group, either substituted or unsubstituted: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, C1-C6 alkyl-5-12 heteroaryl, NR' a R' bC1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m replace;

[0013] Alternatively, R1 and R2, together with the carbon atoms they are attached to, may form a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to the presence of one or more R atoms. m replace;

[0014] Alternatively, when n is 2, 3, or 4, the two R1s located on adjacent carbon atoms, together with the carbon atoms they are connected to, constitute a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to being formed by one or more R1s. m replace;

[0015] Each L is independently a bond, -CHR'1-, -O-, -S-, -CO-, -COO-, -S(=O)2-;

[0016] q is an integer from 1 to 10;

[0017] R'1 is independently selected from the following group of substituent or unsubstituted groups: H, amino, C1-C. 15 Alkyl, C1-C 15 Alkylamino, C6-C 15 Aryl, C2-C 15 alkenyl, C2-C 15 alkynyl group, C1-C 15 Alkyl hydroxyl, C1-C 15 Alkyl aldehyde group, C1-C 15 Alkyl ester group, thioC1-C 15 Alkyl ester group, -Rc-COO-Rc”, -Rc-CO-Rc”, -Rc-O-Rc”-, -Rc-S-Rc”, 5-15 membered heteroaryl, 5-12 membered heterocyclic group; wherein, the substitution refers to being replaced by one or more R m replace;

[0018] R' a 、R' b R a and R b Each group is independently selected from the following group, whether substituted or unsubstituted: hydrogen, C1-C. 15 Alkyl, C1-C 15 Alkylamino, C2-C 15 alkenyl, C2-C 15 alkynyl group, C1-C 15 Alkyl hydroxyl, C1-C 15 Alkyl aldehyde group, C1-C 15Alkyl sulfonyl, -Rc-COO-Rc”, -Rc-CO-Rc”, -Rc-O-Rc”-, -Rc-S-Rc”, C3-C 12 cycloalkyl, C4-C 12 Cycloalkenyl, 5-12 membered heterocyclic group, C6-C 12 aryl, 5-12 membered heteroaryl, tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc), phthaloyl (Pht), acetyl (Ac), trifluoroacetyl (Tfa), benzyl (Bn), triphenylmethyl (Tr); or R a and R b It combines with the attached N atom to form a 3-8 substituted or unsubstituted heterocyclic group, or R' a and R' b The N atom attached to it combines to form a 3-8 substituted or unsubstituted heterocyclic group; wherein, the substitution refers to being formed by one or more R atoms. m replace;

[0019] Rc is independently selected from the following group of substituent or unsubstituted groups: none, C1-C 15 Alkylene, C2-C 15 alkenyl, C2-C 15 Ethyne group, C3-C 12 Cycloalkylene, C4-C 12 Cycloalkylene, 3-12 membered heterocyclic cycloalkylene, C6-C 12 arylene, 5-12 heteroarylene; wherein, the substitution refers to being replaced by one or more R m replace;

[0020] Rc” is independently selected from the following group of substituent or unsubstituted groups: C1-C 15 Alkyl, C1-C 15 Alkylamino, C2-C 15 alkenyl, C2-C 15 alkynyl group, C3-C 12 cycloalkyl, C4-C 12 Cycloalkenyl, 3-12 membered heterocyclic group, C6-C 12 Aryl, 5-12 membered heteroaryl; wherein, the substitution refers to being replaced by one or more R m replace;

[0021] R m Selected from the following groups, whether substituted or unsubstituted: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 10 Aryl, 5-10 membered heteroaryl; among which, R mSubstitution in this context refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0022] Constraints: When n is 1 and R1 = R2 = H, R is...

[0023] When n is 2, X is 0 and R1 = R2 = H, R is not methyl, ethyl, or benzyl.

[0024] In another preferred embodiment, the monomer has the structure shown in Formula II.

[0025]

[0026] Where X, R1, R2, L, q, R a and R b The definition is as described above.

[0027] In another preferred embodiment, the monomer has the structure shown in Formula III.

[0028]

[0029] in,

[0030] f is 0 or 1;

[0031] R 1a R 1b R 1c R 1d R 1e R 1f Each group is independently selected from the following group, whether substituted or unsubstituted: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C1-C6 alkenyl, C2-C6 alkynyl, C3-C6 alkylhydroxyl, C1-C6 alkylolyl, C1-C6 alkyne, C2-C6 alkylolyl, C3-C6 alkylolyl, C1 ... 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, NR' a R' b C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m Replace; when f is 0, R 1a R 1b R 1c R 1d It cannot be hydrogen at the same time;

[0032] Or R1a and R 1b Together with the carbon atoms they are attached to, they form substituted or unsubstituted C3-C atoms. 12 Cycloalkyl, substituted or unsubstituted C4-C 12 Cycloalkenyl or 5-12 membered heterocyclic group; wherein, the substitution refers to being replaced by one or more R groups. m replace;

[0033] Or R 1c and R 1d Together with the carbon atoms they are attached to, they form substituted or unsubstituted C3-C atoms. 12 Cycloalkyl, substituted or unsubstituted C4-C 12 Cycloalkenyl or substituted or unsubstituted 5-12 membered heterocyclic groups; wherein, the substitution refers to being substituted by one or more R m replace;

[0034] Or R 1a and R 1c Together with the carbon atoms connected to them, they form substituted or unsubstituted 3-12 membered carbon rings or heterocycles; wherein, substitution refers to the presence of one or more R atoms. m replace;

[0035] Or when f is 1, R 1e and R 1f Together with the carbon atoms they are attached to, they form substituted or unsubstituted C3-C atoms. 12 Cycloalkyl, substituted or unsubstituted C4-C 12 Cycloalkenyl or 5-12 membered heterocyclic group; wherein, the substitution refers to being replaced by one or more R groups. m replace;

[0036] Or when f is 1, R 1c and R 1e Together with the carbon atoms connected to them, they form substituted or unsubstituted 3-12 membered carbon rings or heterocycles; wherein, substitution refers to the presence of one or more R atoms. m replace;

[0037] Z is selected from the following group, either substituted or unsubstituted: C1-C 12 Alkyl, C1-C 12 Haloalkyl, C1-C 12 Alkyl hydroxyl, C1-C 12 Alkoxy, C1-C 12 Alkyl sulfonyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 3-12 membered heterocyclic, C1-C6 alkyl-C6-C12 Aryl, C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester Wherein, the substitution refers to being replaced by one or more R m replace;

[0038] R m Selected from the following groups, whether substituted or unsubstituted: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, or 3-12 membered heterocyclic; wherein, R m Substitution in this context refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0039] L, q, R' a 、R' b R a and R b The definition is as described above.

[0040] In another preferred embodiment, the 3-12 membered carbon ring or heterocycle is selected from the group consisting of: C6-C 12 Aryl, C3-C 12 cycloalkyl, C4-C 12 Cycloalkenyl, 3-12 heterocyclic, 5-12 heteroaryl.

[0041] In another preferred embodiment, the monomer has a structure as shown in formula IV or V:

[0042]

[0043] In the formula,

[0044] Ring A is independently selected from the group consisting of substituted or unsubstituted C6-C. 12 aryl, substituted or unsubstituted C3-C 12 Cycloalkyl, substituted or unsubstituted C4-C 12 Cycloalkenyl, substituted or unsubstituted 3-12-membered heterocyclic group or substituted or unsubstituted 5-12-membered heteroaryl, wherein the substitution refers to being substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy.

[0045]

[0046] In the formula, t is an integer between 0 and 5;

[0047] R 1g Selected from the following group: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl or 3-12 membered heterocyclic;

[0048] R 1c R 1d R 1e R 1f The definitions of Z and f are as described above.

[0049] In another preferred embodiment, the monomer has the structure shown in Formula VI.

[0050]

[0051] In the formula,

[0052] Z is selected from the following group, whether substituted or unsubstituted: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C1-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 3-8 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester Wherein, the substitution refers to being replaced by one or more R m replace;

[0053] R 1a R 1b R 1c R 1d Each of the following is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, or C1-C6 alkyl-C6-C 12 Aryl, NR' a R' b Wherein, the substitution refers to being replaced by one or more R m replace;

[0054] R m Selected from the following groups, whether substituted or unsubstituted: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12Aryl, 5-12 membered heteroaryl, or 3-12 membered heterocyclic; wherein, R m Substitution in this context refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0055] Among them, L, q, R' a 、R' b R a and R b The definition is as described above.

[0056] In another preferred embodiment, in formula VI, Z is selected from the following group, whether substituted or unsubstituted: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3-8 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, Wherein, the substitution refers to being replaced by one or more R m replace;

[0057] Among them, L, q, R m R a and R b The definition is as described above.

[0058] In another preferred embodiment, Partially -(CH2) r -、-(CH2) r' -S(=O)2-、-(CH2) r' -C(=O)-, where r and r' are each an independent integer from 1 to 16, preferably r and r' are each an independent integer of 2, 3, 4, 5, 6, 7 or 8.

[0059] In another preferred embodiment, the monomer is selected from:

[0060]

[0061] In another preferred embodiment, the intracyclic anhydride monomer is selected from the intracyclic anhydride monomers shown in the examples.

[0062] In a second aspect, the present invention provides a method for preparing the intracyclic anhydride monomer of Formula I as described in the first aspect, comprising the following steps:

[0063] s1) In an inert solvent, compound A is reacted with phosphorus halide to obtain monomer of formula I;

[0064]

[0065] in,

[0066] R5 is selected from the following group, either substituted or unsubstituted: C1-C 12 Alkyl, C6-C 12 Aryl, 3-12 membered heterocyclic, 5-12 membered heteroaryl, 3-8 membered cycloalkyl; the substitution refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, phenyl, C1-C6 alkyl, C1-C6 haloalkyl, C 1- C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12 Aryl;

[0067] X is either S or O;

[0068] The definitions of R1, R2, R, and n are as described above.

[0069] In another preferred embodiment, R5 is a halogenated C6-C12 aryl, benzyl, p-methoxybenzyl, etc.

[0070] In another preferred embodiment, the method for preparing the monomer of formula I further includes the step of:

[0071]

[0072] (s0) In an inert solvent and in the presence of a base, compound 2 and compound 1 are reacted to give compound A;

[0073] In the formula,

[0074] R6 is selected from: substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C1-C6 alkyl carboxyl groups;

[0075] The substitution refers to substitution by one or more substituents selected from the group consisting of: halogen, hydroxyl, amino, -C1-C6 alkyl, -C1-C6 haloalkyl, -C1-C6 alkoxy, -C1-C6 haloalkoxy;

[0076] The definitions of R1, R2, R, R5, X, and n are as described above.

[0077] In another preferred embodiment, the method for preparing the monomer of formula I further includes the step of:

[0078] (s0-1) In an inert solvent, in the presence of a base, compound R-NH2 reacts with compound The reaction, followed by hydrolysis, yields compound 2;

[0079]

[0080] In the formula,

[0081] M is selected from: Cl, Br, I, OTs;

[0082] M' is selected from: C1-C6 alkyl, benzyl;

[0083] The definitions of R1, R2, R, and n are as described above.

[0084] In another preferred embodiment, the reaction temperature in step (s0) is 10-70°C; more preferably, it is 20°C-60°C.

[0085] In another preferred embodiment, the reaction time in step (s0) is 10 hours to 4 days.

[0086] In another preferred embodiment, in step (s0), the reaction time is generally 2-3 days at room temperature.

[0087] In another preferred embodiment, in step (s0), the reaction time is approximately 18 hours at 60°C.

[0088] In another preferred embodiment, step (s0) involves dissolving compound 2 and a base in an inert solvent, adding compound 1, and stirring to react. After the reaction is complete, the pH of the reaction solution is adjusted to approximately 3 with hydrochloric acid, extracted three times with ethyl acetate, and the organic phase is dried, concentrated, and purified by column chromatography to obtain compound 3.

[0089] In another preferred embodiment, in step (s0), the base is an inorganic base.

[0090] In another preferred embodiment, in step (s0), the base is independently selected from the group consisting of sodium hydroxide, potassium hydroxide, lithium hydroxide, potassium carbonate, sodium carbonate, cesium carbonate, sodium bicarbonate, or combinations thereof; preferably sodium hydroxide or sodium bicarbonate.

[0091] In another preferred embodiment, in step (s0), the inert solvent is independently selected from the group consisting of water (e.g., deionized water), methanol, ethanol, isopropanol, n-butanol, or combinations thereof; preferably water (e.g., deionized water), methanol, or combinations thereof.

[0092] In another preferred embodiment, the reaction temperature in step (s1) is 0℃±25℃.

[0093] In another preferred embodiment, the reaction time in step (s1) is 1-12 hours.

[0094] In another preferred embodiment, step (s1) involves dissolving compound A obtained in (s0) in an inert solvent, adding phosphorus halide at 0°C under inert gas protection, and reacting the mixture. After the reaction is complete, the solvent is removed, ethyl acetate is added to dissolve the compound, and the mixture is quickly washed three times with ice water. The organic phase is then dried, concentrated, and purified to obtain monomer of formula I.

[0095] In another preferred embodiment, in step (s1), the inert solvent is dry.

[0096] In another preferred embodiment, in step (s1), the inert solvent is independently selected from the group consisting of dichloromethane, tetrahydrofuran, ethyl acetate, dioxane, acetonitrile, or combinations thereof; preferably selected from the group consisting of dichloromethane, ethyl acetate, or combinations thereof.

[0097] In another preferred embodiment, in step (s1), the reaction is carried out under the protection of an inert gas; the inert gas is preferably nitrogen, argon, or a combination thereof.

[0098] In another preferred embodiment, in step (s1), the purification system is selected from the group consisting of ethyl acetate / n-hexane, ethyl acetate / petroleum ether, dichloromethane / n-hexane, dichloromethane / petroleum ether, tetrahydrofuran / n-hexane, tetrahydrofuran / petroleum ether, or combinations thereof, preferably selected from the ethyl acetate / n-hexane system.

[0099] In another preferred embodiment, the monomer of formula I is prepared using the method described above.

[0100] In a third aspect, the present invention provides a polymer or a salt thereof, wherein the monomer of the polymer is a monomer comprising formula (I) as described in the first aspect.

[0101]

[0102] in,

[0103] X is either S or O;

[0104] n is 1, 2, 3 or 4;

[0105] R is independently selected from the following group: C1-C, whether substituted or unsubstituted. 12 Alkyl, C1-C 12 Haloalkyl, C1-C 12 Alkyl hydroxyl, C1-C 12 Alkoxy, 2-12 heteroalkyl, C1-C 12 Alkyl sulfonyl, C2-C 12 alkenyl, C2-C 12 alkynyl group, C3-C 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 3-12 membered heterocyclic, C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester, Wherein, the substitution refers to being replaced by one or more R m replace;

[0106] Each R1 and R2 is independently selected from the following group, either substituted or unsubstituted: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, NR' a R' b C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m replace;

[0107] Alternatively, R1 and R2, together with the carbon atoms they are attached to, may form a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to the presence of one or more R atoms. m replace;

[0108] Alternatively, when n is 2, 3, or 4, the two R1s located on adjacent carbon atoms, together with the carbon atoms they are connected to, constitute a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to being formed by one or more R1s. m replace;

[0109] Each L is independently a bond, -CHR'1-, -O-, -S-, -CO-, -COO-, -S(=O)2-;

[0110] q is an integer between 1 and 10;

[0111] R'1 is independently selected from the following group of substituent or unsubstituted groups: H, amino, C1-C. 15 Alkyl, C1-C 15 Alkylamino, C6-C 15 Aryl, C2-C 15 alkenyl, C2-C 15 alkynyl group, C1-C 15 Alkyl hydroxyl, C1-C 15 Alkyl aldehyde group, C1-C 15 Alkyl ester group, thioC1-C 15 Alkyl ester group, -Rc-COO-Rc”, -Rc-CO-Rc”, -Rc-O-Rc”-, -Rc-S-Rc”, 5-15 membered heteroaryl, 5-12 membered heterocyclic group; wherein, the substitution refers to being replaced by one or more R m replace;

[0112] R' a 、R' b Ra and R b Each group is independently selected from the following group, whether substituted or unsubstituted: hydrogen, C1-C. 15 Alkyl, C1-C 15 Alkylamino, C2-C 15 alkenyl, C2-C 15 alkynyl group, C1-C 15 Alkyl hydroxyl, C1-C 15 Alkyl aldehyde group, C1-C 15 Alkyl sulfonyl, -Rc-COO-Rc”, -Rc-CO-Rc”, -Rc-O-Rc”-, -Rc-S-Rc”, C3-C 12 cycloalkyl, C4-C 12 Cycloalkenyl, 5-12 membered heterocyclic group, C6-C 12 aryl, 5-12 membered heteroaryl, tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenylmethoxycarbonyl (Fmoc), phthaloyl (Pht), acetyl (Ac), trifluoroacetyl (Tfa), benzyl (Bn), triphenylmethyl (Tr); or R a and R b It combines with the attached N atom to form a 3-8 substituted or unsubstituted heterocyclic group, or R' a and R' b The N atom attached to it combines to form a 3-8 substituted or unsubstituted heterocyclic group; wherein, the substitution refers to being formed by one or more R atoms. m replace;

[0113] Rc is independently selected from the following group of substituent or unsubstituted groups: none, C1-C 15 Alkylene, C2-C 15 alkenyl, C2-C 15 Ethyne group, C3-C 12 Cycloalkylene, C4-C 12 Cycloalkylene, 3-12 membered heterocyclic cycloalkylene, C6-C 12 arylene, 5-12 heteroarylene; wherein, the substitution refers to being replaced by one or more R m replace;

[0114] Rc” is independently selected from the following group of substituent or unsubstituted groups: C1-C 15 Alkyl, C1-C 15 Alkylamino, C2-C 15 alkenyl, C2-C 15 alkynyl group, C3-C 12 cycloalkyl, C4-C 12 Cycloalkenyl, 3-12 membered heterocyclic group, C6-C 12Aryl, 5-12 membered heteroaryl; wherein, the substitution refers to being replaced by one or more R m replace;

[0115] R m Selected from the following group (substituted or unsubstituted): halogen, hydroxyl, amino, phenyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl; wherein, R m Substitution in this context refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0116] Constraints: When n is 1 and R1 = R2 = H, R is...

[0117] When n is 2, X is 0 and R1 = R2 = H, R is not methyl, ethyl, or benzyl.

[0118] In another preferred embodiment, the polymer or a salt thereof comprises one or more repeating units represented by formula E.

[0119]

[0120] The definitions of R1, R2, n, and R are as described above.

[0121] In another preferred embodiment, the polymer or a salt thereof comprises one or more repeating units of formula E1.

[0122]

[0123] in,

[0124] R1, R2, R a R b The definitions of L and q are as described above.

[0125] In another preferred embodiment, the polymer or a salt thereof comprises one or more repeating units of formula E3.

[0126]

[0127] Where f is 0 or 1;

[0128] R 1a R 1b R 1c R 1d R 1e R 1f The definition is as described above.

[0129] In another preferred embodiment, the polymer or a salt thereof comprises repeating units of formula E and formula E'.

[0130]

[0131] In the formula,

[0132] n' and n are each independently 1, 2, 3 or 4; each R1 and R2 may be the same or different; R, R1 and R2 are defined as described above.

[0133] In another preferred embodiment, the polymer or a salt thereof contains the structure shown in Formula E6.

[0134]

[0135] In the formula,

[0136] m is an integer between 5 and 50000;

[0137] n and n” are each independently 1, 2, 3 or 4;

[0138] 0% < l ≤ 100%; 0% ≤ k < 100%; where y and z are calculated by dividing the corresponding number of repeating units by the total number of repeating units;

[0139] R1, R2, R”1, and R”2 are each independently selected from the following group, either substituted or unsubstituted: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 12 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, C1-C6 alkyl-5-12 heteroaryl, NR' a R' b C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m replace;

[0140] Alternatively, R1 and R2, together with the carbon atoms they are attached to, may form a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to the presence of one or more R atoms. m replace;

[0141] Alternatively, R”1 and R”2, together with the carbon atoms they are attached to, form substituted or unsubstituted 3-12 membered carbon rings or heterocycles; wherein, substitution refers to the presence of one or more R… m replace;

[0142] Alternatively, when n is 2, 3, or 4, the two R1s located on adjacent carbon atoms, together with the carbon atoms they are connected to, constitute a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to being formed by one or more R1s. m replace;

[0143] Constraints: When n is 1 and R1 = R2 = H, R is...

[0144] When n is 2, X is O and R1 = R2 = H, R is not methyl, ethyl, or benzyl;

[0145] Among them, L, q, R a R b 、R' a 、R' b , R and R m The definition is as described above.

[0146] In another preferred embodiment, the polymer or a salt thereof contains the structure shown in Formula E2.

[0147]

[0148] Where m is an integer between 5 and 50000;

[0149] n1, n2, n3, and n4 are each independently 1, 2, 3, or 4;

[0150] 0% ≤ w < 100%; 0% < x1 ≤ 100%; 0% ≤ y < 100%; 0% ≤ z < 100%; where w, x1, y, and z are calculated by dividing the corresponding number of repeating units by the total number of repeating units;

[0151] R7 is H or a substituted or unsubstituted group of the following: C1-C12 alkyl, C1-C12 haloalkyl, C1-C12 alkylenehydroxy, C1-C12 alkoxy, 2-12 heteroalkyl, C1-C12 alkylenesulfonyl, C2-C12 alkenyl, C2-C12 alkynyl, C3-C12 cycloalkyl, C6-C12 aryl, 5-12 heteroaryl, 3-12 heterocyclic, C1-C6 alkylene-C6-C12 aryl, C1-C6 alkylguanidine, C1-C6 alkylene ester, thioC1-C6 alkylene ester. Wherein, the substitution refers to being replaced by one or more R m replace;

[0152] Each L and q may be the same or different;

[0153] R1, R2, R a R b R mThe definitions of L and q are as described above.

[0154] In another preferred embodiment, the polymer or a salt thereof contains the structure shown in Formula E4.

[0155]

[0156] in,

[0157] n'2 is 1, 2, 3 or 4;

[0158] n'3 is 2, 3, or 4;

[0159] n'4 can be 1, 2, 3, or 4;

[0160] 0% ≤ x1 ≤ 100%; 0% ≤ y < 100%; 0% ≤ z < 100%, and x1 and y are not both 0; where x1, y, and z are calculated by dividing the corresponding number of repeating units by the total number of repeating units;

[0161] The definitions of R, R1, R2, R”1, and R”2 are as described above.

[0162] In another preferred example, w+x1+y+z=1.

[0163] In another preferred embodiment, m is an integer from 10 to 10000; more preferably, m is from 15 to 5000; more preferably, from 20 to 500; more preferably, from 20 to 50; more preferably, from 20 to 40.

[0164] In another preferred embodiment, the polymer or a salt thereof contains one or more of the following structural units:

[0165]

[0166]

[0167] Wherein, n6 is an integer from 5 to 50000, and the amino group contained in the structure also includes its various salt-forming forms, such as sulfonates, iodides, bromides, hydrochlorides, and trifluoroacetates; the carboxylic acid contained in the structure also includes its various salt-forming forms, such as sodium salts, potassium salts, and lithium salts.

[0168] In another preferred embodiment, n6 is an integer from 10 to 10000; more preferably, n6 is from 15 to 5000; more preferably, from 20 to 500; more preferably, from 20 to 50; more preferably, from 5 to 20 (i.e., 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19 or 20).

[0169] In another preferred embodiment, the polymer or its salt further comprises structural units selected from:

[0170]

[0171] Preferably, the polymer is selected from the group consisting of:

[0172]

[0173]

[0174] In the formula, r represents a random copolymer and b represents a block copolymer.

[0175] In another preferred embodiment, the salt of the polymer includes the salt formed by the polymer with an organic or inorganic acid. Preferably, the salt of the polymer is a sulfonate, iodide, bromide, hydrochloride, trifluoroacetate, sodium salt, potassium salt, or lithium salt of the polymer.

[0176] A fourth aspect of the present invention provides a method for preparing a polymer as described in the third aspect, comprising the steps of:

[0177] s) In an inert solvent, in the presence of an initiator, the intracyclic anhydride monomer of Formula I described in the first aspect is subjected to a polymerization reaction to obtain the polymer of the third aspect, wherein the monomer of Formula I and the polymer are as described above.

[0178] In another preferred embodiment, the method for preparing the polymer includes the steps of:

[0179] i) In an inert solvent, in the presence of an initiator, the anhydride monomers of formula I and I' as described above are polymerized to obtain the polymer shown in E6.

[0180]

[0181] In the formula,

[0182] m is an integer between 5 and 50000;

[0183] n and n” are each independently 1, 2, 3 or 4;

[0184] 0% < l ≤ 100%; 0% ≤ k < 100%; where y and z are calculated by dividing the corresponding number of repeating units by the total number of repeating units;

[0185] R1, R2, R”1, and R”2 are each independently selected from the following group, either substituted or unsubstituted: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C 12 cycloalkyl, C6-C 12Aryl, 5-12 membered heteroaryl, 5-12 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, C1-C6 alkyl-5-12 heteroaryl, NR' a R' b C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m replace;

[0186] Alternatively, R1 and R2, together with the carbon atoms they are attached to, may form a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to the presence of one or more R atoms. m replace;

[0187] Alternatively, R”1 and R”2, together with the carbon atoms they are attached to, form substituted or unsubstituted 3-12 membered carbon rings or heterocycles; wherein, substitution refers to the presence of one or more R… m replace;

[0188] Alternatively, when n is 2, 3, or 4, the two R1s located on adjacent carbon atoms, together with the carbon atoms they are connected to, constitute a substituted or unsubstituted 3-12 membered carbon ring or heterocycle; wherein, substitution refers to being formed by one or more R1s. m replace;

[0189] Constraints: When n is 1 and R1 = R2 = H, R is...

[0190] When n is 2 and R1 = R2 = H, R is not methyl, ethyl, or benzyl.

[0191] Among them, L, q, R a R b 、R' a 、R' b , R and R m The definition is as described above.

[0192] In another preferred embodiment, the polymer is a homopolymer, and the polymer is prepared by a method comprising the following steps:

[0193] i”) In an inert solvent, in the presence of an organic base initiator, any intracyclic anhydride monomer of formula (I) is subjected to a polymerization reaction to form the polymer;

[0194] The organic base is independently selected from: amines, amine salts, other organic bases, or combinations thereof;

[0195] The amine is selected from the group consisting of: or combinations thereof;

[0196] The salt of the amine is independently selected from the group consisting of: hydrochloride, hydrobromide, formate, acetate, or trifluoroacetate.

[0197] R m1 R m2 R m3 Each is independently selected from the following group: H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C 12 Aryl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl; wherein, the substitution refers to being affected by one or more R' m replace;

[0198] Among them, R' m Selected from the following groups, whether substituted or unsubstituted: C1-C6 alkyl, C6-C 12 Aryl, C2-C6 alkenyl, C2-C6 alkynyl, -N3, C1-C6 alkyl-(C=O)-O-, C1-C6 alkyl-(C=O)-N-, amino, hydroxyl, mercapto Q3-O-, Q4-S-, 5-6 membered heterocyclic groups, adamantane, calixpyrrole, cyclodextrin, polyethylene glycol; wherein, Q1 and Q2 are each independently selected from the following group: H, C1-C6 alkyl, C1-C6 alkyl-O-(C=O)-, C6-C 14 Aryl-C1-C6 alkyl-O-(C=O)-, and Q1 and Q2 are not both H; or Part of Q3 is independently selected from the following group: C1-C6 alkyl, C6-C 12 Aryl-C1-C6 alkyl; Q4 is independently selected from the group consisting of: C1-C6 alkyl, C6-C 12 Aryl-C1-C6 alkyl, C6-C 12 aryl-C1-C6 alkyl-(C=O)-O-; and R m1 and R m2 Not both H;

[0199] Or R m1 and R m2 The N atom adjacent to it constitutes a substituted or unsubstituted 5-12 membered heterocyclic group; the substitution refers to being substituted by one or more substituents selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy.

[0200] R” m Selected from: halogens, hydroxyl groups, amino groups, C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, C1-C6 haloalkoxy groups, C3-C8 cycloalkyl groups, and 3-8 membered heterocyclic groups;

[0201] R' m Substitution in C refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0202] In another preferred embodiment, Part of

[0203] In another preferred embodiment, the polymer is a copolymer, and the polymer is prepared by a method comprising the following steps:

[0204] (i-1) In an inert solvent, two or more of the intracyclic anhydride monomers of formula I (e.g., 2, 3 or 4) as described in the first aspect; and optionally one or more of the monomers of formula I',

[0205] (i-2) In the presence of an organic base initiator, a polymerization reaction is carried out to form a statisticcoplymer polymer;

[0206] Alternatively (i'-1) in an inert solvent, in the presence of an organic base initiator, the first monomer is first subjected to a polymerization reaction;

[0207] (i'-2) After the polymerization reaction in (i'-1) is completed, add the second monomer to carry out the polymerization reaction.

[0208] And optionally repeat step (i'-2) p times.

[0209] This results in the formation of block copolymer polymers;

[0210]

[0211] Where p is an integer ≥ 1;

[0212] The first monomer and the second monomer are different and are independently either an intracyclic anhydride monomer of formula I and I'.

[0213] The organic base is independently selected from: amines, amine salts, other organic bases, or combinations thereof;

[0214] The amine is selected from the group consisting of: R m1 NH 2 , or combinations thereof;

[0215] The salts of the amine are independently selected from: hydrochloride, hydrobromide, formate, acetate, or trifluoroacetate;

[0216] X, R1, R2, R”1, R”2, R, n, n”, R m1 R m2 R m3 The definition is as described above.

[0217] In another preferred embodiment, in step (i'-3), 50 ≥ p ≥ 1, preferably 20 ≥ p ≥ 2, and preferably p is 1, 2, 3, 4, 5, or 6.

[0218] In another preferred embodiment, the polymerization reaction is carried out in an environment with or without inert gas protection.

[0219] In another preferred embodiment, the polymerization reaction is carried out in any open or closed reactor.

[0220] In another preferred embodiment, the other organic base is selected from: DBU, HMDS, LiHMDS, NaHMDS, KHMDS, and EtONa.

[0221] In another preferred embodiment, the first monomer is any of the above-described Formula I monomers.

[0222] In another preferred embodiment, the second monomer is any of the I' monomers.

[0223] In another preferred embodiment, the first monomer is any of the above-described Formula I monomers, and the second monomer is a Formula I' monomer.

[0224] In another preferred embodiment, the I' monomer is selected from:

[0225] In another preferred embodiment, in the polymerization reaction, the second monomer is added first, and the first monomer is added after the reaction is complete.

[0226] In another preferred embodiment, in the polymerization reaction, after the first monomer is added, another first monomer is added after the reaction is complete.

[0227] In another preferred embodiment, in the polymerization reaction, after the first monomer is added and the reaction is complete, the second monomer is added.

[0228] In another preferred embodiment, after at least one first monomer participates in the polymerization reaction, and the reaction is complete, subsequent feeding includes any of the above-mentioned feeding sequences.

[0229] In another preferred embodiment, the inert solvent in the polymerization reaction is selected from the group consisting of tetrahydrofuran, DMF, DMAc, acetonitrile, dioxane, dimethyl sulfoxide, or combinations thereof. Tetrahydrofuran is preferred.

[0230] In a fifth aspect, the present invention provides a use of the polymer as described in the third aspect, said polymer being usable as an antibacterial, antifungal, antiviral, antimite, antitumor, cell adhesion promoter, tissue engineering agent, drug modifier, protein modifier, protein protectant, cell protectant, tissue and organ cryoprotectant, drug modifier, drug synergist, drug delivery agent, gene delivery and self-assembly agent, surface antifouling agent, surface antibacterial agent, surface modified material, and for modifying medical material substrates.

[0231] In another preferred embodiment, the medical material substrate is selected from the group consisting of PLA, PLGA, HA, PCL, PDS, PU, ​​PTFE, PVP, PVC, PDMS, PEEK, stainless steel, titanium, titanium alloy, and other possible substrate surfaces.

[0232] In another preferred embodiment, the modified medical material substrate refers to the polymer being able to modify the medical material substrate by physical (e.g., doping) or chemical methods.

[0233] In another preferred embodiment, the surface antifouling includes resistance to protein adsorption, cell, bacterial, fungal, and platelet adhesion.

[0234] In another preferred embodiment, the polymer further includes polymer derivatives, wherein the polymer derivatives refer to polymers containing amino groups that have been modified, wherein the amino groups are modified into guanidine groups, diguanidine groups, quaternary ammonium salts, etc.

[0235] In a sixth aspect, the present invention provides a polymerization method using a drug, a polymer, and a diffuser as initiators to initiate the polymerization of an anhydride monomer of formula I described in the first aspect.

[0236] In another preferred embodiment, the diffuser is selected from: polyamide-amine G0-G5 dendritic macromolecules (such as... Polypropyleneimine G0-G5 generation dendritic macromolecules (such as...)

[0237]

[0238] In another preferred embodiment, the drug is selected from: vancomycin, polymyxin, clofarabine, and fingolimod.

[0239] In another preferred embodiment, the polymer is selected from: oxazoline polymers with amino groups on their side chains, α-amino acid polymers with amino groups on their side chains, β-amino acid polymers with amino groups on their side chains, α-peptide polymers with amino groups on their side chains, β-peptide polymers with amino groups on their side chains, and γ-peptide polymers with amino groups on their side chains.

[0240] In another preferred embodiment, the polymer is selected from:

[0241]

[0242] n7 is an integer from 5 to 50000, x = 0.3-1 (e.g., 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1); the amino groups contained in the structure also include their various salt forms, such as sulfonates, iodides, bromides, hydrochlorides, and trifluoroacetates.

[0243] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description

[0244] none Detailed Implementation

[0245] Through long-term and in-depth research, the inventors have invented an intracyclic anhydride monomer as shown in Formula I, and prepared the corresponding polymer through ring-opening polymerization. This polymer can be widely used in biomedical fields such as antibacterial, drug delivery, drug modification, cell adhesion, gene delivery, self-assembly materials, antitumor, tissue engineering, surface antifouling, and cell cryopreservation. Based on the above findings, the inventors have completed this invention.

[0246] the term

[0247] In this invention, unless otherwise specified, the terms used have the general meanings known to those skilled in the art.

[0248] When a substituent is described using a conventional chemical formula written from left to right, it also includes chemically equivalent substituents obtained when the structural formula is written from right to left. For example, -CH2O- is equivalent to -OCH2-.

[0249] Throughout this specification, the terms “optionally substituted” or “may be substituted” indicate that the group may or may not be further substituted or fused with one or more non-hydrogen substituents (to form a polycyclic system). Substituents for suitable chemically appropriate specific functional groups will be apparent to those skilled in the art.

[0250] As used in this text, the term "alkyl" refers to a straight-chain or branched alkyl group containing a number of carbon atoms, wherein "C1-C..." 15"Alkyl" refers to a straight-chain or branched alkyl group having 1 to 15 carbon atoms, including alkyl groups with 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 carbon atoms. Alkyl groups are preferably, for example, C1-C2, C1-C3, C1-C4, C1-C5, C1-C6, C1-C7, C1-C8, C1-C9, or C1-C6. 10 , C2-C3, C2-C4, C2-C5, C2-C6, C3-C4, C3- C5, C3-C6, C3-C7, C3-C8, C4-C5, C4-C6 or C 5-6 Typical "alkyl" compounds include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, and isobutyl. Amyl, isopentyl, heptyl, 4,4-dimethylpentyl, octyl, 2,2,4-trimethylpentyl, nonyl, decyl, undecyl, dodecyl, etc. In this invention, alkyl also includes substituted alkyl groups. "Substituted alkyl" means that one or more positions in an alkyl group are substituted, particularly 1-4 substituents, which can be substituted at any position.

[0251] As used in the text, the term "C1-C" 15 "Alkoxy" refers to a straight-chain or branched alkoxy group having 1-15 carbon atoms, with C1-C2 atoms. 15 Alkyl-O- or -(CH2) p O(CH2) q - Structure, where p and q are each independently 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14, C1-C 15 Alkoxy groups include, but are not limited to, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, pentoxy, hexoxy, -(CH2)O(CH2)-, -(CH2)2O(CH2)-, -(CH2)2O(CH2)2-, etc., with ethoxy being preferred. C1-C 15 Alkoxy groups also include substituted C1-C groups. 15 Alkyl group.

[0252] As used in the text, the term "C1-C" 15 "alkyl hydroxyl" refers to -C1-C 15 alkylene -OH, -C1-C 15 Alkylenes have the definition described above, C1-C 15 Alkyl hydroxyl groups include, but are not limited to, -CH2OH and -CH2CH2OH. (C1-C) 15 Alkyl hydroxyl groups also include substituted C1-C hydroxyl groups. 15 Alkyl hydroxyl.

[0253] As used in the text, the term "C1-C"15 "alkylsulfonyl" refers to C1-C 15 Alkyl S(=O)2-.

[0254] As used in the text, the term "C1-C" 15 Alkylene-C6-C 15 "Aryl" refers to -C1-C 15 Alkyl-C6-C 15 Aryl groups, such as -CH2CH2CH2Ph ​​and -Bn.

[0255] As used in the text, the term "C1-C" 15 "alkyl ester group" refers to C1-C 15 Alkyl C(=O)-O- or -(=O)-O-C1-C 15 alkyl.

[0256] As used in the text, the term "thiocto-C1-C" 15 "alkyl ester group" refers to C1-C 15 Alkyl C(=S)-O- or -(=S)-O-C1-C 15 alkyl.

[0257] As used in this text, the term "guanidinyl" refers to NHC(=NH)NH-.

[0258] As used in the text, the term "C1-C" 15 "alkylcarboxyl" refers to -C1-C 15 Alkyl COOH, such as -CH2COOH, -CH2CH2COOH, -CH2CH2CH2COOH, -CH2CH2CH2CH2COOH, preferably -CH2COOH and -CH2CH2COOH. The alkyl group may be substituted.

[0259] As used in the text, the term "C1-C" 15 "alkyl aldehyde" refers to -C1-C 15 Alkyl CHO, such as -CH2CHO, -CH2CH2CHO, -CH2CH2CH2CHO, -CH2CH2CH2CH2CHO, preferably -CH2CHO and -CH2CH2CHO. The alkyl group may be substituted.

[0260] As used in the text, the term "C1-C" 15 "alkylamino" refers to -C1-C 15 Alkyl-NH2, such as -CH2-NH2, -CH2CH2-NH2, -CH2CH2CH2-NH2, -CH2CH2CH2CH2-NH2, preferably -CH2-NH2, -CH2CH2-NH2. The H in the amino group (-NH2) may also be substituted.

[0261] As used in this text, the term "alkenyl" refers to a straight-chain or branched hydrocarbon having at least two carbon atoms and at least one double bond. Alkenyl groups can include any number of carbon atoms, where "C2-C15 alkenyl" refers to a straight-chain or branched hydrocarbon having 2-15 carbon atoms and at least one double bond, such as C2, C15, etc. 2- C3, C 2- C4, C 2- C5, C 2- C6, C 2- C7, C 2- C8、 C 2- C9, C 2- C 10 C3, C 3- C4, C 3- C5, C 3- C6, C4, C 4- C5, C 4- C6, C5, C 5- C6 and C6. The alkenyl group may have any suitable number of double bonds, including but not limited to 1, 2, 3, 4, 5 or more. Examples of alkenyl groups include, but are not limited to, vinyl (vinyl group)), propenyl, isopropenyl, 1-butenyl, 2-butenyl, isobutenyl, butadienyl, 1-pentenyl, 2-pentenyl, isopentenyl, 1,3-pentadienyl, 1,4-pentadienyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 1,3-hexadienyl, 1,4-hexadienyl, 1,5-hexadienyl, 2,4-hexadienyl, or 1,3,5-hextrienyl. Like the alkyl groups described above, the alkenyl group may be substituted or unsubstituted.

[0262] As used in this text, the term "alkynyl" refers to a straight-chain or branched hydrocarbon having at least two carbon atoms and at least one triple bond. Alynyl groups can include any number of carbon atoms, "C2-C..." 15 "Alkyne group" refers to a straight-chain or branched hydrocarbon with 2-15 carbon atoms and at least one triple bond, such as C2, C3, ... 2- C3, C 2- C4, C 2- C5, C 2- C6, C 2- C7, C 2- C8, C 2- C9, C 2- C 10 C3, C 3- C4, C 3- C5, C 3- C6, C4, C 4- C5, C 4- C6, C5, C 5-C6 and C6. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, isobutynyl, sec-butynyl, butyrynyl, 1-pentynyl, 2-pentynyl, isopentenynyl, 1,3-pentadiynyl, 1,4-pentadiynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 1,3-hexadiynyl, 1,4-hexadiynyl, 1,5-hexadiynyl, 2,4-hexadiynyl, or 1,3,5-hextriynyl. Like the alkyl groups described above, alkynyl groups can be substituted or unsubstituted.

[0263] The term "aryl" refers to an aromatic cyclic hydrocarbon group, in which "C6-C" 15 "Aryl" refers to an aromatic cyclic hydrocarbon compound group containing 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 ring carbon atoms, having 1-5 rings, especially monocyclic and bicyclic groups, such as phenyl, biphenyl, or naphthyl. Any compound containing two or more aromatic rings (bicyclic, etc.) may have its aromatic rings linked by single bonds (e.g., biphenyl) or fused (e.g., naphthalene, anthracene, etc.). "Substituted aryl" refers to an aryl group where one or more positions are substituted, especially 1-3 substituents, which can be substituted at any position.

[0264] As used in this text, the term "heteroaryl" refers to a heteroaryl system containing 1-3 atoms selected from N, O, and S atoms, wherein "5-15-membered heteroaryl" refers to a 5-15-membered heteroaryl system containing 1-3 atoms selected from N, O, and S atoms. The heteroaryl group is preferably a 5- to 10-membered ring, more preferably a 5- or 6-membered ring, and includes, but is not limited to, pyrroleyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, thiadiazolyl, isothiazolyl, furanyl, pyridinyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl, triazolyl, and tetrazolyl. "Heteroaryl" can be substituted or unsubstituted. When substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, deuteralkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, alkylthio, alkylamino, halogen, amino, nitro, hydroxyl, mercapto, cyano, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkylthio, oxo, carboxyl, and carboxylic acid ester.

[0265] As used in this text, the term "cycloalkyl" refers to a fully saturated cyclic hydrocarbon group having several carbon atoms, wherein "C3-C..." 15 "Cycloalkyl" refers to a fully saturated cyclic hydrocarbon group having 3-15 carbon atoms, preferably C3-C4, C3-C5, C3-C6, C3-C7, C3-C8, C3-C9, or C3-C6. 10 "Replacing C3-C" 15"Cycloalkyl" refers to a cycloalkyl group in which one or more positions are substituted, particularly 1-4 substituents, which can be substituted at any position, including but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. In this invention, "cycloalkyl" is intended to include "substituted cycloalkyl".

[0266] As used in this text, the term "cycloalkenyl" refers to an unsaturated cyclic hydrocarbon group with 1-3 double bonds having several carbon atoms, wherein "C4-C 15 "Cycloalkenyl" refers to an unsaturated cyclic hydrocarbon group with 1-3 double bonds and 4-15 carbon atoms, preferably C6-C. 10 Cycloalkenyl, C4-C6 cycloalkenyl, including but not limited to cyclobutenyl, cyclopentenyl, and cyclohexenyl.

[0267] As used in this text, the term "heterocyclic group" refers to a fully saturated or partially unsaturated cyclic group having several (greater than or equal to 3) ring atoms and 1-3 heteroatoms. Specifically, "5-15 membered heterocyclic group" refers to a fully saturated or partially unsaturated cyclic group having 5-15 ring atoms and 1-3 heteroatoms (including, but not limited to, 3-7 membered monocyclic, 6-11 membered bicyclic, or 8-12 membered tricyclic systems). Nitrogen or sulfur atoms may be oxidized, and nitrogen atoms may be quaternized. Heterocyclic groups can be attached to any heteroatom or carbon atom residue in a ring or cyclic molecule. Typical monocyclic heterocycles include, but are not limited to, nitrogen-containing heterocyclic butyl, pyrrolyl, oxoheterocyclic butyl, pyrazolinyl, imidazolinyl, imidazolinyl, oxazolinyl, isoxazolinyl, thiazolinyl, isothiazolinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, 2-oxopiperidinyl, 2-oxopiperidinyl, 2-oxopiperylyl, hexahydroacoxaneyl, 4-piperidinoneyl, tetrahydropyranyl, morpholinyl, thiomorpholinyl, thiomorpholinyl sulfoxide, thiomorpholinyl sulfone, 1,3-dioxaneyl, and tetrahydro-1,1-dioxothiophene, etc. Polycyclic heterocyclic groups include spirocyclic, fused-ring, and bridged-ring heterocyclic groups; wherein the spirocyclic, fused-ring, and bridged-ring heterocyclic groups involved are optionally connected to other groups via single bonds, or further cyclically linked to other cycloalkyl, heterocyclic, aryl, and heteroaryl groups via any two or more atoms on the ring; the heterocyclic group can be substituted or unsubstituted, and when substituted, the substituent is preferably one or more of the following groups, independently selected from alkyl, deuteralkyl, haloalkyl, alkoxy, haloalkoxy, alkenyl, alkynyl, alkylthio, alkylamino, halogen, amino, nitro, hydroxyl, mercapto, cyano, cycloalkyl, heterocyclic, aryl, heteroaryl, cycloalkylthio, oxo, carboxyl, and carboxylic acid ester groups. Heterocyclic groups include, but are not limited to: tetrahydropyrrole, tetrahydrofuranyl, piperidinyl, piperazine, etc.

[0268] In this invention, "carbon ring or heterocycle" alone or as part of other groups refers to a monocyclic or bicyclic saturated, partially saturated or aromatic carbon ring (e.g., cycloalkyl, cycloalkenyl, phenyl, etc. as described above), or a monocyclic or bicyclic saturated, partially saturated or aromatic heterocycle (e.g., heteroalkyl, heterocyclic, heteroaryl, etc. as described above). A 3- to 12-membered carbon ring or heterocycle refers to a carbon ring or heterocycle containing 3-12 ring atoms, preferably a 4- to 8-membered carbon ring or heterocycle, more preferably a 5- to 6-membered carbon ring or heterocycle. Examples of carbocyclic or heterocyclic compounds include, but are not limited to: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopentenyl, cyclohexenyl, cyclopentadienyl, cyclohexadienyl, oxacyclobutane, aziridine, tetrahydro-2H-pyranyl, piperidinyl, piperazinyl, tetrahydrofuranyl, morpholinyl, pyrrolylyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, triazinyl, pyrroleyl, pyrazolyl, imidazolyl, (1,2,3)-triazolyl and (1,2,4)-triazolyl, tetrazolyl, furanyl, thiophenyl, isoxazolyl, thiazolyl, oxazolyl, etc.

[0269] When a substituent is a non-terminal substituent or when a related group loses one hydrogen atom, it becomes a subunit of the corresponding group, usually a divalent group. For example, an alkyl group losing one hydrogen atom becomes an alkylene group (e.g., methylene, ethylene, propylene, isopropylene). ), butylide (such as) ), pentylene (e.g.) ), hexyl (such as) ), subheptagen (such as ) etc.), cycloalkyl corresponding to cycloalkylene (e.g.: (etc.), heterocyclic groups corresponding to subheterocyclic groups (such as: ), cycloalkyl corresponding heterocyclic groups (e.g.: (etc.), alkoxy groups corresponding to alkoxide groups (-CH2O-, -CH2CH2-O- CH2-, -CH2OCH2CH2CH2-, etc.).

[0270] As described in this article, the term "multiple" refers to two or more, such as 2, 3, 4 or 5.

[0271] As described herein, the compounds of this invention can be expanded with any number of substituents or functional groups. Generally, the term "substitution," whether preceding or following the term "optional," in this invention includes the general formula for substituents, meaning the replacement of a hydrogen radical with a substituent of a specified structure. When multiple positions in a particular structure are replaced by multiple specific substituents, each position of the substituent can be the same or different. The term "substitution" as used herein includes all permissible substitutions in organic compounds. In a broad sense, permissible substituents include acyclic, cyclic, branched-unbranched, carbocyclic, and heterocyclic, aromatic and non-aromatic organic compounds. In this invention, heteroatomic nitrogen may be supplemented with hydrogen substituents or any permissible organic compound described above to complete its valence state. Furthermore, this invention is not intended to limit permissible substituted organic compounds in any way.

[0272] In this invention, unless otherwise specified, the groups comprise corresponding substituents and subunits, such as: alkyl groups comprising substituted alkyl groups, cycloalkyl groups comprising substituted cycloalkyl groups, aryl groups comprising substituted aryl groups, heteroaryl groups comprising substituted heteroaryl groups, heterocyclic groups comprising substituted heterocyclic groups, etc. Those skilled in the art will understand that the combinations of substituents contemplated in this invention are stable or chemically feasible combinations. Typical substitutions include, but are not limited to, one or more of the following groups: such as hydrogen, deuterium, halogens (e.g., monohalogen substituents or polyhalogen substituents, the latter such as trifluoromethyl or alkyl groups containing Cl3), nitrile, nitro, oxygen (e.g., =O), trifluoromethyl, trifluoromethoxy, cycloalkyl, C2-C6 alkenyl, C4-C10 cycloalkenyl, C2-C6 ynyl, heterocyclic, aryl, heteroaryl, OR a SR a S(=O)R e S(=O)2R e P(=O)2R e S(=O)2OR e ,P(=O)2OR e NR b R c NR b S(=O)2R e NR b P(=O)2R e S(=O)2NR b R c P(=O)2NR b R c C(=O)OR d C(=O)R a C(=O)NR b R c OC(=O)R a OC(=O)NRb R c NR b C(=O)OR e ,NR d C(=O)NR b R c NR d S(=O)2NR b R c NR d P(=O)2NR b R c NR b C(=O)R a , or NR b P(=O)2R e , where R appears here a It can independently represent hydrogen, deuterium, C1-C6 alkyl, C3-C8 cycloalkyl, C2-C6 alkenyl, C3-C10 cycloalkenyl, C2-C6 ynyl, 3-8 membered heterocyclic, 5-14 membered heteroaryl, or C6-C14 aryl, R b R c and R d It can independently represent hydrogen, deuterium, C1-C6 alkyl, C3-C8 cycloalkyl, 3-8 membered heterocyclic, 5-14 membered heteroaryl, or C6-C14 aromatic ring, or R b and R c It can form heterocycles together with N atoms; R e The term can independently represent hydrogen, C1-C6 alkyl, C3-C8 cycloalkyl, C2-C6 alkenyl, C3-C6 cycloalkenyl, C2-C6 ynyl, 3-8 membered heterocyclic, 5-14 membered heteroaryl, or C6-C14 aryl. The aforementioned typical substituents, such as alkyl, cycloalkyl, alkenyl, cycloalkenyl, ynyl, heterocyclic, heteroaryl, or aryl, and their corresponding substituents and subunits, can be optionally substituted, wherein the alkyl, cycloalkyl, cycloalkenyl, heterocyclic, heteroaryl, or aryl groups have the definitions described above.

[0273] As used herein, the term “substituted” means that any one or more hydrogen atoms on a specified atom are substituted by a substituent selected from the specified substituents, provided that the substitution does not exceed the normal valence of the specified atom, and the resulting compound is stable, i.e., can be isolated, characterized, and tested for bioactivity.

[0274] Unless otherwise stated, it is assumed that any heteroatom in a suboptimal valence state has enough hydrogen atoms to compensate for its valence state.

[0275] As used in this text, the terms "statistic coplymer" or "random" refer to polymers formed by the random linkage of two or more monomers polymerized simultaneously, wherein at least one monomer has an amino or hydroxyl side chain.

[0276] As used in this text, the term "block polymer" refers to a polymer formed by the sequential polymerization of two or more monomers, which consists of different chain segments connected together, wherein at least one monomer has an amino or hydroxyl side chain.

[0277] In this invention, "0.1-0.7" refers to any decimal between 0.1 and 0.7, preferably 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, or 0.7.

[0278] The structural formula or name of the monomer given in this invention may only be an example of a specific configuration or may not be given. The monomer may also include all other configurations corresponding to the given configuration.

[0279] The intracyclic anhydride monomer of the present invention

[0280] The intracyclic anhydride monomer of the present invention has the structure shown in formula (I).

[0281]

[0282] In the formula,

[0283] The definitions of X, n, R1, R2, and R are as described above.

[0284] Preferably, the monomer has the structure shown in Formula II.

[0285]

[0286] Where X, R1, R2, L, q, R a and R b The definition is as described above.

[0287] Preferably, the monomer has the structure shown in Formula III.

[0288]

[0289] Among them, Z, f, R 1a R 1b R 1c R 1d R 1e R 1f The definition is as described above.

[0290] Preferably, R is selected from: substituted or unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, 2-6 heteroalkyl, C1-C6 alkylsulfonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, substituted or unsubstituted C6-C 10 Aryl (e.g., phenyl), substituted or unsubstituted 5-10 membered heteroaryl, substituted or unsubstituted 3-8 membered heterocyclic, C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester, Wherein, the substitution refers to being replaced by one or more R m Replace, R m Selected from the following group (substituted or unsubstituted): halogen, hydroxyl, amino, phenyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 10 Aryl, 5-10 heteroaryl, of which, R m Substitution in C refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0291] Preferably, each R1 and R2 is independently selected from the group consisting of: hydrogen, substituted or unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, 5-10 membered heteroaryl, 5-6 membered heterocyclic, NR' a R' b C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m Replace; R m Selected from: halogens, hydroxyl groups, amino groups, substituted or unsubstituted C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, C1-C6 haloalkoxy groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C6-C6 cycloalkyl groups. 10 aryl, substituted or unsubstituted 5-10 heteroaryl groups; wherein, R m Substitution in C refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0292] Preferably, the monomer has a structure as shown in Formula IV or V:

[0293]

[0294] In the formula, t is an integer between 0 and 5;

[0295] A, R 1c R 1d R 1e R 1f The definitions of Z and f are as described above.

[0296] Preferably, the monomer has the structure shown in Formula VI.

[0297]

[0298] In the formula,

[0299] R 1a R 1b R 1c R 1d The definitions of Z are as described above.

[0300] Preferably, in formulas III-VI above, Z is selected from the following group of substituted or unsubstituted groups: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, 3-8 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester Wherein, the substitution refers to being replaced by one or more R m replace;

[0301] R 1a R 1b R 1c R 1d R 1e R 1f Each of the following is independently hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 haloalkyl, substituted or unsubstituted C1-C6 alkoxy, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, or C1-C6 alkyl-C6-C 12 Aryl, NR' a R' b Wherein, the substitution refers to being replaced by one or more R m replace;

[0302] Rm Selected from the following groups, whether substituted or unsubstituted: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12 Aryl, 5-12 membered heteroaryl, or 3-12 membered heterocyclic; wherein, R m Substitution in this context refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0303] Among them, L, q, R' a 、R' b R a and R b The definition is as described above.

[0304] Preferably, in formulas III-VI above, Z is selected from the following group, whether substituted or unsubstituted: C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C2-C6 alkenyl, C2-C6 alkynyl, C3-C8 cycloalkyl, 3-8 membered heterocyclic, C1-C6 alkyl-C6-C 12 Aryl, Wherein, the substitution refers to being replaced by one or more R m replace;

[0305] Among them, L, q, R m R a and R b The definition is as described above.

[0306] Preferably, in the above formulas, Partially -(CH2) r -、-(CH2) r' -S(=O)2-、-(CH2) r' -C(=O)-, where r and r' are each an independent integer from 1 to 16, preferably r and r' are each an independent integer of 2, 3, 4, 5, 6, 7 or 8.

[0307] Preferably, R' a 、R' b R a and R bEach is independently selected from the group consisting of: hydrogen, substituted or unsubstituted C1-C6 alkyl, C1-C6 alkylamino, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, C1-C6 alkylhydroxy, C1-C6 alkylaldehyde, C1-C6 alkylsulfonyl, -Rc-COO-Rc”, -Rc-CO-Rc”, -Rc-O-Rc”-, -Rc-S-Rc”, substituted or unsubstituted C3-C 12 Cycloalkyl, substituted or unsubstituted C4-C 10 Cycloalkenyl, substituted or unsubstituted 5-12 membered heterocyclic groups, substituted or unsubstituted C6-C 10 Aryl, substituted or unsubstituted 5-10 membered heteroaryl, tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenemethyloxycarbonyl (Fmoc), phthaloyl (Pht), acetyl (Ac), trifluoroacetyl (Tfa), benzyl (Bn), triphenylmethyl (Tr), wherein the substitution refers to being substituted by one or more R m Replace; R m Selected from the following group, whether substituted or unsubstituted: halogen, hydroxyl, amino, phenyl, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl; wherein, R m Substitution in C refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0308] The method for preparing intracyclic anhydride monomers of the present invention

[0309] The method for preparing the intracyclic anhydride monomer of Formula I in this invention comprises the following steps:

[0310] s1) In an inert solvent, compound A is reacted with phosphorus halide to obtain monomer of formula I;

[0311]

[0312] in,

[0313] R5 is selected from the following group, either substituted or unsubstituted: C1-C 12 Alkyl, C6-C 12 Aryl, 3-12 membered heterocyclic, 5-12 membered heteroaryl, 3-8 membered cycloalkyl; the substitution refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, phenyl, C1-C6 alkyl, C1-C6 haloalkyl, C 1- C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12Aryl; preferably, R5 is a halogenated C6-C 12 Aryl, benzyl, p-methoxybenzyl, etc.

[0314] X is either S or O;

[0315] The definitions of R1, R2, R, and n are as described above.

[0316] Preferably, the method for preparing the intracyclic anhydride monomer includes the following steps:

[0317]

[0318] In an inert solvent, compound B is reacted with phosphorus halide to give monomer of formula III;

[0319] in,

[0320] R5 is selected from the following group of substituent or unsubstituted groups: C1-C6 alkyl, benzyl;

[0321] The substitution refers to being replaced by one or more substituents selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 alkoxy;

[0322] R 1a R 1b R 1c R 1d R 1e R 1f The definitions of f are as described above.

[0323] Preferably, in steps s1) and s1'), the inert solvent is selected from dichloromethane, ethyl acetate, chloroform, etc.

[0324] Preferably, in steps s1) and s1'), the phosphorus halide is selected from phosphorus trichloride, phosphorus tribromide, phosphorus pentachloride, etc.

[0325] Preferably, the method for preparing the monomer of formula I further includes the step of:

[0326]

[0327] (s0) In an inert solvent and in the presence of a base, compound 2 and compound 1 are reacted to give compound A;

[0328] In the formula,

[0329] R6 is selected from: substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C1-C6 alkyl carboxyl groups;

[0330] The substitution refers to substitution by one or more substituents selected from the group consisting of: halogen, hydroxyl, amino, -C1-C6 alkyl, -C1-C6 haloalkyl, -C1-C6 alkoxy, -C1-C6 haloalkoxy;

[0331] The definitions of R1, R2, R, R5, and n are as described above.

[0332] Preferably, the method for preparing the monomer of formula I further includes the step of:

[0333] In an inert solvent, in the presence of a base (such as triethylamine), compound R-NH2 reacts with compound... The reaction, followed by hydrolysis, yields compound 2;

[0334]

[0335] The definitions of M, M', R1, R2, R, R5, and n are as described above. Preferably, M is bromine and M' is a C1-C3 alkyl group.

[0336] The polymer of the present invention

[0337] In this invention, the polymer comprises peptide-like polymers, peptides, and hybrid polymers of peptides.

[0338] In this invention, the polymer comprises a salt of the polymer.

[0339] Preferably, the monomer of the polymer is a polymer comprising a monomer of Formula I as shown above.

[0340]

[0341] in,

[0342] The definitions of X, n, R1, R2, and R are as described above.

[0343] Preferably, the polymer comprises one or more repeating units of formula E.

[0344]

[0345] The definitions of R1, R2, n, and R are as described above.

[0346] Preferably, the polymer comprises one or more repeating units of formula E1.

[0347]

[0348] in,

[0349] R1, R2, R a R b The definitions of L and q are as described above.

[0350] Preferably, the polymer comprises one or more repeating units of formula E3.

[0351]

[0352] Where f is 0 or 1;

[0353] R 1a R 1b R 1c R 1d R 1e R 1f The definition is as described above.

[0354] Preferably, the polymer comprises repeating units of formula E and formula E'.

[0355]

[0356] In the formula,

[0357] n' and n are each independently 1, 2, 3 or 4; each R1 and R2 may be the same or different; R, R1 and R2 are defined as described above.

[0358] Preferably, the polymer is a hybrid polymer of peptides and peptides, wherein the peptide component contains all natural or non-natural amino acids.

[0359] In another preferred embodiment, the amino acid may be selected from the group consisting of glycine, alanine, valine, leucine, isoleucine, phenylalanine, tryptophan, tyrosine, aspartic acid, asparagine, glutamic acid, lysine, glutamine, methionine, serine, threonine, cysteine, proline, histidine, arginine, and derivatives derived from the above amino acids.

[0360] In another preferred embodiment, the polymer contains the structure shown in Formula E6.

[0361]

[0362] In the formula,

[0363] m is an integer from 5 to 50000; preferably, m is an integer from 10 to 10000; more preferably, m is 15 to 5000; more preferably, 20 to 500; more preferably, 20 to 50; more preferably, 20 to 40.

[0364] n and n” are each independently 1, 2, 3 or 4;

[0365] 0% < l ≤ 100%; 0% ≤ k < 100%; where y and z are calculated by dividing the corresponding number of repeating units by the total number of repeating units;

[0366] The definitions of R1, R2, R”1, R”2, and R are as described above.

[0367] Preferably, R1, R2, R”1, and R”2 are each independently selected from the group consisting of: hydrogen, substituted or unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy, C1-C6 alkylsulfonyl, substituted or unsubstituted C2-C6 alkenyl, substituted or unsubstituted C2-C6 alkynyl, substituted or unsubstituted C3-C8 cycloalkyl, substituted or unsubstituted C6-C 10 Aryl, 5-10 membered heteroaryl, 5-6 membered heterocyclic, NR' a R' b C1-C6 alkylguanidine, C1-C6 alkyl ester, thioC1-C6 alkyl ester; wherein, the substitution refers to being replaced by one or more R m Replace; R m Selected from: halogens, hydroxyl groups, amino groups, substituted or unsubstituted C1-C6 alkyl groups, C1-C6 haloalkyl groups, C1-C6 alkoxy groups, C1-C6 haloalkoxy groups, substituted or unsubstituted C3-C8 cycloalkyl groups, substituted or unsubstituted C6-C6 cycloalkyl groups. 10 aryl, substituted or unsubstituted 5-10 heteroaryl groups; wherein, R m Substitution in C refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 haloalkoxy, and C3-C8 cycloalkyl.

[0368] In this invention, the salts that the polymer may form are also within the scope of this invention. Unless otherwise stated, the polymers in this invention are understood to include their salts. As used herein, the term "salt" refers to a salt that is formed in an acidic or basic form by an inorganic or organic acid and a base.

[0369] The polymers of this invention contain basic segments, such as amino groups, which may form salts with organic or inorganic acids. Typical acids that can form salts include acetates (such as acetic acid or trihaloacetic acids, such as trifluoroacetic acid), adipates, alginates, ascorbic acid salts, aspartate salts, benzoates, benzenesulfonates, hydrogen sulfates, borates, butyrates, citrates, camphor salts, camphor sulfonates, cyclopentanepropionate, diethylene glycol salts, dodecyl sulfates, ethanesulfonates, fumarates, glucono-2-phosphates, glycerol phosphates, hemisulfates, heptarates, hexanoates, hydrochlorides, and hydrobromic acid salts. Hydroiodates, hydroxyethanesulfonates (e.g., 2-hydroxyethanesulfonate), lactates, maleates, methanesulfonates, naphthalenesulfonates (e.g., 2-naphthalenesulfonate), nicotinates, nitrates, oxalates, pectates, persulfates, phenylpropionates (e.g., 3-phenylpropionates), phosphates, picrates, neopentanoates, propionates, salicylates, succinates, sulfates (e.g., those formed with sulfuric acid), sulfonates, tartrates, thiocyanates, toluenesulfonates such as p-toluenesulfonate, dodecanoates, etc.

[0370] Some polymers of this invention may contain acidic fragments, including but not limited to carboxylic acids, which may form salts with various organic or inorganic bases. Typical base-formed salts include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, and salts formed with organic bases (such as organic amines), such as benzylamine, dicyclohexylamine, hepatopanylamine (a salt formed with N,N-di(dehydroabietic)ethylenediamine), N-methyl-D-glucosamine, N-methyl-D-glucosamide, tert-butylamine, and salts formed with amino acids such as arginine, lysine, etc.

[0371] Method for preparing the polymer of the present invention

[0372] In this invention, the synthesis of the polymer as described above includes the following steps:

[0373] s) In an inert solvent, in the presence of an initiator, the intracyclic anhydride monomer of Formula I as described above is polymerized to obtain the polymer as described above.

[0374] Preferably, the synthesis of the polymer comprises the following steps:

[0375] i) In an inert solvent, in the presence of an initiator, the anhydride monomers of formula I and I' as described above are polymerized to obtain the polymer shown in E6.

[0376]

[0377] In the formula,

[0378] The definitions of m, n, n”, l, k, R1, R2, R”1, R”2, and R are as described above.

[0379] Preferably, the preparation of the polymer includes the following steps:

[0380] s') In an inert solvent, in the presence of an initiator, monomer I-2 and optionally monomers I-1, I-3, I-4, or combinations thereof are polymerized to obtain the polymer E2.

[0381] The structures of monomers I-1, I-2, I-3, I-4 and polymer E2 are shown below:

[0382]

[0383] in,

[0384] In equations I-1, I-2, I-3, I-4, and E2, each L and q may be the same or different, and each R1 and R2 may be the same or different.

[0385] m, w, x1, y, z, n1, n2, n3, n4, R1, R2, L, q, R a R b The definitions of R7 and X are as described above.

[0386] Preferably, the peptide-like polymer is a hybrid polymer of peptides and peptides, and the preparation of the hybrid polymer of peptides and peptides includes the following steps:

[0387] In an inert solvent, in the presence of an initiator, monomer I and optionally monomer M are polymerized to obtain the peptide-like and peptide hybrid polymers E4 and E5; wherein the structures of monomer M and polymers E4 and E5 are as follows:

[0388]

[0389] Among them, m, w, x1, y, z, n1, n2, n3, R1, R2, R1', R2', R1”, R2”, L, q, R a R b The definitions of R7 and X are as described above.

[0390] Preferably, the polymer is a homopolymer, and its preparation method includes the following steps:

[0391] i”) In an inert solvent, in the presence of an organic base initiator, any intracyclic anhydride monomer of formula (I) is subjected to a polymerization reaction to form the polymer;

[0392] The organic base is independently selected from: amines, amine salts, other organic bases, or combinations thereof;

[0393] The amine is selected from the group consisting of: R m1 NH2, or combinations thereof;

[0394] The salt of the amine is independently selected from the group consisting of: hydrochloride, hydrobromide, formate, acetate, or trifluoroacetate.

[0395] R m1 R m2 R m3 The definition is as described above.

[0396] Preferably, the polymer is a copolymer, and its preparation method includes the following steps:

[0397] (i-1) In an inert solvent, two or more of the intracyclic anhydride monomers of formula I (e.g., 2, 3, or 4); and optionally one or more of the monomers of formula I', are mixed.

[0398] (i-2) In the presence of an organic base initiator, a polymerization reaction is carried out to form a statisticcoplymer polymer;

[0399] Alternatively (i'-1) in an inert solvent, in the presence of an organic base initiator, the first monomer is first subjected to a polymerization reaction;

[0400] (i'-2) After the polymerization reaction in (i'-1) is completed, add the second monomer to carry out the polymerization reaction.

[0401] And optionally repeat step (i'-2) p times.

[0402] This results in the formation of block copolymer polymers;

[0403]

[0404] Where p is an integer ≥ 1;

[0405] The first monomer and the second monomer are different and are independently either an intracyclic anhydride monomer of formula I and I'.

[0406] The organic base is independently selected from: amines, amine salts, other organic bases, or combinations thereof;

[0407] The amine is selected from the group consisting of: R m1 NH2, or combinations thereof;

[0408] The salts of the amine are independently selected from: hydrochloride, hydrobromide, formate, acetate, or trifluoroacetate;

[0409] X, R1, R2, R”1, R”2, R, n, n”, R m1 R m2 R m3 The definition is as described above.

[0410] Uses of the polymer of this invention

[0411] The polymers of this invention possess antibacterial, antifungal, antiviral, anti-mite, antitumor, cell adhesion-promoting, tissue engineering, drug modification, protein modification, protein protection, cell protection, tissue and organ cryoprotection, drug modification, drug synergy, drug delivery, gene delivery and self-assembly materials, surface antifouling, surface antibacterial, and surface modification functions, and can be used to modify medical material substrates (such as PLA, PLGA, HA, PCL, PDS, PU, ​​PTFE, PVP, PVC, PDMS, PEEK, stainless steel, titanium, titanium alloys and other possible substrate surfaces).

[0412] Preferably, the antibacterial material is in solution form or surface coating form.

[0413] Preferably, the antibacterial target is a microorganism such as bacteria and fungi, which may include Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Acinetobacter baumannii (A. baumannii), Enterobacter aerogenes (E. aerogenes), Klebsiella pneumoniae (K. pneumoniae), Serratia marcescens (S. marcescens), Enterobacter Cloacae (E. cloacae), Bacillus subtilis (B. subtilis), Staphylococcus aureus (S. aureus), Staphylococcus epidermidis (S. epidermidis), Candida albicans (C. albicans), and Cryptococcus neoformans (C. neoformans).

[0414] Preferably, the antibacterial use includes antimicrobial activity against free microbial cells, biofilms, and spores.

[0415] Preferably, the polymer is used to treat tumors.

[0416] Preferably, the tumor is selected from the group consisting of: melanoma, skin cancer, glioma, mesothelioma, lymphoma, leukemia, breast cancer, ovarian cancer, cervical cancer, glioblastoma, multiple myeloma, prostate cancer, Burkitt lymphoma, head and neck cancer, colon cancer, colorectal cancer, non-small cell lung cancer, small cell lung cancer, esophageal cancer, gastric cancer, pancreatic cancer, hepatobiliary cancer, gallbladder cancer, small bowel cancer, rectal cancer, kidney cancer, bladder cancer, prostate cancer, penile cancer, urethral cancer, testicular cancer, vaginal cancer, uterine cancer, thyroid cancer, parathyroid cancer, adrenal cancer, pancreatic endocrine carcinoma, carcinoid tumor, bone cancer, retinoblastoma, Hodgkin lymphoma, non-Hodgkin lymphoma, Kaposi's sarcoma, multicentric Kastelman's disease, AIDS-related primary exudative lymphoma, neuroectodermal tumors, or rhabdomyosarcoma.

[0417] The main advantages of this invention are:

[0418] 1. This invention is the first to synthesize α-NNCA and α-NNTA monomers with amino groups in their side chains. Then, α-peptide polymers with amino groups in their side chains are synthesized by ring-opening polymerization, as well as hybrid polymers of α-peptides and peptides prepared by copolymerization with NCA or NTA monomers. This invention fundamentally solves the traditional problem of synthesizing functional α-peptide polymers with amino groups in their side chains. Furthermore, the synthesized α-peptide polymers and hybrid polymers of α-peptides and peptides have multiple functions such as surface antibacterial, solution antibacterial, self-assembly materials, cell adhesion, and antitumor activity.

[0419] 2. The new β-NNTA or γ-NNTA monomers and corresponding peptide polymers and hybrid peptides prepared by this invention can rapidly and easily synthesize a large number of peptide and hybrid peptide libraries, which can be used for screening for antibacterial activity, antitumor activity, cell adhesion activity and other bioactivities, as well as polymer function studies of other peptides.

[0420] 3. The α-NNCA and α-NNTA monomers with amino groups in the side chain of this invention are novel monomers synthesized for the first time. Compared with the α-NNCA and α-NNTA monomers without amino groups in the side chain reported by other patents, the amino functional groups in the side chain give the polymerized peptides positive charge and water solubility, endowing the peptides with important advantages in biological activities such as antibacterial activity, antitumor activity, and cell adhesion activity screening.

[0421] 4. The β-NNTA and γ-NNTA monomers in this invention are novel monomers designed and synthesized for the first time. Compared with existing β-NNCA monomers, the β-NNTA and γ-NNTA of this invention show significant advantages in monomer stability and side chain structure diversity.

[0422] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are weight percentages and parts by weight. Unless otherwise specified, the experimental materials and reagents used in the following embodiments are commercially available. The present invention will be further illustrated below with reference to specific embodiments.

[0423] Example

[0424] Example A-1. Synthesis of α-NCA monomer with side chain amino group

[0425]

[0426] Triphosgene (6.5 g, 22 mmol) was dissolved in dry tetrahydrofuran and set aside for later use. Under nitrogen protection, the triphosgene solution was added to a suspension of N-ε-tert-butoxycarbonyl-L-lysine (12.3 g, 50 mmol) and α-pinene (20.5 mL, 132 mmol) in dry tetrahydrofuran in an ice-water bath, and the mixture was stirred. The mixture was then transferred to an oil bath at 50 °C and stirred under nitrogen for about 2 hours. The solvent was then removed by rotary evaporation under reduced pressure. The product was then dissolved in ethyl acetate, quenched with ice water and ice-saturated brine respectively, and dried with anhydrous magnesium sulfate. The crude product was recrystallized three times with dry ethyl acetate and n-hexane to obtain 7.5 g of colorless crystals.

[0427] Example A-2 Synthesis of hydrophobic α-NTA monomer

[0428]

[0429] S-ethoxythiocarbonyl mercaptoacetic acid (9.0 g, 50.0 mmol) was dissolved in a flask containing 500 mL of deionized water. Solid sodium bicarbonate (16.8 g, 200.0 mmol) was added to the flask and stirred until dissolved. Then, L-glutamic acid-5-benzyl ester (11.8 g, 50.0 mmol) was added and stirred to react. The reaction was carried out at 50 °C for about 48 hours. Then, 1 M hydrochloric acid solution was slowly added dropwise to adjust the pH to about 3. The organic matter in the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and then quenched with saturated brine and dried with anhydrous magnesium sulfate. The crude product was purified by recrystallization from ethyl acetate and n-hexane to obtain 12 g of white solid intermediate.

[0430] Under nitrogen protection, a dry white intermediate (1.6 g, 5.0 mmol) was dissolved in a dry dichloromethane solution (50 mL). The mixture was stirred in an ice bath at 0 °C, and then phosphorus tribromide solution (1.4 g, 5.0 mmol) was added dropwise. After the addition was complete, the temperature was raised to 25 °C, and the reaction was continued for 6 hours. After the reaction was completed, the organic phase was washed three times with deionized water at 0 °C. The organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was purified by recrystallization from ethyl acetate and n-hexane under nitrogen protection, yielding a white solid product of 1.0 g.

[0431] Example A-3 Synthesis of hydrophobic β-NTA monomer

[0432]

[0433] The experimental method was the same as in Example A-2 above, except that 3-amino-3-phenylpropionic acid (8.2 g, 50 mmol) was used instead of L-glutamic acid-5-benzyl ester (11.8 g, 50 mmol).

[0434] Example 1: Synthesis of α-NNCA monomers with amino groups in the side chain

[0435]

[0436] N-Benzyloxycarbonyl ethylenediamine hydrochloride (3.9 g, 20.0 mmol) and triethylamine (2.2 g, 22.0 mmol) were weighed and dissolved in 150 mL of dichloromethane. Ethyl bromoethyl (3.3 g, 20.0 mmol) was then slowly added dropwise at room temperature. The reaction mixture was heated to 55 °C for 12 h. The reaction solution was washed three times with 100 mL of deionized water, dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain a yellow oily intermediate compound (3.0 g, yield 53.5%). The intermediate compound (2.8 g, 10.0 mmol) was dissolved in 100 mL of methanol, and di-tert-butyl dicarbonate (2.2 g, 10.0 mmol) was added. The mixture was reacted at 60 °C for 12 h. After drying the solvent, intermediate compound 1 was...

[0437] Intermediate 1 was redissolved in a mixture of tetrahydrofuran / methanol / water (60 mL / 40 mL / 20 mL), and then 40.0 mmol of 1M sodium hydroxide solution was added dropwise. After stirring at room temperature for 5 h, the pH of the reaction solution was adjusted to about 7 with 1M hydrochloric acid solution. After concentration, the intermediate compound before ring closure was extracted by column chromatography. Under nitrogen protection, the dried oily yellow intermediate (2.0 g, 5.7 mmol) was dissolved in a dry dichloromethane solution (100 mL). The mixture was stirred under ice bath conditions at 0 °C, and then phosphorus tribromide solution (1.5 g, 5.7 mmol) was added dropwise. After the addition was completed, the temperature was raised to room temperature and the reaction was continued for 1 hour. After the reaction was completed, the organic phase was washed twice with deionized water at 0 °C, dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent to obtain the crude product. Under nitrogen protection, the crude product was purified by recrystallization from dichloromethane and n-hexane to obtain a white solid product 2 (0.8 g, yield 50.7%). 1 H NMR (600MHz, CDCl3) δ7.36-7.30 (m, 5H), 5.34 (br, 1H), 5.06 (s, 2H), 4.16 (s, 2H), 3.46 (t, J = 5.7Hz, 2H), 3.38 (t, J = 6Hz, 2H). 13 C NMR (150MHz, CDCl3): δ165.58,157.09,153.02,136.26,128.71,128.42,128.18,67.19,49.34, 43.82,38.32.HRESI-MS: m / z calculated for C 13 H 14 N₂NaO₅[M+Na] + :301.0800; Found: 301.0801.

[0438] Example 2: Synthesis of α-NNCA monomers with trifluorobenzyl side chains

[0439]

[0440] 15.3 g (87.3 mmol) of 4-(trifluoromethyl)benzylamine was weighed and added to a round-bottom flask containing 300 mL of CH2Cl2 and a stir bar. After uniform dispersion, triethylamine (13.35 mL, 96.3 mmol) and ethyl bromoacetate (9.8 mL, 87.3 mmol) were slowly added sequentially under ice bath conditions. The reaction mixture was then heated at 55 °C for 12 h. The reaction solution was washed three times with 100 mL of deionized water, dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain a yellow oily intermediate compound (8.0 g, yield 35.0%). The intermediate compound (6.5 g, 25.0 mmol) was dissolved in 250 mL of methanol, and di-tert-butyl dicarbonate (11.0 g, 50.0 mmol) was added. The mixture was reacted at 60 °C for 12 h, and the solvent was dried to obtain intermediate 3.

[0441] Intermediate compound 3 was redissolved in a mixture of tetrahydrofuran / methanol / water (60 mL / 40 mL / 20 mL), and then 4 g of 1M sodium hydroxide solution was added dropwise. After stirring at room temperature for 5 h, the pH of the reaction solution was adjusted to approximately 7 with 1M hydrochloric acid solution. After concentration, the intermediate compound (7.7 g) before ring closure was extracted by column chromatography. Under nitrogen protection, a white intermediate (1.9 g, 5.7 mmol) was dissolved in a dry dichloromethane solution (100 mL). The mixture was stirred under an ice bath at 0 °C, and then phosphorus tribromide solution (1.5 g, 5.7 mmol) was added dropwise. After the addition was complete, the temperature was raised to room temperature and the reaction continued for 2 h. After the reaction was completed, the organic phase was washed twice with deionized water at 0 °C, dried over anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. Under nitrogen protection, the crude product was purified by recrystallization from dichloromethane and n-hexane to give a white solid product 4 (0.8 g, yield 54%). 1 H NMR (600MHz, CDCl3): δ7.66 (d, J = 7.9 Hz, 2H), 7.43 (d, J = 7.9 Hz, 2H), 4.63 (s, 2H), 4.00 (s, 2H). HREI-MS:m / z calculated for C 11 H8F3NO3[M] + :259.0456; Found:259.0455.

[0442] Example 3: Synthesis of α-NNTA monomers with amino groups in the side chain

[0443]

[0444] N-Benzyloxycarbonylethylenediamine hydrochloride (3.9 g, 20.0 mmol) and triethylamine (2.2 g, 22.0 mmol) were weighed and dissolved in 150 mL of dichloromethane. Ethyl bromoethyl (3.3 g, 20.0 mmol) was then slowly added dropwise at room temperature. The reaction mixture was heated to 55 °C for 12 h. The reaction solution was washed three times with 100 mL of deionized water, dried over anhydrous magnesium sulfate, filtered, concentrated, and purified by column chromatography to obtain a yellow oily intermediate compound (3.0 g, yield 53.5%). The intermediate compound was redissolved in a mixture of tetrahydrofuran / methanol / water (60 mL / 40 mL / 20 mL), and then 40.0 mmol of 1 M sodium hydroxide solution was added dropwise. After stirring at room temperature for 5 h, the pH of the reaction solution was adjusted to approximately 7 with 1 M hydrochloric acid solution. Concentration yielded the hydrolyzed intermediate compound 5.

[0445] S-ethoxythiocarbonyl mercaptoacetic acid (1.8 g, 10.1 mmol) was dissolved in a 50 mL N,N-dimethylformamide flask. Triethylamine (3.0 g, 30.3 mmol) and DMAP (0.3 g, 2.0 mmol) were added to the flask and stirred until dissolved. Then, hydrolyzed intermediate 5 (2.5 g, 10.1 mmol) was added and stirred to react. The reaction was carried out at room temperature for about 48 hours. Then, 1 M hydrochloric acid solution was slowly added dropwise to adjust the pH to about 3. The organic matter in the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and then quenched with saturated brine and dried with anhydrous magnesium sulfate. The crude product was rapidly purified by petroleum ether and ethyl acetate system to obtain a white solid (1.7 g, yield 49%). Under nitrogen protection, a dry white solid (1.7 g, 5.0 mmol) was dissolved in a dry dichloromethane solution (120 mL). The mixture was stirred in an ice bath at 0 °C, and then phosphorus tribromide solution (1.3 g, 5.0 mmol) was added dropwise. After the addition was complete, the mixture was brought to room temperature and the reaction continued for 3 hours. After the reaction was completed, the organic phase was washed three times with deionized water at 0 °C. The organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was purified by recrystallization from ethyl acetate and n-hexane under nitrogen protection to give a white solid product 6 (1.1 g, yield 73%). 1 H NMR (400MHz, CDCl3): δ7.34-7.38 (m, 5H), 5.09 (s, 3H), 4.28 (s, 2H), 3.64 (t, J = 5.6, 2H), 3.44 (dd, J = 5.6, 2H). 13C NMR (100MHz, CDCl3): δ 193.65, 166.24, 156.92, 136.3, 128.73, 128.44, 128.26, 67.23, 60.33, 44.05, 38.76.

[0446] Example 4: Synthesis of β-NNTA monomers with amino-containing side chains

[0447]

[0448] N-Benzyloxycarbonyl ethylenediamine hydrochloride (15.0 g, 65 mmol) was dissolved in 300 mL of ethanol, and triethylamine (18 mL, 130 mmol) was added. The mixture was stirred under ice bath conditions at 0 °C, and then tert-butyl acrylate (14.2 g, 68 mmol) was added dropwise. After the addition was complete, the temperature was raised to 25 °C and the reaction was carried out for 24 hours. After the reaction was completed, the organic phase was washed three times with deionized water, dried over anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was rapidly purified using a petroleum ether and ethyl acetate system to obtain a pale yellow oily intermediate (10.5 g, yield 50%). Intermediate 1 (10.5 g) was added to trifluoroacetic acid (10 mL) and stirred at room temperature. 100 mL of deionized water was added to the reaction solution, and the mixture was washed three times with dichloromethane. The aqueous phase was evaporated to dryness to obtain intermediate 7 (8.7 g, yield >99%).

[0449] S-ethoxythiocarbonyl mercaptoacetic acid (9.0 g, 50.0 mmol) was dissolved in a 200 mL N,N-dimethylformamide flask. Triethylamine (25 mL, 184.2 mmol) and DMAP (1.5 g, 10.0 mmol) were added to the flask and stirred until dissolved. Then, intermediate 7 (13.3 g, 50.0 mmol) was added. The mixture was stirred under nitrogen protection for 48 hours. Then, 1 M hydrochloric acid solution was slowly added dropwise to adjust the pH to about 3. The organic matter in the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and then quenched with saturated brine and dried with anhydrous magnesium sulfate. The crude product was rapidly separated and purified using a petroleum ether and ethyl acetate system to obtain a yellow oily intermediate (3.1 g, yield 17.5%). Under nitrogen protection, a dry, oily yellow intermediate (1.8 g, 5.1 mmol) was dissolved in a dry dichloromethane solution (100 mL). The mixture was stirred in an ice bath at 0 °C, and then phosphorus tribromide solution (0.57 mL, 6.1 mmol) was added dropwise. After the addition was complete, the temperature was raised to 25 °C and the reaction was continued for 3 hours. After the reaction was completed, the organic phase was washed three times with deionized water at 0 °C. The organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent to obtain the crude product. The crude product was purified by recrystallization with ethyl acetate and n-hexane under nitrogen protection to obtain a white solid product 8 (1.3 g, yield 83%).1 H NMR (400MHz, CDCl3): δ 7.30-7.37(m,5H,Ph),5.09(s,2H,PhCH2),3.68(t,J=6.0Hz,2H,NCH2),3.59(t,J=6.0Hz, 2H,N HCH2 CH2CO), 3.44 (q, J = 6.0 Hz 2H, NC H2 CH2NH),2.78(t,J=6.0Hz,2H, NHCH2 CH2 CO). 13 C NMR (100MHz, CDCl3): δ196.75,163.78,156.91,136.42,128.74,128.45, 128.23,67.12,48.87,44.82,40.84,39.10.

[0450] Example 5: Synthesis of β-NNTA monomer with p-fluorobenzyl side chain

[0451]

[0452] 8.1 g (65 mmol) of p-fluorobenzylamine was dissolved in 300 mL of dichloromethane, and 18 mL (130 mmol) of triethylamine was added. The mixture was stirred and mixed under ice bath conditions at 0 °C. Then, ethyl bromopropionate (12.3 g (68 mmol) was added dropwise. After the addition was complete, the temperature was raised to 25 °C and the reaction was carried out for 24 hours. After the reaction was completed, the organic phase was washed three times with deionized water, dried over anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was rapidly purified using a petroleum ether and ethyl acetate system to obtain a pale yellow oily intermediate (5.7 g, yield 39%). The intermediate (5.7 g) was redissolved in a mixture of tetrahydrofuran / methanol / water (60 mL / 40 mL / 20 mL), and then 130 mmol of 1 M sodium hydroxide solution was added dropwise. After stirring at room temperature for 5 h, the pH of the reaction solution was adjusted to about 7 with 1 M hydrochloric acid solution. After concentration, the hydrolyzed intermediate compound 9 (5.0 g, yield >99%) was obtained directly.

[0453] S-ethoxythiocarbonyl mercaptoacetic acid (7.3 g, 40.4 mmol) was dissolved in a flask containing 100 mL of deionized water. Sodium hydroxide (4.8 g, 121.2 mmol) was added to the flask and stirred until dissolved. Then, intermediate 9 (8.0 g, 40.4 mmol) was added and stirred to react. The reaction was carried out at room temperature for about 48 hours. Then, 1 M hydrochloric acid solution was slowly added dropwise to adjust the pH to about 3. The organic matter in the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and then quenched with saturated brine and dried with anhydrous magnesium sulfate. The crude product was rapidly separated and purified using a petroleum ether and ethyl acetate system to obtain a white solid (3.6 g, yield 31%). Under nitrogen protection, a dry white solid (3.3 g, 11.6 mmol) was dissolved in a dry dichloromethane solution (120 mL). The mixture was stirred in an ice bath at 0 °C, and then phosphorus tribromide solution (1.1 mL, 11.6 mmol) was added dropwise. After the addition was complete, the mixture was brought to room temperature and the reaction continued for 3 hours. After the reaction was completed, the organic phase was washed three times with deionized water at 0 °C. The organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was purified by recrystallization from ethyl acetate and n-hexane under nitrogen protection, yielding a white solid product 10 (2.0 g, yield 72%). 1 H NMR (400MHz, CDCl3): δ7.29-7.31(m,2H,Ph),7.05-7.09(m,2H,Ph),4.71(s,2H,PhCH2), 3.51(t,J=6.0Hz,2H,NCH2),2.76(t,J=6.0Hz,2H,NHCH2CH2CO).EI-MS:m / z calculated for C 11 H 10 FNO2S: 239.04; Found: 239.1.

[0454] Example 6: Synthesis of β-NNTA monomer with cyclopropyl side chain

[0455]

[0456] Cyclopropylamine (9.4 g, 164 mmol) was dissolved in 700 mL of dichloromethane, and triethylamine (25 mL, 178 mmol) was added. The mixture was stirred under ice bath conditions at 0 °C, and then ethyl bromopropionate (29.7 g, 164 mmol) was added dropwise. After the addition was complete, the temperature was raised to 25 °C and the reaction was carried out for 24 hours. After the reaction was completed, the organic phase was washed three times with deionized water, dried over anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was rapidly purified using a petroleum ether and ethyl acetate system to obtain a pale yellow oily intermediate (7.2 g, yield 28%). The intermediate compound was then redissolved in a mixture of tetrahydrofuran / methanol / water (60 mL / 40 mL / 20 mL), and then 7.3 g of 1 M sodium hydroxide solution was added dropwise. After stirring at room temperature for 5 hours, the pH of the reaction solution was adjusted to approximately 7 with 1 M hydrochloric acid solution, and the solvent was removed by vortexing to obtain intermediate compound 11.

[0457] S-ethoxythiocarbonyl mercaptoacetic acid (3.6 g, 20.2 mmol) was dissolved in a flask containing 100 mL of deionized water. Sodium hydroxide (2.4 g, 60.0 mmol) was added to the flask and stirred until dissolved. Then, intermediate compound 11 (2.6 g, 20.2 mmol) was added and stirred to react. The reaction was carried out at room temperature for about 48 hours. Then, 1 M hydrochloric acid solution was slowly added dropwise to adjust the pH to about 3. The organic matter in the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and then quenched with saturated brine and dried with anhydrous magnesium sulfate. The crude product was rapidly separated and purified using a petroleum ether and ethyl acetate system to obtain a white solid (3.6 g, yield 82%). Under nitrogen protection, a dry white solid (2.5 g, 11.6 mmol) was dissolved in a dry dichloromethane solution (120 mL). The mixture was stirred in an ice bath at 0 °C, and then phosphorus tribromide solution (1.1 mL, 11.6 mmol) was added dropwise. After the addition was complete, the mixture was brought to room temperature and the reaction continued for 1 hour. After the reaction was completed, the organic phase was washed three times with deionized water at 0 °C. The organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was purified by recrystallization from ethyl acetate and n-hexane under nitrogen protection to give a white solid product 12 (1.6 g, yield 82%). 1 H NMR (400MHz, CDCl3): δ3.65-3.68 (t, J=6.0Hz, 2H, NCH2), 2.77-2.85 (m, 3H, COCH2 and NCH),0.92-0.97(m,2H,NCHCH2),0.75-0.79(m,2H,NCHCH2). 13C NMR (100MHz, CDCl3): δ197.23,164.18,45.62,41.51,32.20,8.00.HRESI-MS: m / z calculated for C7H9NNaO2S[M+Na] + :194.0252; Found:194.0251.

[0458] Example 7: Synthesis of β-NNTA monomer of side-chain thiophene

[0459]

[0460] 3-Aminoethylthiophene (20.9 g, 164 mmol) was dissolved in 700 mL of dichloromethane, and triethylamine (25 mL, 178 mmol) was added. The mixture was stirred under ice bath conditions at 0 °C, and then ethyl bromopropionate (29.7 g, 164 mmol) was added dropwise. After the addition was complete, the temperature was raised to 25 °C and the reaction was carried out for 24 hours. After the reaction was completed, the organic phase was washed three times with deionized water, dried over anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was rapidly purified using a petroleum ether and ethyl acetate system to obtain a pale yellow oily intermediate (13.4 g, yield 36%). The intermediate compound was then redissolved in a mixture of tetrahydrofuran / methanol / water (120 mL / 80 mL / 40 mL), and a 1M sodium hydroxide solution containing 9.4 g was added dropwise. After stirring at room temperature for 5 h, the pH of the reaction solution was adjusted to about 7 with 1M hydrochloric acid solution. The aqueous phase was extracted three times with 200 mL of ethyl acetate, and the organic phase was dried over anhydrous magnesium sulfate and filtered. The solvent was then removed by vortexing to obtain intermediate compound 13 (11.4 g, yield 97%).

[0461] S-ethoxythiocarbonyl mercaptoacetic acid (3.6 g, 20.2 mmol) was dissolved in a flask containing 100 mL of deionized water. Sodium hydroxide (2.4 g, 60.0 mmol) was added to the flask and stirred until dissolved. Then, intermediate compound 13 (4.0 g, 20.2 mmol) was added and stirred to react at room temperature for about 48 hours. Then, 1 M hydrochloric acid solution was slowly added dropwise to adjust the pH to about 3. The organic matter in the aqueous phase was extracted three times with ethyl acetate. The organic phases were combined and then quenched with saturated brine and dried with anhydrous magnesium sulfate. The crude product was rapidly separated and purified using a petroleum ether and ethyl acetate system to obtain a white solid (3.9 g, yield 67%). Under nitrogen protection, a dry white solid (3.3 g, 11.6 mmol) was dissolved in a dry dichloromethane solution (120 mL). The mixture was stirred in an ice bath at 0 °C, and then phosphorus tribromide solution (1.1 mL, 11.6 mmol) was added dropwise. After the addition was complete, the mixture was brought to room temperature and the reaction continued for 1 hour. After the reaction was completed, the organic phase was washed three times with deionized water at 0 °C. The organic phase was dried with anhydrous magnesium sulfate, filtered, and concentrated to remove the solvent, yielding a crude product. The crude product was purified by recrystallization from ethyl acetate and n-hexane under nitrogen protection, yielding a white solid product 14 (2.4 g, yield 85%). 1 H NMR (400MHz, CDCl3): δ7.18-7.20 (dd, J1=4.8Hz, J2=0.8Hz, 1H), 6.88- 6.96(m,2H),3.82(t,J=6.8Hz,2H),3.42(t,J=6.0Hz,2H),3.20(t,J=6.4Hz,2H),2.63(t,J=6.0Hz,2H). 13 CNMR (100MHz, CDCl3): δ196.96,162.54,140.31,127.30,126.06,124.51, 52.37,45.71,40.84,28.37.

[0462] Example 8: Preparation of α-peptide homopolymers with side-chain amino groups by polymerization of α-NNCA monomers initiated by p-tert-butylbenzylamine

[0463]

[0464] In a nitrogen-protected glove box, accurately weigh p-tert-butylbenzylamine (163.3 mg, 1.0 mmol) and prepare a 1 M solution with dry N,N-dimethylformamide for later use.

[0465] Accurately weigh the α-NNCA monomer with the side-chain amino group and prepare 1 mL of 1 M tetrahydrofuran solution. Then add 50 μL of 1 M p-tert-butylbenzylamine solution and seal the container. Remove the reaction flask from the glove box and stir the reaction at 60 °C for 4 days.

[0466] In the above reaction mixture, 45 mL of cold n-hexane was added. The precipitated white flocculent precipitate was collected by centrifugation, dried under a nitrogen stream, and redissolved in tetrahydrofuran (2.0 mL). Then, a large amount of cold n-hexane (45 mL) was added, and precipitation occurred. This dissolution-precipitation process was repeated three times to obtain 210 mg of α-peptide polymers with protected side-chain amino groups.

[0467] The molecular weight (Mn) and molecular weight distribution (PDI) of the polymer were determined by gel permeation chromatography (GPC) to be 4900 and 1.1, respectively.

[0468] 210 mg of α-peptide polymer with protected side-chain amino groups was obtained, and 2 mL of (33 wt.%) hydrobromic acid / acetic acid solution and 2 mL of trifluoroacetic acid were added. After reacting for 6 h, the polymer was dried under a nitrogen stream, and then 45 mL of frozen diethyl ether was added to precipitate a white precipitate. The dissolution-precipitation process was repeated three times to obtain α-peptide polymer with deprotected side-chain amino groups. After filtration and lyophilization, the polymer was used for antibacterial activity testing.

[0469] Example 9: Preparation of α-peptide homopolymers by open-air polymerization of α-NNTA monomers initiated by p-tert-butylbenzylamine.

[0470]

[0471] The polymerization reaction was similar to that in Example 8, except that it was carried out under open conditions. 1 mL of a 1M solution of α-NNTA monomer with a side-chain amino group and 50 μL of a 1M solution of p-tert-butylbenzylamine were mixed and stirred at 60°C for 4 days. The reaction was then repeated three times using a dissolution-precipitation process with tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain α-peptide polymers with protected side-chain amino groups.

[0472] The polymer was identified by gel permeation chromatography (GPC) and its molecular weight Mn = 6500 and molecular weight distribution PDI = 1.1.

[0473] Example 10: Preparation of α-peptide homopolymers with thiol-terminated groups by polymerization of α-NNCA monomers initiated by 2-triphenylmethylmercaptoethylamine.

[0474]

[0475] Similar to Example 8, in a nitrogen-protected glove box, 1 mL of a 1M concentration of α-NNCA monomer with side-chain amino groups and 50 μL of a 1M concentration of 2-triphenylmethylmercaptoethylamine solution were mixed and stirred for 4 days at 60°C. The reaction was then repeated three times using a dissolution-precipitation process with tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain 195 mg of α-peptide polymer with protected side-chain amino groups.

[0476] The molecular weight (Mn) and molecular weight distribution (PDI) of the polymer were determined by gel permeation chromatography (GPC) to be 4900 and 1.1, respectively.

[0477] 195 mg of α-peptide polymer with protected side-chain amino groups was obtained, and 2 mL of (33 wt.%) hydrobromic acid / acetic acid solution and 2 mL of trifluoroacetic acid were added. 40 μL of triethylsilane was also added. After reacting for 6 h, the polymer was dried under a nitrogen stream, and then 45 mL of frozen diethyl ether was added to precipitate a white precipitate. The dissolution-precipitation process was repeated three times to obtain the α-peptide polymer with deprotected side-chain amino groups. After filtration and lyophilization, the polymer was used for surface antibacterial activity testing.

[0478] Example 11: Preparation of α-peptide homopolymers with naphthyl groups by 1-naphthylmethylamine-initiated polymerization of α-NNCA monomers.

[0479]

[0480] Similar to Example 8, 1 mL of 1M α-NNCA monomer with side-chain amino groups and 50 μL of 1M 1-naphthylmethylamine solution were mixed and stirred for 4 days at 60°C under nitrogen protection. The reaction was then repeated three times by dissolution-precipitation with tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain 205 mg of α-peptide polymer with protected side-chain amino groups.

[0481] The molecular weight (Mn) and molecular weight distribution (PDI) of the polymer were determined by gel permeation chromatography (GPC) to be 5100 and 1.1, respectively.

[0482] 205 mg of α-peptide polymer with protected side-chain amino groups was obtained, and 2 mL of (33 wt.%) hydrobromic acid / acetic acid solution and 2 mL of trifluoroacetic acid were added. After reacting for 6 h, the polymer was dried under a nitrogen stream, and then 45 mL of frozen diethyl ether was added to precipitate a white precipitate. The dissolution-precipitation process was repeated three times to obtain α-peptide polymer with deprotected side-chain amino groups. After filtration and lyophilization, the polymer was used for assembly performance testing.

[0483] Example 12: Preparation of β-peptide homopolymers with p-fluorobenzyl side chains by polymerization of β-NNTA monomers initiated by p-tert-butylbenzylamine

[0484]

[0485] The polymerization reaction was similar to that in Example 8. In a nitrogen-protected glove box, 1 mL of a 0.5 M solution of p-fluorobenzyl β-NNTA monomer with a side chain and 50 μL of a 0.5 M solution of p-tert-butylbenzylamine in N,N-dimethylformamide were mixed and stirred at room temperature for 4 days. The reaction was then repeated three times via a dissolution-precipitation process using tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain 77 mg of a β-peptide polymer with a p-fluorobenzyl side chain.

[0486] The polymer was identified by gel permeation chromatography (GPC) with a DP of 20 and a molecular weight distribution PDI of 1.1.

[0487] Example 13: Preparation of β-peptide homopolymers with p-fluorobenzyl side chains by open-air polymerization of β-NNTA monomers initiated by p-tert-butylbenzylamine.

[0488]

[0489] The polymerization reaction was similar to that in Example 12, except that it was carried out under open conditions. 1 mL of a 0.5 M N,N-dimethylformamide solution of p-fluorobenzyl β-NNTA monomer with a side chain concentration of 0.5 M and 50 μL of an N,N-dimethylformamide solution of p-tert-butylbenzylamine with a side chain concentration of 0.5 M were mixed and stirred at 60°C for 2 days. The reaction was then repeated three times using a dissolution-precipitation process with tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain 71 mg of a β-peptide polymer with a p-fluorobenzyl side chain.

[0490] The polymer was identified by gel permeation chromatography (GPC) with a DP of 19 and a molecular weight distribution (PDI) of 1.1. These results confirm that β-NNTA polymerization can be successfully carried out under open conditions, demonstrating the advantages of this polymerization method in terms of experimental operating conditions.

[0491] Example 14: Preparation of β-peptide homopolymers with p-fluorobenzyl side chains by open-air polymerization of β-NNTA monomers initiated by 3A-amino-3A-deoxy-(2AS,3AS)-β-cyclodextrin hydrate.

[0492]

[0493] Under open conditions, 1 mL of a 0.5 M N,N-dimethylformamide solution of p-fluorobenzyl β-NNTA monomer with a side chain and 50 μL of a 0.5 M N,N-dimethylformamide solution of 3A-amino-3A-deoxy-(2AS,3AS)-β-cyclodextrin hydrate with a side chain were mixed and stirred at 60 °C for 2 days. The reaction was then repeated three times via a dissolution-precipitation process using tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain 82 mg of a β-peptide polymer with a p-fluorobenzyl side chain.

[0494] The polymer was identified by gel permeation chromatography (GPC) with a DP of 19 and a molecular weight distribution PDI of 1.2.

[0495] Example 15: Preparation of gram-scale β-peptide homopolymers by open-air polymerization of β-NNTA monomers initiated by p-tert-butylbenzylamine.

[0496]

[0497] Under open conditions, 20 mL of acetonitrile containing 0.5 M cyclopropyl β-NNTA monomer and 1 mL of N,N-dimethylformamide containing 0.5 M p-tert-butylbenzylamine were mixed and stirred at 60 °C for 2 days. Then, the mixture was stirred for 24 h with a mixture of tetrahydrofuran and n-hexane (4 mL and 95 mL), and after filtration, 1.1 g of β-peptide polymer with a cyclopropyl side chain was obtained.

[0498] By nuclear magnetic resonance hydrogen spectrum ( 1 The polymer was identified by H NMR and laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF-MS) with a DP of 19 and a molecular weight distribution PDI of 1.2.

[0499] Example 16: Preparation of β-peptide homopolymers with side-chain amino groups by open-air polymerization of β-NNTA monomers initiated by p-tert-butylbenzylamine

[0500]

[0501] Under open conditions, 1 mL of a 0.5 M N,N-dimethylformamide solution of the side-chain amino β-NNTA monomer and 50 μL of a 0.5 M N,N-dimethylformamide solution of p-tert-butylbenzylamine were mixed and stirred at 60 °C for 2 days. The reaction was then repeated three times via a dissolution-precipitation process using tetrahydrofuran and n-hexane (2 mL and 45 mL) to obtain 113 mg of β-peptide polymer with protected side-chain amino groups.

[0502] The polymer was identified by gel permeation chromatography (GPC) with a DP of 18 and a molecular weight distribution PDI of 1.1.

[0503] 113 mg of β-peptide polymer with protected side-chain amino groups was obtained, and 2 mL of (33 wt.%) hydrobromic acid / acetic acid solution and 2 mL of trifluoroacetic acid were added. After reacting for 6 h, the polymer was dried under a nitrogen stream, and then 45 mL of frozen diethyl ether was added to precipitate a white precipitate. The dissolution-precipitation process was repeated three times to obtain 108 mg of β-peptide polymer with deprotected side-chain amino groups. After filtration and lyophilization, the polymer was used for assembly performance testing.

[0504] Example 17: Preparation of a library of α-peptide copolymers with side-chain amino groups by polymerization of α-NNCA monomers and hydrophobic monomers initiated by 2-triphenylmethylmercaptoethylamine in a glove box.

[0505]

[0506] The polymer synthesis method is the same as in Example 8, except that the monomer is a mixture of N-4-trifluoromethylbenzyl α-NNCA and α-NNCA with protected side-chain amino groups, with a mixing ratio of x:y ranging from 1:9 to 7:3. After the polymerization reaction, the reaction solution was transferred to 50 mL centrifuge tubes, and 45 mL of petroleum ether was added to precipitate a white precipitate. The precipitate was separated by centrifugation and redissolved in 2 mL of tetrahydrofuran. 45 mL of n-hexane was added again to precipitate the precipitate. The polymer obtained by copolymerizing two or more monomers in a set ratio was purified through three dissolution-precipitation processes. The dried polymer was added to 1 mL of trifluoroacetic acid, 1 mL of hydrobromic acid / acetic acid solution, and 40 μL of triethylsilane. After shaking overnight at room temperature, excess trifluoroacetic acid was blown off, and the resulting viscous liquid was dissolved in 0.5 mL of methanol. Then, 45 mL of frozen diethyl ether was added to precipitate a white precipitate. The dissolution-precipitation process was repeated three times to obtain an amphiphilic α-peptide random polymer. The deprotected polymer was dissolved again in 5 mL of ultrapure water, filtered, lyophilized, and then used for subsequent bioactivity testing.

[0507] The polymer before deprotection was characterized by GPC with DP = 18-20 and PDI = 1.1-1.2.

[0508] Example 18: Preparation of a library of β-peptide copolymers with side-chain amino groups by open-air polymerization of β-NNTA monomers and hydrophobic monomers initiated by p-tert-butylbenzylamine.

[0509]

[0510] The polymer synthesis method is the same as in Example 17, except that the monomer is a mixture of N-4-fluorobenzyl β-NNTA and β-NNTA with protected side-chain amino groups, with a mixing ratio of x:y ranging from 1:9 to 7:3. After the polymerization reaction, the reaction solution was transferred to 50 mL centrifuge tubes, and 45 mL of petroleum ether was added to precipitate a white precipitate. The precipitate was separated by centrifugation and redissolved in 2 mL of tetrahydrofuran. 45 mL of n-hexane was added again to precipitate the precipitate. The polymer obtained by copolymerizing two or more monomers in a set ratio was purified through three dissolution-precipitation processes. The dried polymer was added to 1 mL of trifluoroacetic acid and 1 mL of hydrobromic acid / acetic acid solution. After shaking overnight at room temperature, excess trifluoroacetic acid was blown off, and the resulting viscous liquid was dissolved in 0.5 mL of methanol. Then, 45 mL of frozen diethyl ether was added to precipitate a white precipitate. The dissolution-precipitation process was repeated three times to obtain an amphiphilic α-peptide random polymer. The deprotected polymer was dissolved again in 5 mL of ultrapure water, filtered, lyophilized, and then used for subsequent bioactivity testing.

[0511] The polymer before deprotection was characterized by GPC with DP = 17-20 and PDI = 1.1-1.2.

[0512] Example 19: Preparation of α-peptide / α-peptide random copolymers by polymerization of α-NNTA monomers and α-NCA with side-chain amino groups initiated by p-tert-butylbenzylamine in a glove box.

[0513]

[0514] The polymer synthesis method is the same as in Example 6, except that the monomer is a mixture of N-benzyloxycarbonylethyl α-NNTA and N-BocLysα-NCA, with a mixing ratio of x:y of 1:1.

[0515] The reactivity after copolymerization was post-treated three times with tetrahydrofuran and n-hexane, and the polymer was then vacuum dried to obtain a hybrid peptide composed of α-peptides and α-peptides. The polymer was characterized by GPC with a DP of 18 and a PDI of 1.2.

[0516] Example 20: Preparation of β-peptide / α-peptide random copolymers by polymerization of α-NNCA monomers and β-NTA with side-chain amino groups initiated by p-tert-butylbenzylamine in a glove box.

[0517]

[0518] The polymer synthesis method is the same as in Example 17, except that the monomer is a mixture of β-NTA with a side chain benzyl ester and α-NNCA with a side chain amino protected, and the mixing ratio x:y is 1:1.

[0519] The reactivity after copolymerization was post-treated three times with tetrahydrofuran and n-hexane, and the polymer was then vacuum dried to obtain a hybrid peptide composed of β-peptides and α-peptides. The polymer was characterized by GPC with a DP of 17 and a PDI of 1.1.

[0520] Example 21: Preparation of α-peptide / β-peptide random copolymers by polymerization of α-NNTA monomers and β-NNTA with side-chain amino groups initiated by p-tert-butylbenzylamine in a glove box.

[0521]

[0522] The polymer synthesis method is the same as in Example 17, except that the monomer is a mixture of β-NNTA monomer with p-fluorobenzyl side chain and N-Boc Lysα-NCA, with a mixing ratio of x:y of 1:1.

[0523] The reactivity after copolymerization was post-treated three times with tetrahydrofuran and n-hexane, and the polymer was then vacuum dried to obtain a hybrid peptide composed of β-peptides and α-peptides. The polymer was characterized by GPC with a DP of 20 and a PDI of 1.2.

[0524] Example 22: Preparation of random copolymers of β-peptides / β-peptides with side-chain amino groups by polymerization of α-NNTA monomers and β-NNTA initiated by p-tert-butylbenzylamine under open conditions.

[0525]

[0526] The polymer synthesis method is the same as in Example 16, except that the monomer is a mixture of β-NTA with a side-chain phenyl group and β-NNTA with a side-chain amino group protected, with a mixing ratio of 1:1.

[0527] The reactivity after copolymerization was post-treated three times with tetrahydrofuran and n-hexane, and the polymer was then vacuum dried to obtain a hybrid peptide composed of β-peptides and β-like peptides. The polymer was characterized by GPC with a DP of 20 and a PDI of 1.2.

[0528] Example 23: Preparation of β-peptide / β-peptide block copolymers with side-chain amino groups by polymerization of α-NNTA monomers and β-NTA initiated by p-tert-butylbenzylamine under open conditions.

[0529]

[0530] The polymer synthesis method is as described in Example 13. After the β-NNTA monomer with a p-fluorobenzyl side chain is polymerized by p-tert-butylbenzylamine, the β-NNTA monomer with the positively charged side chain protected is added. After the second monomer has reacted completely, the polymer is post-processed to prepare a block β-peptide / β-peptide copolymer. GPC analysis showed that the first block polymer (β-peptide) had a DP of 10 and a PDI of 1.18; the block β-peptide / β-peptide copolymer had a DP of 18 and a PDI of 1.13.

[0531] Example 24: Application of α-NNCA monomer monomer polymerization to prepare α-peptide homopolymers with side-chain amino groups as solution antibacterial materials

[0532]

[0533] The polymer synthesis method is as described in Example 10, wherein the ratio between the α-NNCA monomer protected by the Cbz-side amino group and the initiator is 40:1, 20:1, 10:1, and 5:1. After the reaction, the deprotected polymer was purified by post-treatment, dissolved again in 5 mL of ultrapure water, filtered, and lyophilized for subsequent bioactivity testing.

[0534] The minimum inhibitory concentration (MIC) was determined using the following method: bacteria were cultured overnight in LB liquid medium (Luria-Bertani Broth) at 37°C in a shaker at 150 rpm. The resulting bacterial cells were collected by centrifugation and redispersed in MH (Mueller-Hinton Broth) medium. The absorbance (OD) at 600 nm was read using a microplate reader. 600 (When OD) 600 When the concentration of Staphylococcus aureus is 1, the concentration is approximately 1.5 × 10⁻⁶. 9 (cfu / mL). Dilute the bacterial culture with MH medium to 2×10⁻⁶. 5 Prepare cfu / mL solution. Dilute the polymer with MH medium in a 96-well plate to a concentration ranging from 400 to 3.13 μg / mL. Then add 50 μL of the diluted bacterial solution to each well, making the total volume of bacterial solution and polymer 100 μL. Gently shake for 10 seconds and incubate at 37°C for 9 hours. Then read the OD value using a microplate reader. 600 In the same 96-well plate, four wells were treated with only MH medium as a negative control, and four wells were treated with both MH medium and bacterial culture (without polymer) as a positive control. Two parallel samples were tested each time, and the tests were repeated twice at different time points. The percentage of bacterial growth in each well was calculated using the formula... Calculations were performed. The calculated data was then plotted as a line graph, with the MIC value being the minimum concentration at which the polymer inhibited bacterial growth.

[0535] The polymer was tested for minimum inhibitory concentrations against a variety of bacteria, including methicillin-resistant Staphylococcus aureus USA300, methicillin-resistant Staphylococcus aureus Mu50, Bacillus subtilis BR-151, Escherichia coli JM109, and Pseudomonas aeruginosa ATCC. 90 27) Multidrug-resistant Pseudomonas aeruginosa ATCC 15 442), naturally resistant to sulfamethoxazole and tetracycline: *Pseudomonas aeruginosa* O1 and *Acinetobacter baumannii* ATCC BAA-747. The tested 5-40 mer α-peptide polymers showed minimum inhibitory concentrations (MICs) between 3.13 μg / mL and 12.5 μg / mL against Staphylococcus aureus USA300, Staphylococcus aureus Mu50, and *Bacillus subtilis* BR-151 (positive bacteria), and against the negative bacteria *Pseudomonas aeruginosa* ATCC. 15 442. Pseudomonas aeruginosa ATCC 90 The minimum inhibitory concentrations (MICs) against α-peptide polymers 27, Pseudomonas aeruginosa O1, and Escherichia coli JM109 were 12.5 μg / mL–25 μg / mL; the MICs against Acinetobacter baumannii ATCC BAA-747 were 100 μg / mL–200 μg / mL. MIC test results demonstrate that these α-peptide polymers possess strong and broad-spectrum antibacterial activity.

[0536] Example 25: Application of α-peptide copolymers with side-chain amino groups prepared by polymerization of α-NNCA monomers and hydrophobic monomers as solution antifungal materials.

[0537]

[0538] The polymer synthesis method was the same as in Example 17. The deprotected polymer was dissolved again in ultrapure water, filtered, and lyophilized for subsequent bioactivity testing. The α-peptide random copolymers with positively charged side chains and p-fluorobenzyl groups showed good activity against strains such as Candida albicans K1, clinical strains Candida albicans R02, Cryptococcus neoformans H99, and Cryptococcus neoformans MY737, ranging from 1.56 μg / mL to 100 μg / mL. The polymers with a positive charge to hydrophobicity ratio of 7:3 showed minimum inhibitory concentrations (MFCs) of 3.13 μg / mL (C. albicans K1) and 1.56 μg / mL (C. neoformans).

[0539] Example 26: Application of β-peptide copolymers with side-chain amino groups prepared by polymerization of β-NNTA monomers and hydrophobic monomers as ultra-broad-spectrum antibacterial materials.

[0540]

[0541] The polymer synthesis method is the same as in Example 18. The deprotected polymer is dissolved again in ultrapure water, filtered, lyophilized, and then used for subsequent bioactivity testing. The antibacterial activity of α-peptide random copolymers with positively charged side chains and p-fluorobenzyl groups against standard and clinical strains of positive-positive bacteria, negative-positive bacteria, and fungi was tested. Specifically, polymers with a positive charge:hydrophobicity ratio of 6:4 showed MICs of 12.5 μg / mL, 12.5 μg / mL, and 6.25 μg / mL against positive-positive bacteria *S. aureus* ATCC6538, *S. aureus* USA300, *S. epidermidis* ATCC49134, and *B. subtilis* BR151, respectively. Against negative-positive bacteria *P. aeruginosa* ATCC9027, *P. aeruginosa* O1, *E. coli* ATCC25922, *E. coli* R02, *A. baumannii* ATCC BAA-747, and *A. baumannii* R02, MICs showed 6.25 μg / mL, 6.25 μg / mL, and 6.25 μg / mL, respectively. Antibacterial activity was observed at 25 μg / mL, 25 μg / mL, 25 μg / mL, and 12.5 μg / mL; the minimum inhibitory concentrations against Candida albicans K1 and Cryptococcus neoformans H99 were 3.13 μg / mL and 1.56 μg / mL, respectively, demonstrating high antibacterial activity against clinically and standardly resistant positive bacteria, negative bacteria, and fungi, confirming its application prospects as an ultra-broad-spectrum antibacterial material.

[0542] Example 27 Application of α-peptide homopolymers with side-chain amino groups prepared by 2-triphenylmethylmercaptoethylamine-initiated synthesis of α-NNCA monomers as surface coating antibacterial materials

[0543]

[0544] The polymer synthesis method was the same as in Example 10, except that a deprotected α-peptide polymer with thiol-terminated ends was grafted onto the surface of a gold sheet. The surface sterilization test was performed as follows: bacteria were cultured overnight in LB liquid medium (Luria-Bertani Broth) at 37°C in a shaker at 150 rpm. After culture, 7.5 mL of bacterial solution was taken from the conical flask, centrifuged at 4000 rpm for 5 min to collect the bacteria, and then redispersed in PBS and centrifuged again. This process of centrifuging the PBS-dispersed bacterial solution was repeated three times before collecting the bacterial solution. The absorbance (OD) at 600 nm was read using a microplate reader. 600 Quantification of colony counts. The bacterial culture was diluted with PBS to a concentration of 1×10⁻⁶. 5CFU / mL was prepared for use. The prepared polymer antibacterial surface was placed in a 24-well plate, with PBS as a control. 80 μL of the bacterial suspension at the above concentration was added to the polymer gold sheet surface. 80 μL of the bacterial suspension was directly added to the wells as a blank control. PBS was added to the blank wells to control humidity. The plates were incubated statically at 37°C for 2.5 hours. The plates were then removed, and 1920 μL of PBS was added to each well for dilution. The plates were sonicated for 3 min, mixed for 2 min using a mixer, and 30 μL was pipetted onto LB agar medium and incubated at 37°C. After colony counting, surface antibacterial activity was analyzed. The experimental group was denoted as C. sample The blank control is denoted as C. control The antibacterial activity (bacterial kill rate) of the substrate surface is calculated using the following formula:

[0545]

[0546] The surface bactericidal effect of α-peptide copolymers with side-chain amino groups on Methicillin-resistant Staphylococcus aureus (MRSA). Experimental results show that the surface of this α-peptide homopolymer can achieve a bactericidal rate of up to 99.9% against MRSA, demonstrating excellent surface bactericidal efficacy.

[0547] Example 28 Application of α-peptide copolymers with side-chain amino groups prepared by polymerization of α-NNCA monomers and hydrophobic monomers initiated by 2-triphenylmethylmercaptoethylamine as cell adhesion materials

[0548]

[0549] The polymer synthesis method is the same as in Example 17, except that the hydrophobic monomer is an α-NNCA monomer with a benzyl side chain, and the ratio of the monomer with an amino side chain to y is 1:9 to 7:3 (i.e., 1:9, 2:8, 3:7, 4:6, 5:5, 6:4, 7:3). After the polymerization reaction is complete, the reaction solution is transferred to a 50 mL centrifuge tube, and 45 mL of petroleum ether is added to precipitate a white precipitate. The precipitate is separated by centrifugation and redissolved in 1.5 mL of tetrahydrofuran. 45 mL of n-hexane is added again to precipitate the precipitate. The polymer obtained by copolymerizing two or more monomers in a set ratio after purification through three dissolution-precipitation processes is purified. The dried polymer was added to 1 mL of trifluoroacetic acid, 1 mL of hydrobromic acid and acetic acid solution, and 40 μL of triethylsilane. After gently shaking overnight at room temperature, excess trifluoroacetic acid was blown off, and the resulting viscous liquid was dissolved in 0.5 mL of methanol. Then, 45 mL of frozen diethyl ether was added to precipitate a white precipitate. This dissolution-precipitation process was repeated three times to obtain a random polymer with deprotected side-chain amino groups and terminal thiol groups. The deprotected polymer was dissolved again in 5 mL of ultrapure water, filtered, and lyophilized for subsequent bioactivity testing.

[0550] The amino acid polymer was grafted onto the surface of a glass substrate using the following method: The cleaned and activated glass substrate was modified with 3-aminopropyltriethoxysilane as an amino modifier, then the aminated substrate was modified with PEG, and finally the amino acid polymer and positive control peptide (RGD) were grafted onto it. Cells were collected by trypsin digestion and placed in centrifuge tubes, and the cell density was adjusted to 8 × 10⁶ cells / mL. 4 Cells / mL; cells were seeded into wells on the surface of the amino acid polymer; the polymer surface was placed in a culture dish and incubated at 37°C. After 2 hours of incubation, the adhesion, spreading, and aggregation of cells on the polymer surface were observed under an inverted microscope; subsequently, the polymer surface with adhered cells was immersed in culture medium for 24–48 hours, and the morphology of cell adhesion and growth on the amino acid polymer surface was observed in multiple areas using an inverted fluorescence microscope, and the cell surface coverage area (%) was calculated. The experimental results showed that mouse embryonic fibroblasts (NIH 3T3) exhibited different adhesion effects on the glass surface grafted with amino acid polymers after 48 hours. The polymer with a side-chain amino monomer to hydrophobic monomer ratio of 4:6 showed a similar cell adhesion effect to the positive control RGD. At the same time, the number of cells growing on the surface grafted with polymers was 80% of the number of cells on the positive control RGD surface. Cell adhesion is a crucial step in the interaction between cells and materials in tissue engineering. Cells can only carry out subsequent behaviors such as proliferation, migration, and differentiation after adhesion. Therefore, supporting cell adhesion is an essential property of biomaterials in tissue engineering applications.

[0551] Example 29: Application of α-peptide copolymers with side-chain amino groups prepared by polymerization of tert-butylbenzylamine-initiated α-NNCA monomers and hydrophobic monomers as antitumor materials.

[0552]

[0553] The polymer synthesis method is the same as in Example 17, except that the monomer ratio (x:y) of the side-chain amino group monomer and the hydrophobic monomer is 1:9 to 7:3. The cytotoxicity assay (MTT cell proliferation assay) was performed using the following method, with a density of 3 × 10⁻⁶ cells / mL. 4 NCI-H460, U87, and B16 cells were seeded into 96-well plates, 100 μL per well. Cells were cultured at 37°C for 24 hours. After removing the old culture medium, culture medium containing different concentrations of amino acid polymers was added, with three replicates for each concentration. After culturing at 37°C for 24 hours, 10 μL of MTT solution (5 mg / mL, prepared in PBS) was added to each well, and incubation continued for 4 hours, then the culture was terminated. The culture supernatant was carefully aspirated from the wells, and 150 μL of DMSO was added to each well. The plates were shaken for 10 minutes to dissolve any crystals. The same 96-well plate included a control group (cells without any amino acid polymer treatment) and a blank control group (no cells seeded, only DMSO added). The absorbance (OD value) of each well was measured at 570 nm using a microplate reader, and cell viability was calculated: % cell viability = (OD value / % cell viability) 聚合物 –OD 空白 ) / (OD 对照 –OD 空白 )×100. Based on this, plot the cell viability as a function of amino acid polymer concentration, and obtain the lowest amino acid concentration (IC50) that causes 50% mammalian cell death from the curve. 50 ).

[0554] Tested a series of polymers with different amino acid ratios (from 10% β) 3 -HNle+100%β 2 -LDAP up to 30% beta 3 -HNle+70%β 2 -LDAP) showed cytotoxicity against various tumor cell types (NCI-H460 lung cancer cells, U87 glioma cells, and B16 melanoma cells). Experimental results indicated that when the ratio of positively charged monomers to hydrophobic monomers was 4:6, the amino acid polymer CS1179-3 showed IC50 in B16 melanoma cells. 50 The concentration was 50 μg / mL, demonstrating a good anti-tumor effect.

[0555] Example 30: Application of β-peptide homopolymers with side-chain amino groups prepared by β-NNTA polymerization initiated by 3A-amino-3A-deoxy-(2AS,3AS)-β-cyclodextrin hydrate as self-assembly materials.

[0556]

[0557] The polymer was synthesized using the same method as in Example 14. The polymer was dissolved again in 5 mL of ultrapure water, filtered, and lyophilized before being used for subsequent self-assembly tests.

[0558] The polymer self-assembled structure was prepared by dissolving 1 mg of polymer in an appropriate volume of DMSO, then adding 7 times the volume of ultrapure water to prepare a 1 mg / mL solution. The solution was stirred at a medium speed of 390 rpm for 2 hours, then allowed to stand for 2 days, and then the self-assembled solution was subjected to DLS testing.

[0559] The particle size and dispersibility of the self-assembled samples were tested using dynamic light scattering (DLS). Samples were placed in PS cuvettes, with a volume of approximately 1.5 mL per test. Each sample was tested three times, at a temperature of 25°C, and at a test angle of 90 degrees. Data processing involved cumulative analysis of the experimental correlation function and calculation of the diffusion coefficient using the Stokes-Einstein equation.

[0560] DLS experiments showed that the α-peptide homopolymers formed a relatively stable self-assembled structure in water, with a particle size of 700-800 nm and a dispersibility PD of 0.2.

[0561] Example 31: Application of α-peptide homopolymers with side-chain amino groups prepared by 1-naphthylmethylamine-initiated polymerization of α-NNCA monomers as self-assembly materials.

[0562]

[0563] The polymer synthesis method is the same as in Example 11. The deprotected polymer is dissolved again in 5 mL of ultrapure water, filtered, lyophilized, and then used for subsequent self-assembly tests.

[0564] The self-assembled polymer structure was prepared as follows: 1 mg of the deprotected amphiphilic polymer was dissolved in an appropriate volume of ultrapure water to prepare a 1 mg / mL solution. Then, 15% (v / v) of THF was added, and the solution was stirred at a medium speed of 390 rpm for 2 h, followed by standing for 12 h. The self-assembled solution was then subjected to DLS testing.

[0565] The particle size and dispersibility of the self-assembled samples were tested using dynamic light scattering (DLS). Samples were placed in PS cuvettes, with a volume of approximately 1.5 mL per test. Each sample was tested three times, at a temperature of 25°C, and at a test angle of 90 degrees. Data processing involved cumulative analysis of the experimental correlation function and calculation of the diffusion coefficient using the Stokes-Einstein equation.

[0566] DLS experiments showed that β-peptide homopolymers formed relatively stable self-assembled structures in water, with particle sizes of 60-100 nm and a dispersibility PD of 0.23.

[0567] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.

Claims

1. A polymer or a salt thereof for antibacterial purposes, characterized in that, The polymer chain segments are shown in Formula E4: in, m is an integer between 10 and 500; n'2 is 1 or 2; n'3 is 1 or 2; n'4 is 1 or 2; 0% < x1 ≤ 100%; 0% ≤ y < 100%; 0% ≤ z < 100%; where x1, y, and z are calculated by dividing the corresponding number of repeating units by the total number of repeating units; R is independently selected from the following group: C1-C 12 Alkyl, C1-C 12 Haloalkyl, C3-C 10 cycloalkyl, C6-C 10 Aryl, 5-10 membered heteroaryl, 3-8 membered heterocyclic, C1-C6 alkylguanidine; wherein, the C1-C6... 12 The alkyl group is unsubstituted or contains one or more R groups. m replace; Each of R1, R2, R”1 and R”2 is independently selected from the following group: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy; Partially -(CH2) r -, r is 2, 4, 5, 6, 7 or 8; R a For H, R b It is hydrogen; R m Selected from the following group, substituted or unsubstituted: phenyl and C3-C8 cycloalkyl, wherein R m Substitution in this context refers to substitution by one or more groups selected from the group consisting of halogens, C1-C6 alkyl groups, and C1-C6 haloalkyl groups.

2. The polymer or its salt as claimed in claim 1, characterized in that, n'2, n'3, and n'4 are all 2.

3. A polymer or a salt thereof, characterized in that, The polymer chain segments are shown in E6: m is an integer between 5 and 500; n and n” are both 2; 0% < l ≤ 100%; 0% ≤ k < 100%; where l and k are calculated by dividing the corresponding number of repeating units by the total number of repeating units; R is selected from C1-C6 alkylguanidine and R1, R2, R”1 and R”2 are each independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; Each L is an independent bond or -CHR'1-; q is an integer from 1 to 10; R'1 is independently selected from the following group: H, C1-C3 alkyl; R a For H, R b hydrogen.

4. An intracyclic anhydride monomer, characterized in that, The monomer has the structure shown in formula (I). in, X is S; n is 1 or 2; R is a C1-C6 alkylguanidine or Each R1 and R2 is independently selected from the following unsubstituted groups: hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C1-C6 alkylhydroxy, C1-C6 alkoxy; Each L is an independent bond or -CHR'1-; q is an integer from 1 to 10; R'1 is independently selected from the following group: H or C1-C3 alkyl; R a For H and R b Each group is independently selected from the following group, whether substituted or unsubstituted: hydrogen, C1-C6 alkyl, tert-butoxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenyloxycarbonyl (Fmoc), phthaloyl (Pht), acetyl (Ac), trifluoroacetyl (Tfa), benzyl (Bn), triphenylmethyl (Tr). Constraints: When n is 1 and R1 = R2 = H, R is...

5. The intracyclic anhydride monomer as described in claim 4, characterized in that, The monomer has the structure shown in Formula II. Where X is S; Each L is independently -CHR'1-; R'1 is hydrogen, and q is an integer from 1 to 10; R1, R2, R a and R b The definition is as described in claim 4.

6. The intracyclic anhydride monomer as described in claim 4, characterized in that, The monomer has the structure shown in Formula VI. In the formula, Z is selected from the following group: C1-C6 alkylguanidine and R 1a R 1b R 1c R 1d Each is independently hydrogen, C1-C6 alkyl, or C1-C6 haloalkyl; Each L is an independent bond or -CHR'1-; q is an integer from 1 to 10; R'1 is independently selected from the following group: H, C1-C3 alkyl; R a For H, R b Each group is independently selected from the following group: hydrogen, C1-C6 alkyl tert-butyloxycarbonyl (Boc), benzyloxycarbonyl (Cbz), fluorenyloxycarbonyl (Fmoc), phthaloyl (Pht), acetyl (Ac), trifluoroacetyl (Tfa), benzyl (Bn), and triphenylmethyl (Tr).

7. The intracyclic anhydride monomer as described in claim 4, characterized in that, The monomer is selected from:

8. A method for preparing an intracyclic anhydride monomer as described in claim 4, characterized in that, It includes the following steps: s1) In an inert solvent, compound A is reacted with phosphorus halide to obtain monomer of formula I; in, R5 is selected from the following group, either substituted or unsubstituted: C1-C 12 Alkyl, C6-C 12 aryl, 3-12 membered heterocyclic, 5-12 membered heteroaryl, 3-8 membered cycloalkyl; the substitution refers to substitution by one or more groups selected from the group consisting of: halogen, hydroxyl, amino, phenyl, C1-C6 alkyl, C1-C6 haloalkyl, C 1- C6 alkoxy, C1-C6 haloalkoxy, C3-C8 cycloalkyl, C6-C 12 Aryl; X is S; Furthermore, before step s1), the following step is also included: (s0) In an inert solvent and in the presence of a base, compound 2 and compound 1 are reacted to give compound A; In the formula, R6 is selected from: substituted or unsubstituted C1-C6 alkyl or substituted or unsubstituted C1-C6 alkyl carboxyl groups; The substitution refers to substitution by one or more substituents selected from the group consisting of: halogen, hydroxyl, amino, -C1-C6 alkyl, -C1-C6 haloalkyl, -C1-C6 alkoxy, -C1-C6 haloalkoxy; The definitions of R1, R2, R, R5, X, and n are as described in claim 4.

9. The preparation method according to claim 8, characterized in that, It also includes the following steps: (s0-1) In an inert solvent, in the presence of a base, compound R-NH2 reacts with compound The reaction, followed by hydrolysis, yields compound 2; In the formula, M is selected from: Cl, Br, I, OTs; M' is selected from: C1-C6 alkyl, benzyl; The definitions of R1, R2, R, and n are as described in claim 8.

10. A polymer or a salt thereof, characterized in that, The polymer segments are composed of one or more structural units selected from the following: Where n6 is an integer between 5 and 50; Alternatively, the polymer segments may be composed of one or more structural units selected from those shown above and one or more structural units selected from those shown below: , where n6 is an integer between 5 and 50.

11. A polymer or a salt thereof, characterized in that, The polymer contains the following structural units: Where n6 is a positive integer between 5 and 50.

12. A polymer or a salt thereof, characterized in that, The polymer is selected from the group consisting of: In the formula, r represents a random copolymer and b represents a block copolymer.

13. Use of a polymer as described in any one of claims 1-3 or 10-11 in the preparation of a medicament for antibacterial purposes.

14. The use as described in claim 13, characterized in that, The intended use is for preparing drugs with surface antibacterial properties or for antibacterial modification of medical material substrates.

15. A polymerization method, characterized in that, The polymer is initiated by using a drug, polymer, or diffuser as an initiator to initiate the polymerization of the intracyclic anhydride monomer as described in any one of claims 4-7.

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