A apigenin betaine compound and its preparation method

Abstract

This invention discloses a apigenin-betaine compound and its preparation method. The compound uses apigenin (Api) as its core, with -O-(CH2) at the 7', 4', and / or 5-position hydroxyl groups. n -N + (CH3)2-CH2COO ‑ Fragment substitution (n=2~12, x=1~3) forms an internal salt-type zwitterionic structure. In preparation, apigenin is first reacted with bromool Br(CH2). n A mitsunobu reaction was performed on OH under triphenylphosphine / dialkyl azodicarbonate conditions to obtain mono / polysubstituted bromoalkoxylated apigenin; subsequently, nucleophilic substitution with N,N-dimethylglycine under alkaline conditions yielded the target product. This structure, possessing both a tunable alkyl chain and a betaine cation / anion pair, significantly enhances the solubility and hydration capacity of apigenin in aqueous / alcoholic media, strengthens its affinity and stability for biomembranes, thereby improving in vivo absorption and distribution and potentially maintaining its antioxidant and anti-inflammatory activities. The method is mild, with a wide solvent and temperature range, suitable for scale-up and formulation applications.

Description

Technical Field

[0001] This invention relates to the technical field of synthesizing apigenin derivatives, and in particular to an apigenin betaine compound and its preparation method. Background Technology

[0002] Apogenin is non-toxic and possesses well-defined and broad pharmacological effects, including various biological functions such as antioxidation, anti-inflammation, and sedation. Particularly noteworthy is its protective effect on the central nervous system through its antioxidant, anti-inflammatory, and dopamine-regulating activities. It can also improve neurodegenerative diseases, depression, and cerebral ischemia. The mechanisms of action of apigenin are as follows: First, it inhibits nerve cell death by suppressing caspase activation and cytochrome c release. Second, it upregulates the expression of brain-derived neurotrophic factor (BDNF), restoring the extracellular signal-regulated kinase / BDNF signaling pathway's role in promoting neurogenesis and growth, as well as the repair function of damaged nerve cells, thereby significantly improving learning and memory deficits. Furthermore, it may maintain the integrity of the blood-brain barrier by upregulating blocking protein levels. Therefore, apigenin can improve the pathological symptoms of various neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia-reperfusion injury, and depression through multiple mechanisms.

[0003] Apigenin also possesses various pharmacological activities, including lowering blood pressure and blood lipids, resisting atherosclerosis, anti-tumor, antiviral, and bactericidal effects.

[0004] However, due to its poor water and fat solubility, its absorption and distribution in the body are inhibited, resulting in low bioavailability and inability to fully exert its efficacy. Summary of the Invention

[0005] The purpose of this invention is to overcome the above-mentioned problems existing in the prior art and provide a apigenin betaine compound and its preparation method, so as to improve and adjust the poor water solubility and fat solubility of apigenin and improve its absorption and distribution in vivo.

[0006] To achieve the above objectives, the first aspect of the present invention provides a apigenin betaine compound having the following general chemical structural formula:

[0007] (1)

[0008] or

[0009] (2)

[0010] Api represents apigenin residues;

[0011] n represents the length of the alkyl chain connecting apigenin and betaine groups, i.e., the number of times -CH2- is repeated, n=2~12;

[0012] x represents the number and position of the hydroxyl groups that are substituted on the apigenin molecule, x = 1 to 3;

[0013] x=1 indicates that the hydroxyl group at position 7 of the apigenin molecule is replaced;

[0014] x=2 indicates that the hydroxyl groups at positions 7 and 4′ of apigenin are substituted;

[0015] x=3 indicates that the hydroxyl groups at positions 7, 4′, and 5 of apigenin are all substituted.

[0016] The alkyl betaine compounds derived from apigenin provided by this invention introduce alkyl betaine zwitterionic fragments into the apigenin molecular backbone, thereby achieving dual regulation of hydrophilicity and lipophilicity.

[0017] This compound was created by introducing -O-(CH2) into the hydroxyl site of the apigenin molecule. n -N + (CH3)2-CH2COO - The structure allows the molecule to simultaneously possess positively charged quaternary ammonium cations and carboxylic acid anions, thus forming an internal salt-type zwitterionic structure. This structure significantly improves the molecule's polarity and hydration capacity, resulting in a marked increase in the compound's solubility in water and ethanol compared to the original apigenin, solving the problem of low bioavailability caused by poor solubility of apigenin. While maintaining the conjugated system of the carbonyl group and phenolic hydroxyl group in the apigenin core, this compound still possesses bioactive centers such as antioxidant, anti-inflammatory, and free radical scavenging properties; the introduction of the betaine group enhances the molecule's stability in biological membrane environments, further improving its antioxidant capacity, with an activity level higher than that of the apigenin itself. The introduction of the alkyl chain increases the molecule's affinity for lipid membranes, while the betaine group ensures high water solubility. The combination of these amphoteric characteristics significantly improves the compound's absorption, distribution, and permeability in vivo, enabling it to more effectively cross the blood-brain barrier and exhibiting stronger brain tissue distribution and neuroprotective effects in animal models.

[0018] By adjusting the alkyl chain length (n = 2–12) and the number of substitution sites (x = 1–3), a balance can be achieved between solubility, lipophilicity, and biomembrane affinity to meet the performance requirements of different applications, endowing the compound with good structural tunability and broad application scope. Simultaneously, the alkyl betaine structural fragment is stable in neutral and weakly acidic environments, is not easily oxidized or polymerized, and the preparation conditions are mild. The resulting compound exhibits an internal salt structure, facilitating its application in oral liquid formulations or functional foods. Therefore, this invention, by introducing an tunable-length alkyl betaine structural fragment, significantly improves the solubility, bioavailability, and stability of apigenin, achieving an overall enhancement of functional performance while maintaining its pharmacological properties.

[0019] A second aspect of the present invention provides a method for preparing the apigenin-derived alkyl betaine compounds as described above, comprising the following steps:

[0020] S1: Starting with apigenin and bromool, a mono- or poly-substituted bromoalkoxy apigenin is obtained via the Mitsunobu reaction.

[0021] S2: Using bromoalkoxyapigenin and N,N-dimethylglycine as raw materials, the reaction is carried out under alkaline conditions to obtain the target product, apigenin-derived alkyl betaine compounds.

[0022] The general formula for the above reaction is as follows: Figure 1 As shown, the Mitsunobu reaction (photocatalytic reaction) is a nucleophilic substitution reaction involving an alcohol and an acidic compound in the presence of triphenylphosphine and dialkyl azodicarbonate. Under mild conditions, it converts the hydroxyl group into a desirable leaving group, thereby achieving site-directed substitution of the hydroxyl group on the apigenin molecule and providing a reaction site for the subsequent introduction of a bromoalkoxy group. By controlling the reaction conditions (such as solvent type, temperature, molar ratio, and reaction time), monosubstituted, disubstituted, or trisubstituted products can be synthesized in a controlled manner.

[0023] When the obtained intermediate reacts with N,N-dimethylglycine, the bromine atom acts as a leaving group and undergoes nucleophilic substitution with the tertiary amine group in the glycine molecule to generate a quaternary ammonium salt structure, ultimately yielding a apigenin derivative with a betaine-type quaternary ammonium cation.

[0024] As a further improvement of the present invention, the reaction solvent in step S1 is selected from any one or more of THF, DMF, DMSO, DCM, chloroform, methyl ether, toluene, and C5-8 alkanes; the reaction solvent in step S2 is selected from any one or more of methanol, ethanol, acetonitrile, THF, DMF, DMSO, and methyl ether.

[0025] As a further improvement of the present invention, the reaction temperature in step S1 is 0-20℃; the reaction temperature in step S2 is 50-100℃.

[0026] As a further improvement of the present invention, the ratio of apigenin to bromoethanol in step S1 is 1:1 to 3; and the ratio of bromoalkoxyapigenin and N,N-dimethylglycine in step S2 is 1:2 to 5.

[0027] As a further improvement of the present invention, the reaction time in step S1 is 10 to 24 hours; the reaction time in step S2 is 10 to 24 hours.

[0028] As a further improvement of the present invention, the alkali in the alkaline condition of step S2 is any one or more of alkali metal hydroxides, alkaline earth metal hydroxides, alkali metal carbonates, alkali metal bicarbonates, alkaline earth metal carbonates, alkaline earth metal bicarbonates, alkali metal phosphates, and alkali metal salts of C1-8 alcohols.

[0029] The present invention, by adopting the above technical solution, has the following beneficial effects:

[0030] 1. The alkyl betaine compounds derived from apigenin of the present invention introduce glycine betaine structural fragments into the molecular backbone of apigenin, thereby retaining and improving the basic properties of apigenin such as antioxidant activity. The antioxidant activity of the alkyl betaine compounds derived from apigenin disclosed in this invention is 5-8 times that of apigenin.

[0031] 2. The alkyl betaine compounds derived from apigenin of the present invention introduce glycine betaine structural fragments into the apigenin molecular skeleton, thereby improving the solubility properties of apigenin. The solubility of the alkyl betaine compounds derived from apigenin disclosed in the present invention in water and anhydrous ethanol is 140,000 to 180,000 times and 600 to 1,000 times that of apigenin, respectively. Attached Figure Description

[0032] Figure 1 This is a schematic diagram of the general reaction formula for alkyl betaine compounds derived from apigenin.

[0033] Figure 2 This is a schematic diagram of the reaction process of apigenin-derived alkyl betaine compounds in Example 1.

[0034] Figure 3 This is a schematic diagram of the reaction process of apigenin-derived alkyl betaine compounds in Example 2.

[0035] Figure 4 This is a schematic diagram of the reaction process of apigenin-derived alkyl betaine compounds in Example 3.

[0036] Figure 5 This is a schematic diagram of the reaction process of apigenin-derived alkyl betaine compounds in Example 4.

[0037] Figure 6This is a schematic diagram of the reaction process of apigenin-derived alkyl betaine compounds in Example 5.

[0038] Figure 7 The bar chart shows the antioxidant efficacy test results of compound 3-2, blank control, and apigenin in Example 2. Detailed Implementation

[0039] The following provides a detailed description of specific embodiments of the present invention. It should be understood that the specific embodiments described herein are for illustrative and explanatory purposes only and are not intended to limit the scope of the invention.

[0040] Unless otherwise defined, all scientific and technical terms used in this invention have the same meaning as commonly understood by one of ordinary skill in the art.

[0041] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. 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 of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0042] Unless otherwise specified, all materials and reagents used in the following examples are commercially available.

[0043] The present invention will now be described in detail with reference to specific embodiments, which are intended to understand rather than limit the invention.

[0044] The apigenin (purity ≥98%, purchased from Sinopharm Chemical Reagent Co., Ltd.), 2-bromoethanol (analytical grade, Sinopharm), 3-bromopropanol (analytical grade, Sinopharm), triphenylphosphine (analytical grade, Aladdin), diisopropyl azodicarbonate (DIAD, analytical grade, Alfa Aesar), N,N-dimethylglycine (purity ≥98%, Aladdin), potassium carbonate (analytical grade), and other organic solvents (THF, DCM, ethanol, methanol, acetonitrile, DMF, etc.) used in the experiment were all of analytical grade or higher and were used directly without further purification.

[0045] Example 1

[0046] Target product: Compound 3-1 (n=2, x=1)

[0047] In this embodiment, the reaction process of the apigenin-derived alkyl betaine compounds is as follows: Figure 2 As shown.

[0048] The specific preparation method is as follows:

[0049] S1: In a 250 mL three-necked flask, add apigenin (compound 1, 2.7 g, 10 mmol), triphenylphosphine (5.24 g, 20 mmol), and 2-bromoethanol (2.5 g, 20 mmol), and dissolve in tetrahydrofuran (THF, 30 mL) (if dissolution is incomplete, add 10 mL of dichloromethane). Under a continuous nitrogen atmosphere, cool to 5 °C in an ice bath, and slowly add DIAD (4.04 g, 20 mmol) dropwise over 10 min using a constant-pressure dropping funnel, keeping the system temperature ≤10 °C.

[0050] After removing the ice bath, the reaction was stirred at room temperature for about 16 hours, and the reaction endpoint was detected by TLC (methanol / dichloromethane = 1:10).

[0051] The reaction solution was concentrated to dryness under reduced pressure and purified by silica gel column chromatography (200-300 mesh, methanol / dichloromethane gradient 0-5%). The target fraction was collected and evaporated to dryness to give monosubstituted intermediate compound 2-1 (2.0 g, yield about 72%, light yellow solid).

[0052] S2: Compound 2-1 (1.88 g, 5 mmol), N,N-dimethylglycine (1.50 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol), and anhydrous ethanol (20 mL) were added to a 100 mL round-bottom flask. A reflux condenser was connected, and the mixture was reacted in an oil bath at 80 °C for 14 h under nitrogen protection. After the reaction was completed, the ethanol was removed under reduced pressure as monitored by TLC.

[0053] Add the residue to deionized water (5 mL), adjust the pH to 4–5 with glacial acetic acid, and then dissolve it in methanol (5 mL).

[0054] Purified by C18 reversed-phase column chromatography (mobile phase: water / acetonitrile = 5% → 95%, gradient elution for 30 min), and evaporated to dryness, the target product compound 3-1 was obtained (1.95 g, yield approximately 68%, light yellow powder). The product was further purified by... 1 HNMR, 13 The structure was correctly characterized by CNMR and ESI-MS, and the purity was >95%.

[0055] Example 2

[0056] Target product: Compound 3-2 (n=2, x=2)

[0057] In this embodiment, the reaction process of the apigenin-derived alkyl betaine compounds is as follows: Figure 3 As shown.

[0058] The specific preparation method is as follows:

[0059] S1: Add apigenin (2.7g, 10mmol), triphenylphosphine (7.86g, 30mmol) and 2-bromoethanol (3.8g, 30mmol) to a 250mL three-necked flask, add THF (30mL) to dissolve (add 10mL of DCM if necessary), and cool to 5°C in an ice bath under continuous nitrogen protection.

[0060] DIAD (6.06 g, 30 mmol) was added dropwise slowly, and the system temperature was controlled not to exceed 10 °C. The reaction was carried out for 20 h.

[0061] The reaction endpoint was monitored by TLC. After concentration under reduced pressure, the mixture was purified by silica gel column chromatography (200-300 mesh, methanol / dichloromethane gradient 0-5%) to give the disubstituted intermediate compound 2-2 (2.1 g, yield about 69%, light yellow solid).

[0062] S2: Compound 2-2 (1.90 g, 5 mmol), N,N-dimethylglycine (1.50 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol), and anhydrous ethanol (20 mL) were added to a flask. A reflux condenser was connected, and the mixture was reacted in an oil bath at 85 °C for 16 h. After the reaction was completed by TLC, the ethanol was removed under reduced pressure. The residue was added to water (5 mL), and acetic acid was added dropwise to adjust the pH to 4.5. Then, methanol (5 mL) was added to dissolve the residue.

[0063] Purified by C18 reversed-phase column chromatography (mobile phase: water / acetonitrile = 10 → 90%, gradient elution for 30 min), and evaporated to dryness, the target product compound 3-2 was obtained (2.02 g, yield approximately 67%, pale yellow powder). 1 HNMR, 13 CNMR and ESI-MS characterization, purity >95%.

[0064] Example 3

[0065] Target product: Compound 3-3 (n=2, x=3)

[0066] In this embodiment, the reaction process of the apigenin-derived alkyl betaine compounds is as follows: Figure 4 As shown.

[0067] The specific preparation method is as follows:

[0068] S1: In a 250 mL three-necked flask, add apigenin (2.7 g, 10 mmol), triphenylphosphine (10.48 g, 40 mmol), and 2-bromoethanol (5.0 g, 40 mmol). Dissolve the apigenin in a mixed solvent of THF (30 mL) and DCM (10 mL). Cool to 5 °C in an ice bath under continuous nitrogen protection. Slowly add DIAD (8.08 g, 40 mmol) using a constant pressure funnel and react for 24 h.

[0069] After the reaction was confirmed to be complete by TLC, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography (200-300 mesh, methanol / dichloromethane gradient 0-5%) to give the trisubstituted intermediate compound 2-3 (2.2 g, yield about 65%, pale yellow solid).

[0070] S2: Compound 2-3 (1.90 g, 5 mmol), N,N-dimethylglycine (1.80 g, 18 mmol), potassium carbonate (3.0 g, 22 mmol), and anhydrous ethanol (25 mL) were added to a flask. A reflux condenser was assembled, and the reaction was carried out at 90 °C for 18 h under a nitrogen atmosphere. After the reaction endpoint was detected by TLC, the mixture was cooled, the ethanol was removed under reduced pressure, water (5 mL) was added to adjust the pH to 4–5, and then methanol (5 mL) was added to dissolve the ethanol.

[0071] Purified by C18 reversed-phase column chromatography (mobile phase: water / acetonitrile = 5 → 95%, gradient elution for 30 min), and evaporated to dryness, the target product compound 3-3 was given as a pale yellow solid (2.00 g, yield approximately 63%). 1 HNMR, 13 CNMR and ESI-MS characterization, purity >95%.

[0072] Example 4

[0073] Target product: Compounds 3-4 (n=3, x=1)

[0074] In this embodiment, the reaction process of the apigenin-derived alkyl betaine compounds is as follows: Figure 5 As shown.

[0075] The specific preparation method is as follows:

[0076] S1: Add apigenin (2.7g, 10mmol), triphenylphosphine (5.24g, 20mmol) and 3-bromopropanol (2.9g, 20mmol) to a 250mL three-necked flask, add THF (30mL) to dissolve (add 10mL of DCM if necessary), cool to 5°C in an ice bath under continuous nitrogen protection, slowly add DIAD (4.04g, 20mmol), and stir at room temperature for 18h.

[0077] After the reaction endpoint was detected by TLC, the mixture was concentrated under reduced pressure and purified by silica gel column chromatography (methanol / dichloromethane gradient 0-5%) to give monosubstituted intermediate compound 2-4 (2.0 g, yield about 70%, light yellow solid).

[0078] S2: Compound 2-4 (1.88 g, 5 mmol), N,N-dimethylglycine (1.50 g, 15 mmol), potassium carbonate (2.76 g, 20 mmol), and anhydrous ethanol (20 mL) were added to a round-bottom flask and refluxed at 85 °C for 14 h under a nitrogen atmosphere. After the reaction, the mixture was cooled, the ethanol was removed under reduced pressure, water (5 mL) was added to adjust the pH to 4–5, and then methanol (5 mL) was added to dissolve the compound. The solution was purified by elution using a C18 reversed-phase column (mobile phase: water / acetonitrile = 5 → 95%, gradient elution for 30 min) to obtain the target product compound 3-4 (1.92 g, yield approximately 69%, light yellow powder). 1 HNMR, 13 CNMR and ESI-MS characterization showed that the structure was consistent with the design and the purity was >95%.

[0079] Example 5

[0080] Target products: Compounds 3-5 (n=3, x=2)

[0081] In this embodiment, the reaction process of the apigenin-derived alkyl betaine compounds is as follows: Figure 6 As shown.

[0082] The specific preparation method is as follows:

[0083] S1: Add apigenin (2.7 g, 10 mmol), triphenylphosphine (7.86 g, 30 mmol), and 3-bromopropanol (4.35 g, 30 mmol) to a 250 mL three-necked flask, and dissolve them in THF (30 mL) (add 10 mL of DCM if necessary). Cool to 5 °C in an ice bath under continuous nitrogen protection. Slowly add DIAD (6.06 g, 30 mmol) dropwise using a constant pressure dropping funnel, keeping the system temperature ≤10 °C, and react at room temperature for 20 h.

[0084] The reaction solution was concentrated under reduced pressure and purified by silica gel column chromatography (200-300 mesh, methanol / dichloromethane gradient 0-5%) to give the disubstituted intermediate compound 2-5 (2.1 g, yield about 67%, pale yellow solid).

[0085] S2: Add compound 2-5 (1.90 g, 5 mmol), N,N-dimethylglycine (1.60 g, 16 mmol), potassium carbonate (3.00 g, 22 mmol), and anhydrous ethanol (20 mL) to a flask. Connect a condenser and heat to 90 °C for 18 h under a nitrogen atmosphere. After the reaction is complete, cool and remove the ethanol under reduced pressure. Add deionized water (5 mL) to adjust the pH to 4–5, and then add methanol (5 mL) to dissolve.

[0086] Purified by C18 reversed-phase column chromatography (mobile phase: water / acetonitrile = 5 → 95%, gradient elution for 30 min), and evaporated to dryness, the target product compound 3-5 was obtained (2.00 g, yield approximately 65%, light yellow powder). 1 HNMR, 13 CNMR and ESI-MS characterization showed that the structure was correct and the purity was >95%.

[0087] The product compounds 3-1 to 3-5 of Examples 1 to 5 above 1 HNMR data and 13 CNMR data are shown in Tables 1-10.

[0088] Table 1 Compound 3-1 1 HNMR data (400MHz, DMSO)

[0089] Compound 3-2 in Table 2 1 HNMR data (400MHz, DMSO)

[0090]

[0091] Table 3 Compound 3-3 1 HNMR data (400MHz, D2O)

[0092]

[0093] Table 4 Compounds 3-4 1 HNMR data (400MHz, DMSO)

[0094]

[0095] Table 5 Compounds 3-5 1 HNMR data (400MHz, DMSO)

[0096]

[0097] Table 6 Compound 3-1 13 CNMR data (101MHz, DMSO)

[0098]

[0099] Table 7 Compound 3-2 13 CNMR data (101MHz, DMSO)

[0100]

[0101] Table 8 Compound 3-3 13CNMR data (101 MHz, D2O)

[0102]

[0103] Table 9 Compounds 3-4 13 CNMR data (101MHz, DMSO)

[0104]

[0105] Table 10 Compounds 3-5 13 CNMR data (101MHz, DMSO)

[0106]

[0107] Performance testing:

[0108] 1. Solubility test procedure:

[0109] Sample preparation: Accurately weigh a certain amount of apigenin betaine compound and use water or ethanol of known concentration as a solvent.

[0110] Dissolution process: Dissolve the sample at a constant temperature of 25°C using a magnetic stirrer until the sample is completely dissolved or reaches equilibrium.

[0111] Detection method:

[0112] The absorbance of the solution was determined using a UV-Vis spectrophotometer.

[0113] Based on the standard curve, the solubility of a compound is estimated by calculating its concentration in the solution.

[0114] The test results are shown in Table 11 below:

[0115] Table 11

[0116]

[0117] 2. Antioxidant efficacy test

[0118] The antioxidant activity of apigenin-derived alkyl betaines was evaluated using a zebrafish model. Zebrafish embryos or juveniles were grown under standard culture conditions and exposed to solutions of different concentrations of apigenin and apigenin derivatives. H₂O₂ was used as a ROS inducer to induce ROS generation before treatment. In the experiments, zebrafish were treated with different concentrations (e.g., 1 μM, 10 μM, 50 μM, 100 μM) of apigenin derivatives, and PBS solution was used as a blank control.

[0119] After treatment, ROS levels were determined using dihydroethidium (DHE) staining. DHE oxidizes in the presence of ROS, producing red fluorescence, which was measured using a fluorescence microscope or a fluorescence microplate reader. The ROS scavenging rate was calculated by determining the difference in fluorescence intensity between the treatment and control groups. The formula for ROS scavenging rate is: (Fluorescence intensity of control group - Fluorescence intensity of treatment group) / Fluorescence intensity of control group × 100%.

[0120] Test results are as follows Figure 7 As shown in the results, the antioxidant activity of apigenin-derived alkyl betaines in the zebrafish model was significantly higher than that of apigenin itself. Experimental data showed that apigenin-derived compound 3-2 exhibited a significant effect in ROS scavenging, achieving a scavenging rate of 55.2%, significantly higher than the 16.7% ROS scavenging rate of apigenin. This indicates that apigenin-derived alkyl betaines possess stronger antioxidant activity, effectively scavenging ROS and improving oxidative stress.

[0121] The above description is merely a preferred embodiment of the present invention. The scope of protection of the present invention is not limited to the above embodiments. All technical solutions falling within the scope of the present invention's concept are within the scope of protection of the present invention. It should be noted that for those skilled in the art, any improvements and modifications made without departing from the principles of the present invention should also be considered within the scope of protection of the present invention.

Claims

1. A apigenin betaine compound, characterized in that, It has the following chemical structural formula: （1） （2） （3） （4） （5）。 2. A method for preparing the apigenin-derived alkyl betaine compound according to claim 1, characterized in that, Includes the following steps: S1: Starting with apigenin and bromool, a mono- or poly-substituted bromoalkoxy apigenin is obtained via the Mitsunobu reaction. S2: Using bromoalkoxyapigenin and N,N-dimethylglycine as raw materials, the reaction is carried out under alkaline conditions to obtain the target product, apigenin-derived alkyl betaine compounds.

3. The method for preparing alkyl betaine compounds derived from apigenin according to claim 2, characterized in that, The reaction in step S1 also includes a reaction solvent, which is selected from any one or more of THF, DMF, DMSO, DCM, chloroform, methyl ether, toluene, and C5-8 alkanes; the reaction in step S2 also includes a reaction solvent, which is selected from any one or more of methanol, ethanol, acetonitrile, THF, DMF, DMSO, and methyl ether.

4. The method for preparing alkyl betaine compounds derived from apigenin according to claim 2, characterized in that, The reaction temperature in step S1 is 0–20°C; the reaction temperature in step S2 is 50–100°C.

5. The method for preparing alkyl betaine compounds derived from apigenin according to claim 2, characterized in that, In step S1, the ratio of apigenin to bromoethanol is 1:1 to 3; in step S2, the ratio of bromoalkoxyapigenin to N,N-dimethylglycine is 1:2 to 5.

6. The method for preparing alkyl betaine compounds derived from apigenin according to claim 2, characterized in that, The reaction time in step S1 is 10 to 24 hours; the reaction time in step S2 is 10 to 24 hours.

7. The method for preparing alkyl betaine compounds derived from apigenin according to claim 2, characterized in that, In step S2, the alkaline condition uses any one or more of the following: alkali metal hydroxide, alkaline earth metal hydroxide, alkali metal carbonate, alkali metal bicarbonate, alkaline earth metal carbonate, alkaline earth metal bicarbonate, alkali metal phosphate, and alkali metal salt of C1-8 alcohol.

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