Preparation method of dipeptide-2

Abstract

The invention provides a preparation method of dipeptide-2, which comprises the following specific steps: carrying out amino protection on L-valine by using 2-(trimethylsilyl) ethoxycarbonyl, carrying out condensation reaction on the product and L-tryptophan benzyl ester, carrying out deprotection to remove the 2-(trimethylsilyl) ethoxycarbonyl, removing benzyl under a palladium-carbon hydrogenation condition, and purifying to obtain the dipeptide-2. Belongs to the technical field of organic synthesis. According to the method, 2-(trimethylsilyl) ethoxycarbonyl is adopted as an amino acid protecting group, amino groups can be accurately and specifically protected, the operation steps of protecting the amino acids are simplified, conditions are simple to control and easy to implement, meanwhile, a dipeptide intermediate is generated through a condensation reaction, and a good product foundation is laid for subsequent preparation steps of dipeptide-2; in addition, the process reaction is rapid, the operation steps are simple and clear, the used reagents are easy to purchase and low in price, the method is very suitable for industrial large-scale production, and a new synthesis way is provided for preparation of the dipeptide-2.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a method for preparing dipeptide-2. Background Art

[0002] Dipeptide-2 is an important ingredient in cosmetics. It is composed of two standard amino acids, valine and tryptophan. Its unique structure gives dipeptide-2 the ability to be a highly effective skin conditioner, which can effectively improve skin condition. Dipeptide-2 has been widely used in eye care products such as eye creams, which helps to eliminate eye edema and dark circles. At the same time, the structure of dipeptide-2 is similar to the lipid structure in the epidermis, so it is regarded as a natural skin moisturizing factor (NMF), which can maintain the integrity of the intercellular structure of the epidermis, prevent skin irritation, and help skin regeneration. In the prior art, dipeptide-2 can be prepared by biosynthesis. For example, a study found a novel method, using the recombinant histagged protein ligase in porcine pleuropneumoniae (APP) serotype 1 strain 4074, at 37°C, in a pH 8 buffer solution, through an enzyme-catalyzed reaction, L-valine and L-tryptophan reacted for 16 hours, and dipeptide-2 was successfully synthesized. In addition, chemical synthesis methods are also used to prepare dipeptide-2. For example, a study used carboxybenzyloxycarbonyl (Cbz)-protected valine as a starting material, followed by activation with bis(pentafluorophenyl) carbonate, and the activated valine reacted with the sodium salt of tryptophan to generate a Cbz-protected dipeptide-2 intermediate, and finally the Cbz protecting group was removed by a catalytic hydrogenolysis step, thereby obtaining the final product dipeptide-2. In addition, patent CN113929734A reports another method for synthesizing dipeptide-2, which firstly protects valine with phthalic anhydride to obtain phthalyl valine, then reacts with thionyl chloride to generate phthalyl valyl chloride; then reacts with N-hydroxysuccinimide to obtain phthalyl valyl succinimide as an activated ester, and then reacts the activated ester with tryptophan to generate phthalyl valyl tryptophan; finally, the phthalyl group is removed to obtain dipeptide-2. Patent CN 114634547A also reports a method for synthesizing dipeptide-2, which uses valine and triphosgene as raw materials, synthesizes an intermediate, and then reacts with tryptophan under alkaline conditions to synthesize dipeptide-2. The various methods reported face challenges when applied to large-scale industrial production, mainly due to high costs or too harsh reaction conditions. For example, although enzyme-catalyzed reactions have potential, their activity is susceptible to various factors such as temperature, pH value and substrate concentration. These factors limit the scale and efficiency of enzyme-catalyzed reactions, making it difficult for enzyme-catalyzed methods to be widely used in large-scale industrial production. In the field of chemical synthesis, the dipeptide-2 synthesis method uses bis(pentafluorophenyl) carbonate to activate valine, and the Cbz protecting group needs to be removed by catalytic hydrogenolysis, but the reagents involved in this method are expensive, increasing production costs. In addition, the method described in patent CN113929734A uses thionyl chloride reagents, and a large amount of sulfur dioxide toxic gas will be generated during the reaction, which not only pollutes the environment, but also increases the safety risks in the production process; and although patent CN114634547A simplifies the reaction steps, it uses a large amount of toxic triphosgene as a reagent, which may not only pose a threat to human health, but also may cause serious environmental pollution problems, and is therefore not conducive to large-scale industrial production. In summary, these methods have certain limitations and challenges when applied to large-scale production. In view of the problems encountered in the current chemical synthesis of dipeptide-2, the present invention is intended to provide a new chemical method for the synthesis of dipeptide-2 and to provide a new solution for its application research and scale-up. Summary of the invention

[0003] Technical problems to be solved: In view of the above technical problems, the purpose of the present invention is to provide a method for preparing dipeptide-2, which specifically includes protecting the amino group of L-valine with 2-(trimethylsilyl)ethoxycarbonyl, condensing the product with L-tryptophan benzyl ester, removing the 2-(trimethylsilyl)ethoxycarbonyl by deprotection, debenzylation under catalytic hydrogenolysis conditions, and filtering and purifying, belonging to the technical field of organic synthesis. The present invention adopts 2-(trimethylsilyl)ethoxycarbonyl as an amino acid protecting group, which can accurately and specifically protect the amino group, simplify the operation steps of protecting amino acids, and the condition control is simple and easy to implement. At the same time, a dipeptide intermediate is generated by a condensation reaction, which lays a good product foundation for the subsequent preparation steps of dipeptide-2; in addition, the process of the present invention reacts rapidly, the operation steps are concise and clear, and the reagents used are easy to purchase and low in price, which is very suitable for industrial large-scale production, and provides a new synthetic route for the preparation of dipeptide-2.

[0004] Technical solution: A method for preparing dipeptide-2, comprising the following steps: S1. L-valine is amino-protected by 2-(trimethylsilyl)ethoxycarbonyl to obtain 2-(trimethylsilyl)ethoxycarbonyl L-valine; S2.2-(trimethylsilyl)ethoxycarbonyl L-valine and L-tryptophan benzyl ester undergo condensation reaction to generate 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester; S3. Deprotecting 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester using a deprotecting agent to obtain L-valyl L-tryptophan benzyl ester; S4. L-valyl L-tryptophan benzyl ester is hydrolyzed under palladium-carbon hydrogenation conditions to obtain dipeptide-2; its synthesis reaction formula is as follows. Furthermore, the method for protecting the amino group in step S1 is: using a substance containing 2-(trimethylsilyl)ethoxycarbonyl to protect the amino group of L-valine in reaction solvent A, and then adding triethylamine to treat at room temperature for 36-48 hours. Furthermore, the molar ratio of L-valine, the substance containing 2-(trimethylsilyl)ethoxycarbonyl and triethylamine is 1.0:(1.1-1.3):(1.5-2); and the reaction solvent A is a combination of 1,4-dioxane and water. Furthermore, the method for the condensation reaction in step S2 is: using 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine as condensation agents, 2-(trimethylsilyl)ethoxycarbonyl L-valine and L-tryptophan benzyl ester are reacted in reaction solvent B at room temperature for 6-12 hours. Furthermore, the molar ratio of the 2-(trimethylsilyl)ethoxycarbonyl L-valine, L-tryptophan benzyl ester, 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine is 1.0:(1.0-1.3):(1.2-1.5):(3.0-3.5). Furthermore, the reaction solvent B includes but is not limited to dichloromethane, 1,2-dichloroethane, and tetrahydrofuran. Furthermore, the deprotection reagent in step S3 includes but is not limited to tetrabutylammonium fluoride, tetramethylammonium fluoride, and tetraethylammonium fluoride. Furthermore, the amount of the deprotection reagent added is 2-4 times the molar mass of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester. Furthermore, the specific method of hydrolysis in step S4 is: using palladium carbon as a debenzylation reagent, reacting L-valyl L-tryptophan benzyl ester at room temperature for 12-24 hours and filtering and purifying to obtain dipeptide-2. Furthermore, the mass ratio of L-valyl L-tryptophan benzyl ester to palladium carbon is 1.0:(0.1-0.2). Beneficial effects: 1. In the preparation method of dipeptide-2 of the present invention, 2-(trimethylsilyl)ethoxycarbonyl is used as an amino protecting group, which can firmly bind to the amino group of valine to form a stable amino acid derivative, thereby effectively protecting the amino group from interference from other reaction conditions. The reaction conditions are relatively mild and easy to control, and will not induce other unnecessary side reactions, thereby achieving accurate and specific protection of the amino group. At the same time, the preparation process of the protected amino acid is greatly simplified, making it simple to operate and easy to implement. 2. The present invention uses a benzyl ester derivative of another target amino acid and a 2-(trimethylsilyl)ethoxycarbonyl protected amino acid to obtain a dipeptide-2 intermediate by a condensation reaction, which can not only reduce the occurrence of side reactions in the condensation reaction and increase the yield of the dipeptide-2 intermediate, but also has mild reaction conditions and simple operation, thus laying a good substrate foundation for the subsequent synthesis of dipeptide-2. 3. In the present invention, the removal of the amino protecting group can obtain a pure compound only through a simple operation, without the need for cumbersome post-treatment steps, thereby optimizing the entire synthesis method. Moreover, the removal of the benzyl group can also be achieved by catalytic hydrogenolysis to obtain a high-purity dipeptide-2, successfully avoiding the use of toxic chemical reagents and the generation of toxic gases. The process is simple, mild, high-yield, and low-cost, fully embodying the concept of green chemistry, and not only providing a new solution for the relevant application research of the preparation of dipeptide-2, but also providing a practical path for future large-scale production, showing broad application prospects. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 is the hydrogen spectrum of dipeptide-2 in Example 1; Figure 2 This is the carbon spectrum of dipeptide-2 in Example 1. DETAILED DESCRIPTION The present invention will be further described below in conjunction with embodiments, which are explanations of the present invention and are not limited to the following embodiments: Example 1 A method for preparing dipeptide-2 comprises the following steps: S1. 20 mL 1,4-dioxane, 20 mL H2O, 20 mmol L-valine (2.34 g), 22 mmol 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dione (5.7 g), and 30 mmol triethylamine (4.2 mL) were added to a 100 mL flask in sequence, and the mixture was then reacted at room temperature for 36 h; after the reaction was completed, saturated sodium bisulfate was added to the reaction system for acidification, and then 50 mL ethyl acetate was used for extraction 3 times, and the combined organic phase was washed once with 30 mL saturated brine; then the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to finally obtain 5.0 g 2-(trimethylsilyl)ethoxycarbonyl L-valine, and the yield was 95%; S2. To a 100 mL flask, 50 mL of dichloromethane, 19 mmol of 2-(trimethylsilyl)ethoxycarbonyl L-valine (5.0 g), 19 mmol of L-tryptophan benzyl ester (5.6 g), and 22.8 mmol of 6-Chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU, 9.43 g) and 57 mmol N,N-diisopropylethylamine (DIPEA, 9.9 mL), and then the mixture was reacted at room temperature for 6 h; after the reaction, the solvent was evaporated under vacuum to obtain a crude reaction product system, the crude product was diluted with 100 mL of ethyl acetate, and washed with 15 mL of water, 15 mL of hydrochloric acid (1N aqueous solution), 15 mL of saturated sodium bicarbonate aqueous solution and 15 mL of water in sequence, and each washing step was repeated 2 times; then the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum, and finally the product was purified by column chromatography (eluent: 30% ethyl acetate / petroleum ether) to obtain 9.1 g of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester, and the yield was 89%; S3. 20 mL of tetrahydrofuran, 17 mmol of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester (9.1 g) and 34 mL of a 1 M tetrabutylammonium fluoride (TBAF) THF solution were added to a 100 mL flask, and the mixture was reacted at 60° C. for 12 h; after completion of the reaction, the solvent was removed under vacuum to obtain a crude product, which was then dissolved in 100 mL of ethyl acetate and washed twice with 20 mL of water. Afterwards, the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to obtain 5.9 g of L-valyl L-tryptophan benzyl ester, with a yield of 88%; S4. 15.0mmol L-valyl L-tryptophan benzyl ester (5.9g) was dissolved in 40mL methanol, and then 0.59g palladium / carbon catalyst (loading amount was 10% on carbon, water content was about 55%) was added to the reaction system, and the reaction was started by bubbling hydrogen for 15 minutes; under a continuous hydrogen atmosphere, the reaction was continued for 12h. After the reaction was completed, the catalyst was removed by filtration to obtain a methanol solution; the solvent was removed under vacuum conditions, and then recrystallized to obtain 4.1g dipeptide-2 as a white solid, with a yield of 90%. Depend on Figure 1 It can be seen that the H NMR spectrum data of dipeptide-2 in Example 1: 1 HNMR (400MHz, C2D6OS) δ = 10.89 (s, 1H), 8.26 (d, J = 7.0H, 1H), 7.56 (d, J = 7.8Hz, 1H), 7.31 (d , J=8.0Hz, 1H), 7.17 (d, J=1.7Hz, 1H), 7.03 (t, J=7.5Hz, 1H), 6.94 (t, J=7.4Hz, 1H), 4.86 (s, 1H), 4.43 (d, J=5.4Hz, 1H), 3.32 (d, J=4.9Hz, 1H), 3.21 (dd, J=14.6, 4.9Hz, 1H), 3.07 (dd, J= 14.6, 7.4Hz, 1H), 2.03 (dd, J=12.1, 6.7Hz, 1H), 0.88 (d, J=6.9H, 1H), 0.79 (d, J=6.8Hz, 1H). Depend on Figure 2 It can be seen that the NMR carbon spectrum data of dipeptide-2 in Example 1: 13 CNMR (100MHz, C2D6OS) δ = 174.1, 170.7, 136.2, 127.7, 123.7, 120.8, 118.6, 118.2, 111.3, 110.7, 58.6, 54.2, 30.6, 27.8, 22.0, 19.1, 17.2. Example 2 A method for preparing dipeptide-2 comprises the following steps: S1. 20 mL 1,4-dioxane, 20 mL H2O, 20 mmol L-valine (2.34 g), 24 mmol 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dione (6.2 g), and 40 mmol triethylamine (5.6 mL) were added to a 100 mL flask in sequence, and the mixture was then reacted at room temperature for 24 h; after the reaction was completed, saturated sodium bisulfate was added to the reaction system for acidification, and then 50 mL ethyl acetate was used for extraction 3 times, and the combined organic phase was washed once with 30 mL saturated brine; then the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to finally obtain 5.07 g 2-(trimethylsilyl)ethoxycarbonyl L-valine, and the yield was 97%; S2. To a 100 mL flask, 60 mL of dichloromethane, 19.4 mmol of 2-(trimethylsilyl)ethoxycarbonyl L-valine (5.0 g), 19.4 mmol of L-tryptophan benzyl ester (5.7 g), and 23.3 mmol of 6-Chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU, 9.6 g) and 58.2 mmol N,N-diisopropylethylamine (DIPEA, 10.1 mL), and then the mixture was reacted at room temperature for 7 h; after the reaction, the solvent was evaporated under vacuum to obtain a crude reaction product system, the crude product was diluted with 100 mL of ethyl acetate, and washed with 15 mL of water, 15 mL of hydrochloric acid (1N aqueous solution), 15 mL of saturated sodium bicarbonate aqueous solution and 15 mL of water in sequence, and each washing step was repeated twice; then the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum, and finally the product was purified by column chromatography (eluent: 30% ethyl acetate / petroleum ether) to obtain 9.5 g of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester, and the yield was 91%; S3. 30 mL of tetrahydrofuran, 17.6 mmol of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester (9.5 g) and 53 mL of a 1 M tetrabutylammonium fluoride (TBAF) THF solution were added to a 200 mL flask, and the mixture was reacted at 60° C. for 6 h; after completion of the reaction, the solvent was removed under vacuum to obtain a crude product, which was then dissolved in 100 mL of ethyl acetate and washed twice with 20 mL of water. Afterwards, the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to obtain 6.2 g of L-valyl L-tryptophan benzyl ester, with a yield of 89%; S4. 15.7 mmol L-valyl L-tryptophan benzyl ester (6.2 g) was dissolved in 50 mL methanol, and then 0.62 g of palladium / carbon catalyst (loading amount was 10% on carbon, water content was about 55%) was added to the reaction system, and the reaction was started by bubbling hydrogen for 15 minutes; under a continuous hydrogen atmosphere, the reaction was continued for 14 h. After the reaction was completed, the catalyst was removed by filtration to obtain a methanol solution; the solvent was removed under vacuum conditions, and then recrystallization was performed to obtain 4.2 g of dipeptide-2 as a white solid, with a yield of 88%. Example 3 A method for preparing dipeptide-2 comprises the following steps: S1. 20 mL 1,4-dioxane, 20 mL H2O, 20 mmol L-valine (2.34 g), 24 mmol 1-[2-(trimethylsilyl)ethoxycarbonyloxy]pyrrolidine-2,5-dione (6.2 g), and 30 mmol triethylamine (4.2 mL) were added to a 100 mL flask in sequence, and the mixture was then reacted at room temperature for 36 h; after the reaction, saturated sodium bisulfate was added to the reaction system for acidification, and then 50 mL ethyl acetate was used for extraction 3 times, and the combined organic phase was washed once with 30 mL saturated brine; then the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to finally obtain 4.9 g 2-(trimethylsilyl)ethoxycarbonyl L-valine, and the yield was 94%; S2. To a 100 mL flask, 60 mL of dichloromethane, 18.8 mmol of 2-(trimethylsilyl)ethoxycarbonyl L-valine (4.9 g), 20.7 mmol of L-tryptophan benzyl ester (6.1 g), and 22.6 mmol of 6-Chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate (HCTU, 9.3 g) and 56.4 mmol N,N-diisopropylethylamine (DIPEA, 9.8 mL), and then the mixture was reacted at room temperature for 7 h; after the reaction, the solvent was evaporated under vacuum to obtain a crude reaction product system, the crude product was diluted with 100 mL of ethyl acetate, and washed with 15 mL of water, 15 mL of hydrochloric acid (1N aqueous solution), 15 mL of saturated sodium bicarbonate aqueous solution and 15 mL of water in sequence, and each washing step was repeated twice; then the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum, and finally the product was purified by column chromatography (eluent: 30% ethyl acetate / petroleum ether) to obtain 9.2 g of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester, and the yield was 91%; S3. 20 mL of tetrahydrofuran, 17.1 mmol of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester (9.2 g) and 34.2 mL of a 1 M tetrabutylammonium fluoride (TBAF) THF solution were added to a 100 mL flask, and the mixture was reacted at 60° C. for 12 h; after completion of the reaction, the solvent was removed under vacuum to obtain a crude product, which was then dissolved in 100 mL of ethyl acetate and washed twice with 20 mL of water. Afterwards, the organic phase was dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to obtain 6.0 g of L-valyl L-tryptophan benzyl ester, with a yield of 86%; S4. 14.7 mmol L-valyl L-tryptophan benzyl ester (6.0 g) was dissolved in 40 mL methanol, and then 0.6 g of palladium / carbon catalyst (loading amount was 10% on carbon, water content was about 55%) was added to the reaction system, and the reaction was started by bubbling hydrogen for 15 minutes; the reaction was continued for 12 hours under a continuous hydrogen atmosphere. After the reaction was completed, the catalyst was removed by filtration to obtain a methanol solution; the solvent was removed under vacuum conditions, and then recrystallized to obtain 4.0 g of dipeptide-2 as a white solid, with a yield of 89%. The above is only a preferred embodiment of the present invention and does not limit the present invention in any form. Any technician familiar with the art can make many possible changes and modifications to the technical solution of the present invention by using the above disclosed methods and technical contents without departing from the spirit and technical solution of the present invention, or modify it into an equivalent embodiment of equivalent changes. Therefore, any simple modification, equivalent replacement, equivalent change and modification made to the above embodiments according to the technical essence of the present invention without departing from the content of the technical solution of the present invention still falls within the scope of protection of the technical solution of the present invention.

Claims

1. A method for preparing dipeptide-2, characterized in that: The following steps are involved: S1. L-valine is amino-protected by 2-(trimethylsilyl)ethoxycarbonyl to obtain 2-(trimethylsilyl)ethoxycarbonyl L-valine; S2.2-(trimethylsilyl)ethoxycarbonyl L-valine and L-tryptophan benzyl ester undergo condensation reaction to generate 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester; S3. Deprotecting 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester using a deprotecting agent to obtain L-valyl L-tryptophan benzyl ester; S4. L-valyl L-tryptophan benzyl ester is hydrolyzed under palladium carbon hydrogenation conditions to obtain dipeptide-2.

2. The method for preparing dipeptide-2 according to claim 1, characterized in that: The method for protecting the amino group in step S1 is: using a substance containing 2-(trimethylsilyl)ethoxycarbonyl to protect the amino group of L-valine in reaction solvent A, and then adding triethylamine to treat at room temperature for 36-48 hours.

3. The method for preparing dipeptide-2 according to claim 2, characterized in that: The molar ratio of L-valine, the substance containing 2-(trimethylsilyl)ethoxycarbonyl and triethylamine is 1.0:(1.1-1.3):(1.5-2); and the reaction solvent A is a composition of 1,4-dioxane and water.

4. The method for preparing dipeptide-2 according to claim 1, characterized in that: The method for the condensation reaction in step S2 is: using 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine as condensation agents, 2-(trimethylsilyl)ethoxycarbonyl L-valine and L-tryptophan benzyl ester are reacted in reaction solvent B at room temperature for 6-12 hours.

5. The method for preparing dipeptide-2 according to claim 4, characterized in that: The molar ratio of 2-(trimethylsilyl)ethoxycarbonyl L-valine, L-tryptophan benzyl ester, 6-chlorobenzotriazole-1,1,3,3-tetramethyluronium hexafluorophosphate and N,N-diisopropylethylamine is 1.0:(1.0-1.3):(1.2-1.5):(3.0-3.5).

6. The method for preparing dipeptide-2 according to claim 4, characterized in that: The reaction solvent B includes but is not limited to dichloromethane, 1,2-dichloroethane, and tetrahydrofuran.

7. The method for preparing dipeptide-2 according to claim 1, characterized in that: The deprotection reagent in step S3 includes but is not limited to tetrabutylammonium fluoride, tetramethylammonium fluoride, and tetraethylammonium fluoride.

8. The method for preparing dipeptide-2 according to claim 6, characterized in that: The added amount of the deprotection reagent is 2-4 times the molar mass of 2-(trimethylsilyl)ethoxycarbonyl L-valyl L-tryptophan benzyl ester.

9. The method for preparing dipeptide-2 according to claim 1, characterized in that: The specific method of hydrolysis in step S4 is: using palladium carbon as a debenzylation reagent, reacting L-valyl L-tryptophan benzyl ester at room temperature for 12-24 hours and filtering and purifying to obtain dipeptide-2.

10. The method for preparing dipeptide-2 according to claim 8, characterized in that: The mass ratio of the L-valyl L-tryptophan benzyl ester to palladium carbon is 1.0:(0.1-0.2).

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