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

Abstract

The present disclosure provides a method for synthesizing an amide and/or a polypeptide using an unprotected amino acid as an ammonia component. In the method for preparing the polypeptide, an amino acid or peptide fragment with amino and carboxyl groups both unprotected is used as an ammonia component for the synthesis of a polypeptide, and after an -acyloxyenamide derivative of a carboxylic acid forms an amide bond or peptide bond with the amino group of the unprotected amino acid or peptide fragment, the next peptide bond construction cycle can be carried out without removing the carboxyl protecting group.

Claims

1. A method for preparing an amide and/or a polypeptide, comprising the following steps: ##STR00037## reacting a compound of Formula IV with a compound of Formula V in solvent II, and then carrying out a nucleophilic substitution reaction with a compound of Formula II and an alkaline additive in solvent I to prepare a compound of Formula III; wherein R.sup.1 is selected from 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 is selected from hydrogen, deuterium, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, silyl, or alkylsilyl; R.sup.3 is selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R.sup.4 is selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residue, or a polypeptide fragment; and EWG is selected from nitro, cyano, sulfonyl, arylsulfonyl, alkanoyl, and phosphonyl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, silyl, and alkylsilyl are optionally unsubstituted or substituted with one or more R.sup.11, with each R.sup.11 being independently selected from halogen, hydroxyl, carbonyl, and C.sub.1-C.sub.6 alkyl.

2. 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 the amide and/or polypeptide further comprises after the reaction, removing the solvent II before the nucleophilic substitution reaction.

3. A method for preparing an amide and/or a polypeptide, comprising the following steps: ##STR00038## dissolving a compound of Formula I, a compound of Formula II and an alkaline additive in solvent I for a nucleophilic substitution reaction to prepare a compound of Formula III, wherein R.sup.1 is selected from 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 is selected from hydrogen, deuterium, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, silyl, or alkylsilyl; R.sup.3 is selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, or heteroaryl; R.sup.4 is selected from alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, an amino acid residue, or a polypeptide fragment; and EWG is selected from nitro, cyano, sulfonyl, arylsulfonyl, alkanoyl, and phosphonyl; wherein the alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, silyl, and alkylsilyl are optionally unsubstituted or substituted with one or more R.sup.11, with each R.sup.11 being independently selected from halogen, hydroxyl, carbonyl, and C.sub.1-C.sub.6 alkyl.

4. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the alkaline additive includes an organic base and/or an inorganic base.

5. The method for preparing an amide and/or a polypeptide according to claim 4, wherein the organic base includes at least one of trimethylamine, triethylamine, tripropylamine, N,N-dimethylethylamine, N,N-diethylmethylamine, N,N-diisopropylethylamine, N-methylpyrrolidine, N-methylpiperidine, N-methylmorpholine, tributylamine, tribenzylamine, dimethylbenzylamine, N,N-dimethylaniline, pyridine, 2-methylpyridine, 2,6-dimethylpyridine, 4-dimethylaminopyridine, quinoline, quinine, tetramethylguanidine, imidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylene diamine, tetramethylethylenediamine, tetraethylethylenediamine, tetramethylpropylenediamine, tetraethylpropylenediamine, tetrabutylammonium iodide, tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, or tetrabutylammonium hydroxide; and the inorganic base includes at least one of sodium bicarbonate, sodium carbonate, lithium bicarbonate, lithium carbonate, potassium bicarbonate, potassium carbonate, cesium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium bicarbonate, or calcium hydroxide.

6. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the molar ratio of the alkaline additive to the compound of Formula II is (0.1-20): 1.

7. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the solvent I includes at least one of water, acetonitrile, ethanol, isopropanol, tert-butanol, ethylene glycol, 1,2-propanediol, 2,3-butanediol, 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; and the solvent II includes at least one of dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, toluene, acetonitrile, methanol, or ethanol.

8. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the nucleophilic substitution reaction is carried out at a temperature of 20 C. to 150 C.

9. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the compound of Formula II includes any one of an amino acid compound, a polypeptide compound with both free amino and carboxyl groups, or other compounds with both amino and carboxyl groups.

10. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the method for preparing the amide and/or the polypeptide comprises the following steps: dissolving a compound of Formula II and an alkaline additive in solvent I, and then adding a compound of Formula I for a nucleophilic substitution reaction to prepare a compound of Formula III.

11. The method for preparing an amide and/or a polypeptide according to claim 3, wherein a preparation method for the compound of Formula I comprises the following steps: ##STR00039## dissolving a compound of Formula IV and a compound of Formula V in solvent II to obtain a mixture, and reacting the mixture under stirring to prepare the compound of Formula I; wherein R.sup.1, R.sup.2, R.sup.3 and EWG are defined as in claim 3.

12. The method for preparing an amide and/or a polypeptide according to claim 3, wherein the method for preparing the amide and/or the polypeptide comprises the following steps: ##STR00040## S1: dissolving a compound of Formula IV and a compound of Formula V in solvent II to obtain a mixture, and reacting the mixture under stirring to prepare a compound of Formula I; and S2: dissolving the compound of Formula I, a compound of Formula II and an alkaline additive in solvent I for a nucleophilic substitution reaction to prepare a compound of Formula III; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and EWG are defined as in claim 3.

13. The method for preparing an amide and/or a polypeptide according to claim 12, wherein the compound of Formula IV includes at least one of a fatty acid, an aromatic acid, a heterocyclic acid, an acetylenic acid, an alkenoic acid, an amino acid, a polypeptide carboxylic acid, and derivatives of the above compounds.

14. The method for preparing an amide and/or a polypeptide according to claim 12, wherein the molar ratio of the compound of Formula IV to the compound of Formula V is 1: (0.1-5).

15. (canceled)

16. The method for preparing an amide and/or a polypeptide according to claim 1, wherein the alkaline additive includes an organic base and/or an inorganic base; wherein the organic base includes at least one of trimethylamine, triethylamine, tripropylamine, N,N-dimethylethylamine, N,N-diethylmethylamine, N,N-diisopropylethylamine, N-methylpyrrolidine, N-methylpiperidine, N-methylmorpholine, tributylamine, tribenzylamine, dimethylbenzylamine, N,N-dimethylaniline, pyridine, 2-methylpyridine, 2,6-dimethylpyridine, 4-dimethylaminopyridine, quinoline, quinine, tetramethylguanidine, imidazole, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylene diamine, tetramethylethylenediamine, tetraethylethylenediamine, tetramethylpropylenediamine, tetraethylpropylenediamine, tetrabutylammonium iodide, tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, or tetrabutylammonium hydroxide; and the inorganic base includes at least one of sodium bicarbonate, sodium carbonate, lithium bicarbonate, lithium carbonate, potassium bicarbonate, potassium carbonate, cesium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, calcium bicarbonate, or calcium hydroxide; wherein the molar ratio of the alkaline additive to the compound of Formula II is (0.1-20): 1.

17. The method for preparing an amide and/or a polypeptide according to claim 1, wherein the solvent I includes at least one of water, acetonitrile, ethanol, isopropanol, tert-butanol, ethylene glycol, 1,2-propanediol, 2,3-butanediol, 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; and the solvent II includes at least one of dichloromethane, chloroform, 1,2-dichloroethane, diethyl ether, toluene, acetonitrile, methanol, or ethanol.

18. The method for preparing an amide and/or a polypeptide according to claim 1, wherein the nucleophilic substitution reaction is carried out at a temperature of 20 C. to 150 C.

19. The method for preparing an amide and/or a polypeptide according to claim 1, wherein the compound of Formula II includes any one of an amino acid compound, a polypeptide compound with both free amino and carboxyl groups, or other compounds with both amino and carboxyl groups.

20. The method for preparing an amide and/or a polypeptide according to claim 1, wherein the method for preparing the amide and/or the polypeptide comprises the following steps: ##STR00041## S1: dissolving a compound of Formula IV and a compound of Formula V in solvent II to obtain a mixture, and reacting the mixture under stirring to prepare a compound of Formula I; and S2: dissolving the compound of Formula I, a compound of Formula II and an alkaline additive in solvent I for a nucleophilic substitution reaction to prepare a compound of Formula III; wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4 and EWG are defined as in claim 1.

21. The method for preparing an amide and/or a polypeptide according to claim 19, wherein the compound of Formula IV includes at least one of a fatty acid, an aromatic acid, a heterocyclic acid, an acetylenic acid, an alkenoic acid, an amino acid, a polypeptide carboxylic acid, and derivatives of the above compounds; wherein the molar ratio of the compound of Formula IV to the compound of Formula V is 1: (0.1-5).

Description

DETAILED DESCRIPTION

[0042] The concept and technical effects of the present disclosure will be described below clearly and completely in conjunction with examples, so as to fully understand the object, characteristics and effects of the present disclosure. Obviously, the described examples are merely some, rather than all, of the examples of the present disclosure. Based on the examples of the present disclosure, other examples obtained by those skilled in the art without involving any inventive effort all fall within the scope of protection of the present disclosure.

Example 1

[0043] In this example, a polypeptide of Formula 1 was prepared, and the specific process was as follows:

##STR00010##

[0044] Cbz-Gly-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Ala-OH (1 mmol), triethylamine (1 mmol), 3 mL of N,N-dimethylformamide, and 1 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=2 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid with a yield of 95%.

[0045] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0046] .sup.1H NMR (400 MHz, DMSO) 12.63 (s, 1H), 8.15 (d, J=7.2 Hz, 1H), 7.43 (t, J=5.9 Hz, 1H), 7.38-7.30 (m, 5H), 5.04 (s, 2H), 4.29-4.19 (m, 1H), 3.71-3.62 (m, 2H), 1.28 (d, J=7.2 Hz, 3H). [0047] .sup.13C NMR (100 MHz, DMSO) =174.1, 168.9, 156.5, 137.1, 128.4, 127.8, 127.7, 65.5, 47.5, 43.3, 17.4. [0048] HRMS (ESI) m/z calcd. for C.sub.13H.sub.16N.sub.2NaO.sub.5 [M+Na].sup.+: 303.0951, found: 303.0950.

Example 2

[0049] In this example, a polypeptide of Formula 2 was prepared, and the specific process was as follows:

##STR00011##

[0050] Cbz-Leu-OH (0.5 mmol) and N-methyl-N-methylsulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Phe-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=2 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and subjected to column chromatography isolation to obtain a pure product as a white solid, dr>99:1, with a yield of 97%.

[0051] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0052] .sup.1H NMR (400 MHz, MeOD-d.sub.4) 7.36-7.26 (m, 5H), 7.24-7.14 (m, 5H), 5.06 (s, 2H), 4.69 (dd, J=8.0, 5.3 Hz, 1H), 4.26-4.14 (m, 1H), 3.18 (dd, J=13.8, 5.1 Hz, 1H), 3.00 (dd, J=13.8, 8.1 Hz, 1H), 1.67-1.59 (m, 1H), 1.52-1.41 (m, 2H), 0.96-0.85 (m, 6H). [0053] .sup.13C NMR (100 MHz, MeOD-d.sub.4) 174.9, 174.3, 158.2, 138.0, 138.0, 130.4, 129.4, 129.3, 128.9, 128.7, 127.7, 67.6, 54.7, 42.0, 38.3, 25.7, 23.4, 22.0. [0054] HRMS (ESI) m/z calcd. for C.sub.23H.sub.28N.sub.2NaO.sub.5 [M+Na].sup.+: 435.1890, found: 435.1883.

Example 3

[0055] In this example, a polypeptide of Formula 3 was prepared, and the specific process was as follows:

##STR00012##

[0056] Cbz-Ser(tBu)-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.5 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Leu-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), 3 mL of dimethylsulfoxide, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and subjected to column chromatography isolation, and after filtration, a solid was collected to obtain a pure product as a white solid, dr>99:1, with a yield of 93%.

[0057] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0058] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.98 (d, J=7.9 Hz, 1H), 7.38-7.28 (m, 5H), 7.21 (d, J=8.5 Hz, 1H), 5.04 (s, 2H), 4.29-4.23 (m, 1H), 4.18-4.12 (m, 1H), 3.50-3.43 (m, 2H), 1.70-1.62 (m, 1H), 1.56-1.47 (m, 2H), 1.10 (s, 9H), 0.86 (dd, J=16.6, 6.3 Hz, 6H). [0059] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.9, 169.7, 155.8, 137.0, 128.3, 127.8, 127.7, 72.8, 65.5, 62.0, 55.4, 50.3, 40.3, 27.2, 24.1, 22.9, 21.4. [0060] HRMS (ESI) m/z calcd. for C.sub.21H.sub.32N.sub.2NaO.sub.6 [M+Na].sup.+: 431.2153, found: 431.2149.

Example 4

[0061] In this example, a polypeptide of Formula 4 was prepared, and the specific process was as follows:

##STR00013##

[0062] Cbz-Thr-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Leu-OH (1 mmol), sodium carbonate (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=2 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 94%.

[0063] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0064] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.06 (d, J=7.7 Hz, 1H), 7.41-7.17 (m, 10H), 6.95 (d, J=8.7 Hz, 1H), 5.05 (s, 2H), 4.48 (q, J=7.3 Hz, 1H), 3.96 (dd, J=8.2, 5.2 Hz, 1H), 3.88-3.76 (m, 1H), 3.05 (dd, J=13.7, 5.0 Hz, 1H), 2.93 (dd, J=13.6, 8.1 Hz, 1H), 1.01 (d, J=6.1 Hz, 3H). [0065] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 172.6, 170.0, 156.0, 137.3, 137.0, 129.2, 128.3, 128.1, 127.8, 127.7, 126.4, 66.8, 65.5, 60.5, 53.3, 36.9, 19.6. [0066] HRMS (ESI) m/z calcd. for C.sub.21H.sub.24N.sub.2NaO.sub.6 [M+Na].sup.+: 423.1527, found: 423.1524.

Example 5

[0067] In this example, a polypeptide of Formula 5 was prepared, and the specific process was as follows:

##STR00014##

[0068] Boc-Met-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.5 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Leu-OH (1 mmol), triethylamine (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and subjected to column chromatography isolation to obtain a pure product as a white solid, dr>99:1, with a yield of 94%.

[0069] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0070] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.97 (d, J=7.8 Hz, 1H), 7.34-7.16 (m, 5H), 6.91 (d, J=8.2 Hz, 1H), 4.46 (q, J=8.0 Hz, 1H), 4.01 (q, J=7.9 Hz, 1H), 3.07 (dd, J=13.8, 4.9 Hz, 1H), 2.92 (dd, J=13.9, 8.7 Hz, 1H), 2.45-2.29 (m, 2H), 2.01 (s, 3H), 1.85-1.64 (m, 2H), 1.37 (s, 9H). [0071] .sup.13C NMR (100 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. [0072] HRMS (ESI) m/z calcd. for C.sub.19H.sub.28N.sub.2NaO.sub.5S [M+Na].sup.+: 419.1611, found: 419.1609.

Example 6

[0073] In this example, a polypeptide of Formula 6 was prepared, and the specific process was as follows:

##STR00015##

[0074] Boc-Ala-OH (0.5 mmol) and N-methyl-N-methylsulfonyl ethynylamine (0.5 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Lys(Cbz)-OH (1 mmol), potassium carbonate (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and subjected to column chromatography isolation to obtain a pure product as a white solid, dr>99:1, with a yield of 94%.

[0075] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0076] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.88 (d, J=7.8 Hz, 1H), 7.39-7.27 (m, 5H), 7.20 (t, J=5.8 Hz, 1H), 6.86 (d, J=7.7 Hz, 1H), 5.00 (s, 2H), 4.20-4.13 (m, 1H), 4.03-3.96 (m, 1H), 3.01-2.94 (m, 2H), 1.75-1.65 (m, 1H), 1.63-1.53 (m, 1H), 1.37 (s, 9H), 1.34-1.26 (m, 3H), 1.17 (d, J=7.1 Hz, 3H). [0077] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.6, 172.8, 156.1, 155.1, 137.3, 128.4, 127.8, 127.7, 78.1, 65.2, 51.7, 49.6, 40.1, 30.9, 29.0, 28.2, 22.6, 18.1. [0078] HRMS (ESI) m/z calcd. for C.sub.22H.sub.34N.sub.2O.sub.7 [M+H].sup.+: 452.2391, found: 452.2390.

Example 7

[0079] In this example, a polypeptide of Formula 7 was prepared, and the specific process was as follows:

##STR00016##

[0080] Cbz-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Thr-OH (1 mmol), sodium bicarbonate (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=2 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with ethyl acetate and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 92%.

[0081] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0082] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.67 (d, J=8.6 Hz, 1H), 7.53 (d, J=7.7 Hz, 1H), 7.39-7.26 (m, 5H), 5.03 (s, 2H), 4.25-4.14 (m, 3H), 1.24 (d, J=7.1 Hz, 3H), 1.06 (d, J=6.1 Hz, 3H). [0083] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.0, 172.2, 155.8, 137.1, 128.5, 127.9, 127.8, 66.5, 65.5, 57.5, 50.2, 20.4, 18.2. [0084] HRMS (ESI) m/z calcd. for C.sub.15H.sub.20N.sub.2O.sub.6 [M+Na].sup.+: 347.1214, found: 347.1221.

Example 8

[0085] In this example, a polypeptide of Formula 8 was prepared, and the specific process was as follows:

##STR00017##

[0086] Cbz-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, H-Gln-OH (1 mmol) was added, 3 mL of acetonitrile and 1.5 mL of water were added as a solvent, and N,N-diisopropylethylamine (1 mmol) was added. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=1 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 97%.

[0087] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0088] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.13 (d, J=7.6 Hz, 1H), 7.59-7.12 (m, 7H), 6.79 (s, 1H), 5.09-4.95 (m, 2H), 4.22-4.05 (m, 2H), 2.22-2.07 (m, 2H), 2.01-1.91 (m, 1H), 1.86-1.73 (m, 1H), 1.22 (d, J=7.1 Hz, 3H). [0089] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.6, 173.3, 172.7, 155.7, 137.1, 128.4, 127.8, 127.8, 65.4, 51.6, 49.9, 31.4, 27.0, 18.2. [0090] HRMS (ESI) m/z calcd. for C.sub.16H.sub.21N.sub.3NaO.sub.6 [M+Na].sup.+: 374.1323, found: 374.1321.

Example 9

[0091] In this example, a polypeptide of Formula 9 was prepared, and the specific process was as follows:

##STR00018##

[0092] Cbz-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Trp-OH (1 mmol), cesium carbonate (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=1 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and subjected to column chromatography isolation to obtain a pure product as a light yellow solid, dr>99:1, with a yield of 93%.

[0093] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0094] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 10.89 (s, 1H), 8.12-8.03 (m, 1H), 7.57 (t, J=6.0 Hz, 1H), 7.44 (dd, J=8.1, 4.1 Hz, 1H), 7.34 (d, J=15.7 Hz, 8H), 7.20 (s, 1H), 7.07 (s, 1H), 6.98 (s, 1H), 5.13-4.94 (m, 3H), 4.54 (s, 1H), 4.15 (q, J=5.8, 4.9 Hz, 2H), 3.22 (d, J=14.3 Hz, 2H), 3.17-3.05 (m, 2H), 1.26-1.19 (m, 7H). [0095] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.3, 172.6, 155.7, 137.1, 136.1, 128.4, 127.8, 127.8, 127.4, 123.8, 121.0, 118.4, 118.3, 111.4, 109.7, 65.5, 53.0, 50.0, 27.1, 18.3. [0096] HRMS (ESI) m/z calcd. for C.sub.22H.sub.23N.sub.3NaO.sub.5 [M+Na].sup.+: 432.1530, found: 432.1530.

Example 10

[0097] In this example, a polypeptide of Formula 10 was prepared, and the specific process was as follows:

##STR00019##

[0098] Fmoc-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Phe-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=1 with 2 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, and subjected to column chromatography isolation to obtain a pure product as a white solid, dr>99:1, with a yield of 91%.

[0099] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0100] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.02 (d, J=7.5 Hz, 1H), 7.89 (d, J=7.5 Hz, 2H), 7.74 (d, J=6.8 Hz, 1H), 7.48 (d, J=7.7 Hz, 1H), 7.42 (t, J=7.4 Hz, 2H), 7.33 (t, J=7.3 Hz, 2H), 7.27-7.16 (m, 4H), 4.50-4.39 (m, 1H), 4.26 (d, J=6.1 Hz, 1H), 4.24-4.18 (m, 1H), 4.12-4.06 (m, 1H), 3.07 (dd, J =13.7, 4.8 Hz, 1H), 2.93 (dd, J =13.7, 8.4 Hz, 1H), 1.20 (d, J =7.1 Hz, 3H). [0101] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 172.8, 172.4, 155.6, 143.9, 143.8, 140.7, 137.4, 129.2, 128.1, 127.6, 127.1, 126.3, 125.3, 120.1, 65.7, 53.5, 49.9, 46.6, 36.7, 18.2. [0102] HRMS (ESI) m/z calcd. for C.sub.22H.sub.23N.sub.3NaO.sub.5 [M+Na].sup.+: 432.1530, found: 432.1530.

Example 11

[0103] In this example, a polypeptide of Formula 11 was prepared, and the specific process was as follows:

##STR00020##

[0104] Cbz-Ala-Leu-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.5 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Phe-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), and 5 mL of ethylene glycol were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=1 with 2 M hydrochloric acid, the aqueous phase was extracted twice with dichloromethane, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 93%.

[0105] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0106] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.04 (d, J=7.6 Hz, 1H), 7.86 (d, J=8.3 Hz, 1H), 7.43 (d, J=7.6 Hz, 1H), 7.37-7.17 (m, 10H), 5.02 (s, 2H), 4.47-4.41 (m, 1H), 4.36-4.30 (m, 1H), 4.10-4.04 (m, 1H), 3.07 (dd, J=13.9, 5.2 Hz, 1H), 2.93 (dd, J=13.8, 8.5 Hz, 1H), 1.67-1.50 (m, 1H), 1.43 (d, J=6.7 Hz, 1H), 1.17 (d, J=7.0 Hz, 3H), 0.90-0.76 (m, 6H). [0107] 13C NMR (100 MHz, DMSO-d6) 8 172.8, 172.2, 171.9, 155.7, 137.5, 137.1, 129.2, 128.4, 128.2, 127.8, 127.8, 126.4, 65.4, 53.4, 51.0, 50.1, 41.1, 36.7, 24.1, 23.1, 21.8, 18.2. [0108] HRMS (ESI) m/z calcd. for C.sub.26H.sub.33N.sub.3NaO.sub.6 [M+Na].sup.+: 506.2262, found: 506.2253.

Example 12

[0109] In this example, a polypeptide of Formula 12 was prepared, and the specific process was as follows:

##STR00021##

[0110] Cbz-Ala-Phe-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.5 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Met-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), and 5 mL of 2,3-butanediol were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=1 with 2 M hydrochloric acid, the aqueous phase was extracted twice with dichloromethane, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 93%.

[0111] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0112] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.18 (d, J=7.3 Hz, 1H), 7.94 (d, J=7.7 Hz, 1H), 7.43 (d, J=7.0 Hz, 1H), 7.40-7.12 (m, 10H), 5.10-4.93 (m, 2H), 4.60-4.51 (m, 1H), 4.41-4.34 (m, 1H), 4.05-3.98 (m, 1H), 3.14-3.03 (m, 1H), 2.91-2.79 (m, 1H), 2.52-2.42 (m, 2H), 2.04 (s, 3H), 2.02-1.95 (m, 1H), 1.93-1.85 (m, 1H), 1.13 (d, J=7.1 Hz, 3H). [0113] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.2, 172.3, 171.0, 155.8, 137.7, 137.0, 129.4, 128.4, 128.0, 127.9, 127.8, 126.3, 65.6, 53.6, 51.1, 50.4, 37.3, 30.9, 29.7, 18.1, 14.7. [0114] HRMS (ESI) m/z calcd. for C.sub.25H.sub.31N.sub.3NaO.sub.6S [M+Na].sup.+: 524.1826, found: 524.1824.

Example 13

[0115] In this example, a polypeptide of Formula 13 was prepared, and the specific process was as follows:

##STR00022##

[0116] Cbz-Ala-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Gln(Trt)-OH (1 mmol), sodium bicarbonate (2 mmol), and 5 mL of dichloromethane were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted once with ethyl acetate and washed twice with water, the organic phase was washed once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a light yellow solid, dr>99:1, with a yield of 90%.

[0117] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0118] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.59 (s, 1H), 8.05 (d, J=8.2 Hz, 1H), 7.93 (t, J=6.5 Hz, 1H), 7.44 (t, J=5.9 Hz, 1H), 7.38-7.14 (m, 22H), 5.06-4.97 (m, 2H), 4.37-4.29 (m, 1H), 4.22-4.15 (m, 1H), 4.11-4.05 (m, 1H), 2.41-2.29 (m, 2H), 1.99-1.88 (m, 1H), 1.79-1.69 (m, 1H), 1.26-1.16 (m, 6H). [0119] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.3, 172.1, 172.0, 171.2, 155.7, 144.9, 137.0, 128.5, 128.3, 127.8, 127.7, 127.4, 126.3, 69.3, 65.4, 51.6, 50.0, 47.9, 32.6, 27.3, 18.3, 18.1. [0120] HRMS (ESI) m/z calcd. for C.sub.38H.sub.40N.sub.4NaO.sub.7 [M+Na].sup.+: 687.2789, found: 687.2874.

Example 14

[0121] In this example, a polypeptide of Formula 14 was prepared, and the specific process was as follows:

##STR00023##

[0122] Cbz-Phe-Gly-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Phe-Ser (tBu)-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 92%.

[0123] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0124] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.33-8.17 (m, 2H), 8.05 (d, J=8.4 Hz, 1H), 7.52 (d, J=8.5 Hz, 1H), 7.38-7.13 (m, 15H), 5.02-4.87 (m, 2H), 4.77-4.65 (m, 1H), 4.43-4.35 (m, 1H), 4.32-4.25 (m, 1H), 3.80-3.74 (m, 1H), 3.69-3.60 (m, 2H), 3.57-3.52 (m, 1H), 3.11-2.98 (m, 2H), 2.83-2.68 (m, 2H), 1.13 (s, 9H). [0125] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 171.8, 171.6, 171.1, 168.4, 155.9, 138.2, 137.8, 137.0, 129.3, 129.2, 128.3, 128.2, 128.1, 128.0, 127.7, 127.4, 126.3, 72.9, 65.3, 61.6, 56.2, 53.6, 53.1, 41.9, 37.8, 37.5, 27.2. [0126] HRMS (ESI) m/z calcd. for C.sub.35H.sub.42N.sub.4NaO.sub.8 [M+Na].sup.+: 669.2895, found: 669.2900.

Example 15

[0127] In this example, a polypeptide of Formula 15 was prepared, and the specific process was as follows:

##STR00024##

[0128] Cbz-Phe-Gly-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Glu (tBu)-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), and 5 mL of 2,3-butanediol were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 89%.

[0129] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0130] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.38-8.28 (m, 1H), 8.14 (d, J=6.9 Hz, 1H), 7.96 (d, J=6.0 Hz, 1H), 7.57 (d, J=7.6 Hz, 1H), 7.35-7.15 (m, 10H), 4.95 (s, 2H), 4.41-4.18 (m, 3H), 3.82-3.71 (m, 2H), 3.10-3.01 (m, 1H), 2.83-2.71 (m, 1H), 2.36-2.18 (m, 2H), 2.05-1.90 (m, 1H), 1.88-1.72 (m, 1H), 1.38 (s, 9H), 1.27-1.19 (m, 3H). [0131] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 173.1, 172.2, 171.9, 171.5, 168.2, 156.0, 138.1, 137.0, 129.2, 128.3, 128.0, 127.7, 127.4, 126.2, 79.8, 65.3, 56.3, 51.1, 47.9, 42.1, 37.3, 31.3, 27.7, 26.4, 18.3. [0132] HRMS (ESI) m/z calcd. for C.sub.31H.sub.41N.sub.4O.sub.9 [M+H].sup.+: 613.2868, found: 613.2865.

Example 16

[0133] In this example, a polypeptide of Formula 16 was prepared, and the specific process was as follows:

##STR00025##

[0134] Cbz-Tyr (tBu)-Gly-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the dichloromethane was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Gly-Phe-OH (1 mmol), sodium carbonate (1 mmol), 3 mL of acetonitrile, and 1.5 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 96%.

[0135] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0136] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.38-8.26 (m, 1H), 8.18 (d, J=6.6 Hz, 1H), 8.11-7.96 (m, 1H), 7.64-7.43 (m, 1H), 7.36-7.15 (m, 12H), 6.86 (d, J=7.4 Hz, 2H), 5.01-4.86 (m, 2H), 4.53-4.43 (m, 1H), 4.35-4.26 (m, 1H), 3.84-3.70 (m, 4H), 3.12-3.00 (m, 2H), 2.97-2.88 (m, 1H), 2.80-2.69 (m, 1H), 1.26 (s, 9H). [0137] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 172.8, 172.0, 169.0, 168.6, 156.0, 153.5, 137.5, 137.0, 132.8, 129.8, 129.2, 128.3, 128.3, 127.7, 127.5, 126.5, 123.3, 77.6, 65.4, 56.3, 53.6, 42.2, 41.7, 36.9, 36.8, 28.6.

Example 17

[0138] In this example, a polypeptide of Formula 17 was prepared, and the specific process was as follows:

##STR00026##

[0139] Cbz-Gly-Ala-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Ala-Phe-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), and 5 mL of 2,3-butanediol were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 89%.

[0140] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0141] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00 (t, J=6.8 Hz, 3H), 7.51-7.41 (m, 1H), 7.42-7.16 (m, 10H), 5.04 (s, 2H), 4.47-4.38 (m, 1H), 4.31 (p, J=7.2 Hz, 2H), 3.66 (d, J=5.9 Hz, 2H), 3.06 (dd, J=13.8, 5.1 Hz, 1H), 2.93 (dd, J=13.6, 8.5 Hz, 1H), 1.19 (t, J=8.1 Hz, 6H). [0142] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 172.7, 172.0, 171.7, 168.8, 156.5, 137.4, 137.1, 129.2, 128.4, 128.2, 127.8, 127.7, 126.5, 65.5, 53.5, 48.0, 43.5, 36.7, 18.4, 18.1. [0143] HRMS (ESI) m/z calcd. for C.sub.25H.sub.30N.sub.4NaO.sub.7 [M+Na].sup.+: 521.2007, found: 521.2009.

Example 18

[0144] In this example, a polypeptide of Formula 18 was prepared, and the specific process was as follows:

##STR00027##

[0145] Cbz-Ala-Ser (tBu)-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Phe-OH (1 mmol), tributylamine (1 mmol), and 5 mL of dichloromethane were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 95%.

[0146] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0147] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.97 (d, J=7.8 Hz, 1H), 7.74 (d, J=7.7 Hz, 1H), 7.49 (d, J=7.3 Hz, 1H), 7.39-7.14 (m, 10H), 5.02 (s, 2H), 4.53-4.44 (m, 1H), 4.38-4.30 (m, 1H), 4.16-4.07 (m, 1H), 3.49-3.38 (m, 2H), 3.10-3.03 (m, 1H), 2.97-2.88 (m, 1H), 1.19 (d, J=6.9 Hz, 3H), 1.09 (s, 9H). [0148] .sup.13C NMR (101 MHz, DMSO) =172.4, 172.3, 169.5, 155.7, 137.3, 137.0, 129.2, 128.3, 128.2, 127.8, 127.7, 126.4, 72.9, 65.4, 61.7, 53.3, 53.0, 50.1, 36.9, 27.1, 18.1. [0149] HRMS (ESI) m/z calcd. for C.sub.27H.sub.35N.sub.3NaO.sub.7 [M+Na].sup.+: 536.2367, found: 536.2372.

Example 19

[0150] In this example, a polypeptide of Formula 19 was prepared, and the specific process was as follows:

##STR00028##

[0151] Cbz-Ala-Cys(Trt)-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Phe-OH (1 mmol), N-methylmorpholine (0.5 mmol), triethylamine (1 mmol), and 5 mL of dichloromethane were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 95%.

[0152] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0153] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.18-7.99 (m, 2H), 7.56 (d, J=7.4 Hz, 1H), 7.36-7.14 (m, 25H), 5.12-4.91 (m, 2H), 4.46-4.32 (m, 2H), 4.14-4.04 (m, 1H), 3.09-2.99 (m, 1H), 2.95-2.85 (m, 1H), 2.44-2.30 (m, 2H), 1.19 (d, J=7.2 Hz, 3H). [0154] .sup.13C NMR (101 MHz, DMSO) =172.4, 172.3, 169.5, 155.8, 144.3, 137.2, 137.0, 129.1, 129.1, 128.4, 128.2, 128.1, 127.8, 127.8, 126.8, 126.5, 65.8, 65.5, 53.5, 51.6, 50.2, 36.7, 33.8, 18.2. [0155] HRMS (ESI) m/z calcd. for C.sub.42H.sub.41N.sub.3NaO.sub.6S [M+Na].sup.+: 738.2608, found: 738.2615.

Example 20

[0156] In this example, a polypeptide of Formula 20 was prepared, and the specific process was as follows:

##STR00029##

[0157] Cbz-Ala-Glu(tBu)-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Asp(tBu)-OH (1 mmol), N,N-dimethylaniline (0.5 mmol), triethylamine (1 mmol), and 5 mL of dichloromethane were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 97%.

[0158] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0159] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.19 (d, J=7.9 Hz, 1H), 7.98 (d, J=8.1 Hz, 1H), 7.47 (d, J=7.5 Hz, 1H), 7.39-7.28 (m, 5H), 5.07-4.99 (m, 2H), 4.60-4.52 (m, 1H), 4.37-4.28 (m, 1H), 4.14-4.05 (m, 1H), 2.74-2.66 (m, 1H), 2.61-2.52 (m, 1H), 2.31-2.16 (m, 2H), 1.98-1.83 (m, 1H), 1.81-1.63 (m, 1H), 1.42-1.34 (m, 18H), 1.21 (d, J=7.2 Hz, 3H). [0160] .sup.13C NMR (101 MHz, DMSO) =172.4, 172.1, 171.8, 170.8, 169.2, 155.7, 137.0, 128.4, 127.8, 127.8, 80.4, 79.6, 65.4, 51.4, 50.1, 48.7, 37.2, 31.1, 27.8, 27.8, 27.7, 18.1. [0161] HRMS (ESI) m/z calcd. for C.sub.28H.sub.41N.sub.3NaO.sub.10 [M+Na].sup.+: 602.2684, found: 602.2690.

Example 21

[0162] In this example, a polypeptide of Formula 21 was prepared, and the specific process was as follows:

##STR00030##

[0163] Cbz-Ala-Glu(tBu)-Asp(tBu)-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Gly-OH (1 mmol), 2,6-dimethylpyridine (2 mmol), and 5 mL of dichloromethane were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 93%.

[0164] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0165] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.14 (d, J=8.0 Hz, 1H), 8.10-7.95 (m, 2H), 7.47 (d, J=7.2 Hz, 1H), 7.40-7.22 (m, 5H), 5.10-4.94 (m, 2H), 4.67-4.55 (m, 1H), 4.30-4.21 (m, 1H), 4.13-4.04 (m, 1H), 3.82-3.67 (m, 2H), 2.76-2.62 (m, 1H), 2.50-2.36 (m, 1H), 2.32-2.10 (m, 2H), 2.02-1.82 (m, 1H), 1.82-1.62 (m, 1H), 1.39 (s, 9H), 1.37 (s, 9H), 1.20 (d, J=6.9 Hz, 3H). [0166] .sup.13C NMR (101 MHz, DMSO) =172.8, 171.8, 170.9, 170.8, 170.4, 169.2, 155.8, 137.0, 128.3, 127.8, 127.8, 80.2, 79.6, 65.5, 52.0, 50.1, 49.4, 40.9, 37.4, 31.1, 27.8, 27.7, 27.3, 18.0. [0167] HRMS (ESI) m/z calcd. for C.sub.30H.sub.44N.sub.4NaO.sub.11 [M+Na].sup.+: 659.2899, found: 659.2905.

Example 22

[0168] In this example, a polypeptide of Formula 22 was prepared, and the specific process was as follows:

##STR00031##

[0169] Cbz-Ala-Phe-Met-OH (0.5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which H-Glu(tBu)-OH (1 mmol), pyridine (2 mmol), and 5 mL of dichloromethane were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, dr>99:1, with a yield of 92%.

[0170] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0171] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.13 (d, J=7.5 Hz, 1H), 8.07 (d, J=7.4 Hz, 1H), 7.93 (d, J=7.3 Hz, 1H), 7.43 (d, J=7.1 Hz, 1H), 7.40-7.28 (m, 5H), 7.25-7.15 (m, 5H), 5.09-4.93 (m, 2H), 4.60-4.49 (m, 1H), 4.44-4.36 (m, 1H), 4.28-4.20 (m, 1H), 4.05-3.98 (m, 1H), 3.09-3.00 (m, 1H), 2.90-2.80 (m, 1H), 2.49-2.40 (m, 2H), 2.33-2.23 (m, 2H), 2.03 (s, 3H), 2.02-1.89 (m, 2H), 1.88-1.74 (m, 2H), 1.39 (s, 9H), 1.14 (d, J=7.0 Hz, 3H). [0172] .sup.13C NMR (101 MHz, DMSO) =173.0, 172.4, 171.5, 170.9, 170.7, 155.7, 137.6, 136.9, 129.3, 128.3, 127.9, 127.8, 127.7, 126.2, 79.8, 65.5, 53.6, 51.7, 51.1, 50.3, 37.2, 32.2, 31.2, 29.3, 27.7, 26.3, 18.0, 14.6. [0173] HRMS (ESI) m/z calcd. for C.sub.34H.sub.46N.sub.4NaO.sub.9S [M+Na].sup.+: 709.2878, found: 709.2884.

Example 23

[0174] In this example, an amide of Formula 23 was prepared, and the specific process was as follows:

##STR00032##

[0175] 18-(Tert-butoxy)-18-oxooctadecanoic acid (0.5 mmol) and N-methyl-N-methylsulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the solvent was removed by distillation under reduced pressure, and the remaining mixture was transferred to a system, in which H-Glu-OtBu (1 mmol), N,N-diisopropylethylamine (1 mmol), 3 mL of dimethylsulfoxide, and 3 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, with a yield of 95%.

[0176] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0177] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.00 (d, J=7.6 Hz, 1H), 4.16-4.09 (m, 1H), 2.29-2.23 (m, 2H), 2.12 (dt, J=21.7, 7.3 Hz, 4H), 1.90 (dt, J=13.5, 6.6 Hz, 1H), 1.75 (dd, J=14.1, 6.7 Hz, 1H), 1.52-1.44 (m, 4H), 1.41-1.37 (m, 18H), 1.27-1.21 (m, 24H). [0178] .sup.13C NMR (101 MHz, DMSO) 173.53, 172.25, 172.08, 171.03, 80.26, 79.16, 79.14, 51.81, 34.97, 34.74, 29.96, 29.00, 28.96, 28.91, 28.82, 28.76, 28.60, 28.53, 28.33, 27.68, 27.55, 26.24, 25.20, 24.55. [0179] HRMS (ESI) m/z calcd. for C.sub.31H.sub.57NNaO.sub.7 [M+Na].sup.+: 578.4027, found: 578.4034.

Example 24

[0180] In this example, an amide of Formula 24 was prepared, and the specific process was as follows:

##STR00033##

[0181] Fmoc--Ala-OH (0.5 mmol) and N-methyl-N-methylsulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the solvent was removed by distillation under reduced pressure, and the remaining mixture was transferred to a system, in which H-Phe-OH (1 mmol), N,N-diisopropylethylamine (1 mmol), 3 mL of acetonitrile, and 3 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, with a yield of 90%.

[0182] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0183] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.24 (d, J=7.6 Hz, 1H), 7.88 (d, J=7.5 Hz, 2H), 7.69 (d, J=7.2 Hz, 2H), 7.41 (t, J=7.4 Hz, 2H), 7.33 (t, J=7.4 Hz, 2H), 7.29-7.13 (m, 6H), 4.53-4.42 (m, 1H), 4.29 (d, J=6.5 Hz, 2H), 4.22 (d, J=6.4 Hz, 1H), 3.21-3.05 (m, 3H), 2.89 (dd, J=13.2, 9.4 Hz, 1H), 2.30 (dq, J=19.6, 13.0, 10.2 Hz, 2H). [0184] .sup.13C NMR (101 MHz, DMSO) 173.05, 170.26, 155.99, 143.90, 140.72, 137.67, 129.06, 128.12, 127.59, 127.05, 126.36, 125.15, 120.07, 65.39, 53.43, 46.75, 36.98, 36.84, 35.40. [0185] HRMS (ESI) m/z calcd. for C.sub.27H.sub.26N.sub.2NaO.sub.5 [M+Na].sup.+: 481.1734, found: 481.1739.

Example 25

[0186] In this example, an amide of Formula 25 was prepared, and the specific process was as follows:

##STR00034##

[0187] Boc-Phe-OH (0.5 mmol) and N-methyl-N-methylsulfonyl ethynylamine (0.55 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the solvent was removed by distillation under reduced pressure, and the remaining mixture was transferred to a system, in which -aminobutyric acid (1 mmol), triethylamine (1 mmol), and 3 mL of N,N-dimethylformamide, and 3 mL of water were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 15 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product as a white solid, with a yield of 96%.

[0188] The experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0189] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 7.96-7.78 (m, 1H), 7.23 (td, J=17.3, 15.8, 6.9 Hz, 5H), 6.81 (d, J=8.3 Hz, 1H), 4.16-3.99 (m, 1H), 3.07 (dq, J=11.8, 6.2 Hz, 2H), 2.92 (dd, J=13.6, 4.8 Hz, 1H), 2.81-2.67 (m, 1H), 2.17 (t, J=7.4 Hz, 2H), 1.59 (p, J=6.6 Hz, 2H), 1.31 (s, 9H). [0190] .sup.13C NMR (101 MHz, DMSO) 174.14, 171.41, 155.09, 138.08, 129.12, 127.94, 126.11, 77.95, 55.76, 37.88, 37.70, 30.91, 28.10, 24.47. [0191] HRMS (ESI) m/z calcd. for C.sub.18H.sub.26N.sub.2NaO.sub.5 [M+Na].sup.+: 373.1734, found: 373.1738.

Example 26

[0192] In this example, carfilzomib was prepared, and the specific process was as follows:

##STR00035##

[0193] Chloroacetic acid (5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (5.5 mmol) were taken and dissolved in 5 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the product was transferred to a system, in which L-homophenylalanine (10 mmol), triethylamine (10 mmol), acetonitrile (10 mL), and water (5 mL) were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 20 mL of water was added, the product was acidified to pH=2 with 1 M hydrochloric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining a pure product. The above steps were repeated for condensation with L-phenylalanine, L-leucine, and (2S)-2-amino-4-methyl-1-[(2R)-2-methyloxiranyl]-1-pentanone trifluoroacetate in order to finally obtain an intermediate, which was reacted with morpholine (10 mmol), potassium iodide (KI, 5 mmol) and tetrahydrofuran (THF, 30 mL) in a reaction flask under stirring at room temperature under nitrogen protection. The reaction process was monitored by TLC and HPLC. After the reaction was completed, the reaction liquid was concentrated, water and ethyl acetate were added, the mixture was extracted three times with ethyl acetate, the organic phases were combined and dried over anhydrous magnesium sulfate, and the reaction liquid was concentrated and recrystallized with ethyl acetate and petroleum ether to obtain carfilzomib as a white solid with an overall yield of 70%. The structural formula and the experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0194] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 8.25 (d, J=6.8 Hz, 1H), 8.09 (d, J=7.7 Hz, 1H), 7.97 (d, J=7.7 Hz, 1H), 7.90 (d, J=7.6 Hz, 1H), 7.33-7.23 (m, 2H), 7.23-7.02 (m, 8H), 4.61-4.49 (m, 1H), 4.43-4.32 (m, 2H), 4.32-4.23 (m, 1H), 3.71-3.51 (m, 4H), 3.41-3.32 (m, 1H), 3.12 (d, J=4.2 Hz, 1H), 3.06-2.85 (m, 4H), 2.81-2.70 (m, 1H), 2.57-2.51 (m, 1H), 2.47-2.38 (m, 4H), 1.93-1.76 (m, 2H), 1.69-1.59 (m, 1H), 1.55-1.47 (m, 1H), 1.43-1.28 (m, 7H), 0.89-0.83 (m, 6H), 0.83-0.76 (m, 6H). [0195] .sup.13C NMR (100 MHz, DMSO-d.sub.6) 208.2, 171.5, 171.0, 170.8, 168.8, 141.4, 137.3, 129.1, 128.2, 128.2, 127.8, 126.1, 125.8, 66.1, 61.3, 58.7, 53.2, 53.0, 51.8, 51.5, 51.1, 49.2, 40.7, 38.5, 37.4, 34.3, 31.4, 24.5, 24.1, 23.2, 23.0, 21.6, 21.0, 16.3. [0196] HRMS (ESI) m/z calcd. for C.sub.40H.sub.58N.sub.5O.sub.7 [M+H].sup.+: 720.4331, found: 720.4335.

Example 27

[0197] In this example, octreotide was prepared, and the specific process was as follows:

##STR00036##

[0198] Boc-D-Phe-OH (5 mmol) and N-methyl-N-p-toluenesulfonyl ethynylamine (5.5 mmol) were taken and dissolved in 20 mL of dichloromethane, and the mixture was reacted under stirring at room temperature. The reaction process was monitored by TLC. When the raw material acid was completely consumed, the solvent was removed by distillation under reduced pressure, and the product was transferred to a system, in which H-Cys(Trt)-OH (10 mmol), N,N-diisopropylethylamine (10 mmol), acetonitrile (40 mL), and water (20 mL) were mixed under stirring in advance, and reacted. The reaction process was monitored by TLC. After the reaction was completed, 50 mL of water was added, the product was acidified to pH=3 with 10% citric acid, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed once with water and once with a saturated table salt solution, dried over anhydrous sodium sulfate, distilled under reduced pressure to remove the solvent, recrystallized with dichloromethane and diethyl ether, and filtered to collect a solid, thus obtaining Boc-D-Phe-Cys(Trt)-OH. The above steps were repeated for condensation with H-D-Trp-OH, H-Lys(Boc)-OH, H-Thr(tBu)-OH, H-Cys(Trt)-OH, and L-threoninol in order to obtain a protected linear chain Boc-D-Phe-Cys(Trt)-Phe-D-Trp-Lys(Boc)-Thr(tBu)-Cys(Trt)-Thr-ol of octreotide, and the intermediate was added to a reaction flask, in which trifluoroacetic acid (42.5 mL), 1,2-ethanedithiol (2.5 mL), triisopropylsilane (2.5 mL) and water (2.5 mL) had been mixed in advance, and stirred. The reaction was monitored by TLC and HPLC. After the reaction was completed, recrystallization with diethyl ether was carried out to obtain a linear chain of octreotide. Finally, the linear chain of octreotide was dissolved in water and diluted to a concentration of 104 M, the solution was adjusted to pH =8 with 1 mmol aqueous ammonia, air was introduced for oxidation for 48 h at room temperature, and after freeze-drying, octreotide was obtained as a white solid with an overall yield of 45%.

[0199] The structural formula and the experimental data of magnetic resonance imaging and mass spectrometry of the product were as follows: [0200] .sup.1H NMR (400 MHz, DMSO-d.sub.6) 10.88 (s, 1H), 9.04 (d, J=8.2 Hz, 1H), 8.70 (d, J=4.5 Hz, 1H), 8.52 (d, J=7.5 Hz, 1H), 8.40 (d, J=7.3 Hz, 1H), 8.34 (d, J=8.4 Hz, 1H), 8.28-8.09 (m, 3H), 7.98-7.85 (m, 3H), 7.71 (d, J=8.5 Hz, 1H), 7.45 (d, J=7.8 Hz, 1H), 7.39-7.26 (m, 8H), 7.21-7.18 (m, 2H), 7.14-7.05 (m, 4H), 7.02-6.97 (m, 2H), 5.09 (d, J=4.0 Hz, 1H), 5.03-4.97 (m, 1H), 4.90-4.85 (m, 1H), 4.83-4.72 (m, 1H), 4.64 (s, 1H), 4.42 (dd, J=8.4, 5.4 Hz, 1H), 4.24 (dd, J=14.5, 7.5 Hz, 2H), 4.12-4.06 (m, 1H), 4.00-3.92 (m, 2H), 3.66-3.61 (m, 1H), 3.18 (dd, J=13.8, 5.2 Hz, 1H), 3.02-2.95 (m, 3H), 2.92-2.72 (m, 7H), 2.65-2.57 (m, 2H), 1.73-1.64 (m, 1H), 1.42-1.31 (m, 3H), 1.11 (d, J=6.2 Hz, 3H), 1.05 (d, J=6.4 Hz, 3H), 0.89-0.77 (m, 2H). [0201] .sup.13C NMR (101 MHz, DMSO-d.sub.6) 172.53, 171.87, 170.65, 170.39, 169.59, 168.47, 168.10, 136.81, 136.14, 134.76, 129.66, 129.04, 128.54, 128.09, 127.23, 127.05, 126.44, 123.69, 120.90, 118.26, 118.18, 111.34, 109.03, 66.63, 64.23, 60.20, 58.58, 55.90, 55.22, 53.97, 53.36, 53.23, 52.55, 52.01, 44.17, 42.39, 38.78, 38.52, 37.42, 30.26, 26.44, 26.38, 22.03, 19.92, 19.50. [0202] HRMS (ESI) m/z calcd. for C.sub.49H.sub.67N.sub.10O.sub.10S.sub.2[M+H].sup.+: 1019.4478, found: 1019.4483.

[0203] The present disclosure provides a method for synthesizing an amide and/or a polypeptide using an unprotected amino acid as an ammonia component. In the preparation method for the polypeptide, after a peptide bond is constructed, the next amino acid can be directly condensed without deprotection operation, thereby reducing many unnecessary protecting agents, deprotecting agents and purification solvents, and reducing the use of chemicals and the generation of chemical wastes. Furthermore, the cost of polypeptide synthesis is greatly reduced, the atomic economy and step economy of polypeptide synthesis are improved, the efficiency of polypeptide synthesis is greatly improved, energy conservation and emission reduction are efficiently achieved, so that it has broad industrial application prospects.

[0204] The examples of the present disclosure have been described in detail above; however, the present disclosure is not limited to the above examples, and various changes can also be made within the knowledge of those of ordinary skill in the related technical field without departing from the gist of the present disclosure. In addition, the examples of the present disclosure and the features in the examples can be combined with each other without conflict.