Aromatic dipeptide functionalized mercapto compounds, methods of making and using the same

Abstract

The application relates to the technical field of compound synthesis, and discloses an aromatic dipeptide functionalized mercapto compound, 3,5-di(triphenylmethylthio)benzoic acid is obtained by adding 3,5-di(methylmercapto)benzoic acid and pyridine into a solution of chloromethyl triphenylphosphonium, purifying after sufficient reaction; then the 3,5-di(triphenylmethylthio)benzoic acid is mixed with N-hydroxysuccinimide and dissolved in an organic solvent, EDC.HCl is added, purifying after sufficient reaction; then 2,5-dioxopyrrolidin-1-yl 3,5-bis(triphenylmethylthiomethyl)benzoate is obtained; then phenylalanine-tryptophan and triethylamine are added, purifying after sufficient reaction; then (3,5-bis(triphenylmethylthiomethyl)benzoyl)tryptophylphenylalanine is obtained; then trifluoroacetic acid and triethylsilane are added, purifying after sufficient reaction; and finally the aromatic dipeptide functionalized mercapto compound is obtained. The aromatic dipeptide functionalized mercapto compound can quickly and effectively identify sodium and potassium ions, and has relatively low detection limit and relatively loose detection condition.

Description

A thiol compound functionalized with an aromatic dipeptide, its preparation method and application Technical Field

[0001] This invention relates to the field of compound synthesis technology, and in particular to an aromatic dipeptide-functionalized thiol compound, its preparation method, and its application in metal ion detection. Background Technology

[0002] Sodium and potassium ions play a vital role in our daily lives. For the human body, they are essential components, maintaining osmotic balance in the body's life systems, playing a crucial role in transmitting biological information, and widely participating in various physiological processes. For the human environment, sodium and potassium ions enter plants and animals through water and soil, affecting their growth and development. Furthermore, since the Industrial Revolution, with rapid industrial development, numerous different types of Na and K metal salts have been applied. Although sodium and potassium ions are both alkali metal ions with extremely similar electronic structures and chemical properties, they often produce different effects in laboratory experiments and industrial production. The similarity in morphology, properties, and color of their metal salts makes it difficult to quickly distinguish between Na and K ions in daily life, laboratory experiments, and industrial production.

[0003] To date, both laboratory and industrial production still use potassium antimonate and sodium cobalt nitrite to identify sodium and potassium ions separately. This method has high detection limits, leading to large reagent consumption. Furthermore, each reagent can only detect one metal ion and has strict pH requirements. Therefore, developing a reagent with lower detection limits, more flexible detection conditions, and the ability to effectively and rapidly identify sodium and potassium ions is of paramount importance. Summary of the Invention

[0004] In view of this, the present invention provides an aromatic dipeptide-functionalized thiol compound and applies the compound to a metal ion detection reagent to solve the problems of high detection limit and harsh detection conditions of existing metal ion detection reagents.

[0005] To solve the above-mentioned technical problems, the present invention adopts the following technical solution:

[0006] The first objective of this invention is to provide an aromatic dipeptide-functionalized thiol compound, the molecular structure of which is as follows:

[0007]

[0008] A second objective of this invention is to provide a method for preparing the above-mentioned aromatic dipeptide-functionalized thiol compound, comprising the following steps:

[0009] (1) Mix triphenylmethylchloromethane solution with 3,5-bis(meththio)benzoic acid solution, then add pyridine, stir and react for 15-25 h, separate and purify to obtain 3,5-bis(triphenylmethylthio)benzoic acid;

[0010] (2) Mix 3,5-bis(triphenylmethylthio)benzoic acid with N-hydroxysuccinimide and dissolve it in an organic solvent. Continue to add EDC·HCl, stir the reaction, separate and purify to obtain 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate.

[0011] (3) Under a protective atmosphere, 2,5-dioxyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan, and triethylamine were added to DMF and reacted for 20-30 h. After separation and purification, (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine was obtained.

[0012] (4) Under a protective atmosphere, trifluoroacetic acid was added to (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine, and the reaction was allowed to proceed. After the reaction was completed, triethylsilane was added to the solution, and the mixture was separated and purified to obtain an aromatic dipeptide-functionalized thiol compound.

[0013] Preferably, in the above method for preparing the aromatic dipeptide-functionalized thiol compound, the molar ratio of triphenylmethylchloromethane, 3,5-di(methimero)benzoic acid and pyridine in step (1) is 10-15:2-5:5-10, and more preferably 12.9:3.81:8.6;

[0014] And / or the triphenylmethylchloromethane solution is a solution obtained by dissolving triphenylmethylchloromethane in degassed dichloromethane;

[0015] And / or the 3,5-bis(methmercapto)benzoic acid solution is a solution obtained by dissolving 3,5-bis(methmercapto)benzoic acid in degassed acetonitrile.

[0016] Preferably, in the above method for preparing the functionalized thiol compound of aromatic dipeptide, the stirring reaction temperature in step (1) is 20-35°C, and the stirring reaction is further followed by vacuum concentration and column purification process;

[0017] More preferably, the developing solvent in the column purification process is a mixture of petroleum ether and ethyl acetate in a volume ratio of 3:1.

[0018] Preferably, in the above method for preparing the functionalized thiol compound of aromatic dipeptide, the molar ratio of 3,5-bis(triphenylthio)benzoic acid, N-hydroxysuccinimide and EDC·HCl in step (2) is 1:3-5:3-5, and more preferably 1:4:4.

[0019] Preferably, in the above method for preparing the aromatic dipeptide-functionalized thiol compound, step (2) specifically includes the following steps:

[0020] (2-1) Mix 3,5-bis(triphenylthio)benzoic acid with N-hydroxysuccinimide and dissolve it in an organic solvent, then cool it in an ice bath.

[0021] (2-2) Add EDC·HCl, stir for 10-20 min, then raise the temperature to 20-35℃ and continue stirring for 10-15 h to obtain a mixture;

[0022] (2-3) Dilute the mixture with water, adjust the pH to acidic, and obtain the precipitate. After filtration and vacuum drying, it is ready.

[0023] Preferably, in the above-mentioned method for preparing the functionalized thiol compound of aromatic dipeptide, the molar ratio of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan and triethylamine in step (3) is 0.2-0.6:1-1.5:2-2.5, and more preferably 0.47:1.2:2.2.

[0024] Preferably, in the above method for preparing the functionalized thiol compound of aromatic dipeptide, the stirring reaction in step (3) is carried out under a protective atmosphere at 20-35°C for 20-30 h to obtain a mixture;

[0025] The reaction process further includes: diluting the mixture with water, adjusting the pH to acidic, obtaining a precipitate, filtering and vacuum drying the precipitate.

[0026] Preferably, in the above-mentioned method for preparing the functionalized thiol compound of aromatic dipeptide, the molar ratio of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine, trifluoroacetic acid and triethylsilane in step (4) is 0.05-0.15:15-20:0.2-0.6, and more preferably 0.09:18.85:0.44.

[0027] Preferably, in the above method for preparing the aromatic dipeptide-functionalized thiol compound, step (4) specifically includes:

[0028] (4-1) Under a protective atmosphere, degassed trifluoroacetic acid was added to (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine and stirred at 20-35°C for 3-5 hours.

[0029] (4-2) Add triethylsilane, stir at 20-35℃ for 20-50 min, remove volatiles under vacuum, wash the solid precipitate and dry it under vacuum.

[0030] A third objective of this invention is to provide an application of the above-mentioned aromatic dipeptide-functionalized thiol compound in the identification of metal ions.

[0031] Preferably, in the application of the above-mentioned aromatic dipeptide-functionalized thiol compounds in the identification of metal ions, the metal ions include sodium ions and potassium ions.

[0032] This invention discloses an aromatic dipeptide-functionalized thiol compound, which has the following advantages compared with the prior art:

[0033] This invention innovatively combines aromatic dipeptides with a thiol host to prepare aromatic dipeptide-functionalized thiol compounds, which can be used to prepare rapid and effective detection reagents for identifying sodium and potassium ions. Compared with existing methods that use potassium antimonate and sodium cobalt nitrite to identify sodium and potassium ions separately, this invention can identify sodium and potassium ions using only one detection reagent, and has a relatively low detection limit, more lenient detection conditions, and can effectively and rapidly identify sodium and potassium ions.

[0034] Furthermore, the aromatic dipeptide-functionalized thiol compounds of this invention have great application potential in the fields of medicine, pesticides, dyes, and polymer materials. The development of these compounds has significant research value and practical application value. Attached Figure Description

[0035] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0036] Figure 1 shows 3,5-bis(triphenylthio)benzoic acid. 1 H NMR spectrum;

[0037] Figure 2 shows the high-resolution mass spectrum of 3,5-bis(triphenylthio)benzoic acid;

[0038] Figure 3 shows 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate. 1 H NMR spectrum;

[0039] Figure 4 shows the high-resolution mass spectrum of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate.

[0040] Figure 5 shows (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine. 1 H NMR spectrum;

[0041] Figure 6 shows the high-resolution mass spectrum of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine;

[0042] Figure 7 shows aromatic dipeptide-functionalized thiol compounds. 1 H NMR spectrum;

[0043] Figure 8 shows the high-resolution mass spectrum of the aromatic dipeptide-functionalized thiol compound.

[0044] Figure 9 shows the application of aromatic dipeptide-functionalized thiol compounds in Na. + K + Schematic diagram of the identification results;

[0045] Figure 10 shows the application of aromatic dipeptide-functionalized thiol compounds in Na. + K + Schematic diagram of the identification results (2). Detailed Implementation

[0046] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0047] This invention innovatively combines an aromatic dipeptide with a thiol host to prepare an aromatic dipeptide-functionalized thiol compound, as well as a detection reagent that can rapidly and effectively identify sodium and potassium ions. This aromatic dipeptide-functionalized thiol compound has great application potential in the fields of medicine, pesticides, dyes, and polymer materials.

[0048] The synthesis steps of aromatic dipeptide-functionalized thiol compounds are described below through specific examples.

[0049] Example 1

[0050] The preparation process of an aromatic dipeptide-functionalized thiol compound is as follows:

[0051]

[0052] (1) Synthesis of 3,5-bis(triphenylthio)benzoic acid (D-2)

[0053] Under a nitrogen atmosphere, a mixed solution was prepared by dissolving triphenylmethylchloromethane (3.6 g, 12.9 mmol) in degassed dichloromethane (30 mL) and a mixed solution was prepared by dissolving 3,5-di(methimazole)benzoic acid (0.80 g, 3.81 mmol) in degassed acetonitrile (90 mL). The two mixed solutions were then combined in a 300 mL two-necked flask, and pyridine (0.69 mL, 8.6 mmol) was added. The solution was stirred at room temperature for 20 hours to obtain a pale yellow, clear, transparent solution. Vacuum concentration yielded a crude product, a pale yellow solid, which was purified by column chromatography (PE / EA = 3:1) to collect a white solid (1.47 g, 55.1%). f Raw material: 0; Product: 0.25.

[0054] Figure 1 shows 3,5-bis(triphenylthio)benzoic acid. 1 Figure 2 shows the high-resolution mass spectrum of 3,5-bis(triphenylthio)benzoic acid, along with its 1H NMR spectrum. 1 H NMR (400MHz, CDCl3) δ7.65 (s, 2H), 7.45 (d, J=7.1Hz, 12H), 7.30 (t, J=7.5Hz, 13H), 7.22 (t, J=7.3Hz, 6H), 3.31 (s, 4H); 13 C NMR (101MHz, CDCl3) δ144.54, 138.10, 129.66, 128.06, 126.86, 67.69, 36.43.MS: m / z: calcd: 697.2240; found: 697.2229 [M-H + ].

[0055] (2) Synthesis of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate (D-3)

[0056] A mixture of 3,5-bis(triphenylmethylthio)benzoic acid (0.41 g, 1.5 mmol) and N-hydroxysuccinimide (NHS) (0.69 g, 6 mmol) was dissolved in DMF (50 mL) and cooled in an ice bath. EDC·HCl (1.15 g, 6 mmol) was added to the solution, and the mixture was stirred in a melted ice bath for 15 min, followed by stirring at room temperature for 12 h. The mixture was diluted with water (50 mL), and acidic solution was added dropwise with 1 M HCl, resulting in an immediate white precipitate. The precipitate was collected by filtration and dried under vacuum to give a pure white solid, 2,5-dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate (0.78 g, 65.2%). RF starting material: 0; product: 0.487.

[0057] Figure 3 shows the 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate. 1 Figure 4 shows the high-resolution mass spectrum of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate. 1 H NMR (400MHz, CDCl3) δ7.62 (s, 2H), 7.46 (d, J=8.3Hz, 12H), 7.32 (t, J=7.5Hz, 13H), 7.24 (t, J=7.2Hz, 6H), 3.35 (s, 4H), 2.92 (s, 4H); 13 CNMR (101MHz, CDCl3) δ169.15, 146.89, 144.40, 138.70, 136.14, 129.62, 129.51, 128.06, 127.96 , 127.30, 126.89, 125.19, 67.74, 36.22, 25.72.MS: m / z: calcd: 817.5369; found: 817.5792[M+Na + ].

[0058] (3)(3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine)

[0059] Synthesis of (D-4)

[0060] 2,5-Dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate (0.22 g, 0.47 mmol) was dissolved in a 100 mL two-necked flask containing DMF (30 mL). Phenylalanine-tryptophan (Trp-phe) (0.43 g, 1.2 mmol) and triethylamine (0.3 mL, 2.2 mmol) were added. The solution was stirred for 24 hours at room temperature under a nitrogen atmosphere. The mixture was diluted with water (50 mL), and acidity was reached by adding 1 M HCl dropwise. A powdery white precipitate immediately appeared. The precipitate was collected by filtration and dried under vacuum to obtain a powdery white solid (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine (0.41 g, 84.9%). RF feedstock 1:0, feedstock 2:0; product: 0.312.

[0061] Figure 5 shows (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine) 1 Figure 6 shows the high-resolution mass spectrum of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine. 1 H NMR (400MHz, CDCl3) δ7.63 (s, 1H), 7.47 (dd, J=7.6, 2.2Hz, 30H), 7.07–7.02 (m, 4 H), 6.96 (d, J=13.9Hz, 5H), 3.36 (s, 4H), 3.31 (s, 4H), 2.99 (s, 1H), 2.92 (s, 1H). 13 C NMR (101MHz, CDCl3) δ173.66, 169.22, 146.88, 144.50, 144.39, 138.69, 138.15, 136.16, 135.65, 133.66, 129.64, 129.61, 129.25, 128.50, 128 .06, 127.30, 126.88, 126.42, 123.71, 118.73, 111.43, 109.92, 67.64, 54.02, 36.41, 25.70.MS: m / z: calcd: 1030.3718; found: 1030.3715 [M-H + ].

[0062] (4) Synthesis of aromatic dipeptide-functionalized thiol compounds (D-5)

[0063] In a Schlenk tube containing (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine (0.1 g, 0.09 mmol), degassed trifluoroacetic acid (1.4 mL, 18.85 mmol) was added under N2. The solution was stirred at room temperature for 4 hours, followed by the addition of triethylsilane (0.07 mL, 0.44 mmol). Precipitation was immediately observed. The mixture was stirred for another 30 minutes, and volatiles were removed under vacuum. The remaining solid was washed with Et2O and dried under vacuum to give a pale green solid (3,5-bis(mercaptomethyl)benzoyl)tryptophanylphenylalanine (0.05 g, 88.4%). RF starting material: 0.48g; product: 0g.

[0064] Figure 7 shows an aromatic dipeptide-functionalized thiol compound. 1 Figure 8 shows the high-resolution mass spectrum of the aromatic dipeptide-functionalized thiol compound, along with its NMR spectrum. 1 H NMR (400MHz, MeOD) δ7.98 (d, J=1.7Hz, 1H), 7.56–7.16 (m, 2H), 7.20–7.12 (m, 10H), 3.79 (d, J=8.6Hz, 4H), 3.69 (s, 4H), 2.90 (d, J=2.0Hz, 2H). 13 CNMR (101MHz, DMSO) δ173.18, 142.41, 137.89, 129.60, 128.65, 126.89, 126.30, 53.93, 31.13, 29.00, 27.98.MS: m / z: calcd: 546.1527; found: 546.1519 [M-H + ].

[0065] The aromatic dipeptide-functionalized thiol compound prepared in Example 1 was applied to Na + K + The specific steps for identification are as follows:

[0066] (1) Dissolve the aromatic dipeptide functionalized thiol compound in methanol to prepare an aromatic dipeptide functionalized thiol compound solution with a concentration of 50 mM.

[0067] (2) According to the volume ratio V 巯基化合物溶液 / V 三乙胺 Triethylamine was added to the above aromatic dipeptide-functionalized thiol compound solution at a ratio of 250:1 to obtain a metal ion detection reagent.

[0068] (3) Take 500uL of metal ion detection reagent and add it to two sample bottles. Add 12.5uL of 2M sodium bromide aqueous solution to one sample bottle and 12.5uL of 2M potassium bromide aqueous solution to the other sample bottle. Observe the changes in the solution.

[0069] As shown in Figure 9, it can be observed that the solution with added sodium bromide turns pink, while the solution with added potassium bromide turns pale yellow, thus distinguishing sodium ions from potassium ions.

[0070] Alternatively, the aromatic dipeptide functionalized thiol compound prepared in Example 1 can be applied to Na + K + The specific steps for identification are as follows:

[0071] (1) Dissolve the aromatic dipeptide functionalized thiol compound in methanol to prepare an aromatic dipeptide functionalized thiol compound solution with a concentration of 50 mM.

[0072] (2) Take 500uL of aromatic dipeptide functionalized thiol compound solution and add it to two sample bottles respectively. Add 12.5uL of 2M sodium bromide aqueous solution to one sample bottle and add 12.5uL of 2M potassium bromide aqueous solution to the other sample bottle.

[0073] (3) According to the volume ratio V 巯基化合物溶液 / V 三乙胺 Add triethylamine to the above solution at a ratio of 250:1 and observe the changes in the solution.

[0074] As shown in Figure 10, it can be observed that the solution with added sodium bromide turns pink, while the solution with added potassium bromide turns pale yellow, thus distinguishing sodium ions from potassium ions.

[0075] Therefore, it can be explained that the use of aromatic dipeptide-functionalized thiol compounds to treat Na + K + During ion detection, the order in which the salt solution or triethylamine is added has no effect on the detection performance; the main component is the aromatic dipeptide-functionalized thiol compound.

[0076] Example 2

[0077] Example 2 is basically the same as Example 1, except that the molar ratio of triphenylmethylchloromethane, 3,5-di(methmercapto)benzoic acid and pyridine is 10:2:5.

[0078] Example 3

[0079] Example 3 is basically the same as Example 1, except that the molar ratio of triphenylmethylchloromethane, 3,5-di(methmercapto)benzoic acid and pyridine is 15:5:10.

[0080] Comparative Example 1

[0081] Comparative Example 1 is basically the same as Example 1, except that the molar ratio of triphenylmethylchloromethane, 3,5-di(methimerol)benzoic acid and pyridine is 8:5:8.

[0082] Comparative Example 2

[0083] Comparative Example 2 is basically the same as Example 1, except that the molar ratio of triphenylmethylchloromethane, 3,5-di(methimerol)benzoic acid and pyridine is 16:3:10.

[0084] Comparative Example 3

[0085] Comparative Example 3 is basically the same as Example 1, except that after adding pyridine, the solution is stirred at room temperature for 10 hours.

[0086] Comparative Example 4

[0087] Comparative Example 4 is basically the same as Example 1, except that after adding pyridine, the solution is stirred at 15°C for 20 hours.

[0088] Comparative Example 5

[0089] Comparative Example 5 is basically the same as Example 1, except that after adding pyridine, the solution is stirred at 35°C for 20 hours.

[0090] The yields of 3,5-bis(triphenylthio)benzoic acid synthesized in Examples 2-3 and Comparative Examples 1-5 were statistically analyzed, and the results are shown in Table 1:

[0091] Table 1

[0092]

[0093]

[0094] As shown in Table 1, the ratio of raw materials, reaction temperature, and reaction time have a significant impact on the yield of 3,5-bis(triphenylthio)benzoic acid during its synthesis.

[0095] Example 4

[0096] Example 4 is basically the same as Example 1, except that the molar ratio of 3,5-bis(triphenylthio)benzoic acid, N-hydroxysuccinimide and EDC·HCl is 1:3:3.

[0097] Example 5

[0098] Example 5 is basically the same as Example 1, except that the molar ratio of 3,5-bis(triphenylthio)benzoic acid, N-hydroxysuccinimide and EDC·HCl is 1:5:5.

[0099] Comparative Example 6

[0100] Comparative Example 6 is basically the same as Example 1, except that the molar ratio of 3,5-bis(triphenylthio)benzoic acid, N-hydroxysuccinimide and EDC·HCl is 1:2:4.

[0101] Comparative Example 7

[0102] Comparative Example 7 is basically the same as Example 1, except that the molar ratio of 3,5-bis(triphenylthio)benzoic acid, N-hydroxysuccinimide and EDC·HCl is 2:4:4.

[0103] Comparative Example 8

[0104] Comparative Example 8 is basically the same as Example 1, except that there is no ice bath cooling process.

[0105] A mixture of 3,5-bis(triphenylmethylthio)benzoic acid (0.41 g, 1.5 mmol) and N-hydroxysuccinimide (NHS) (0.69 g, 6 mmol) was dissolved in DMF (50 mL). EDC·HCl (1.15 g, 6 mmol) was added to the solution, and the mixture was stirred at room temperature for 12 h. The mixture was diluted with water (50 mL), and 1 M HCl was added dropwise until acidic, resulting in an immediate white precipitate. The precipitate was collected by filtration and dried under vacuum to obtain a pure white solid, 2,5-dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate.

[0106] The yields of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate synthesized in Examples 4-5 and Comparative Examples 6-8 were statistically analyzed, and the results are shown in Table 2:

[0107] Table 2

[0108] D-2 Yield / % D-3 Yield / % D-4 Yield / % D-5 Yield / % Example 1: 55.16 5.28 4.98 8.4 Example 4: 54.05 7.88 4.68 8.3 Example 5: 54.86 5.48 5.08 8.2 Comparative Example 6: 54.95 1.88 4.88 8.5 Comparative Example 7: 55.24 5.18 4.58 8.4 Comparative Example 8: 55.16 2.18 5.08 8.2 surface

[0109] As shown in Table 2, the ratio of the amount of raw materials added has a significant impact on the yield of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate during its synthesis.

[0110] Example 6

[0111] Example 6 is basically the same as Example 1, except that the molar ratio of 2,5-dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan and triethylamine is 0.2:1:2.

[0112] Example 7

[0113] Example 7 is basically the same as Example 1, except that the molar ratio of 2,5-dioxyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan and triethylamine is 0.6:1.5:2.5.

[0114] Comparative Example 9

[0115] Comparative Example 9 is basically the same as Example 1, except that the molar ratio of 2,5-dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan and triethylamine is 0.8:1.3:2.2.

[0116] Comparative Example 10

[0117] Comparative Example 10 is basically the same as Example 1, except that the solution was stirred for 15 hours at room temperature under a N2 atmosphere.

[0118] Comparative Example 11

[0119] Comparative Example 11 is basically the same as Example 1, except that the solution was stirred at room temperature under a N2 atmosphere for 35 hours.

[0120] The yields of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine synthesized in Examples 6-7 and Comparative Examples 9-11 were statistically analyzed, and the results are shown in Table 3:

[0121] Table 3

[0122] D-2 Yield / % D-3 Yield / % D-4 Yield / % D-5 Yield / % Example 1: 55.16 5.28 4.98 8.4 Example 6: 55.26 5.18 5.58 8.2 Example 7: 54.96 4.87 3.68 8.3 Comparative Example 9: 54.76 4.96 3.18 8.0 Comparative Example 10: 55.06 5.07 2.48 8.5 Comparative Example 11: 55.16 5.08 4.28 8.4 surface

[0123] As shown in Table 3, the ratio of raw material additions and the reaction time have a significant impact on the yield of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine during its synthesis.

[0124] Example 8

[0125] Example 8 is basically the same as Example 1, except that the molar ratio of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine, trifluoroacetic acid and triethylsilane is 0.05:15:0.2.

[0126] Example 9

[0127] Example 8 is basically the same as Example 1, except that the molar ratio of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine, trifluoroacetic acid and triethylsilane is 0.15:20:0.6.

[0128] Comparative Example 12

[0129] Comparative Example 12 is essentially the same as Example 1, except that the molar ratio of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine, trifluoroacetic acid, and triethylsilane is 0.03:16.5:0.3.

[0130] Comparative Example 13

[0131] Comparative Example 13 was essentially the same as Example 1, except that degassed trifluoroacetic acid (1.4 mL, 18.85 mmol) was added to a Schlenk tube containing (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine (0.1 g, 0.09 mmol) under N2, and the mixture was stirred at room temperature for 2 hours. Then, triethylsilane (0.07 mL, 0.44 mmol) was added. Precipitation was immediately observed. The mixture was stirred for another 30 minutes, and the volatiles were removed under vacuum. The remaining solid was washed with Et2O and dried under vacuum to obtain a pale green solid (3,5-bis(thiomethyl)benzoyl)tryptophanylphenylalanine.

[0132] The yields of (3,5-bis(mercaptomethyl)benzoyl)tryptophanylphenylalanine synthesized in Examples 8-9 and Comparative Examples 12-13 were statistically analyzed, and the results are shown in Table 4:

[0133] Table 4

[0134] D-2 Yield / % D-3 Yield / % D-4 Yield / % D-5 Yield / % Example 1: 55.16 5.28 4.98 8.4 Example 8: 55.16 5.38 4.78 9.1 Example 9: 54.76 4.98 4.57 4.2 Comparative Example 1: 55.06 5.18 4.88 8.9 Comparative Example 1: 55.26 5.28 5.15 5.7 surface

[0135] As shown in Table 4, the ratio of raw material additions and the reaction time have a significant impact on the yield of (3,5-bis(mercaptomethyl)benzoyl)tryptophanylphenylalanine during its synthesis.

[0136] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on its differences from other embodiments. Similar or identical parts between embodiments can be referred to interchangeably. The solutions disclosed in the embodiments are described simply because they correspond to the methods disclosed in the embodiments; relevant parts can be found in the method section.

[0137] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A thiol compound functionalized with an aromatic dipeptide, characterized in that, The molecular structural formula of the compound is as follows:

2. A method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 1, characterized in that, The process includes the following steps: (1) mixing a triphenylmethylchloromethane solution with a 3,5-di(meththio)benzoic acid solution, then adding pyridine, stirring for 15-25 h, separating and purifying to obtain 3,5-di(triphenylmethylthio)benzoic acid; (2) mixing 3,5-di(triphenylmethylthio)benzoic acid with N-hydroxysuccinimide and dissolving in an organic solvent, then adding EDC·HCl, stirring for reaction, separating and purifying to obtain 2,5-dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate; (3) under a protective atmosphere, 2,5 - Dioxopyrrolidine-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan, and triethylamine were added to DMF and reacted for 20-30 h. After separation and purification, (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine was obtained; (4) Trifluoroacetic acid was added to (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine under a protective atmosphere and reacted for a long time. After the reaction was completed, triethylsilane was added to the solution and separated and purified to obtain an aromatic dipeptide-functionalized thiol compound.

3. The method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 2, characterized in that, In step (1), the molar ratio of triphenylmethylchloromethane, 3,5-di(meththio)benzoic acid and pyridine is 10-15:2-5:5-10; in step (2), the molar ratio of 3,5-di(triphenylmethylthio)benzoic acid, N-hydroxysuccinimide and EDC·HCl is 1:3-5:3-5; in step (3), the molar ratio of 2,5-dioxopyrrolidone-1-yl 3,5-bis((triphenylmethylthio)methyl)benzoate, phenylalanine-tryptophan and triethylamine is 0.2-0.6:1-1.5:2-2.5; in step (4), the molar ratio of (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine, trifluoroacetic acid and triethylsilane is 0.05-0.15:15-20:0.2-0.

6.

4. The method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 2, characterized in that, The stirring reaction in step (1) also includes a vacuum concentration and column purification process; the developing solvent in the column purification process is a mixed solution of petroleum ether and ethyl acetate with a volume ratio of 2-5:

1.

5. The method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 2, characterized in that, Step (2) specifically includes the following steps: (2-1) Mix 3,5-bis(triphenylthio)benzoic acid and N-hydroxysuccinimide and dissolve them in an organic solvent, then cool in an ice bath; (2-2) Add EDC·HCl, stir for 10-20 min, then heat and continue stirring for 10-15 h to obtain a mixture; (2-3) Dilute the mixture with water, adjust the pH to acidic, obtain a precipitate, filter and vacuum dry it.

6. The method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 2, characterized in that, The stirring reaction described in step (3) further includes: adding water to dilute the mixture, adjusting the pH value to acidic, obtaining a precipitate, filtering and vacuum drying.

7. The method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 2, characterized in that, Step (4) specifically includes the following steps: (4-1) Under a protective atmosphere, degassed trifluoroacetic acid is added to (3,5-bis((triphenylmethylthio)methyl)benzoyl)tryptophanylphenylalanine and stirred for 3-5 hours; (4-2) Triethylsilane is added and stirred for 20-50 minutes. Volatile substances are removed under vacuum, and the solid precipitate is washed and then dried under vacuum.

8. The method for preparing the aromatic dipeptide-functionalized thiol compound according to claim 2, characterized in that, The temperature of the stirring reaction in steps (1)-(4) is 20-35℃.

9. The application of a thiol compound functionalized with an aromatic dipeptide as described in claim 1 in the identification of sodium and potassium ions.

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