Galactose-masked aminoquinoline compound and use thereof
By designing galactose-masked aminoquinoline compounds to activate and release aminoquinoline and butyric acid in the lysosomes of senescent cells, the problem of toxic side effects of existing drugs on normal cells was solved, and efficient and selective clearance of senescent cells was achieved.
Patent Information
- Authority / Receiving Office
- WO · WO
- Patent Type
- Applications
- Current Assignee / Owner
- Filing Date
- 2025-09-30
- Publication Date
- 2026-04-02
AI Technical Summary
Existing drugs targeting aging-related β-galactosidase have toxic side effects on normal cells, making it difficult to selectively eliminate senescent cells.
A galactose-masked aminoquinoline compound was designed. After hydrolysis by esterase, it was activated by senescence-related β-galactosidase in the lysosomes of senescent cells, releasing aminoquinoline and butyrate, which synergistically inhibited the survival of senescent cells.
It achieves efficient and selective removal of senescent cells, reduces toxicity to normal cells, and has broad application prospects in skin anti-aging and body senescent cell removal.
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Figure CN2025125952_02042026_PF_FP_ABST
Abstract
Description
Galactose-masked aminoquinoline compound and application thereof TECHNICAL FIELD
[0001] The present application belongs to the technical field of pharmaceutical compounds, and particularly relates to a galactose-masked aminoquinoline compound and application thereof. BACKGROUND
[0002] Senescent cells are a key factor driving organismal aging. Their accumulation in the body can lead to tissue dysfunction and various age-related diseases, including chronic kidney failure, cardiovascular disease, and neurodegenerative disease. Clearing these senescent cells is expected to reduce chronic low-grade inflammation, improve the repair capacity of tissues, and thus delay or alleviate many age-related diseases.
[0003] A class of functional molecules capable of selectively killing senescent cells, known as Senolytics, is expected to alleviate diseases related to the accumulation of senescent cells. A key feature of senescent cells is the high expression of lysosomal beta-galactosidase, i.e., senescence-associated beta-galactosidase (SA-β-Gal), which is also a major marker of senescent cells in the body. Currently, galactose derivatives targeting senescence-associated beta-galactosidase have been developed, which release different cytotoxic molecules under enzymatic catalysis to inhibit or kill senescent cells. However, most research in this field uses galactose-conjugated broad-spectrum toxic drugs, such as anticancer drugs, which can cause off-target effects, resulting in toxic side effects of these drugs on normal cells, tissues, or organs. SUMMARY
[0004] The present application aims to overcome the defects of the prior art and provides a galactose-masked aminoquinoline compound.
[0005] Another object of the present application is to provide the use of the above-mentioned galactose-masked aminoquinoline compound.
[0006] The technical solution of the present application is as follows:
[0007] A galactose-masked aminoquinoline compound, having the structural formula
[0008] wherein R is acetyl, propionyl or butyryl.
[0009] In a preferred embodiment of the present application, R is butyryl or acetyl.
[0010] Further preferably, R is butyryl.
[0011] The use of the above-mentioned galactose-masked aminoquinoline compound in the preparation of a senescent cell clearing agent.
[0012] Use of the galactose-masked aminoquinoline compound in the preparation of an anti-aging composition.
[0013] An anti-aging composition, the effective component of which comprises the galactose-masked aminoquinoline compound.
[0014] In a preferred embodiment of the present application, the effective component is the galactose-masked aminoquinoline compound.
[0015] An anti-aging composition, the effective component of which comprises the galactose-masked aminoquinoline compound.
[0016] In a preferred embodiment of the present application, the effective component is the galactose-masked aminoquinoline compound.
[0017] The present application has the following beneficial effects:
[0018] 1. After being hydrolyzed by esterase to remove acetylation, propionylation or butyrylation in cells, the present application can be activated by senescence-associated β-galactosidase in lysosomes of senescent cells to release NCQ, so as to inhibit the survival of senescent cells in vivo or in vitro.
[0019] 2. When R is butyryl, the butyric acid released in cells of the present application can synergize with NCQ to inhibit the survival of senescent cells, so as to achieve more efficient and selective removal of senescent cells, and has a broad prospect in the future anti-aging clinical application of skin anti-aging health care and removal of senescent cells in the body. BRIEF DESCRIPTION OF DRAWINGS
[0020] Figure 1 is a schematic diagram of the chemical reaction principle of enzyme-catalyzed release of aminoquinoline and butyric acid according to the present application.
[0021] Figure 2 is a synthesis route diagram of amino chloroquinoline, O-Acetyl-Gal-NCQ and O-Butyl-Gal-NCQ in Example 1 of the present application.
[0022] Figure 3 shows the effect of O-Acetyl-Gal-NCQ and O-Butyl-Gal-NCQ on the survival rate of normal growth and Etoposide-induced senescent mouse MEF cells (mouse embryonic fibroblasts) co-incubated for 12h in Example 2 of the present application.
[0023] Figure 4 shows the effect of O-Butyl-Gal-NCQ on the cell viability of normal growth and replicative senescent human HFF cells (human foreskin fibroblasts; Human Foreskin Fibroblast) co-incubated for 12h in Example 3 of the present application.
[0024] Figure 5 shows the effect of O-Butyl-Gal-NCQ incubation for 6 hours on the subsequent survival rate of normally growing and replicating senescent human HFF cells in Example 4 of the present invention. Detailed Implementation
[0025] The technical solution of the present invention will be further explained and described below with reference to specific embodiments and accompanying drawings.
[0026] Example 1
[0027] The synthesis of O-Acetyl-Gal-NCQ is shown in Figure 2A, and specifically includes the following steps:
[0028] (1) According to the literature method (F.Yu.,Y.Wang,Y.Hang,W.Tang,Z.Zhao,D. (Journal of Polymer Science Part A: Polymer Chemistry 2019, 57, 2235-2242) Synthesis of CQ-N3. Compound CQ-N3 (1.40 g, 3.89 mmol) and triphenylphosphine (6.12 g, 23.34 mmol) were dissolved in a mixed solution of tetrahydrofuran (40 mL) and deionized water (8 mL), and reacted at room temperature for 12 h. After removing the solvent by rotary evaporation, the reaction system was purified by silica gel column chromatography (eluent: dichloromethane / methanol, 10:1) to give the compound aminochloroquinoline (NCQ) (73%, 0.95 g).
[0029] (2) S1 was synthesized according to the literature method (Y.Cai, H.Zhou, Y.Zhu, Q.Sun, Y.Ji, A.Xue, Y.Wang, W.Chen, X.Yu, L.Wang, H.Chen, TLCLi, H.Deng, Cell Research 2020, 7, 574-589). Compound S1 (1000 mg, 1.5 mmol) was dissolved in dichloromethane (15 mL), and then aminochloroquinoline (554 mg, 1.66 mmol) and N,N-diisopropylethylamine (585 mg, 4.5 mmol) were added sequentially. The mixture was stirred at room temperature for 3-5 h. The reaction solution was diluted with dichloromethane (100 mL) and washed sequentially with saturated sodium carbonate aqueous solution (100 mL) and saturated sodium chloride aqueous solution (100 mL). The obtained organic phase was dehydrated with anhydrous sodium sulfate, concentrated under reduced pressure, and purified by silica gel column chromatography (eluent: ethyl acetate / methanol, 3:1) to obtain O-Acetyl-Gal-NCQ (86%, 1113 mg).
[0030] The structural formula of O-Acetyl-Gal-NCQ is as follows: The characterization data thereof are: 1 H NMR (500 MHz, DMSO-d6) δ 8.39 - 8.33 (m, 2H), 7.84 (d, J = 2.1 Hz, 1H), 7.76 (d, J = 2.3 Hz, 1H), 7.66 (dd, J = 8.7, 2.2 Hz, 1H), 7.45 - 7.37 (m, 2H), 7.16 (t, J = 5.8 Hz, 1H), 6.92 (d, J = 8.0 Hz, 1H), 6.50 (d, J = 5.6 Hz, 1H), 5.58 (d, J = 7.6 Hz, 1H), 5.37 (d, J = 3.5 Hz, 1H), 5.31 - 5.20 (m, 2H), 5.01 (s, 2H), 4.48 (t, J = 6.4 Hz, 1H), 4.17 - 4.09 (m, 2H), 3.71 (p, J = 6.6 Hz, 1H), 3.18 (s, 2H), 3.04 (q, J = 6.6 Hz, 2H), 2.44 (dt, J = 20.3, 7.2 Hz, 5H), 2.15 (s, 3H), 2.03 (d, J = 1.5 Hz, 6H), 1.95 (s, 3H), 1.68 (dd, J = 11.7, 5.4 Hz, 1H), 1.48 (dp, J = 26.8, 7.5 Hz, 3H), 1.25 - 1.19 (m, 4H), 0.91 (t, J = 7.1 Hz, 3H). 13 C NMR (151 MHz, DMSO-d6) δ 170.42, 170.32, 170.01, 169.34, 156.29, 152.23, 150.05, 149.58, 148.29, 140.60, 133.87, 133.34, 127.76, 124.85, 124.28, 118.23, 117.93, 99.27, 99.04, 71.26, 70.38, 68.15, 67.55, 64.05, 61.70, 53.40, 52.73, 49.06, 48.11, 47.57, 39.02, 33.68, 23.90, 20.96, 20.85, 20.80, 20.77, 20.28, 12.02. MALDI-TOF MS calculated for C 40 H 50 ClN5O 14 (M)m / z 859.3043, found 859.931.
[0031] O-Butyl-Gal-NCQ synthesis is shown in FIG. 2B, specifically comprising the following steps:
[0032] (1) To β-D-galactose (10 g, 55.6 mmol) was added n-butyric anhydride (87.7 g, 555.6 mmol) and pyridine (48.3 g, 611.2 mmol) and the reaction was stirred at room temperature for 12 h, TLC plate monitoring of the complete conversion of β-D-galactose, then the solvent was removed by oil pump. The resulting residue was dissolved in ethyl acetate (150 mL). The resulting solution was washed with 1 M aqueous hydrochloric acid (150 mL) and saturated aqueous sodium bicarbonate (150 mL) successively. The resulting organic phase was separated and anhydrous sodium sulfate was added to remove the water, then concentrated under reduced pressure to obtain compound S2 (100%, 29.44 g);
[0033] (2) Compound S2 was dissolved in dichloromethane (70 mL), HBr (30% in acetic acid; 30 mL) was added under nitrogen protection and ice bath conditions, and the reaction was carried out for 1 h. The reaction solution was diluted with dichloromethane (200 mL). The resulting solution was washed with ice water (300 mL) and saturated aqueous sodium bicarbonate (300 mL). The organic phase was separated and anhydrous sodium sulfate was added to remove the water, then concentrated under reduced pressure to obtain compound S3 (95%, 23.40 g);
[0034] (3) To a solution of compound S3 (20.0 g, 38.3 mmol) in N,N-dimethylformamide (200 mL) was added 4-hydroxy-3-nitrobenzyl alcohol (7.7 g, 46.0 mmol) and anhydrous potassium carbonate (10.6 g, 76.6 mmol). The reaction solution was stirred at room temperature for 6 h, and then the solvent was removed by rotary evaporation. The resulting residue was dissolved in ethyl acetate (300 mL). The resulting solution was washed with water (300 mL) and saturated aqueous sodium bicarbonate (300 mL), then the organic phase was separated and anhydrous sodium sulfate was added to remove the water, and concentrated under reduced pressure. The resulting residue was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, 1:1) to obtain compound S4 (55%, 12.85 g);
[0035] (4) To a solution of compound S4 (1000 mg, 1.6 mmol) in dichloromethane (15 mL) was added p-nitrophenyl chloroformate (660.0 mg, 3.3 mmol) and pyridine (389.0 mg, 4.9 mmol) successively. The reaction system was stirred at room temperature for 40 min, and then the solvent was removed by rotary evaporation. The residue was separated and purified by silica gel column chromatography (eluent: petroleum ether / ethyl acetate, 3:1) to obtain compound S5 (82%, 1045 mg);
[0036] (5) The compound S5 (1000 mg, 1.29 mmol) was dissolved in dichloromethane (15 mL), and then aminochloroquine (NCQ, 475.0 mg, 1.4 mmol) and N,N-diisopropylethylamine (500.0 mg, 3.9 mmol) were sequentially added to the reaction system. After the reaction solution was stirred at room temperature for 3-5 h, it was diluted with dichloromethane (100 mL). The obtained solution was sequentially washed with saturated aqueous sodium carbonate solution (100 mL) and saturated aqueous sodium chloride solution (100 mL). After the organic phase was separated, it was dehydrated with anhydrous sodium sulfate, concentrated under reduced pressure, and separated and purified by silica gel column chromatography (eluent: ethyl acetate / methanol, 5:1) to obtain the compound O-Butyl-Gal-NCQ (86%, 1065.00 mg).
[0037] The structural formula of the O-Butyl-Gal-NCQ is Its characterization data are as follows: 1 H NMR (500 MHz, DMSO-d6) δ 8.70 (d, J = 9.1 Hz, 1H), 8.45 (dd, J = 6.4, 1.9 Hz, 1H), 8.13 (s, 1H), 7.97 (s, 1H), 7.86 (d, J = 2.2 Hz, 1H), 7.66 (dd, J = 8.7, 2.2 Hz, 1H), 7.56 (dd, J = 9.1, 2.3 Hz, 2H), 7.43 (d, J = 8.7 Hz, 1H), 6.72 (d, J = 6.4 Hz, 1H), 5.68 (d, J = 7.8 Hz, 1H), 5.41 (d, J = 3.7 Hz, 1H), 5.34 (dd, J = 10.5, 3.4 Hz, 1H), 5.28 (dd, J = 10.4, 7.8 Hz, 1H), 5.03 (s, 2H), 4.56 (t, J = 6.6 Hz, 1H), 4.17-4.09 (m, 2H), 3.91 (q, J = 6.9 Hz, 1H), 2.95 (s, 4H), 2.45-2.38 (m, 2H), 2.32-2.20 (m, 4H), 2.16 (td, J = 7.4, 5.8 Hz, 2H), 1.88-1.78 (m, 1H), 1.71 (s, 2H), 1.60 (p, J = 7.2 Hz, 3H), 1.56-1.42 (m, 7H), 1.30-1.21 (m, 4H), 1.13 (t, J = 7.2 Hz, 3H), 0.94 (t, J = 7.4 Hz, 3H), 0.89-0.80 (m, 10H). 13C NMR (151 MHz, DMSO-d6) δ 172.71, 172.16, 171.70, 156.33, 152.57, 148.36, 140.44, 135.98, 133.89, 132.93, 125.99, 125.55, 124.42, 123.75, 118.02, 117.04, 99.20, 98.72, 71.23, 70.36, 68.02, 67.42, 64.34, 61.49, 52.13, 51.17, 48.84, 47.57, 36.42, 35.65, 35.63, 35.59, 35.52, 32.76, 20.07, 18.60, 18.32, 18.24, 18.09, 13.82, 13.73, 13.71, 13.64. MALDI-TOF MS calculated for C 48 H 66 ClN5O 14 (M+H + )m / z 972.4295, found 972.063.
[0038] Example 2
[0039] Preparation of 10 mM CQ-OH standard solution: 3.4 mg of CQ-OH was dissolved in 1 mL of dimethyl sulfoxide to obtain a 10 mM CQ-OH standard solution.
[0040] Preparation of 10 mM O-Acetyl-Gal-NCQ standard solution: 8.6 mg of O-Acetyl-Gal-NCQ prepared in Example 1 was dissolved in 1 mL of dimethyl sulfoxide to obtain a 10 mM O-Acetyl-Gal-NCQ standard solution.
[0041] Preparation of 10 mM O-Butyl-Gal-NCQ standard solution: 9.7 mg of O-Butyl-Gal-NCQ prepared in Example 1 was dissolved in 1 mL of dimethyl sulfoxide to obtain a 10 mM O-Butyl-Gal-NCQ standard solution.
[0042] The three standard solutions (CQ-OH, O-Acetyl-Gal-NCQ and O-Butyl-Gal-NCQ) were mixed with cell culture solution at volume ratios of 1 :4000, 1 :2000, 1 :1000, 1 :500, respectively, to obtain cell culture solutions of 2.5 μM, 5 μM, 10 μM, 20 μM of the corresponding compounds, respectively. The cell culture solutions of CQ-OH, O-Acetyl-Gal-NCQ and O-Butyl-Gal-NCQ at different concentrations were incubated with normal growing and Etoposide-induced senescent mouse MEF cells (mouse embryonic fibroblasts) in 96-well plates for 12 h, and then the cell viability (ATP level) was determined using the CellTiter-Glo® Luminescent Cell Viability Assay commercial kit. CellTiter-Glo® Luminescent Cell Viability Assay commercial kit.
[0043] The results are shown in Figure 3: at 20 μM, CQ-OH caused a 10% decrease in the viability of normal MEF cells and a 30% decrease in the viability of senescent MEF cells; O-Acetyl-Gal-NCQ caused a 15% decrease in the viability of normal MEF cells and a 60% decrease in the viability of senescent MEF cells; and O-Butyl-Gal-NCQ caused a 25% decrease in the viability of normal MEF cells and a 90% decrease in the viability of senescent MEF cells.
[0044] The results show that CQ-OH has a mild inhibitory effect on the viability of senescent MEF cells (about 20% difference). O-Acetyl-Gal-NCQ is more effective than CQ-OH in inhibiting the viability of senescent MEF cells, supporting the release of aminochinol mediated by senescence-associated β-galactosidase, thereby increasing the anti-senescence efficiency. In comparison with O-Acetyl-Gal-NCQ, O-Butyl-Gal-NCQ further decreases the viability of senescent MEF cells, which supports the combined effect of butyric acid released in the cell and aminochinol, increasing the effectiveness and selectivity of inhibiting the viability of senescent cells.
[0045] Example 3
[0046] The two standard solutions (CQ-OH and O-Butyl-Gal-NCQ) prepared in Example 2 were mixed with cell culture solution at volume ratios of 1 :4000, 1 :2000, 1 :1000, and 1 :500, respectively, to obtain cell culture solutions containing 2.5 μM, 5 μM, 10 μM, and 20 μM of CQ-OH and O-Butyl-Gal-NCQ, respectively. The above cell culture solutions with different concentrations of CQ-OH and O-Butyl-Gal-NCQ were incubated with normal and replicatively senescent human HFF cells (human foreskin fibroblasts) in 96-well plates for 12 h, and then stained with Hoechst 33342 and propidium iodide (PI) to distinguish between dead and live cells. Cell viability (ATP level) was determined using the Luminescent Cell Viability Assay commercial kit.
[0047] The results are shown in Figure 4. At a concentration of 20 μM, O-Butyl-Gal-NCQ removed about 50% of the senescent and about 25% of the normal human HFF cells, while CQ-OH removed about 25% and 15% of the senescent and normal human HFF cells, respectively. This indicates that O-Butyl-Gal-NCQ also effectively inhibits the survival of senescent human HFF cells.
[0048] Example 4
[0049] The O-Butyl-Gal-NCQ standard solution prepared was mixed with cell culture solution at volume ratios of 1 :2000, 1 :1000, 1 :500, and 1 :250, respectively, to obtain cell culture solutions containing 5 μM, 10 μM, 20 μM, and 40 μM of O-Butyl-Gal-NCQ, respectively. The above cell culture solutions with different concentrations of O-Butyl-Gal-NCQ were incubated with normal and replicatively senescent human HFF cells in 96-well plates for 6 h, and then the cells were washed and incubated in fresh cell culture solution for 0, 24, or 48 h. The cells after incubation were stained with Hoechst 33342 and propidium iodide (PI) to distinguish between dead and live cells.
[0050] The results are shown in Figure 5: the survival rate of senescent HFF cells pre-treated with O-Butyl-Gal-NCQ for 6h decreased with time. The survival rate of senescent HFF cells pre-treated with O-Butyl-Gal-NCQ for 12h in fresh medium was close to zero. The survival rate of normal HFF cells pre-treated with O-Butyl-Gal-NCQ for 12h was not significantly affected. In contrast, incubation of O-Butyl-Gal-NCQ with cells for 12h in Example 3 resulted in a 50% decrease in the survival rate of senescent HFF cells and a 25% decrease in the survival rate of normal HFF cells. Pre-treatment of O-Butyl-Gal-NCQ for 6h in this example resulted in a quantitative depletion of senescent HFF cells 48h later, without affecting the survival of normal HFF cells. This result shows that short-term compound treatment further improves the selectivity of O-Butyl-Gal-NCQ in killing senescent HFF cells, indicating that appropriate administration time and mode can improve the selectivity and effectiveness of O-Butyl-Gal-NCQ in inhibiting senescent cells.
[0051] In summary: O-Butyl-Gal-NCQ in the present application is hydrolyzed by esterase in cells to remove butyryl and generate butyric acid and Gal-NCQ. Gal-NCQ is activated by senescence-associated β-galactosidase to release aminoquinoline, which synergizes with butyric acid to promote cell death and achieve more efficient senescent cell depletion (as shown in Figure 1A); O-Acetyl-Gal-NCQ in the present application is hydrolyzed by esterase in cells to remove acetyl, and the generated Gal-NCQ is activated by senescence-associated β-galactosidase to release aminoquinoline, which promotes cell death (as shown in Figure 1B).
[0052] The above merely describes preferred embodiments of the present application, and therefore cannot limit the scope of implementation of the present application. Equivalent changes and modifications made to the scope and content of the present application should still fall within the scope of the present application. Industrial applicability
[0053] The present application discloses a galactose-masked aminoquinoline compound and its application, and its structural formula is wherein R is acetyl, propionyl or butyryl. The present application can be activated by senescence-associated β-galactosidase in the lysosome of senescent cells to release aminoquinoline (NCQ) after hydrolysis by esterase in cells to remove acetylation, propionylation or butyrylation, so as to inhibit the survival of senescent cells in vivo or in vitro, and has industrial applicability.
Claims
1. A galactose masked aminoquinoline compound characterized by: The structural formula is Wherein, R is acetyl, propionyl or butyryl.
2. A galactose masked aminoquinoline compound according to claim 1, wherein: ###0001### The R is butyryl or acetyl.
3. A galactose masked aminoquinoline compound according to claim 2, wherein: ###0002### The R is butyryl.
4. Use of the galactose-masked aminoquinoline compound according to any one of claims 1 to 3 in the manufacture of a senolitic agent.
5. Use of the galactose-masked aminoquinoline compound according to any one of claims 1 to 3 in the manufacture of an anti-aging composition.
6. A senescent cell scavenger, characterized in that: The effective component thereof comprises the galactose-masked aminoquinoline compound according to any one of claims 1 to 3.
7. An agent for eliminating senescent cells according to claim 6, wherein: The effective component thereof is the galactose-masked aminoquinoline compound.
8. An anti-aging composition characterized in that: The effective component thereof comprises the galactose-masked aminoquinoline compound according to any one of claims 1 to 3.
9. An anti-aging composition according to claim 8, wherein: The effective component thereof is the galactose-masked aminoquinoline compound.
10. A synthesis method of a galactose-masked aminoquinoline compound, specifically comprising the following steps: 1) Compound CQ-N3 and triphenylphosphine are dissolved in a solvent, and reacted at room temperature. After the reaction is completed, the solvent is removed, and then compound amino chloroquinoline (NCQ) is obtained through silica gel column chromatography separation and purification; (2) According to the literature method: Y. Cai, H. Zhou, Y. Zhu, Q. Sun, Y. Ji, A. Xue, Y. Wang, W. Chen, X. Yu, L. Wang, H. Chen, T. L. C. Li, H. Deng, Cell Research 2020, 7, 574-589, compound S1 is dissolved in dichloromethane, and then compound amino chloroquinoline and N,N-diisopropylethylamine are added in sequence. After stirring at room temperature for several hours, the reaction product is obtained through purification and separation to obtain O-Acetyl-Gal-NCQ. The structural formula of the O-Acetyl-Gal-NCQ is:
11. A synthesis method of a galactose-masked aminoquinoline compound, specifically comprising the following steps: (1) n-Butyric anhydride and pyridine are added to β-D-galactose, and stirred at room temperature until the conversion of β-D-galactose is complete. Then the solvent is removed by suction. After washing, dehydration, and concentration under reduced pressure, compound S2 is obtained; (2) Compound S2 is dissolved in dichloromethane, and HBr is added under nitrogen protection and ice bath conditions. After the reaction is completed, the solution is diluted and washed. The organic phase is separated, dehydrated, and concentrated under reduced pressure to obtain compound S3; (3) 4-Hydroxy-3-nitrobenzyl alcohol and anhydrous potassium carbonate are added to a solution of compound S3 in N,N-dimethylformamide. After reaction at room temperature, the solvent is removed by rotary evaporation, and compound S4 is obtained through separation and purification; (4) p-Nitrophenyl chloroformate and pyridine are added to a dichloromethane solution of compound S4. After reaction at room temperature, compound S5 is obtained through separation and purification; (5) Compound S5 is dissolved in dichloromethane, and then amino chloroquinoline (NCQ) and N,N-diisopropylethylamine are added in sequence. After dilution, washing, dehydration, concentration under reduced pressure, and silica gel column chromatography separation and purification, the compound O-Butyl-Gal-NCQ is obtained; The structural formula of the O-Butyl-Gal-NCQ is