Intelligent parent dendrimers based on dasas and methods of making the same

Abstract

The application provides a kind of smart parent tree macromolecule based on DASA and a preparation method thereof.Hydrophilic alkoxy ether dendritic unit, combined with hydrophobic visible light responsive DASA, constructs a new type of smart parent tree macromolecule based on DASA.The parent tree macromolecule of the application can self-assemble in aqueous solution and its self-assembly behavior can be controlled by light and temperature.The unique topological structure of alkoxy ether dendritic unit, crowding synergistic effect and temperature-induced multi-stage dehydration collapse mechanism can construct a hydrophobic microenvironment, which can be regulated by changing the end group structure of alkoxy ether unit, alkoxy chain length and alkoxy ether arm number, so as to realize the regulation of the reversible isomerization behavior of DASA in aqueous solution.In addition, the raw materials are environmentally friendly, cheap, low toxicity and have good biocompatibility, which shows great application potential in the fields of biomedicine and photosensitive materials.

Description

Technical Field

[0001] This invention belongs to the field of smart amphiphilic molecules, and relates to a smart amphiphilic dendritic macromolecule based on DASAs and its preparation method. The smart amphiphilic dendritic macromolecule based on DASAs of this invention can have its assembly morphology and isomerization behavior controlled by temperature and visible light in an aqueous phase, and has applications in the fields of biomedicine and photosensitive materials technology. Background Technology

[0002] As a crucial component of environmentally responsive materials, photosensitive materials exhibit many key properties that can undergo controllable and reciprocal changes under external light, including optical properties (color, refractive index, transmittance), mechanical properties (modulus, hardness, viscoelasticity), and electrical properties (conductivity, dielectric properties). Compared to other environmental stimuli, such as temperature, pH, electric fields, magnetic fields, gases, and water, light's advantages as a stimulus source are mainly reflected in two aspects:

[0003] Firstly, the illumination is precisely controllable in both time and space;

[0004] Secondly, the light can be controlled without contacting the material.

[0005] Therefore, photosensitive materials have great appeal in fields such as biomedicine, cancer treatment, chip manufacturing, information storage, aerospace, security and anti-counterfeiting, plate making and printing, and microfluidics.

[0006] In 2014, Alaniz et al. reported a novel class of visible-light-responsive photochromic compounds: donor-acceptor Stenhouse adducts (DASAs). These compounds transform from a hydrophobic, colored conjugated triene structure to a hydrophilic, colorless cyclopentenone structure under visible light irradiation. This process can be reversibly reversed by heating in the dark under certain conditions (Helmy S., Leibfarth F., Oh S., et al. Photoswitching using visible light: a new class of organic photochromic molecules[J]. J. Am. Chem. Soc., 2014, 136, 8169-8172.). The significant differences in color, polarity, structure, and hydrophilicity / hydrophobicity of DASAs before and after isomerization have attracted great interest from researchers. Currently, DASAs have been successfully applied in targeted drug release, orthogonal photoactivation, thermochemical sensors, fluid velocity control, and photothermal actuation. To date, most reported work on DASAs has focused on their isomerization properties in organic solvents. Controlling the reversible isomerization behavior of DASAs in aqueous phases remains a very challenging task (Saha R., Devaraj A., Bhattacharyya S. et al. Unusual Behavior of Donor-Acceptor Stenhouse Adducts in Confined Space of a Water-Soluble Pd). II 8 Molecular Vessel[J].J.Am.Chem.Soc.2019,141,8638-8645.).

[0007] Confined microenvironments are ubiquitous in living organisms and are crucial for supporting life activities and functions. High concentrations of biomolecules within cells form specific confined microenvironments through a balance between self-aggregation and steric hindrance, effectively regulating the mobility, secondary and tertiary structures of biomolecules and their interrelationships, thereby controlling corresponding biochemical processes. To mimic the confined microenvironments in living organisms, the artificial construction of biomimetic confined microenvironments has attracted significant attention and is being used as a novel means to control the morphology, properties, or functions of molecules. The effective construction of tunable confined microenvironments at different scales has demonstrated potential applications in supramolecular chemistry, smart materials, and biochemical control. However, the structures of existing intelligent amphiphilic molecules require further optimization, and the intermolecular synergistic effects need further enhancement in terms of regulatory intelligence to better meet the needs of applications in biomedicine and photosensitive materials technology. Summary of the Invention

[0008] To address the problems of existing technologies, the present invention aims to overcome the shortcomings of existing technologies and provide a class of intelligent amphiphilic dendritic macromolecules based on DASAs and their preparation method. Hydrophilic alkoxy ether dendritic units, combined with hydrophobic visible-light-responsive DASAs, construct a novel class of temperature / visible-light dual-responsive intelligent amphiphilic dendritic macromolecules. The unique dendritic topology and intermolecular crowding synergistic effect of the alkoxy ether dendritic units can construct a hydrophobic microenvironment. By changing the end-group structure of the alkoxy ether units, the alkoxy chain length, and the number of alkoxy ether arms, the microenvironment can be regulated, thereby achieving the control of the reversible isomerization behavior of DASAs in the aqueous phase.

[0009] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0010] A smart amphiphilic dendritic macromolecule based on DASAs has the following general molecular structure formula:

[0011]

[0012] R1 is an alkoxy ether dendritic unit, which can be two-armed, three-armed, four-armed, or six-armed. The structure of R1 is as follows:

[0013]

[0014] In the structure of R1, n = 1 to 4, and R2 = Et or Me;

[0015] Where R3 can be any of the following structures:

[0016]

[0017] Preferably, the smart amphiphilic dendritic macromolecule based on DASAs described in this invention has thermosensitive properties, with a phase transition temperature range of 10–80°C.

[0018] Preferably, the DASA-based smart amphiphilic dendritic macromolecules of the present invention have photochromic properties, and the solution self-assembly behavior of the DASA-based smart amphiphilic dendritic macromolecules can be controlled by changing the temperature or light conditions.

[0019] Preferably, the unique topological structure, crowding synergistic effect, and temperature-induced multi-stage dehydration collapse mechanism of the alkoxy ether dendritic motif based on DASAs described in this invention can construct a hydrophobic microenvironment. By changing at least one of the end-group structure of the alkoxy ether motif, the length of the alkoxy chain, and the number of alkoxy ether arms, the microenvironment can be regulated, thereby achieving the regulation of the reversible isomerization behavior of DASAs in the aqueous phase.

[0020] A method for preparing a smart amphiphilic dendritic macromolecule based on DASAs according to the present invention includes the following steps:

[0021] a. Amide reaction process:

[0022] Under ice-salt bath and nitrogen protection, carboxylic acid-modified dendritic units R1-COOH, HOBT, and DIPEA were dissolved in dry DCM. When the temperature dropped to no higher than 15°C, EDC·HCl was added and the reaction was stirred for at least 30 minutes, followed by the addition of tryptophan and a reaction time of at least 12 hours. After the reaction was completed as monitored by TLC, the mixture was washed with alkali and acid by adding saturated NaHCO3 solution and saturated KHSO4 solution respectively. The organic phase was dried with anhydrous magnesium sulfate, and after filtration, solvent evaporation, and column chromatography purification, the first intermediate product RG-CONH-Tm was obtained, with the following structural formula:

[0023]

[0024] b. Reduction reaction process:

[0025] Under a nitrogen atmosphere, RG-CONH-Tm and Et3SiH obtained in step a were dissolved in TFA and stirred in an oil bath at a temperature not lower than 70°C for at least 4 hours. After the reaction was completed by TLC monitoring, the reaction solvent was removed by vacuum distillation. A NaOH aqueous solution with a mass percentage concentration of 5-10 wt% was added under ice bath conditions to adjust the pH of the mixture to an alkaline mixture with a pH of 8-10. The mixture was then extracted with an organic solvent, washed with brine, and purified by column chromatography to obtain the second intermediate product RG-CONH-T, whose structural formula is as follows:

[0026]

[0027] c. Knoevenagel condensation reaction process:

[0028] The RG-CONH-T obtained in step b was dissolved in anhydrous methanol and reacted with stirring in the dark for at least 30 minutes. Then, the solvent was removed by vacuum distillation, and the product was repeatedly washed with n-hexane to obtain the target product, a smart amphiphilic dendritic macromolecule based on DASAs, with the following structural formula:

[0029]

[0030] Preferably, in step a, the molar ratio of the carboxylic acid-modified dendritic alkoxy ether moiety R1-COOH, HOBT, DIPEA, EDC·HCl and tryptophan is 1:(1.1-1.2):2:(1.4-1.5):(2.3-3).

[0031] Preferably, in step b, the molar ratio of RG-CONH-Tm and Et3SiH is 1:(1.4 to 1.5).

[0032] Preferably, in step c, the molar ratio of RG-CONH-T to the furan derivative is 1:(1.5 to 1.7).

[0033] Preferably, in step c, the furan derivative is the product obtained by reacting R3 with furfural.

[0034] Principle of this invention:

[0035] This invention relates to a smart amphiphilic dendritic macromolecule based on DASAs, the preparation process of which includes the following steps:

[0036] a. An amidation reaction is carried out to obtain the intermediate product RG-CONH-Tm. The reaction method is as follows:

[0037]

[0038] b. Perform a reduction reaction to obtain the intermediate product RG-CONH-T, as follows:

[0039]

[0040] c. Perform a Knoevenagel condensation reaction to obtain the target product, a smart amphiphilic dendritic macromolecule based on DASAs. The reaction method is as follows:

[0041]

[0042] This invention modifies alkoxy ether dendritic units with tryptophan via amidation, and then synthesizes them with furan derivatives via Knoevenagel condensation to obtain intelligent amphiphilic dendritic macromolecules based on DASAs. These macromolecules assemble into microspheres in aqueous solution through hydrophilicity-hydrophobicity driven assembly. The structure of DASAs can be altered by visible light irradiation, and the interaction forces between the amphiphilic dendritic macromolecules and the solution can be controlled by temperature regulation, thereby achieving effective control over the morphology of the assembled structures. The unique dendritic topology and intermolecular crowding synergistic effect of the alkoxy ether dendritic units can construct hydrophobic microenvironments. These microenvironments can be modulated by changing the end-group structure, alkoxy chain length, and number of alkoxy ether arms of the alkoxy ether units, thereby achieving control over the reversible isomerization behavior of DASAs in aqueous solution.

[0043] Compared with the prior art, the present invention has the following obvious and prominent substantive features and significant advantages:

[0044] 1. This invention introduces alkoxy ether dendritic units onto DASAs, increasing their water solubility and making it possible for dendritic DASAs to isomerize in water;

[0045] 2. The intelligent amphiphilic dendritic macromolecules based on DASAs prepared in this invention exhibit a suitable hydrophilic-hydrophobic balance. They can assemble into microspheres in an aqueous phase through hydrophilic-hydrophobic drive, and the structure of DASAs can be changed by visible light irradiation. The interaction force between the amphiphilic dendritic macromolecules and the solution can be controlled by temperature, thereby achieving effective control of the morphology of the assembly.

[0046] 3. This invention introduces alkoxy ether dendritic units, whose unique tree-like topology and intermolecular crowding synergistic effect can construct hydrophobic microenvironments. By changing the end-group structure of the alkoxy ether unit, the length of the alkoxy chain, and the number of alkoxy ether arms, the microenvironment can be regulated, thereby achieving the regulation of the reversible isomerization behavior of DASAs in the aqueous phase.

[0047] 4. The intelligent amphiphilic dendritic macromolecules based on DASAs prepared in this invention possess excellent biocompatibility, visible light-activated reaction characteristics, and effective reversible recovery in the aqueous phase, giving them application potential in fields such as biomedicine and photosensitive materials. Furthermore, the method of this invention is simple, easy to implement, and low in cost, making it suitable for widespread use. Attached Figure Description

[0048] Figure 1 Et-G-CONH-Tm prepared in Example 1 of this invention 1 H NMR spectrum.

[0049] Figure 2 Et-G-CONH-T prepared in Example 1 of this invention 1 H NMR spectrum.

[0050] Figure 3 The De prepared in Example 1 of the present invention 1 H NMR spectrum.

[0051] Figure 4 The UV-Vis absorption spectrum of De prepared in Example 1 of this invention as a function of light exposure time in an aqueous phase is shown.

[0052] Figure 5 These are optical microscope images of De at different temperatures in Embodiment 1 of the present invention.

[0053] Figure 6 This shows the change in absorbance of the De chromophore (632nm) in Embodiment 1 of the present invention with visible light irradiation and light-shielded heating time. Detailed Implementation

[0054] The above solution will be further described below with reference to specific embodiments. The preferred embodiments of the present invention are described in detail below:

[0055] Example 1:

[0056] In this embodiment, a method for preparing a smart amphiphilic dendritic macromolecule based on DASAs is described, with the following specific steps:

[0057] a. Amide reaction process:

[0058] Under ice-salt bath and nitrogen protection, carboxylic acid-modified dendritic units Et-G-COOH (1.4 g, 2.3 mmol), HOBT (0.37 g, 2.7 mmol), and DIPEA (0.60 g, 4.6 mmol) were dissolved in dry DCM (80 mL). When the temperature dropped below 15 °C, EDC·HCl (0.66 g, 3.4 mmol) was added and the mixture was stirred for 30 minutes. Then, tryptophan (0.88 g, 5.4 mmol) was added and the reaction was carried out for 12 hours. After the reaction was completed by monitoring the reaction with TLC, the mixture was washed with alkali and acid by adding saturated NaHCO3 solution and saturated KHSO4 solution respectively. The organic phase was dried with anhydrous magnesium sulfate. After filtration, solvent evaporation, and column chromatography purification, the first intermediate product Et-G-CONH-Tm was obtained.

[0059] Physical properties characterization of the first intermediate product:

[0060] 1 ¹H NMR (500MHz, Chloroform-d): δ=8.86(s,1H,NH),7.64(d,1H,NH),7.40(dt,1H,CH),7.20(ddd,1H,CH),7.14–7.08(m,2H,CH),6.87(s,2H,CH),6.23(t,1H,CH),4.18–4.08(m,6H,CH2),3.82–3.46(m,38H,CH2),3.09(t,2H,CH2),1.19(dt,9H,CH3); The product is Et-G-CONH-Tm; Figure 1 As shown;

[0061] b. The process of the reduction reaction:

[0062] Under a nitrogen atmosphere, Et-G-CONH-Tm (0.80 g, 1.01 mmol) and Et3SiH (0.17 g, 1.46 mmol) prepared in step a were dissolved in TFA (20 mL) and reacted in an oil bath at 70 °C with stirring for 4 hours. After the reaction was completed by monitoring the reaction plate by TLC, TFA was removed by vacuum distillation. The pH of the mixture was adjusted to alkaline (pH = 9) by adding 10 wt% NaOH aqueous solution under ice bath conditions. The second intermediate product Et-G-CONH-T was obtained by organic solvent extraction, brine washing and column chromatography purification.

[0063] Physical properties characterization of the second intermediate product:

[0064] 1 ¹H NMR (500MHz, DMSO-d6) δ=8.41(t,1H,NH),7.18(s,2H,CH),7.05(d,1H,CH),6.91(t,1H,CH),6.54(td,1H,CH),6.49(d,1H,CH),5.43(s,1H,NH),4.22–4.02(m,6H,CH2),3.81–3.37(m,38H,CH2),3.18(td,2H,CH2),3.11(ddd,1H,CH),2.03–1.62(m,2H,CH2),1.08(td,6H,CH3); The product is Et-G-CONH-T; Figure 2 As shown;

[0065] c. Knoevenagel condensation reaction process:

[0066] The Et-G-CONH-T (99 mg, 0.12 mmol) obtained in step b and the trifluoromethylpyrazolone activated furan (61 mg, 0.20 mmol) were dissolved in anhydrous methanol (10 mL), and the mixture was stirred in the dark for 30 minutes. The solvent was removed by vacuum distillation, and the product was washed repeatedly with n-hexane to obtain the target product De.

[0067] Characterize the target product:

[0068] 1 H NMR(500MHz,DMSO-d6)δ=11.55(s,1H,OH),8.44(q,1H,NH),7.91(ddd,1H,CH),7.64(t,2H,CH),7.51( t,2H,CH),7.40(t,1H,CH),7.17(s,2H,CH),7.10(dd,1H,CH),6.89(dt,1H,CH),6.60(dt,1H,CH),6.53 (ddd,1H,CH), 6.28(dd,1H,CH), 5.03(d,1H,CH), 4.10(dt,6H,CH2), 3.91(s,1H,CH), 3.80–3.39(m,38H,CH2), 3.22(m,2H,CH2), 3.04(dd,1H,CH), 2.07–1.66(m,2H,CH2), 1.08(td,9H,CH3); It can be concluded that the target product is the final product De. For example... Figure 3 As shown.

[0069] Experimental test analysis:

[0070] The final product De prepared in this embodiment was used as a sample for analysis and testing:

[0071] I. Photoisomerization behavior of De in aqueous phase

[0072] Prepare a 0.1 mM De aqueous solution and test the change in the absorbance of its chromophore with light exposure time, such as... Figure 4 As shown, the absorption peaks at wavelengths of 500-700 nm belong to the colored triene structure of De, while the absorption peaks at wavelengths of 330-370 nm belong to the colorless cyclopentenone structure of De. With prolonged illumination, the absorbance of the colored triene structure of De decreases, and after 20 minutes of illumination, its absorbance no longer changes, indicating that a photothermal steady state has been reached. Correspondingly, the absorbance of the colorless cyclopentenone structure of De increases, indicating that visible light irradiation in the aqueous phase can induce linear-cyclic isomerization behavior in De.

[0073] II. Temperature-sensitive aggregation behavior of De in aqueous phase

[0074] A 0.5 mM De aqueous solution was prepared, and its temperature-sensitive aggregation process was monitored using an optical microscope. Figure 5 As shown, no material was observed in the optical microscope field of view of the sample at 25℃ and 45℃. When the temperature was raised above the phase transition temperature of De, spherical assemblies with a particle size of about 1 micrometer appeared in the optical microscope field of view, indicating that temperature-sensitive aggregation behavior of De can be induced in the aqueous phase within the temperature range of 25-65℃.

[0075] III. Reversible isomerization behavior of De in aqueous phase

[0076] A 0.1 mM De aqueous solution was prepared, and the changes in its chromophore (632 nm) with visible light irradiation and light-shielded heating time were monitored using a UV-Vis spectrophotometer. Figure 6 As shown in the figure, the De aqueous solution was first treated in the dark, and its initial absorbance was about 1.75. After 40 min, its absorbance decreased to 1.1. Thereafter, with the extension of the dark treatment time, its absorbance remained almost unchanged, indicating that the dark-thermal steady state had been reached. When the sample was irradiated with visible light, the absorbance of the De chromophore decreased, indicating that De underwent linear-cyclic isomerization. After 20 min of light irradiation, the absorbance of the chromophore almost stopped decreasing, indicating that the photothermal steady state had been reached. Further dark-heat treatment (45℃) was carried out, and the absorbance of the De chromophore began to rise rapidly. After 5 min of dark-heat treatment, it almost completely returned to the dark-thermal steady state. This proves that the intelligent amphiphilic dendritic macromolecule De based on DASAs has successfully achieved reversible isomerization in the aqueous phase.

[0077] This embodiment is based on smart amphiphilic dendritic macromolecules of DASAs, which can regulate their isomerization behavior in the aqueous phase using visible light irradiation. Above the phase transition temperature, they can thermosensitively aggregate to form microspheres. In addition, the dendritic topology of the dendritic alkoxy ether moiety and the crowding synergistic effect between molecules can construct a hydrophobic microenvironment, which promotes the rapid and reversible isomerization behavior of DASAs in the aqueous phase.

[0078] Example 2

[0079] This embodiment is basically the same as Embodiment 1, except that:

[0080] In this embodiment, a method for preparing a smart amphiphilic dendritic macromolecule based on DASAs is described, with the following specific steps:

[0081] a. Amide reaction process:

[0082] Carboxylic acid-modified dendritic units Et-G-COOH (2.3 mmol), HOBT (2.76 mmol), and DIPEA (4.6 mmol) were dissolved in dry DCM (80 mL) under ice-salt bath and nitrogen protection. When the temperature dropped below 15 °C, EDC·HCl (3.45 mmol) was added and the mixture was stirred for 30 minutes. Then, tryptophan (6.9 mmol) was added and the reaction was carried out for 12 hours. After the reaction was completed by monitoring the reaction with TLC plate, the mixture was washed with alkali and acid by adding saturated NaHCO3 solution and saturated KHSO4 solution respectively. The organic phase was dried with anhydrous magnesium sulfate. After filtration, solvent evaporation and column chromatography purification, the first intermediate product Et-G-CONH-Tm was obtained.

[0083] b. The process of the reduction reaction:

[0084] Under a nitrogen atmosphere, Et-G-CONH-Tm (1.01 mmol) and Et3SiH (1.515 mmol) obtained in step a were dissolved in TFA (20 mL) and reacted in an oil bath at 70 °C with stirring for 4 hours. After the reaction was completed by monitoring the reaction by TLC plate, TFA was removed by vacuum distillation. The pH of the mixture was adjusted to alkaline (pH=9) by adding 10 wt% NaOH aqueous solution under ice bath conditions. The second intermediate product Et-G-CONH-T was obtained by organic solvent extraction, brine washing and column chromatography purification.

[0085] c. Knoevenagel condensation reaction process:

[0086] The Et-G-CONH-T (0.12 mmol) obtained in step b and the trifluoromethylpyrazolone activated furan (0.18 mmol) were dissolved in anhydrous methanol (10 mL), and the mixture was stirred in the dark for 30 minutes. The solvent was removed by vacuum distillation, and the product was washed repeatedly with n-hexane to obtain the target product De.

[0087] This embodiment is based on smart amphiphilic dendritic macromolecules of DASAs, which can regulate their isomerization behavior in the aqueous phase using visible light irradiation. Above the phase transition temperature, they can thermosensitively aggregate to form microspheres. In addition, the dendritic topology of the dendritic alkoxy ether moiety and the crowding synergistic effect between molecules can construct a hydrophobic microenvironment, which promotes the rapid and reversible isomerization behavior of DASAs in the aqueous phase.

[0088] In summary, the above embodiments of the intelligent amphiphilic dendritic macromolecules utilize hydrophilic alkoxy ether dendration units combined with hydrophobic visible-light-responsive DASAs to construct a novel class of DASA-based intelligent amphiphilic dendritic macromolecules. The amphiphilic dendritic macromolecules of the above embodiments of the present invention can self-assemble in an aqueous phase, and their self-assembly behavior can be regulated by light and temperature. The unique topological structure, crowding synergistic effect, and temperature-induced multi-level dehydration collapse mechanism of the alkoxy ether dendration units can construct a hydrophobic microenvironment. By changing the end-group structure of the alkoxy ether units, the length of the alkoxy chain, and the number of alkoxy ether arms, the microenvironment can be regulated, thereby achieving the control of the reversible isomerization behavior of DASAs in an aqueous phase. Furthermore, the raw materials used in the above embodiments are environmentally friendly, inexpensive, low in toxicity, and have good biocompatibility, demonstrating great application potential in the fields of biomedicine and photosensitive materials.

[0089] The embodiments of the present invention have been described above in conjunction with the accompanying drawings. However, the present invention is not limited to the above embodiments. Various changes can be made according to the purpose of the invention. Any changes, modifications, substitutions, combinations or simplifications made based on the spirit and principle of the technical solution of the present invention shall be equivalent substitutions. As long as they meet the purpose of the invention and do not deviate from the technical principle and inventive concept of the present invention based on DASAs intelligent amphiphilic dendritic macromolecules and their preparation methods, they shall fall within the protection scope of the present invention.

Claims

1. A smart telechelic based on DASAs, characterized in that: Its general molecular structure formula is shown below: R1 is an alkoxy ether dendritic unit, which can be two-armed, three-armed, four-armed, or six-armed. The structure of R1 is as follows: In the structure of R1, n = 1 to 4, and R2 = Et or Me; wherein R3 is 2. A process for the preparation of the smart parent dendrimers based on DASAs according to claim 1, characterized by, Includes the following steps: a. Amide reaction process: Under ice-salt bath and nitrogen protection, carboxylic acid-modified dendritic units R1-COOH, HOBT, and DIPEA were dissolved in dry DCM. When the temperature dropped to no higher than 15°C, EDC·HCl was added and the reaction was stirred for at least 30 minutes, followed by the addition of tryptophan and a reaction time of at least 12 hours. After the reaction was completed as monitored by TLC, the mixture was washed with alkali and acid by adding saturated NaHCO3 solution and saturated KHSO4 solution respectively. The organic phase was dried with anhydrous magnesium sulfate, and after filtration, solvent evaporation, and column chromatography purification, the first intermediate product RG-CONH-Tm was obtained, with the following structural formula: b. Reduction reaction process: Under a nitrogen atmosphere, RG-CONH-Tm and Et3SiH obtained in step a were dissolved in TFA and stirred in an oil bath at a temperature not lower than 70°C for at least 4 hours. After the reaction was completed by TLC monitoring, the reaction solvent was removed by vacuum distillation. A NaOH aqueous solution with a mass percentage concentration of 5-10 wt% was added under ice bath conditions to adjust the pH of the mixture to an alkaline mixture with a pH of 8-10. The mixture was then extracted with an organic solvent, washed with brine, and purified by column chromatography to obtain the second intermediate product RG-CONH-T, whose structural formula is as follows: c. Knoevenagel condensation reaction process: The RG-CONH-T obtained in step b was dissolved in anhydrous methanol and reacted with the furan derivative in the dark with stirring for at least 30 minutes. Then, the solvent was removed by vacuum distillation, and the product was repeatedly washed with n-hexane to obtain the target product, a smart amphiphilic dendritic macromolecule based on DASAs, with the following structural formula: Furan derivatives are 3. The method for preparing the smart amphiphilic dendritic macromolecule based on DASAs according to claim 2, characterized in that: In step a, the molar ratio of carboxylic acid-modified dendritic alkoxy ether moiety R1-COOH, HOBT, DIPEA, EDC·HCl and tryptophan is 1:(1.1~1.2):2:(1.4~1.5):(2.3~3).

4. The method for preparing the smart amphiphilic dendritic macromolecule based on DASAs according to claim 2, characterized in that: In step b, the molar ratio of RG-CONH-Tm and Et3SiH is 1:(1.4 to 1.5).

5. The method for preparing the smart amphiphilic dendritic macromolecule based on DASAs according to claim 2, characterized in that: In step c, the molar ratio of RG-CONH-T to the furan derivative is 1:(1.5 to 1.7).

Images