Method for Synthesizing Amide and/or Polypeptide Using Transient Protected Amino Acid as Ammonia Component

Abstract

The present disclosure discloses a method for synthesizing an amide and/or a polypeptide using a transient protected amino acid as an ammonia component. In this method, an allenone compound is used as a condensing reagent, and a silylation reagent is used to temporarily protect the carboxyl of an amino acid or peptide fragment with amino and carboxyl groups both unprotected first. Then after forming an amide bond with another molecular carboxylic acid or amino acid or -carbonyl alkenyl ester derivative of the C-terminal carboxyl of the polypeptide, the temporarily protected carboxyl is deprotected on site under an acidic condition to obtain a target carboxylic acid product and to cyclicly build new peptide bonds.

Claims

1. A method for preparing an amide and/or a polypeptide, comprising the following steps: ##STR00030## reacting a compound of formula I with a compound of formula II in a solvent I, and carrying out a nucleophilic substitution reaction with a compound of formula III and a silylation reagent in a solvent II, and then obtaining a compound of formula IV after acidification; wherein R.sup.1 comprises alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residual body lacking C-terminal carboxyl, an amino acid derivative residual body or a polypeptide fragment lacking C-terminal carboxyl; R.sup.2 comprises one of aryl, substituted aryl, heteroaryl, and substituted heteroaryl; R.sup.3, R.sup.4 and R.sup.5 each independently comprise one of H, C.sub.1-C.sub.18 hydrocarbonyl, substituted C.sub.1-C.sub.18 hydrocarbonyl, C.sub.1-C.sub.16 acyl, cyano, and C.sub.1-C.sub.16 hydrocarbonyl-carbonyl; R.sup.6 comprises alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residue or a polypeptide fragment.

2. A method for preparing an amide and/or a polypeptide, comprising the following steps: ##STR00031## dissolving a compound of formula V, a compound of formula III and a silylation reagent in a solvent II to perform a nucleophilic substitution reaction, and then preparing a compound of formula IV after acidification; wherein R.sup.1 comprises alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residual body lacking C-terminal carboxyl, an amino acid derivative residual body or a polypeptide fragment lacking C-terminal carboxyl; R.sup.2 comprises one of aryl, substituted aryl, heteroaryl, and substituted heteroaryl; R.sup.3, R.sup.4 and R.sup.5 each independently comprise one of H, C.sub.1-C.sub.18 hydrocarbonyl, substituted C.sub.1-C.sub.18 hydrocarbonyl, C.sub.1-C.sub.16 acyl, cyano, and C.sub.1-C.sub.16 hydrocarbonyl-carbonyl; R.sup.6 comprises alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residue or a polypeptide fragment.

3. The method for preparing an amide and/or a polypeptide according to claim 2, wherein the method for preparing the compound of formula V comprises the following steps: ##STR00032## dissolving a compound of formula I and a compound of formula II in the solvent I to obtain a mixture, and reacting the mixture under stirring to prepare a compound of formula V; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and R.sup.5 are defined as in claim 2.

4. A method for preparing an amide and/or a polypeptide, comprising the following steps: ##STR00033## S1: dissolving a compound of formula I and a compound of formula II in a solvent I to obtain a mixture, and reacting the mixture under stirring to prepare a compound of formula V; S2: dissolving the compound of formula V, the compound of formula III, and the silylation reagent in a solvent II to perform a nucleophilic substitution reaction, and then preparing a compound of formula IV after acidification; wherein R.sup.1 comprises alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residual body lacking C-terminal carboxyl, an amino acid derivative residual body or a polypeptide fragment lacking C-terminal carboxyl; R.sup.2 comprises one of aryl, substituted aryl, heteroaryl, and substituted heteroaryl; R.sup.3, R.sup.4 and R.sup.5 each independently comprise one of H, C.sub.1-C.sub.18 hydrocarbonyl, substituted C.sub.1-C.sub.18 hydrocarbonyl, C.sub.1-C.sub.16 acyl, cyano, and C.sub.1-C.sub.16 hydrocarbonyl-carbonyl; R.sup.6 comprises alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residue or a polypeptide fragment.

5. The method for preparing an amide and/or a polypeptide according to claim 4, wherein when the solvent II is different from the solvent I, the method for preparing an amide and/or a polypeptide further comprises removing the solvent I after the reaction and then performing the nucleophilic substitution reaction.

6. The method for preparing an amide and/or a polypeptide according to claim 4, wherein 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(trimethylsilanyl)trifluoroacetamide, N-methyl-N-(trimethylsilyl)trifluoroacetamide, hexamethyldisilylurea, trimethylsilimidazole, dimethyl dichlorosilane, trimethylchlorosilane and tert-butyldimethylchlorosilane.

7. The method for preparing an amide and/or a polypeptide according to claim 4, wherein a molar ratio of the silylation reagent to the compound of formula III is (0.5-20):1.

8. The method for preparing an amide and/or a polypeptide according to claim 4, wherein the solvent II comprises at least one of acetonitrile, diethyl 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 a polypeptide according to claim 4, wherein the solvent I comprises at least one of dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, toluene, acetonitrile, methanol or ethanol.

10. The method for preparing an amide and/or a polypeptide according to claim 4, wherein a molar ratio of the compound of formula I to the compound of formula II is 1:(1-5).

11. (canceled)

12. The method for preparing an amide and/or a polypeptide according to claim 1, wherein when the solvent II is different from the solvent I, the method for preparing an amide and/or a polypeptide further comprises removing the solvent I after the reaction and then performing the nucleophilic substitution reaction.

13. The method for preparing an amide and/or a polypeptide according to claim 1, wherein 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(trimethylsilanyl)trifluoroacetamide, N-methyl-N-(trimethylsilyl)trifluoroacetamide, hexamethyldisilylurea, trimethylsilimidazole, dimethyl dichlorosilane, trimethylchlorosilane and tert-butyldimethylchlorosilane.

14. The method for preparing an amide and/or a polypeptide according to claim 1, wherein a molar ratio of the silylation reagent to the compound of formula III is (0.5-20):1.

15. The method for preparing an amide and/or a polypeptide according to claim 1, wherein the solvent II comprises at least one of acetonitrile, diethyl 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; wherein the solvent I comprises at least one of dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, toluene, acetonitrile, methanol or ethanol.

16. The method for preparing an amide and/or a polypeptide according to claim 1, wherein a molar ratio of the compound of formula I to the compound of formula II is 1:(1-5).

17. The method for preparing an amide and/or a polypeptide according to claim 3, wherein when the solvent II is different from the solvent I, the method for preparing an amide and/or a polypeptide further comprises removing the solvent I after the reaction and then performing the nucleophilic substitution reaction.

18. The method for preparing an amide and/or a polypeptide according to claim 2, wherein 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(trimethylsilanyl)trifluoroacetamide, N-methyl-N-(trimethylsilyl)trifluoroacetamide, hexamethyldisilylurea, trimethylsilimidazole, dimethyl dichlorosilane, trimethylchlorosilane and tert-butyldimethylchlorosilane.

19. The method for preparing an amide and/or a polypeptide according to claim 2, wherein a molar ratio of the silylation reagent to the compound of formula III is (0.5-20):1.

20. The method for preparing an amide and/or a polypeptide according to claim 2, wherein the solvent II comprises at least one of acetonitrile, diethyl 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; wherein the solvent I comprises at least one of dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, toluene, acetonitrile, methanol or ethanol.

21. The method for preparing an amide and/or a polypeptide according to claim 3, wherein a molar ratio of the compound of formula I to the compound of formula II is 1:(1-5).

Description

DETAILED DESCRIPTION

[0050] The content of the present disclosure will be further described in detail below through specific examples. Unless otherwise specified, the raw materials, reagents or devices used in the examples and comparative examples can be obtained from conventional commercial sources, or can be obtained through existing technical methods. Unless otherwise stated, assays or testing methods are routine in the art.

Example 1

[0051] A polypeptide of formula 1 was prepared in the example, with a specific process as follows:

##STR00009##

[0052] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by Thin Layer Chromatography (TLC). After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Phe-OH (0.2 mmol), N-methyl-N-trimethylsilylacetamide (0.4 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0053] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Phe-OH (0.2 mmol), hexamethyl disily urea (0.4 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 96%.

[0054] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Phe-OH (0.2 mmol), trimethylsilimidazole (0.4 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 18%.

[0055] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Phe-OH (0.2 mmol), N,O-bismethyl trimethylsilylacetamide (0.4 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 94%.

[0056] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichlorocthane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Phe-OH (0.2 mmol), N,O-bismethyl trimethylsilylacetamide (0.4 mmol) and 1 mL 1,2-dichloroethane were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and was dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 94%.

[0057] Fmoc-Leu-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichlorocthane and the mixture was transferred to a system wherein H-Phe-OH (0.2 mmol), N,O-bismethyl trimethylsilylacetamide (0.4 mmol) and 1 mL tetrahydrofuran were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 ml of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 83%.

[0058] Magnetic resonance imaging (NMR) experimental data and mass spectrometry experimental data of the product are as follows:

[0059] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.01 (d, J=7.8 Hz, 1H), 7.89 (d, J=7.6 Hz, 2H), 7.72 (t, J=6.1 Hz, 2H), 7.42 (t, J=7.6 Hz, 3H), 7.32 (t, J=7.4 Hz, 2H), 7.22 (s, 4H), 7.19-7.14 (m, 1H), 4.46 (q, J=7.4 Hz, 1H), 4.32 (t, J=8.6 Hz, 1H), 4.29-4.18 (m, 2H), 4.07 (td, J=9.3, 5.3 Hz, 1H), 3.08 (dd, J=14.0, 5.2 Hz, 1H), 2.94 (dd, J=13.9, 8.6 Hz, 1H), 1.62-1.55 (m, 1H), 1.45-1.36 (m, 2H), 0.88 (d, J=6.6 Hz, 3H), 0.84 (d, J=6.7 Hz, 3H).

[0060] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.7, 172.2, 155.8, 143.9, 143.7, 140.7, 137.4, 129.1, 128.1, 127.6, 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.

Example 2

[0061] A polypeptide of formula 2 was prepared in this example, with a specific process as follows:

##STR00010##

[0062] Boc-Ala-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 94%.

[0063] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0064] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.87 (d, J=7.7 Hz, 1H), 7.28-7.18 (m, J=15.1, 8.1 Hz, 5H), 6.83 (d, J=7.3 Hz, 1H), 4.44 (q, J=7.9 Hz, 1H), 4.06-3.86 (m, 1H), 3.06 (dd, J=13.8, 5.0 Hz, 1H), 2.92 (dd, J=13.8, 8.4 Hz, 1H), 1.36 (s, 9H), 1.13 (d, J=7.0 Hz, 3H).

[0065] .sup.13C NMR (101 MHz, DMSO) 172.7, 172.5, 154.9, 137.3, 129.2, 128.1, 126.4, 78.0, 53.2, 49.6, 36.7, 28.2, 18.1.

Example 3

[0066] A polypeptide of formula 3 was prepared in this example, with a specific process as follows:

##STR00011##

[0067] Boc-Gly-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Ala-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein the yield was 93%.

[0068] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0069] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 12.64 (s, 1H), 8.15 (d, J=7.2 Hz, 1H), 7.44 (t, J=5.9 Hz, 1H), 7.38-7.30 (m, 5H), 5.05 (s, 2H), 4.24 (p, J=7.1 Hz, 1H), 3.71-3.63 (m, 2H), 1.28 (d, J=7.2 Hz, 3H).

[0070] .sup.13C NMR (101 MHz, DMSO-d.sub.6) 174.1, 168.9, 156.5, 137.1, 128.4, 127.9, 127.7, 65.5, 47.5, 43.3, 17.4.

Example 4

[0071] A polypeptide of formula 4 was prepared in this example, with a specific process as follows:

##STR00012##

[0072] Cbz-Ser (tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was purified with column chromatography to obtain a product which was colorless and oily, wherein dr was >99:1 and the yield was 93%.

[0073] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0074] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.01 (d, J=7.7 Hz, 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, 5.3 Hz, 1H), 2.93 (dd, J=13.8, 8.0 Hz, 1H), 1.09 (s, 9H).

[0075] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.4, 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.

Example 5

[0076] A polypeptide of formula 5 was prepared in this example, with a specific process as follows:

##STR00013##

[0077] Boc-Met-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0078] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0079] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 7.94 (d, J=7.8 Hz, 1H), 7.30-7.21 (m, 5H), 6.91 (d, J=8.2 Hz, 1H), 4.42-4.48 (m, 1H), 4.00 (d, J=7.1 Hz, 1H), 3.07 (dd, J=13.9, 5.0 Hz, 1H), 2.92 (dd, J=13.9, 8.7 Hz, 1H), 2.43-2.35 (m, 2H), 2.02 (s, 3H), 1.74 (dq, J=13.7, 7.6, 6.6 Hz, 2H), 1.37 (s, 9H).

[0080] .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.8, 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.

Example 6

[0081] A polypeptide of formula 6 was prepared in this example, with a specific process as follows:

##STR00014##

[0082] Cbz-Trp-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 92%.

[0083] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0084] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 10.82 (s, 1H), 8.26 (s, 1H), 7.65 (d, J=6.7 Hz, 1H), 7.39-6.90 (m, 15H), 4.96 (s, 2H), 4.53 (td, J=8.1, 4.1 Hz, 1H), 4.36 (dt, J=9.2 4.5 Hz, 1H), 3.11 (t, J=13.1 Hz, 2H), 3.04-2.85 (m, 2H).

[0085] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.8, 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.

Example 7

[0086] A polypeptide of formula 7 was prepared in this example, with a specific process as follows:

##STR00015##

[0087] Boc-Ile-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 92%.

[0088] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0089] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 12.72 (s, 1H), 8.06 (d, J=7.9 Hz, 1H), 7.28-7.17 (m, 5H), 6.61 (d, J=9.3 Hz, 1H), 4.50-4.44 (m, 1H), 3.82 (t, J=8.4 Hz, 1H), 3.06 (dd, J=13.9, 4.9 Hz, 1H), 2.90 (dd, J=13.9, 9.2 Hz, 1H), 1.61 (q, J=6.3 Hz, 1H), 1.38 (s, 9H), 1.03 (dq, J=13.9, 8.1, 7.6 Hz, 1H), 0.88-0.82 (m, 1H), 0.77 (t, J=7.4 Hz, 3H), 0.72 (d, J=6.7 Hz, 3H).

[0090] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.8, 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.

Example 8

[0091] A polypeptide of formula 8 was prepared in this example, with a specific process as follows:

##STR00016##

[0092] Fmoc-Cys(Trt)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and was dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0093] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0094] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.89 (d, J=7.6 Hz, 2H), 7.75 (d, J=6.5 Hz, 2H), 7.63 (q, J=8.6 Hz, 1H), 7.41 (t, J=7.5 Hz, 2H), 7.37-7.22 (m, 18H), 7.17-7.10 (m, 5H), 4.48-4.38 (m, 1H), 4.33 (d, J=9.5 Hz, 1H), 4.25 (d, J=5.6 Hz, 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, 4.3 Hz, 2H).

[0095] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.3, 169.6, 155.5, 144.3, 143.6, 140.7, 137.1, 129.1, 128.0, 128.0, 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.

Example 9

[0096] A polypeptide of formula 9 was prepared in this example, with a specific process as follows:

##STR00017##

[0097] Boc-Asn(Trt)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 94%.

[0098] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0099] .sup.1H NMR (400 MHZ, chloroform-d) 7.36 (s, 1H), 7.27-7.16 (m, 20H), 7.06 (d, J=6.8 Hz, 2H), 6.16 (d, J=6.5 Hz, 1H), 4.59 (q, J=6.3 Hz, 1H), 4.45 (q, J=5.7 Hz, 1H), 3.01 (dd, J=13.9, 5.6 Hz, 1H), 2.92 (dd, J=13.7, 6.0 Hz, 1H), 2.84 (d, J=10.2 Hz, 1H), 2.60 (dd, J=14.7, 4.5 Hz, 1H), 1.37 (s, 9H).

[0100] .sup.13C NMR (101 MHz, CDCl.sub.3-d) 173.6, 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.

Example 10

[0101] A polypeptide of formula 10 was prepared in this example, with a specific process as follows:

##STR00018##

[0102] Cbz-Pro-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Phe-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0103] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0104] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.15 (dd, J=39.2, 8.0 Hz, 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 (m 3H).

[0105] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 171.9, 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.

Example 11

[0106] A polypeptide of formula 11 was prepared in this example with a specific process as follows:

##STR00019##

[0107] Cbz-Asp(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Thr(tBu)-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was colorless and oily, wherein dr was >99:1 and the yield was 94%.

[0108] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0109] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 7.91-7.63 (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=6.1 Hz, 3H).

[0110] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 171.7, 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.

Example 12

[0111] A polypeptide of formula 12 was prepared in this example, with a specific process as follows:

##STR00020##

[0112] Cbz-Phe-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Asp(tBu)-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0113] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0114] .sup.1H NMR (400 MHZ, chloroform-d) 7.52-7.31 (m, 1H), 7.23 (s, 2H), 7.18-7.08 (m, 8H), 5.59 (d, J=7.8 Hz, 1H), 4.94 (t, J=8.8 Hz, 2H), 4.71 (dd, J=8.2, 4.1 Hz, 1H), 4.57-4.34 (m, 1H), 3.04 (dd, J=13.5, 5.7 Hz, 1H), 2.94 (dd, J=12.9, 7.7 Hz, 1H), 2.87-2.79 (m, 1H), 2.67 (dd, J=17.0, 4.7 Hz, 1H), 1.32 (s, 9H).

[0115] .sup.13C NMR (101 MHZ, CDCl.sub.3-d) 174.0, 171.5, 170.4, 156.3, 136.2, 136.2, 129.5, 128.8, 128.7, 128.3, 128.1, 127.2, 82.3, 67.2, 56.1, 49.0, 38.6, 37.3, 28.1.

Example 13

[0116] A polypeptide of formula 13 was prepared in this example, with a specific process as follows:

##STR00021##

[0117] Cbz-Phe-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Met-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and was dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 95%.

[0118] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0119] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.34 (d, J=8.1 Hz, 1H), 7.53 (d, J=8.6 Hz, 1H), 7.28 (dt, J=24.6, 8.9 Hz, 10H), 4.95 (s, 2H), 4.49-4.25 (m, 2H), 3.08-2.99 (m, 1H), 2.75 (t, J=12.4 Hz, 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, 6.9 Hz, 1H).

[0120] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 173.3, 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.

Example 14

[0121] A polypeptide of formula 14 was prepared in this example, with a specific process as follows:

##STR00022##

[0122] Boc-Lys(Boc)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Tyr(tBu)-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0123] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0124] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 7.87 (d, J=8.0 Hz, 1H), 7.12 (d, J=8.4 Hz, 2H), 6.85 (d, J=8.3 Hz, 2H), 6.77-6.67 (m, 2H), 4.42 (td, J=8.4, 5.0 Hz, 1H), 3.86 (d, J=8.0 Hz, 1H), 3.01 (dd, J=14.0, 5.0 Hz, 1H), 2.95-2.86 (m, 2H), 2.84 (d, J=9.3 Hz, 1H), 1.38 (s, 18H), 1.26 (s, 9H).

[0125] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.9, 172.1, 155.6, 155.2, 153.6, 131.9, 129.7, 123.4, 78.0, 77.6, 77.3, 54.4, 53.1, 36.1, 31.7, 29.2, 28.6, 28.3, 28.2, 22.8.

Example 15

[0126] A polypeptide of formula 15 was prepared in this example, with a specific process as follows:

##STR00023##

[0127] Cbz-Aib-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Aib-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein the yield was 88%.

[0128] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0129] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.45 (s, 1H), 7.35 (d, J=4.3 Hz, 4H), 7.31 (dd, J=5.0, 3.6 Hz, 1H), 7.27 (s, 1H), 5.02 (s, 2H), 1.34 (s, 12H).

[0130] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 175.8, 173.3, 154.6, 137.1, 128.2, 127.6, 127.5, 65.0, 56.0, 55.1, 25.0, 24.4.

Example 16

[0131] A polypeptide of formula 16 was prepared in this example, with a specific process as follows:

##STR00024##

[0132] Boc-Phe-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein HN-Me-Ala-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 95%.

[0133] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0134] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 7.02-6.95 (m, J=29.2 Hz, 5H), 6.76 (d, J=8.6 Hz, 1H), 4.73-4.46 (m, 1H), 4.40-4.13 (m, 1H), 2.67 (d, J=11.3 Hz, 3H), 2.34 (d, J=67.9 Hz, 1H), 1.05 (s, 9H), 0.89 (d, J=35.5 Hz, 3H).

[0135] .sup.13C NMR (101 MHZ, DMSO) 172.9, 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.

Example 17

[0136] A polypeptide of formula 17 was prepared in this example, with a specific process as follows:

##STR00025##

[0137] Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Val-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol) and 1 mL of acetonitrile were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 95%.

[0138] Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Val-OH (0.2 mmol), hexamethyl disily urea (0.4 mmol) and ImL of acetonitrile were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 94%.

[0139] Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Val-OH (0.2 mmol), N-methyl-N-trimethylsilylacetamide (0.4 mmol) and 1 mL of acetonitrile were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >95.7:4.3 and the yield was 92%.

[0140] Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Val-OH (0.2 mmol), N,O-bistrimethylsilylacetamide (0.4 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >97:3 and the yield was 91%.

[0141] Cbz-Ala-Asp(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloroethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloroethane and the mixture was transferred to a system wherein H-Val-OH (0.12 mmol), N,O-bistrimethylsilylacetamide (0.12 mmol) and 1 mL of 1,2-dichloroethane were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 95%.

[0142] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0143] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.28 (d, J=8.1 Hz, 1H), 7.62 (d, J=8.6 Hz, 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=7.4 Hz, 1H), 4.14 (dd, J=8.6, 5.5 Hz, 1H), 4.05 (q, J=7.2 Hz, 1H), 2.70 (dd, J=16.1, 5.9 Hz, 1H), 2.47 (d, J=7.9 Hz, 1H), 2.05 (q, J=6.7 Hz, 1H), 1.37 (s, 9H), 1.21 (d, J=7.1 Hz, 3H), 0.86 (d, J=6.8 Hz, 6H).

[0144] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 173.1, 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.

Example 18

[0145] A polypeptide of formula 18 was prepared in this example, with a specific process as follows:

##STR00026##

[0146] Cbz-Ala-Tyr(tBu)-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Ala-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 95%.

[0147] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0148] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.24 (d, J=7.1 Hz, 1H), 7.89 (d, J=8.5 Hz, 1H), 7.42 (d, J=7.3 Hz, 1H), 7.38-7.26 (m, 5H), 7.16 (d, J=8.3 Hz, 2H), 6.83 (d, J=8.2 Hz, 2H), 5.08-4.97 (m, 2H), 4.55 (dt, J=8.5, 4.4 Hz, 1H), 4.24 (p, J=7.1 Hz, 1H), 4.00 (q, J=7.0 Hz, 1H), 3.04 (dd, J=13.8, 3.6 Hz, 1H), 2.78 (dd, J=13.7, 9.7 Hz, 1H), 1.31 (d, J=7.2 Hz, 3H), 1.25 (s, 9H), 1.11 (d, J=7.1 Hz, 3H).

[0149] .sup.13C NMR (101 MHz, DMSO-d.sub.6) 174.0, 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.

Example 19

[0150] A polypeptide of formula 19 was prepared in this example, with a specific process as follows:

##STR00027##

[0151] Cbz-Ala-Phe-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Met-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and was dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 92%.

[0152] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0153] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.19 (d, J=7.3 Hz, 1H), 7.95 (d, J=7.7 Hz, 1H), 7.44 (d, J=7.0 Hz, 1H), 7.41-7.13 (m, 10H), 5.11-4.94 (m, 2H), 4.61-4.52 (m, 1H), 4.42-4.35 (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=7.1 Hz, 3H).

[0154] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 173.0, 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.

Example 20

[0155] A polypeptide of formula 20 was prepared in this example, with a specific process as follows:

##STR00028##

[0156] Cbz-Ala-Val-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Thr(tBu)-OH (0.2 mmol), N-trimethylsilylacetamide (0.2 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 92%.

[0157] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0158] .sup.1H NMR (400 MHZ, chloroform-d) 7.48-7.35 (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=7.6 Hz, 1H), 4.45-4.31 (m, 2H), 4.27-4.20 (m, 1H), 2.13-1.99 (m, 1H), 1.33 (d, J=6.8 Hz, 3H), 1.17 (s, 9H), 1.10 (d, J=6.0 Hz, 3H), 0.98-0.86 (m, 6H).

[0159] .sup.13C NMR (101 MHz, CDCl.sub.3-d) 173.1, 172.7, 172.0, 156.2, 136.5, 128.7, 128.3, 128.2, 75.5, 67.1, 67.0, 58.8, 57.8, 50.6, 31.5, 28.4, 19.8, 19.1, 19.0, 18.3.

Example 21

[0160] A polypeptide of formula 21 was prepared in this example, with a specific process as follows:

##STR00029##

[0161] Boc-Ala-Phe-OH (0.1 mmol) and 1-phenylbut-2,3-diene-1-one (0.1 mmol) were taken and dissolved in 1 mL of 1,2-dichloromethane, the mixture was stirred for reaction at a room temperature, and the reaction process was monitored by TLC. After the raw materials were completely consumed, distillation under reduced pressure was performed to remove 1,2-dichloromethane and the mixture was transferred to a system wherein H-Ile-OH (0.12 mmol), N-trimethylsilylacetamide (0.12 mmol) and 1 mL of N,N-dimethylformamide were stirred and mixed in advance, and the reaction process was monitored by TLC. After the reaction was completed, 10 mL of water and 0.2 M HCl were added, an aqueous phase was extracted twice with ethyl acetate, organic phases were combined, the mixture was washed once with water, the organic phase was washed once with saturated brine and dried with anhydrous sodium sulfate, distillation under reduced pressure was performed to remove the solvent, and the mixture was recrystallized with diethyl ether. The mixture was filtered to collect a solid to obtain a pure product which was a white solid, wherein dr was >99:1 and the yield was 93%.

[0162] NMR experimental data and mass spectrometry experimental data of the product are as follows:

[0163] .sup.1H NMR (400 MHZ, DMSO-d.sub.6) 8.04 (s, 1H), 7.73 (d, J=6.1 Hz, 1H), 7.20 (d, J=14.5 Hz, 5H), 6.96-6.62 (m, 1H), 4.63 (s, 1H), 4.20 (s, 1H), 3.90 (s, 1H), 3.03 (d, J=12.5 Hz, 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=5.4 Hz, 3H), 0.85 (s, 6H).

[0164] .sup.13C NMR (101 MHZ, DMSO-d.sub.6) 172.7, 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.

[0165] The above examples are preferred examples of the present disclosure, but the examples of the present disclosure are not limited to the above examples. Any other alternations, modifications, substitutions, combinations, and simplifications made without departing from the spirit and principles of the present disclosure should be equivalent substitutions, and are all included in the protection scope of the present disclosure.