Method for synthesizing amides and / or polypeptides using transient protective amino acids as amino components.

Abstract

The present invention provides a method for synthesizing amides and / or polypeptides using transiently protected amino acids as amino components. In this method, an allenyl ketone compound is used as a condensation agent, and a silylation agent is used to temporarily protect the carboxyl group of an amino acid or peptide segment that is not protected at either the amino group or the carboxyl group. Then, an amide bond is formed with an α-carbonyl alkenyl ester derivative of the C-terminal carboxyl group of another molecule's carboxylic acid or amino acid, or polypeptide. The temporarily protected carboxyl group is then deprotected in situ under acidic conditions to obtain the desired carboxylic acid product, and the process is repeated to construct a new amide bond. The allenyl ketone condensation agent effectively avoids racemization, and this "temporary protection" strategy allows the "protection-condensation-deprotection" three-step reaction to be carried out in a one-pot, thus avoiding the consumption of large amounts of chemical reagents, time, manpower, and energy required for the introduction and removal of protecting groups, and improving the step economy and atomic economy of polypeptide synthesis.

Description

[Technical Field]

[0001] The present invention belongs to the field of organic synthesis chemistry, and more particularly to a method for synthesizing amides and / or polypeptides using transiently protected amino acids as amino components. [Background technology]

[0002] Polypeptides are compounds formed by the dehydration condensation of two or more amino acids. They are essential raw materials for the formation of active substances in the human body, such as enzymes, hormones, antibodies, and neurotransmitters, and are the source of all life. Since each amino acid contains a basic α-amino group and an acidic α-carboxyl group, condensation between amino acids produces mixtures of various arbitrary combinations. Therefore, to ensure targeted synthesis, it is necessary to protect reactive groups that do not need to participate in the reaction before the condensation reaction. Commonly used N-terminal protecting groups for amino acids include fluorenyl methoxycarbonyl group (Fmoc), tert-butoxycarbonyl group (Boc), and benzyloxycarbonyl group (Cbz), while C-terminal protecting groups include methyl group (Me), ethyl group (Et), and tert-butyl group (tBu). However, conventional polypeptide synthesis methods require the introduction and removal of protecting groups at each step, which not only wastes large amounts of solvent and reagents but also significantly increases the time cost for researchers. With advancements in chemistry and chemical biology, rapid, efficient, economical, and environmentally friendly polypeptide synthesis methods have become a hot spot in research.

[0003] In 2021, researchers designed and developed a new arenyl ketone-based condensing agent for the synthesis of amide bonds and peptide bonds. This new condensing agent is easy to prepare, has excellent stability, a small molecular weight, mild reaction conditions, and does not require any additives during use. More importantly, this condensing agent does not cause racemization during the activation of the peptide chain and ammonolysis, enabling the N→C polypeptide synthesis strategy and significantly improving the purity and yield of the product. However, since this condensing agent reacts with amino acids with protected carboxyl groups as amino components in the polypeptide synthesis process, a protected polypeptide can be obtained after the reaction is completed. To further extend the peptide chain, a deprotection treatment is required. As a result, polypeptide synthesis has many steps, is time-consuming and laborious, and the cost is also high.

Summary of the Invention

Problems to be Solved by the Invention

[0004] The present invention aims to solve at least one of the above technical problems existing in the prior art. Therefore, the object of the present invention is to provide a method for synthesizing amides and / or polypeptides using transiently protected amino acids as amino components. In this method, an arenyl ketone compound is used as a condensing reagent, and a silylating reagent is used to temporarily protect the carboxyl group of an amino acid or peptide segment in which neither the amino group nor the carboxyl group is protected, and then an α-carbonyl alkenyl ester derivative of the C-terminal carboxyl group of an amino acid or polypeptide of another molecule is formed into a peptide bond. After that, the temporarily protected carboxyl group is deprotected in situ under acidic conditions to obtain the target carboxylic acid product, and new peptide bonds are repeatedly constructed. The condensing agents and activating agents used when synthesizing polypeptides using unprotected amino acids in the prior art can only synthesize dipeptides. When synthesizing tripeptides or polypeptides containing three or more amino acids, conventional condensing agents activate long-chain polypeptides, inducing serious racemization. The arenyl ketone condensing agent used in the present invention can effectively avoid racemization. With this "temporary protection" strategy, the three-step reaction of "protection - condensation - deprotection" can be carried out in one pot, and the conventional three steps can be integrated into one step. Therefore, a large amount of chemical reagents, time, manpower, and energy consumption required for the introduction and removal of protecting groups can be avoided, improving the step economy and atom economy of polypeptide synthesis, and significantly reducing the cost of polypeptide synthesis.

Means for Solving the Problem

[0005] In order to achieve the above object, the technical solution adopted by the present invention is as follows.

[0006] In the first aspect of the present invention, there is proposed a method for preparing amides and / or polypeptides, which includes the step of reacting a compound of formula I and a compound of formula II in solvent I, and then performing a nucleophilic substitution reaction with a compound of formula III and a silylating reagent in solvent II, and acidifying to obtain a compound of formula IV.

Chemical formula

[0007] In some embodiments of the present invention, in R 2 , the substituted aryl group or the substituted heteroaryl group includes an aryl group or a heteroaryl group substituted with at least one selected from a halogen, a C1-C6 alkyl group, a C1-C6 alkoxy group, and a nitro group.)

[0008] In some embodiments of the present invention, R 2 includes one of a phenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-bromophenyl group, a 4-methylphenyl group, a 4-methoxyphenyl group, a 2-methylphenyl group, a 2-methoxyphenyl group, a 3,5-dimethoxyphenyl group, a 3-nitrophenyl group, a 4-nitrophenyl group, a 2,4-dinitrophenyl group, a 3,5-dinitrophenyl group, a pentafluorophenyl group, a 4-trifluoromethylphenyl group, a 3,5-dichlorophenyl group, a 1-naphthyl group, a 2-naphthyl group, a furanyl group, a thienyl group, and a pyridyl group.)

[0009] In some embodiments of the present invention, R 3 , R 4 , and R 5 Each of these groups independently contains one of the following: H, a methyl group, a formyl group, an acetyl group, a propionyl group, a cyano group, a methoxycarbonyl group, an ethoxycarbonyl group, a tert-butoxycarbonyl group, or a benzyloxycarbonyl group.

[0010] In some embodiments of the present invention, the alkyl group refers to a saturated hydrocarbon group having a specific number of carbon atoms. For example, C1-C 18 An alkyl group refers to an alkyl group having 1 to 18 carbon atoms, preferably 1 to 6 carbon atoms. Alkyl groups can be linear or branched. Typical branched alkyl groups have one, two, or three branched chains. Alkyl groups may be optionally substituted with one or more substituents as defined herein. Specific examples of alkyl groups include methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, isopentyl group, 2-methylbutyl group, neopentyl group, 1-ethylpropyl group, n-hexyl group, isohexyl group, 3-methylpentyl group, 2-methylpentyl group, 1-methylpentyl group, 3,3-dimethylbutyl group, 2,2-dimethylbutyl group, 1,1-dimethylbutyl group, 1,2-dimethylbutyl group, 1,3-dimethylbutyl group, 2,3-dimethylbutyl group, 2-ethylbutyl group, 1,2-dimethylpropyl group, neopentyl group, hexyl group, and 2-methylpentyl group.

[0011] In some embodiments of the present invention, the heterocycloalkyl group refers to a fully saturated cyclic group that may exist as a monocyclic, bridging, or spirocyclic ring. Unless otherwise specified, the heterocycle is typically a 3- to 10-membered ring containing 1-3 heteroatoms (preferably 1 or 2 heteroatoms) independently selected from sulfur, oxygen, and / or nitrogen, or a 3- to 7-membered ring containing 1-3 heteroatoms (preferably 1 or 2 heteroatoms) independently selected from sulfur, oxygen, and / or nitrogen. The heterocycloalkyl group may be a 3- to 6-membered ring containing 1 or 2 heteroatoms independently selected from oxygen and nitrogen. Examples of 3-membered heterocycloalkyl groups include, but are not limited to, the oxyranyl, thioxyranyl, and aziranyl groups. Non-limiting examples of 4-membered heterocycloalkyl groups include, but are not limited to, the azetidinyl, oxetanyl, and thietanyl groups. Examples of 5-membered heterocycloalkyl groups include, but are not limited to, the tetrahydrofuranyl group, tetrahydrothienyl group, pyrrolidinyl group, isoxazolidinyl group, oxazolidinyl group, isothiazolidinyl group, thiazolidinyl group, imidazolidinyl group, and tetrahydropyrazolyl group. Examples of 6-membered heterocycloalkyl groups include, but are not limited to, the piperidinyl group, tetrahydropyranyl group, tetrahydrothiaranyl group, morpholinyl group, piperazinyl group, 1,4-thioxanyl group, 1,4-dioxanyl group, thiomorpholinyl group, 1,3-dithianyl group, and 1,4-dithianyl group. Examples of 7-membered heterocycloalkyl groups include, but are not limited to, the azepanyl group, oxepanyl group, and thiepanyl group. The same applies to other polycyclic heterocycles.

[0012] In some embodiments of the present invention, the cycloalkyl group refers to a fully saturated carbon ring that may exist as a monocyclic, crosslinked, or spirocyclic ring. Unless otherwise specified, the carbon ring is typically a 3- to 18-membered ring or a 3- to 10-membered ring. Non-limiting examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, norbornyl (bicyclo[2.2.1]heptyl), bicyclo[2.2.2]octyl, and adamantyl groups.

[0013] In some embodiments of the present invention, the aryl group is selected from phenyl group, o-tolyl group, m-tolyl group, p-tolyl group, 2,4-xylyl group, p-cumenyl group, mesityl group, 1-naphthyl group, 2-naphthyl group, 1-anthranyl group, 2-anthranyl group, 9-anthranyl group, 1-phenanthryl group, 9-phenanthryl group, 1-acenaphthenyl group, 2-azlenyl group, 1-pyrenyl group, 2-triphenylene group, o-biphenyl group, m-biphenyl group, p-biphenyl group, and terphenyl group.

[0014] In some embodiments of the present invention, the heteroaryl group is selected from a preferably 5- to 10-membered heterocyclic group having one or two nitrogen atoms, oxygen atoms, or sulfur atoms, for example, a triazolyl group, a 3-oxadiazolyl group, a 2-furanyl group, a 3-furanyl group, a 2-thienyl group, a 3-thienyl group, a 1-pyrrolyl group, a 2-pyrrolyl group, a 3-pyrrolyl group, a 2-pyridyl group, a 3-pyridyl group, a 4-pyridyl group, or a 2-pyrazineyl group. Examples include the 2-oxazolyl group, 3-isoxazolyl group, 2-thiazolyl group, 3-isothiazolyl group, 2-imidazolyl group, 3-pyrazolyl group, 2-quinolyl group, 3-quinolyl group, 4-quinolyl group, 5-quinolyl group, 6-quinolyl group, 7-quinolyl group, 8-quinolyl group, 1-isoquinolyl group, 2-quinoxalinyl group, 2-benzofuranyl group, 2-benzothienyl group, N-indolyl group, and N-carbazolyl group.

[0015] In some embodiments of the present invention, R 1The C-terminal carboxyl group-less amino acid residue or C-terminal carboxyl group-less amino acid derivative residue described herein refers to the portion of an amino acid or amino acid derivative that remains after the C-terminal carboxyl group has been removed. Preferably, the C-terminal carboxyl group-less amino acid residue includes at least one of an α-amino acid residue, a β-amino acid residue, or a γ-amino acid residue. Preferably, the C-terminal carboxyl group-less amino acid derivative residue includes an amino acid residue with a protected C-terminal amino group, for example, an amino acid residue with a protected C-terminal amino group that is protected by an N-alkoxycarbonyl group and / or an N-acyl group. Preferably, α-amino acids are generally defined by formula [ka] It is represented as, in this case, R 1 In this, the amino acid residue lacking the C-terminal carboxyl group is given by formula [ka] It is a base represented by the formula [ka] The group represented by can be in an R or S configuration. Specifically, the amino acid residue lacking the C-terminal carboxyl group is represented by formula [ka] The group is selected from those represented by . Preferably, the amino acid derivative residue lacking a C-terminal carboxyl group is selected from among the above-mentioned amino acid residues lacking a C-terminal carboxyl group in which the C-terminal amino group is protected with an N-alkoxycarbonyl group and / or an N-acyl group.

[0016] In some embodiments of the present invention, when solvent II and solvent I are different, the method for preparing the amide and / or polypeptide further includes the step of removing solvent I after the reaction and then carrying out the nucleophilic substitution reaction.

[0017] In some embodiments of the present invention, the acidifying agent for acidification includes organic acids and / or inorganic acids.

[0018] The term "acidifying agent" refers to any material that lowers the pH of a solution when dissolved in water. In some embodiments, the acidifying agent may be an inorganic acid and / or organic acid that, when dissolved in water, can lower the pH of a solution to 5 or less (e.g., pH ≤ 4, pH ≤ 3, pH ≤ 2, pH ≤ 1).

[0019] Inorganic acids include hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, potassium dihydrogen phosphate, sodium dihydrogen phosphate, sulfonic acid, aminosulfonic acid, sulfuric acid, nitric acid, or any combination thereof. However, embodiments are not limited to these. Organic acids include citric acid, lactic acid, tartaric acid, fumaric acid, trifluoroacetic acid, phthalic acid, acetic acid, oxalic acid, malonic acid, adipic acid, phytic acid, succinic acid, glutaric acid, maleic acid, malic acid, mandelic acid, ascorbic acid, benzoic acid, methanesulfonic acid, p-toluenesulfonic acid, salicylic acid, capric acid, hexanoic acid, caprylic acid, lauric acid, arachidic acid, erucic acid, linoleic acid, linolenic acid, oleic acid, palmitic acid, myristic acid, ethanedisulfonic acid (edisilic acid), stearic acid, or any combination thereof. However, embodiments are not limited to these.

[0020] In a second aspect of the present invention, another method for preparing amides and / or polypeptides is proposed, comprising the steps of dissolving compound V, compound III, and a silylation reagent in solvent II, carrying out a nucleophilic substitution reaction, and acidifying the solvent to obtain compound IV. [ka] (Here, R1 , R 2 , R 3 , R 4 , R 5 , R 6 The definition is as stated above.

[0021] In this invention, compound III (a compound containing both an amino group and a carboxyl group) exists as an intramolecular amphoteric ion under neutral conditions, resulting in low solubility, and the amino group lacks nucleophilicity, making condensation reactions difficult. By using a silylation reagent (transient protective reagent), the carboxyl group of compound III can be temporarily protected to form a silyl ester compound, while simultaneously releasing the amino group. Furthermore, a nucleophilic substitution reaction can be carried out with compound V to form a peptide bond, yielding compound IV, a polypeptide, and also generating compound VI as a by-product. The reaction mechanism is as follows. [ka]

[0022] In some embodiments of the present invention, the silylation reagent comprises at least one of N-trimethylsilylacetamide, N-methyl-N-trimethylsilylacetamide, N-trimethylsilylpyrrolidone, N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide, N,O-bis(tert-butyldimethylsilyl)acetamide, N,O-bistrimethylsilylacetamide, N,O-bis(trimethylsilyl)trifluoroacetamide, N-methyl-N-(trimethylsilyl)trifluoroacetamide, 1,3-bis(trimethylsilyl)urea, trimethylsilylumidazole, dimethyldichlorosilane, trimethylchlorosilane, and tert-butyldimethylchlorosilane.

[0023] In some embodiments of the present invention, the compound of formula III is an organic compound having both an amino group and a carboxyl group. Preferably, the compound of formula III includes any of the following: an amino acid compound, a polypeptide compound in which both the amino group and the carboxyl group are free, or any other compound having both an amino group and a carboxyl group. More preferably, the compound of formula III includes any of the following: an α-amino acid, a β-amino acid, a γ-amino acid, or a polypeptide compound in which neither the amino group nor the carboxyl group is protected. Even more preferably, the compound of formula III includes any of the following: glycine, alanine, leucine, isoleucine, proline, valine, phenylalanine, tyrosine, serine, threonine, cysteine, methionine, aspartic acid, glutamic acid, asparagine, glutamine, tryptophan, histidine, lysine, arginine, citrulline, or any derivative of the above amino acids. Any of the 21 amino acids included in the compound of formula III may be L-configured native α-amino acids and / or their corresponding D-configured α-amino acids.

[0024] In some embodiments of the present invention, the molar ratio of the silylation reagent to the compound of formula III is (0.5-20):1, preferably (1-15):1, and more preferably (2-10):1.

[0025] In some embodiments of the present invention, the solvent II comprises at least one of acetonitrile, ethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, toluene, m-xylene, dichloromethane, 1,2-dichloroethane, or chloroform.

[0026] In some embodiments of the present invention, the temperature of the nucleophilic substitution reaction is -20°C to 150°C, preferably 0°C to 90°C, and more preferably 5°C to 50°C.

[0027] In some embodiments of the present invention, the duration of the nucleophilic substitution reaction is at least about 10 minutes, preferably 10 minutes to 72 hours.

[0028] In some embodiments of the present invention, the method for preparing the amide and / or polypeptide includes the steps of dissolving the compound of formula III and a silylation reagent in solvent II, then adding the compound of formula V, and carrying out a nucleophilic substitution reaction to obtain the compound of formula IV.

[0029] In some embodiments of the present invention, the method for preparing the polypeptide includes the steps of stirring the compound of formula III and the silylation reagent in solvent II at 20°C to 50°C for 5 minutes to 24 hours to dissolve them, then adding the compound of formula V, and carrying out a nucleophilic substitution reaction to obtain the compound of formula IV.

[0030] In some embodiments of the present invention, the method for preparing the amide and / or polypeptide further comprises a step of purifying the product after the nucleophilic substitution reaction, wherein the purification includes at least one of extraction, recrystallization, or column chromatography.

[0031] In some embodiments of the present invention, a method for preparing compound V of formula includes the steps of dissolving compound I and compound II of formula in solvent I, stirring and reacting them to obtain compound V of formula. [ka] (Here, R 1 , R 2 , R 3 , R 4 , R 5 The definition is as stated above.

[0032] In some embodiments of the present invention, the solvent I comprises at least one of dichloromethane, chloroform, 1,2-dichloroethane, ethyl ether, toluene, acetonitrile, methanol, or ethanol.

[0033] In some embodiments of the present invention, the compound of formula I is a carboxylic acid compound. Preferably, the compound of formula I comprises at least one of fatty acids, aromatic acids, heterocyclic acids, alkynic acids, olefinic acids, N-acyl amino acids, N-alkoxycarbonyl amino acids, or polypeptide carboxylic acids. More preferably, the compound of formula I comprises at least one of N-benzyloxycarbonyl amino acids, N-tert-butoxycarbonyl amino acids, N-fluorenylmethoxycarbonyl amino acids, N-acetyl amino acids, or polypeptide carboxylic acids.

[0034] In some embodiments of the present invention, the molar ratio of compound I to compound II is 1:(1-5), preferably 1:(1-4), and more preferably 1:(1-2).

[0035] In some embodiments of the present invention, the temperature of the stirring reaction is -20°C to 90°C, preferably 0°C to 50°C.

[0036] In a third aspect of the present invention, step S1 involves dissolving compound I and compound II in solvent I, stirring and reacting them to obtain compound V, A method for preparing amides and / or polypeptides is proposed, comprising step S2, which involves dissolving compound V, compound III, and a silylation reagent in solvent II, carrying out a nucleophilic substitution reaction, and acidifying the solution to obtain compound IV. [ka] (Here, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 The definition is as stated above. In a fourth aspect of the present invention, the use of a method for preparing amides and / or polypeptides in the preparation of amides and / or polypeptides is proposed. [Effects of the Invention]

[0037] The beneficial effects of the present invention are as follows:

[0038] In the polypeptide preparation method of the present invention, an allenyl ketone compound is used as a condensation reagent, an inexpensive unprotected amino acid is used as a starting material, and the amino acid is temporarily protected with a silylation reagent before the condensation reaction is carried out. This allows for a one-pot "protection-condensation-deprotection" process, integrating a three-step reaction into one step. After the peptide bond is formed, the desired polypeptide carboxylic acid is obtained by a simple acidification treatment, which can then be directly used for the subsequent amino acid condensation. Furthermore, based on the characteristics of allenyl ketone condensing agents, this method completely avoids the formation of racemization byproducts, ensuring the yield and purity of the product. This method saves large amounts of reagents and solvents used in conventional methods for "introducing protecting groups to amino acids" and "removing protecting groups from the product," significantly reducing the generation of chemical waste, saving time, labor, and energy consumption, drastically reducing the cost of polypeptide synthesis, improving atomic and step economies in polypeptide synthesis, efficiently achieving energy conservation and emission reduction, and significantly improving the efficiency of polypeptide synthesis, thus offering great potential for future industrial applications. [Modes for carrying out the invention]

[0039] The present invention will be described in more detail below through specific examples. Unless otherwise specified, the raw materials, reagents, or apparatus used in the examples and comparative examples can all be obtained commercially or by conventional technical means. Unless otherwise specified, the test methods or measurement methods are conventional methods in the art. [Examples]

[0040] Example 1 This embodiment prepares a polypeptide of formula 1, and the specific process is as follows. Fmco-L-Leu-L-Phe-OH(1) [ka] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.2 mmol), N-methyl-N-trimethylsilylacetamide (0.4 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Fmoc-Leu-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.2 mmol), 1,3-bis(trimethylsilyl)urea (0.4 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 96%. Fmoc-Leu-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.2 mmol), trimethylsilylumidazole (0.4 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 18%. Fmoc-Leu-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 94%. Fmoc-Leu-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol), and 1 mL of 1,2-dichloroethane, and reacted while the reaction process was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 94%. Fmoc-Leu-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol), and 1 mL of tetrahydrofuran, and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 83%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1H NMR(400MHz,DMSO-d6)δ8.01(d,J=7.8Hz,1H),7.89(d,J=7.6Hz,2H),7.72(t,J=6.1Hz,2H),7.42(t,J =7.6Hz,3H),7.32(t,J=7.4Hz,2H),7.22(s,4H),7.19-7.14(m,1H),4.46(q,J=7.4Hz,1H),4.32(t,J= 8.6Hz,1H),4.29-4.18(m,2H),4.07(td,J=9.3,5.3Hz,1H),3.08(dd,J=14.0,5.2Hz,1H),2.94(dd,J= 13.9,8.6Hz,1H),1.62-1.55(m,1H),1.45-1.36(m,2H),0.88(d,J=6.6Hz,3H),0.84(d,J=6.7Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ172.7,172.2,155.8,143.9,143.7,140.7,137.4,129.1,128.1,1 27.6,127.0,126.33,125.3,120.1,65.5,53.2,53.0,46.7,40.7,36.7,24.1,23.0,21.5.

[0041] Example 2 This embodiment prepares the polypeptide of formula 2, and the specific process is as follows. Boc-L-Ala-L-Phe-OH(2) [ka] Boc-Ala-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 94%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.87(d,J=7.7Hz,1H),7.28-7.18(m,J=15.1,8.1Hz,5H),6.83(d,J=7.3Hz,1H),4.44(q,J=7.9Hz ,1H),4.06-3.86(m,1H),3.06(dd,J=13.8,5.0Hz,1H),2.92(dd,J=13.8,8.4Hz,1H),1.36(s,9H),1.13(d,J=7.0Hz,3H). 13 C NMR(101MHz,DMSO)δ172.7,172.5,154.9,137.3,129.2,128.1,126.4,78.0,53.2,49.6,36.7,28.2,18.1.

[0042] Example 3 This embodiment prepares the polypeptide of formula 3, and the specific process is as follows. Cbz-Gly-L-Ala-OH(3) [ka] Boc-Gly-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Ala-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid in 93% yield. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ12.64(s,1H),8.15(d,J=7.2Hz,1H),7.44(t,J=5.9Hz,1H),7.38- 7.30(m,5H),5.05(s,2H),4.24(p,J=7.1Hz,1H),3.71-3.63(m,2H),1.28(d,J=7.2Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ174.1,168.9,156.5,137.1,128.4,127.9,127.7,65.5,47.5,43.3,17.4.

[0043] Example 4 This embodiment prepares the polypeptide of formula 4, and the specific process is as follows. Cbz-L-Ser(tBu)-L-Phe-OH(4) [ka] Cbz-Ser(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined with the aqueous phase, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, and the mixture was purified by column chromatography to obtain a colorless oily substance with a dr>99:1 ratio and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ8.01(d,J=7.7Hz,1H),7.38-7.16(m,11H),5.05(s,2H),4.51-4.45(m,1H),4.15- 4.10(m,1H),3.43-3.39(m,2H),3.06(dd,J=13.8,5.3Hz,1H),2.93(dd,J=13.8,8.0Hz,1H),1.09(s,9H). 13 C NMR(101MHz,DMSO-d6)δ172.4,169.6,155.7,137.2,136.9,129.1,128.3,128.1,127.7,127.6,126.4,72.8,65.4,61.8,55.3,53.3,36.8,27.1.

[0044] Example 5 This embodiment prepares the polypeptide of formula 5, and the specific process is as follows. Boc-L-Met-L-Phe-OH(5) [ka] Boc-Met-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.94(d,J=7.8Hz,1H),7.30-7.21(m,5H),6.91(d,J=8.2Hz,1H),4.42-4.48(m,1H),4.00(d,J=7.1Hz,1H),3.07 (dd,J=13.9,5.0Hz,1H),2.92(dd,J=13.9,8.7Hz,1H),2.43-2.35(m,2H),2.02(s,3H),1.74(dq,J=13.7,7.6,6.6Hz,2H),1.37(s,9H). 13 C NMR(101MHz,DMSO-d6)δ172.8,171.6,155.2,137.3,129.2,128.1,126.4,78.2,53.6,53.2,36.7,31.9,29.6,28.2,14.6.

[0045] Example 6 This embodiment prepares the polypeptide of formula 6, and the specific process is as follows. Cbz-L-Trp-L-Phe-OH(6) [ka] Cbz-Trp-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 92%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ10.82(s,1H),8.26(s,1H),7.65(d,J=6.7Hz,1H),7.39-6.90(m,15H),4.96(s,2 H),4.53(td,J=8.1,4.1Hz,1H),4.36(dt,J=9.2,4.5Hz,1H),3.11(t,J=13.1Hz,2H),3.04-2.85(m,2H). 13 C NMR(101MHz,DMSO-d6)δ172.8,171.8,155.7,137.4,137.0,136.1,129.2,128.3,128.2,127.7 ,127.4,127.3,126.4,123.8,120.9,118.5,118.2,111.3,110.2,65.3,55.4,53.4,36.8,27.8.

[0046] Example 7 This embodiment prepares the polypeptide of formula 7, and the specific process is as follows. Boc-L-Ile-L-Phe-OH(7) [ka] Boc-Ile-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 92%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ12.72(s,1H),8.06(d,J=7.9Hz,1H),7.28-7.17(m,5H),6.61 (d,J=9.3Hz,1H),4.50-4.44(m,1H),3.82(t,J=8.4Hz,1H),3.06(dd,J=13.9,4.9Hz, 1H),2.90(dd,J=13.9,9.2Hz,1H),1.61(q,J=6.3Hz,1H),1.38(s,9H),1.03(dq,J=13 .9,8.1,7.6Hz,1H),0.88-0.82(m,1H),0.77(t,J=7.4Hz,3H),0.72(d,J=6.7Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ172.8,171.4,155.2,137.5,129.1,128.1,126.4,78.0,58.7,53.2,36.8,36.7,28.2,24.3,15.2,10.9.

[0047] Example 8 This embodiment prepares the polypeptide of formula 8, and the specific process is as follows. Fmoc-L-Cys(Trt)-L-Phe-OH(8) [ka] Fmoc-Cys(Trt)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.89(d,J=7.6Hz,2H),7.75(d,J=6.5Hz,2H),7.63(q,J= 8.6Hz,1H),7.41(t,J=7.5Hz,2H),7.37-7.22(m,18H),7.17-7.10(m,5H),4.48- 4.38(m,1H),4.33(d,J=9.5Hz,1H),4.25(d,J=5.6Hz,2H),4.04(dt,J=19.7,8.3 Hz,1H),3.08-3.00(m,1H),2.95-2.86(m,1H),2.41(dq,J=15.5,6.9,4.3Hz,2H). 13C NMR(101MHz,DMSO-d6)δ172.3,169.6,155.5,144.3,143.6,140.7,137.1,129.1,128.0,1 28.0,127.6,127.0,126.7,126.3,125.3,120.0,65.9,53.9,53.3,46.6,36.6,33.9,26.3.

[0048] Example 9 This embodiment prepares the polypeptide of formula 9, and the specific process is as follows. Boc-L-Asn(Trt)-L-Phe-OH(9) [ka] Boc-Asn(Trt)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 94%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1H NMR (400MHz, chloroform-d) δ7.36(s,1H),7.27-7.16(m,20H),7.06(d,J=6.8Hz,2H),6.16(d,J=6.5Hz,1H),4.59(q,J=6.3Hz,1H),4.45(q,J= 5.7Hz,1H),3.01(dd,J=13.9,5.6Hz,1H),2.92(dd,J=13.7,6.0Hz,1H),2.84(d,J=10.2Hz,1H),2.60(dd,J=14.7,4.5Hz,1H),1.37(s,9H). 13 C NMR(101MHz,CDCl3-d)δ173.6,171.8,170.6,155.9,144.3,135.9,129.4,128.8,128.6,128.0,127.1,127.0,70.9,53.7,51.5,38.1,37.4,28.3.

[0049] Example 10 This embodiment prepares the polypeptide of formula 10, and the specific process is as follows. Cbz-L-Pro-L-Phe-OH(10) [ka] Cbz-Pro-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ8.15(dd,J=39.2,8.0Hz,1H),7.41-7.14(m,10H),5.13-4.84(m,2H),4.54-4.44(m,1H), 4.28-4.21(m,1H),3.41-3.30(m,2H),3.10-3.00(m,1H),2.98-2.86(m,1H),2.13-1.96(m,1H),1.76-1.66(m3H). 13 C NMR(101MHz,DMSO-d6)δ171.9,171.8,171.0,170.8,153.1,152.8,136.6,136.5,136.0,128.2,128.0,127.4,127.2,127.1,127.0, 126.7,126.4,126.0,125.4,125.3,64.9,64.7,58.7,58.3,52.4,52.1,46.0,45.4,38.3,38.1,37.9,35.6,29.9,28.6,22.6,21.8.

[0050] Example 11 This embodiment prepares a polypeptide of formula 11, and the specific process is as follows. Cbz-L-Asp(tBu)-L-Thr(tBu)-OH(11) [ka] Cbz-Asp(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Thr(tBu)-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain a pure product as a colorless oil with a ratio of dr > 99:1 and a yield of 94%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.91-7.63(m,2H),7.37-7.26(m,10H),5.09-5.02(m,2H),4.61-4.48(m,2H),4.46 -4.38(m,2H),4.17-4.08(m,1H),2.78-2.68(m,1H),2.52-2.45(m,1H),1.37(s,9H),1.10(d,J=6.1Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ171.7,171.2,169.3,155.9,138.4,136.9,128.3,128.1, 127.8,127.7,127.4,127.4,80.1,74.5,70.2,65.6,56.4,51.4,37.4,27.7,16.1.

[0051] Example 12 This embodiment prepares the polypeptide of formula 12, and the specific process is as follows. Cbz-L-Phe-L-Asp(tBu)-OH(12) [ka] Cbz-Phe-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Asp(tBu)-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR (400MHz, chloroform-d) δ7.52-7.31(m,1H),7.23(s,2H),7.18-7.08(m,8H),5.59(d,J=7.8Hz,1H),4.94(t,J=8.8Hz,2H),4.71(dd,J=8.2,4.1Hz, 1H),4.57-4.34(m,1H),3.04(dd,J=13.5,5.7Hz,1H),2.94(dd,J=12.9,7 .7Hz,1H),2.87-2.79(m,1H),2.67(dd,J=17.0,4.7Hz,1H),1.32(s,9H). 13 C NMR(101MHz,CDCl3-d)δ174.0,171.5,170.4,156.3,136.2,136.2,129.5,1 28.8,128.7,128.3,128.1,127.2,82.3,67.2,56.1,49.0,38.6,37.3,28.1.

[0052] Example 13 This embodiment prepares the polypeptide of formula 13, and the specific process is as follows. Cbz-L-Phe-L-Met-OH(13) [ka] Cbz-Phe-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Met-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 95%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ8.34(d,J=8.1Hz,1H),7.53(d,J=8.6Hz,1H),7.28(dt,J=24.6,8.9Hz,10H),4.95(s,2H),4.49-4.25(m,2H) ,3.08-2.99(m,1H),2.75(t,J=12.4Hz,1H),2.06(s,3H),2.02(s,1H),1.96-1.77(m,1H),1.38(s,1H),1.20(q,J=10.7,6.9Hz,1H). 13 C NMR(101MHz,DMSO-d6)δ173.3,171.9,155.9,138.2,137.1,129.3,128.4,128.1,127.7,127.5,126.3,65.2,56.1,51.0,37.4,30.8,29.7,14.7.

[0053] Example 14 This embodiment prepares a polypeptide of formula 14, and the specific process is as follows. Boc-L-Lys(Boc)-L-Tyr(tBu)-OH(14) [ka] Boc-Lys(Boc)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Tyr(tBu)-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.87(d,J=8.0Hz,1H),7.12(d,J=8.4Hz,2H),6.85(d,J=8.3Hz,2H),6.77-6.67(m,2H),4.42(td,J=8.4,5. 0Hz,1H),3.86(d,J=8.0Hz,1H),3.01(dd,J=14.0,5.0Hz,1H),2.95-2.86(m,2H),2.84(d,J=9.3Hz,1H),1.38(s,18H),1.26(s,9H). 13C NMR(101MHz,DMSO-d6)δ172.9,172.1,155.6,155.2,153.6,131.9,129.7,12 3.4,78.0,77.6,77.3,54.4,53.1,36.1,31.7,29.2,28.6,28.3,28.2,22.8.

[0054] Example 15 This embodiment prepares the polypeptide of formula 15, and the specific process is as follows. Cbz-Aib-Aib-OH(15) [ka] Cbz-Aib-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Aib-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid in 88% yield. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.45(s,1H),7.35(d,J=4.3Hz,4H),7.31(dd,J=5.0,3.6Hz,1H),7.27(s,1H),5.02(s,2H),1.34(s,12H). 13C NMR(101MHz,DMSO-d6)δ175.8,173.3,154.6,137.1,128.2,127.6,127.5,65.0,56.0,55.1,25.0,24.4.

[0055] Example 16 This embodiment prepares a polypeptide of formula 16, and the specific process is as follows. Boc-L-Phe-LN-Me-Ala-OH(16) [ka] Boc-Phe-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing HN-Me-Ala-OH (0.2 mmol), N-trimethylsilylacetamide (0.2 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 95%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ7.02-6.95(m,J=29.2Hz,5H),6.76(d,J=8.6Hz,1H),4.73-4.46(m,1H),4.4 0-4.13(m,1H),2.67(d,J=11.3Hz,3H),2.34(d,J=67.9Hz,1H),1.05(s,9H),0.89(d,J=35.5Hz,3H). 13C NMR(101MHz,DMSO)δ172.9,171.6,155.2,137.7,129.4,128.1,126.3,78.1,52.3,52.1,36.8,31.2,28.2,14.1.

[0056] Example 17 This embodiment prepares the polypeptide of formula 17, and the specific process is as follows. ZL-Ala-L-Asp(tBu)-L-Val-OH(17) [ka] Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Val-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol), and 1 mL of acetonitrile, and reacted while monitoring the reaction process by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 95%. Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Val-OH (0.2 mmol), 1,3-bis(trimethylsilyl)urea (0.4 mmol), and 1 mL of acetonitrile, and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 94%. Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Val-OH (0.2 mmol), N-methyl-N-trimethylsilylacetamide (0.4 mmol), and 1 mL of acetonitrile, and reacted while monitoring the reaction process by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>95.7:4.3 and a yield of 92%. Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Val-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol), and N,N-dimethylformamide (1 mL) and reacted, while the reaction process was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>97:3 and a yield of 91%. Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloroethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloroethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Val-OH (0.12 mmol), N,O-bistrimethylsilylacetamide (0.12 mmol), and 1 mL of 1,2-dichloroethane, and reacted while monitoring the reaction process by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 95%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1H NMR(400MHz,DMSO-d6)δ8.28(d,J=8.1Hz,1H),7.62(d,J=8.6Hz,1H),7.52(d,J=7.3 Hz,1H),7.43-7.27(m,5H),5.11-4.94(m,2H),4.63(q,J=7.4Hz,1H),4.14(dd,J=8.6 ,5.5Hz,1H),4.05(q,J=7.2Hz,1H),2.70(dd,J=16.1,5.9Hz,1H),2.47(d,J=7.9Hz,1 H),2.05(q,J=6.7Hz,1H),1.37(s,9H),1.21(d,J=7.1Hz,3H),0.86(d,J=6.8Hz,6H). 13 C NMR(101MHz,DMSO-d6)δ173.1,170.7,169.7,156.2,137.4,128.8,128.3,128.2,80.6,65.9,57.6,50.6,49.8,37.4,30.4,28.1,19.5,18.6,18.2.

[0057] Example 18 This embodiment prepares the polypeptide of formula 18, and the specific process is as follows. ZL-Ala-L-Tyr(tBu)-L-Aal-OH(18) [ka] Cbz-Ala-Tyr(tBu)-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Ala-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 95%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ8.24(d,J=7.1Hz,1H),7.89(d,J=8.5Hz,1H),7.42(d,J=7.3Hz,1H), 7.38-7.26(m,5H),7.16(d,J=8.3Hz,2H),6.83(d,J=8.2Hz,2H),5.08-4.97(m,2H),4.55(dt ,J=8.5,4.4Hz,1H),4.24(p,J=7.1Hz,1H),4.00(q,J=7.0Hz,1H),3.04(dd,J=13.8,3.6Hz,1 H),2.78(dd,J=13.7,9.7Hz,1H),1.31(d,J=7.2Hz,3H),1.25(s,9H),1.11(d,J=7.1Hz,3H). 13 C NMR(101MHz,DMSO-d6)δ174.0,172.2,170.9,155.7,153.4,137.0,132.4,129.9, 128.4,127.9,127.8,123.4,77.6,65.5,53.4,50.5,47.7,36.9,28.6,18.2,17.2.

[0058] Example 19 This embodiment prepares a polypeptide of formula 19, and the specific process is as follows. ZL-Ala-L-Phe-L-Met-OH(19) [ka] Cbz-Ala-Phe-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Met-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 92%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ8.19(d,J=7.3Hz,1H),7.95(d,J=7.7Hz,1H),7.44(d,J= 7.0Hz,1H),7.41-7.13(m,10H),5.11-4.94(m,2H),4.61-4.52(m,1H),4.42-4.3 5(m,1H),4.06-3.99(m,1H),3.15-3.04(m,1H),2.92-2.80(m,1H),2.53-2.43(m ,2H),2.05(s,3H),2.03-1.96(m,1H),1.94-1.86(m,1H),1.14(d,J=7.1Hz,3H). 13C NMR(101MHz,DMSO-d6)δ173.0,172.3,170.9,154.9,137.5,129.3,127.9,126.2,78.1,53.2,50.9,49.9,37.5,30.8,29.6,28.2,18.1,14.6.

[0059] Example 20 This embodiment prepares the polypeptide of formula 20, and the specific process is as follows. ZL-Ala-L-Val-L-Thr(tBu)-OH(20) [ka] Cbz-Ala-Val-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Thr(tBu)-OH (0.2 mmol), N-trimethylsilylacetamide (0.2 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr>99:1 and a yield of 92%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1H NMR (400MHz, chloroform-d) δ7.48-7.35(m,1H),7.36-7.28(m,5H),7.07-7.02(m,1H),5.99-5.83(m,1H),5.15-5.01(m,2H),4.48(d,J=7.6Hz, 1H),4.45-4.31(m,2H),4.27-4.20(m,1H),2.13-1.99(m,1H),1.33(d,J=6.8Hz,3H),1.17(s,9H),1.10(d,J=6.0Hz,3H),0.98-0.86(m,6H). 13 C NMR(101MHz,CDCl3-d)δ173.1,172.7,172.0,156.2,136.5,128.7,128.3,12 8.2,75.5,67.1,67.0,58.8,57.8,50.6,31.5,28.4,19.8,19.1,19.0,18.3.

[0060] Example 21 This embodiment prepares a polypeptide of formula 21, and the specific process is as follows. Boc-L-Ala-L-Phe-L-Ile-OH(21) [ka] Boc-Ala-Phe-OH (0.1 mmol) and 1-phenylbuta-2,3-dien-1-one (0.1 mmol) were dissolved in 1 mL of 1,2-dichloromethane and reacted with stirring at room temperature, while the reaction process was monitored by TLC. Once the starting materials were completely consumed, 1,2-dichloromethane was removed by vacuum distillation, and the mixture was transferred to a pre-mixed system containing H-Ile-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol), and N,N-dimethylformamide (1 mL), and the reaction was monitored by TLC. After the reaction was complete, 10 mL of water and 0.2 M HCl were added, the aqueous phase was extracted twice with ethyl acetate, the organic phase was combined, washed once with water, the organic phase was washed once with saturated brine, the organic phase was dried over anhydrous sodium sulfate, the solvent was removed by vacuum distillation, recrystallized with ethyl ether, and the solid was collected by filtration to obtain the pure product as a white solid with a dr > 99:1 and a yield of 93%. Nuclear magnetic resonance (NMS) and mass spectrometry (MS) experimental data of the products: 1 H NMR(400MHz,DMSO-d6)δ8.04(s,1H),7.73(d,J=6.1Hz,1H),7.20(d,J=14.5Hz,5H),6.96-6.62(m,1H),4.63(s,1H),4.20(s,1H),3.9 0(s,1H),3.03(d,J=12.5Hz,1H),2.90-2.73(m,1H),1.77(s,1H),1.36(s,9H),1.26-1.16(m,2H),1.09(d,J=5.4Hz,3H),0.85(s,6H). 13 C NMR(101MHz,DMSO-d6)δ172.7,172.4,170.8,154.9,137.4,129.3,127.9,126.1,78.1,56.3,53.1,49.9,37.5,36.5,28.1,24.6,18.1,15.5,11.2.

[0061] The above embodiments represent preferred embodiments of the present invention, but the embodiments of the present invention are not limited to those embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principles of the present invention constitute equivalent substitutions and are all within the scope of protection of the present invention.

Claims

1. A method for preparing amides and / or polypeptides, A method for preparing an amide and / or polypeptide, characterized by comprising the steps of reacting a compound of formula I and a compound of formula II in solvent I, then carrying out a nucleophilic substitution reaction with a compound of formula III and a silylation reagent in solvent II, and acidifying the mixture to obtain a compound of formula IV. 【Chemistry 1】 (Here, R １ includes an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an amino acid residue lacking a C-terminal carboxyl group, an amino acid derivative residue lacking a C-terminal carboxyl group, or a polypeptide fragment, and R ２ includes one of an aryl group, a substituted aryl group, a heteroaryl group, and a substituted heteroaryl group, and R ３ , R ４ , and R ５ each independently include one of H, C １ - C １８ hydrocarbon group, substituted C １ - C １８ hydrocarbon group, C １ - C １６ acyl group, cyano group, C １ - C １６ hydrocarbon group-carbonyl group, and R ６ includes an alkyl group, a cycloalkyl group, a heterocycloalkyl group, an aryl group, a heteroaryl group, an amino acid residue, or a polypeptide fragment.)

2. A method for preparing amides and / or polypeptides, A method for preparing an amide and / or polypeptide, characterized by comprising the steps of dissolving a compound of formula V, a compound of formula III, and a silylation reagent in solvent II, carrying out a nucleophilic substitution reaction, and acidifying the solution to obtain a compound of formula IV. 【Chemistry 2】 (Here, R １ , R ２ , R ３ , R ４ , R ５ , R ６ The definition is as described in claim 1.

3. The method for preparing compound V is characterized by comprising the step of dissolving compound I and compound II in solvent I, stirring and reacting them to obtain compound V, as described in claim 2. 【Transformation 3】 (Here, R １ , R ２ , R ３ , R ４ , R ５ The definition is as described in claim 1.

4. A method for preparing amides and / or polypeptides, Step S1 involves dissolving compound I and compound II in solvent I, stirring, and reacting them to obtain compound V. A method for preparing an amide and / or polypeptide, characterized by comprising step S2, which involves dissolving a compound of formula V, a compound of formula III, and a silylation reagent in solvent II, carrying out a nucleophilic substitution reaction, and acidifying the solution to obtain a compound of formula IV. 【Chemistry 4】 (Here, R １ , R ２ , R ３ , R ４ , R ５ , R ６ The definition is as described in claim 1.

5. The method for preparing the amide and / or polypeptide according to any one of claims 1, 3, or 4, characterized in that, when solvent II and solvent I are different, the method for preparing the amide and / or polypeptide further comprises the step of removing solvent I after the reaction and then carrying out the nucleophilic substitution reaction.

6. The method for preparing an amide and / or polypeptide according to any one of claims 1, 2, or 4, characterized in that the silylation reagent comprises at least one of N-trimethylsilylacetamide, N-methyl-N-trimethylsilylacetamide, N-trimethylsilylpyrrolidone, N-(tert-butyldimethylsilyl)-N-methyltrifluoroacetamide, N,O-bis(tert-butyldimethylsilyl)acetamide, N,O-bistrimethylsilylacetamide, N,O-bis(trimethylsilyl)trifluoroacetamide, N-methyl-N-(trimethylsilyl)trifluoroacetamide, 1,3-bis(trimethylsilyl)urea, trimethylsilylumidazole, dimethyldichlorosilane, trimethylchlorosilane, and tert-butyldimethylchlorosilane.

7. The method for preparing an amide and / or polypeptide according to any one of claims 1, 2, or 4, characterized in that the molar ratio of the silylation reagent to the compound of formula III is (0.5 to 20):

1.

8. The method for preparing an amide and / or polypeptide according to any one of claims 1, 2, or 4, characterized in that the solvent II comprises at least one of acetonitrile, ethyl ether, ethylene glycol dimethyl ether, ethylene glycol diethyl ether, dioxane, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N-methylpyrrolidone, toluene, m-xylene, dichloromethane, 1,2-dichloroethane, or chloroform.

9. The method for preparing an amide and / or polypeptide according to any one of claims 1, 3, or 4, characterized in that the solvent I comprises at least one of dichloromethane, chloroform, 1,2-dichloroethane, ethyl ether, toluene, acetonitrile, methanol, or ethanol.

10. A method for preparing an amide and / or polypeptide according to any one of claims 1, 3, or 4, characterized in that the molar ratio of compound I to compound II is 1:(1 to 5).

11. Use of the method for preparing amides and / or polypeptides in the preparation of amides and / or polypeptides.

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