CN108836957A - The purposes of paeonol derivative with vascular relaxing activity - Google Patents

Abstract

The invention provides a use of paeonol derivatives with vasodilation activity: carry out methylation reaction of 2,4-dihydroxyvalerophenone under alkaline conditions, and the reaction products are sequentially extracted, dried, and separated by column chromatography After recrystallization, 2-hydroxy-4-methoxyvalerophenone was obtained. Through screening the pharmacological activity of paeonol derivatives, the present invention finds that 2-hydroxy-4-methoxyvalerophenone has strong vasodilation activity and low toxicity, and can be applied to the treatment of ischemic cardiovascular diseases, Preparation of blood pressure and other drugs related to vasodilation activity. The preparation method of 2-hydroxy-4-methoxyvalerophenone adopted in the present invention shortens the reaction time, improves the product yield, and is beneficial to its popularization and application in related fields.

Description

Use of paeonol derivatives with vasodilation activity

technical field

The invention belongs to the field of plant natural products, in particular to the vasodilation activity of paeonol derivatives (PD).

Background technique

Natural products are valued by new drug researchers because of their wide range of biological activities, and they are often used as lead compounds for innovative drug development for structural modification and transformation. Paeonol, also known as paeonol and paeoniflorin, has a chemical name of 2-hydroxy-4-methoxyacetophenone, and is an active ingredient mainly extracted from the root bark of Xu Changqing, peony, and peony. Pharmacological studies have found that paeonol has significant inhibitory effects on esophageal cancer, liver cancer, colon cancer, and leukemia. In addition, paeonol has the effects of antibacterial and anti-inflammatory, antipyretic and analgesic, anticoagulant, antiallergic, immune regulation, anti-atherosclerosis, inhibition of allergy and inhibition of the central nervous system. For example, it has obvious analgesic effect on the pain caused by physical or chemical factors such as tail pressure and acetic acid; It has obvious inhibitory effect on the inflammatory reaction caused by toxins, etc.; it has obvious antipyretic effect on the rise in body temperature caused by typhoid vaccine and triple vaccine. It has inhibitory effect on type II, III, and IV allergies. In addition, paeonol also has sedative, hypnotic, antibacterial, antiviral, anti-inflammatory, anti-oxidative, swelling and pain-relieving effects.

Drug targets refer to the binding sites of drugs in the body, including gene sites, receptors, enzymes, ion channels, nucleic acids and other biomacromolecules. Small-molecule target drugs refer to small-molecule compounds and small-molecule active ingredients of natural medicines that can bind to specific parts or molecules in the body, which can specifically produce structural or functional effects on the protein or nucleic acid to which the target belongs, and change the disease. Signaling pathways or proteins and nucleic acids. Since the molecular weight of small molecule target drugs is usually less than 900Da, they are easily absorbed by the body and can quickly pass through cell membranes and various biological barriers. Paeonol has a simple structure and a variety of pharmacological effects, and is an ideal lead compound in the development of innovative drugs. Through the method of chemical structure modification and transformation, a series of paeonol derivatives can be synthesized, and it is expected to screen small molecular active ingredients with medicinal value. For example, Wang Jiangkai et al. reported the antitumor activity of paeonol derivatives (including 2-hydroxy-4-methoxyvalerophenone) (Synthesis and Antitumor Activity of Paeonol and Its Derivatives, 2010). But at present, there is no research report on the vasodilation activity of paeonol derivatives.

Contents of the invention

The object of the present invention is to provide a use of paeonol derivatives with vasodilation activity.

To achieve the above object, the present invention adopts the following technical solutions:

Use of paeonol derivatives in the preparation of vasoactive drugs, the paeonol derivatives being 2-hydroxyl-4-methoxyvalerophenone.

Preferably, the 2-hydroxy-4-methoxyvalerophenone has a vasodilation effect.

Preferably, the vasodilatory effect is partially endothelium-dependent.

Use of the above-mentioned 2-hydroxy-4-methoxyvalerophenone in the preparation of medicines for treating ischemic cardiovascular diseases.

Use of the above-mentioned 2-hydroxy-4-methoxyvalerophenone in the preparation of antihypertensive drugs.

Preferably, the use of the 2-hydroxy-4-methoxyvalerophenone in the preparation of medicines for treating hypertension.

The preparation method of above-mentioned 2-hydroxyl-4-methoxy valerophenone comprises the following steps:

Methylation reaction of 2,4-dihydroxyvalerophenone was carried out under alkaline conditions, and the reaction was terminated after TLC monitored the disappearance of raw materials. -Methoxyvalerophenone.

Preferably, the methylating reagent used in the methylation reaction is dimethyl sulfate.

Preferably, the conditions of the methylation reaction are as follows: the reaction temperature is 57-63°C, the reaction time is 55-65min, avoiding side reactions, reverse reactions and other processes that are not conducive to the formation of the target product, effectively generating the target compound, improving yield.

Preferably, the reagents used in the extraction include saturated NaHCO ₃ solution and saturated NaCl solution, which increases the yield.

The beneficial effects of the present invention are reflected in:

Through screening the pharmacological activity of paeonol derivatives, the present invention finds that 2-hydroxy-4-methoxyvalerophenone has strong vasodilation activity and low toxicity, and can be applied to the treatment of ischemic cardiovascular diseases, Preparation of blood pressure and other drugs related to vasodilation activity.

The preparation method of 2-hydroxyl-4-methoxyvalerophenone adopted in the present invention shortens the reaction time, improves the product yield, and is conducive to the use of 2-hydroxyl-4-methoxyvalerophenone in related fields (such as pharmacy ) to promote the application.

Description of drawings

Figure 1 is a schematic diagram of the synthetic route of 2-hydroxyl-4-methoxyvalerophenone.

Fig. 2 is the NMR spectrum of 2-hydroxyl-4-methoxyvalerophenone.

Fig. 3 is the relaxing effect of 2-hydroxyl-4-methoxyvalerophenone to PE (10 μ M), KCl (60mM) pre-contraction rat superior mesenteric artery (intact endothelium); Data represent with mean ± standard error, n =10, *P<0.05 and **P<0.01 vs. DMSO.

Fig. 4 is the relaxing effect of 2-hydroxyl-4-methoxyvalerophenone on PE (10 μ M), KCl (60 mM) pre-contraction rat superior mesenteric artery (endothelial incompleteness); Data are expressed with mean ± standard error, n=10, *P<0.05 and **P<0.01 vs. DMSO.

Figure 5 is the effect of 2-hydroxyl-4-methoxyvalerophenone on the systolic blood pressure (SBP) of spontaneously hypertensive rats; data are represented by mean ± standard error, n=10, *P<0.05 and ** P<0.01 vs. SHR.

Figure 6 is the effect of 2-hydroxyl-4-methoxyvalerophenone on the diastolic blood pressure (DBP) of spontaneously hypertensive rats: the data are represented by mean ± standard error, n=10, *P<0.05 and ** P<0.01 vs. SHR.

Detailed ways

The present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments.

The present invention uses paeonol as a lead compound, through chemical structure modification and transformation, synthesizes a series of derivatives, conducts activity research on them to obtain the structure-activity relationship between its chemical structure and pharmacological action, and then designs and synthesizes a series of derivatives with low toxicity and biological Compounds with more significant activity and promising prospects for pharmaceutical development.

(1) Synthesis of Paeonol Derivatives

The invention adopts classic Friedel-Crafts acylation reaction, takes resorcinol as raw material, zinc chloride as catalyst, and reacts with various organic acids to obtain 2,4-dihydroxyphenyl ketone compounds. After a methylation reaction, a series of paeonol derivatives are obtained. The following is an example of the synthesis of 2-hydroxy-4-methoxyvalerophenone (the serial number is PD2).

2-Hydroxy-4-methoxyphenylpentanone, C ₁₂ H ₁₆ O ₃ , namely 1-(2-hydroxy-4-methoxyphenyl)pentan-1-one, molecular weight: 208.25, structural formula as follows:

Two-step reaction is adopted to synthesize 2-hydroxyl-4-methoxyvalerophenone, and the synthetic route is shown in Figure 1.

The first step: the synthesis of 2,4-dihydroxyvalerophenone

Take 2.2g (20mmol) resorcinol, 3.3mL n-valeric acid (30mmol) and 3.3g (24mmol) anhydrous zinc chloride, stir in an oil bath at 120.0°C, monitor the reaction by TLC, and reflux for 4.0h. After the reaction solution was cooled to room temperature, the orange-red viscous mother solution was poured into ice water, and the crystallization situation was observed. It was found that the product was grouped into dark red lumps. Add ethyl acetate to the reaction product, wash it repeatedly with 3% dilute hydrochloric acid solution to remove excess zinc salt, then extract it with saturated _NaHCO3 solution and saturated NaCl solution for 3 times, measure its pH value between 5 and 6, and use anhydrous MgSO ₄ dry. After recovering the solvent, pass through a silica gel column and elute with petroleum ether: ethyl acetate = 25:1 (volume ratio) to obtain a light yellow oily liquid. After methanol recrystallization, 0.9 g of goose yellow flaky crystals were obtained, with a yield of 24.2%. Melting point: 61.1°C. NMR data: ¹ HNMR(CD ₃ CD),δ:0.96(3H,t,-CH ₃ ),1.45(2H,t,-CH ₂ ),1.72(2H,t,-CH ₂ ),2.95(2H, t, -CH ₂ CO), 6.24 (H, s, Ph-3H), 6.38 (1H, d, Ph-5H), 7.76 (1H, dd, Ph-7H), OH peak was not seen.

The second step: the synthesis of 2-hydroxy-4-methoxyvalerophenone

Take 0.9g (5mmol) of 2,4-dihydroxyvalerophenone, dissolve it in acetone, add 0.7g (5mmol) of anhydrous K ₂ CO ₃ , 0.47mL (5mmol) of dimethyl sulfate, stir, and reflux in a water bath at 60°C After reacting for 1 h, the reaction product was added with ethyl acetate, extracted three times with saturated NaHCO ₃ solution and saturated NaCl solution respectively, and the organic phases were combined to obtain a colorless and clear solution, which was dried over anhydrous MgSO ₄ . After recovering the solvent, pass through a silica gel column and elute with petroleum ether: ethyl acetate = 15:1 (volume ratio) to obtain a light yellow oily liquid. After methanol recrystallization, 1.1 g of a light yellow liquid is obtained, with a yield of 92.4%.

See Figure 2, NMR data of the product: ¹ HNMR((CD ₃ ) ₂ CO),δ:0.98(3H,m,-CH ₃ ),1,75(2H,m,-CH ₂ ),2.85～2.99(4H ,m,-CH ₂ ),3.89(3H,s,-OCH ₃ ),6,42(1H,s,Ph-3H),6.52(1H,d,Ph-5H),7.87(1H,2,Ph -6H) 12.89 (1H,s,Ph-OH). It is determined that the obtained is 2-hydroxy-4-methoxyvalerophenone (PD2), which is a mixture of light yellow solid and liquid at normal temperature. When the temperature is 37°C, PD2 is in the state of light yellow transparent liquid with a density of 0.99g/ mL.

(2) Screening of paeonol derivatives for vasodilation activity

Based on 66 compounds to be screened, high potassium (60mM KCl, KPSS) and phenylephrine (PE) were used to induce rat isolated superior mesenteric artery vasoconstriction model, and 4 compounds were preliminarily screened out with obvious vasodilation activity (VS. Paeonol), respectively PD2, PD4, PD8, PD9, see Table 1 for specific results.

Table 1. Preliminary screening results of vasodilator activity of paeonol derivatives

Since Paeonol Derivative No. 2 has stronger vasodilation activity compared with other screening compounds, the following experiments are conducted on the vasodilation mechanism and druggability of Paeonol Derivative No. 2.

(3) Mechanism of 2-hydroxy-4-methoxyvalerophenone (PD2) relaxing blood vessels

3.1. Experimental materials

1. Experimental animals

Sprague-Dawley (SD) rats, male, weighing 200g-300g, were purchased from the Experimental Animal Center of Xi'an Jiaotong University (permit number: SCXK (Shaanxi) 2008-008). Breeding conditions: In the SPF grade animal room of the Institute of Basic and Translational Medicine, Xi'an Medical College, 12h light/dark alternation, room temperature controlled at 19-26°C, humidity controlled at 40%-70%, airflow controlled at 0.13-0.18m/s , the number of air changes is controlled at 10-20 times/h, the noise is less than 60 decibels, free to drink water, and fed with ordinary animal feed.

2. Experimental equipment

Four-channel microvascular tensiometer (DMT Company, Denmark, model: 620); PowerLab eight-channel physiological recorder (Adinstruments Company, Australia, model: 8/35); stereo microscope (Olympus Company, Japan, model: SZX-T ); Adjustable vortex mixer (Serro Czech Company, USA, model MX-S); multi-functional circulating constant temperature water bath (Haichangji Geological Instrument Co., Ltd., model: HWY-10).

3. Drugs to be tested

2-Hydroxy-4-methoxyvalerophenone (provided by the Chemical Drug Research Department of Shaanxi Pharmaceutical Research Institute), and DMSO was used as a solvent for administration.

4. Solution preparation

1) Physiological salt buffer solution (PSS) preparation:

NaCl (119mM), KCl (4.6mM), NaH ₂ PO ₄ 2H ₂ O (1.2mM), MgCl ₂ 6H ₂ O (1.2mM), NaHCO ₃ (15mM) and Glucose H ₂ O (5.5mM) .

Weigh the medicines according to the final concentration of the PSS formula, dissolve them in 900mL deionized water in turn, add 1.5mL of CaCl ₂ (1M) at the end, set the volume to 1000mL with deionized water, dissolve them completely by ultrasonication, and adjust the pH (HCL or NaOH) =7.4, stored at 4°C for later use.

2) Preparation of physiological salt buffer solution (KPSS) containing high potassium (60mM):

NaCl (63.6mM), KCl (60mM), NaH ₂ PO ₄ 2H ₂ O (1.2mM), MgCl ₂ 6H ₂ O (1.2mM), NaHCO ₃ (15mM) and Glucose H ₂ O (5.5mM) .

Weigh the drug according to the final concentration of the KPSS formula, dissolve it in 900mL of deionized water in turn, add 1.5mL of CaCl ₂ (1M) at the end, set the volume to 1000mL with deionized water, dissolve it completely by ultrasonication, and adjust the pH (HCL or NaOH) =7.4, stored at 4°C for later use.

3) Preparation of PE solution:

Weigh 20.367 mg of PE, dissolve it in 10 mL of normal saline, dissolve it completely by ultrasonication, and store it at 4°C for future use (the original concentration of PE is 10 mM).

4) Acetylcholine (Ach) solution preparation:

Weigh 18.166mg of Ach, dissolve it in 10mL of normal saline, dissolve it completely by ultrasonication, store at 4°C for future use (the original concentration of Ach is 10mM).

3.2. Experimental method

1. Preparation of isolated rat superior mesenteric artery ring specimens

The SD rats were killed by _CO2 asphyxiation, fixed in the supine position, the abdominal cavity was quickly opened, and the intestines were taken out. The removed intestines were placed in 4°C pre-cooled PSS, and the superior mesenteric artery was found under a stereomicroscope and removed. Fix it and isolate the superior mesenteric artery. 1mL 4°C PSS was used to wash blood clots in blood vessels, remove fat and connective tissue around blood vessels, and cut the separated superior mesenteric artery into vascular rings with a length of 2-3mm.

2. Balance the vascular ring

Hang the prepared vascular ring in the bath of the microvascular tensiometer (containing 95% O ₂ , 5% CO ₂ saturated 37 ° C PSS solution 5mL), place the vascular ring in the bath, change the liquid once, manually adjust to zero, Equilibrate for 60 minutes (change the medium every 20 minutes).

3. Adjust pretension and observe vascular activity

Adjust the pretension of the well-balanced vascular ring to 2mN, replace it with fresh PSS, stimulate the vascular ring twice with KPSS and PE solution after stabilization, and check the activity of the vascular ring. Wash with fresh PSS continuously for 3 times, stabilize for 60min, and carry out subsequent experiments.

4. Ach verifies whether the vascular endothelium is complete

Add 5 mL of KPSS and PE solution into the bath, and add 50 μL of Ach (10 ^-3 M) after the vasoconstriction reaches the maximum value and stabilize, and observe whether the vascular ring relaxes, so as to judge whether the endothelium of the vascular ring is complete (after adding Ach, the vascular ring has no Relaxation or a relaxation rate of less than 70% indicates that the endothelium of the vascular ring is incomplete; after adding Ach, the relaxation rate of the vascular ring is greater than or equal to 70%, indicating that the endothelium of the vascular ring is complete).

5. Vasodilation activity

Use KPSS or PE solution to pre-shrink the vascular ring. After reaching equilibrium, add 10 ^-9 M-10 ^-3 M 2-hydroxy-4-methoxyvalerophenone (the control group is given DMSO) respectively, observe and record the vascular ring Changes in tension. After adding sequentially, after the vascular ring reaches the maximum contraction and is stable, wash it with PSS solution for 3 times, wait for the vascular tension to return to the base value, stabilize it for 60 minutes, and then use KPSS or PE solution to detect the toxicity of the drug to the blood vessel (can produce contraction). That is, the drug is considered non-toxic, otherwise, it is toxic). The maximum contraction range of the vascular ring induced by KPSS or PE solution was 100%, and the percentages of responses of different concentrations were calculated, and the cumulative concentration-vascular response curve was made according to the results.

3.3. Experimental results

1. The relaxation effect of 2-hydroxy-4-methoxyvalerophenone (PD2) on the superior mesenteric artery (intact endothelium) of PE or KCl precontracted rats

PD2 (10 ^-9 M-10 ^-3 M) relaxes PE (Emax: 94.59±1.9%, Fig. 3B ) or KCl (Emax: 82.44±8.98%, Fig. 3A ) precontracted rat mesentery in a concentration-dependent manner Arteries (intact endothelium). In addition, there was no difference in the shrinkage ability of blood vessels before and after the experiment, which indicated that PD2 had no toxicity to blood vessels (intact endothelium).

2. The role of endothelial cells in 2-hydroxy-4-methoxyvalerophenone (PD2)-induced relaxation of PE or KCl-precontracted rat superior mesenteric artery (with incomplete endothelium)

PD2 (10 ^-9 M-10 ^-3 M) relaxes PE (Emax: 87.32±3.8%, Figure 4B) or KCl (Emax: 78.31±10.73%, Figure 4A) precontracted rat mesentery in a concentration-dependent manner Arteries (incomplete endothelium). In addition, there was no difference in the contraction ability of blood vessels before and after the experiment, which indicated that PD2 had no toxicity to blood vessels (incomplete endothelium).

3.4. Experimental conclusion

The vasodilation effect of 2-hydroxy-4-methoxyvalerophenone (PD2) is partially endothelium-dependent.

(4) Acute Toxicology Experiment of 2-Hydroxy-4-Methoxyvalerophenone (PD2)

The LD ₅₀ of paeonol derivatives was determined by Bliss method to provide a toxicological basis for their clinical safety application.

4.1. Experimental materials

1. Drugs and solvents

2-Hydroxy-4-methoxyvalerophenone (PD2) was provided by the Chemical Drug Research Department of Shaanxi Pharmaceutical Research Institute. The PD2 sample was stored in the refrigerator under refrigeration. Before use, it was treated in a water bath at 37°C until it was in a liquid state, and diluted with peanut oil. ; Solvent: Luhua peanut oil, manufacturer: Shandong Luhua Group Co., Ltd.

2. Experimental animals

SPF grade healthy KM mice, weighing 18-22g, male and female, 60 in total. Purchased from the Experimental Animal Center of Xi'an Jiaotong University. They were kept in the experimental animal room of Shaanxi Institute of Traditional Chinese Medicine.

4.2. Experimental method

1. Experimental grouping

Mice were given PD2 by intragastric administration, and the Dm was determined to be 19.8 g/kg, and the Dn was 4.754 g/kg.

In the formal test, 60 mice were adaptively fed for 3 days, and divided into groups according to body weight, 10 mice in each group, half male and half male. It was divided into six groups, of which the first to fifth groups were PD2 administration groups, and the sixth group was vehicle control group. The dose group was initially dosed at 19.8 g/kg, diluted with peanut oil at a ratio of 1:0.7, and a total of 5 dose groups were set up, corresponding to PD2 groups 1 to 5. The vehicle control group was given the same volume of peanut oil.

2. Administration method

Intragastric administration, the dosage volume is 20mL/kg. The test animals in the 6 groups were fasted for 12 hours before administration, and the test drug was administered ig according to body weight.

3. Observation indicators

Immediately after the administration, the skin, eyes, hair, activities, food intake, drinking water, defecation, respiratory changes, poisoning manifestations and death of the mice were observed for a total of 14 days. The dead animals were autopsied in time, and the surviving mice were sacrificed and autopsied after 14 days.

4. Result processing

The obtained data were processed with animal acute toxicity LD ₅₀ software, and the median lethal dose (LD ₅₀ ) and its 95% confidence limit were calculated according to the Bliss method.

4.3. Experimental results

The highest dose of PD2 was 19.8g/kg. After 30 minutes of administration, the tested animals showed fluffy and erect hair, closed eyes, less food, and decreased activity. The PD2 group died within 24 hours. Within 48 hours, PD2 group 2, PD2 group 3, and PD2 group 4 died. Animals did not die after 72h. The observation indexes of animals in PD2 groups 2 to 5 returned to normal 72 hours after administration. In the PD2 group, the observed indicators returned to normal 5 days after administration, and the cumulative mortality rate is shown in Table 2.

Table 2. Mortality rate of paeonol derivatives in mice

Regression equation y(Probit)＝0.85975+4.0493Log(D)

4.4. Experimental conclusion

The LD ₅₀ of PD2 was 10.531g/kg (LD ₅ =4.1327g/kg, LD ₉₅ =26.833g/kg) according to the cumulative mortality rate of 14 days, and the 95% credible limit It is 8.2126-13.892g/kg. There was no abnormality after the autopsy of the poisoned dead animals, and the surviving animals were sacrificed after 14 days, and the autopsy showed no abnormality.

(5) Effect of 2-hydroxy-4-methoxyvalerophenone (PD2) on blood pressure in spontaneously hypertensive rats

5.1. Experimental animals and grouping

Spontaneously hypertensive rats (Spontaneously hypertensive rats, SHR), 8 weeks old, male, about 200g. Random grouping: placebo group (normal saline, SHR group), positive control group (captopril, 30mg/Kg, CP group), PD2 dose group (2, 10, 50, 250mg/kg), 10 rats in each group ; In addition, 10 Wistar-Kyoto rats (8 weeks old, male, 200 g) were used as a negative control group (peanut oil, Wistar group). Oral administration for 4 weeks.

5.2. Index detection

The blood pressure of the rats was detected 1w, 2w, 3w, 4w after the administration, and the body weight was detected once a week.

5.3. Experimental results

In the dose group with a concentration of 10 mg/kg, the systolic and diastolic blood pressure decreased significantly from the first week, and the systolic and diastolic blood pressure remained at a low level in the second, third, and fourth weeks. The blood pressure of the dose group with a concentration of 50mg/kg decreased significantly in the 4th week, systolic blood pressure and diastolic blood pressure. However, other dose groups had no effect on blood pressure (see Figure 5 and Figure 6).

5.4. Experimental conclusion

2-Hydroxy-4-methoxyvalerophenone (PD2) has a significant hypotensive effect, which has no dose-dependent effect.

In a word, the present invention uses high potassium (60mM) or phenylephrine (PE) to induce rat isolated superior mesenteric artery vasoconstriction model respectively through the myograph system, adds the compound to be screened, and observes the vascular tension by detecting the change of vascular tension. For relaxation and contraction, the compounds to be screened were screened for vasodilation activity. Finally, compounds with excellent activity were screened out. Pharmacological screening results: 2-hydroxy-4-methoxyvalerophenone has strong vasodilation activity and can be used to treat hypertension and ischemic cardiovascular disease. At the same time, 2-hydroxy-4-methoxyvalerophenone has no toxicity to blood vessels and can be used safely in clinical practice.

Claims (10)

1. The use of paeonol derivative 2-hydroxy-4-methoxyvalerophenone in the preparation of vasoactive drugs. 2. The use according to claim 1, characterized in that: the 2-hydroxy-4-methoxyvalerophenone has a vasodilation effect. 3. The use according to claim 2, characterized in that: the vasodilation effect is endothelium-dependent. 4. Use of paeonol derivative 2-hydroxy-4-methoxyvalerophenone in the preparation of medicines for treating ischemic cardiovascular diseases. 5. The use of paeonol derivative 2-hydroxy-4-methoxyvalerophenone in the preparation of antihypertensive drugs. 6. The use according to claim 5, characterized in that: the use of the 2-hydroxy-4-methoxyvalerophenone in the preparation of medicines for treating hypertension. 7. A preparation method of 2-hydroxy-4-methoxyvalerophenone, characterized in that: comprising the following steps: Methylation reaction of 2,4-dihydroxyvalerophenone was carried out under alkaline conditions, and the reaction was terminated after TLC monitored the disappearance of raw materials. -Methoxyvalerophenone. 8. The method according to claim 7, characterized in that: the methylating reagent used in the methylation reaction is dimethyl sulfate. 9. The method according to claim 7, characterized in that: the conditions of the methylation reaction are: the reaction temperature is 57-63° C., and the reaction time is 55-65 minutes. 10. The method according to claim 7, characterized in that: the reagents used in the extraction include saturated NaHCO ₃ solution and saturated NaCl solution.