New method for preparing monoterpene substituted dihydrochalcone adunctin B

Abstract

The invention provides a novel method for preparing monoterpene substituted dihydrochalcone adunctin B. The method comprises the following steps: by taking commercially available sym-trisphenol as a raw material, carrying out phenolic hydroxyl methylation reaction and Friedel-Crafts reaction to obtain dihydrochalcone; iodosobenzene diacetate and silver carbonate are used for double catalysis; two fragment compounds of dihydrochalcone and alpha-phellandrene are connected through an intermolecular oxidation [3 + 2] cycloaddition reaction, so that the monoterpene substituted dihydrochalcone adunctin B is efficiently prepared. The preparation method takes synthetic organic chemistry as a means, and has the four characteristics of short route, high yield, low cost, simplicity in operation and the like; the total synthesis of the medicinal active natural product monoterpene substituted dihydrochalcone adunctin B is realized; good popularization and application prospects are realized.

Description

Technical Field

[0001] The present invention belongs to the field of chemical biomimetic synthesis of natural medicines, and particularly relates to a new method for preparing monoterpene-substituted dihydrochalcone adunctin B. Background Art

[0002] Natural product chemistry is an important part of medicinal chemistry, combining knowledge of multiple disciplines such as pharmacology, biology, and natural product chemistry. It not only promotes the research and development of more new drugs, with an increasing number of new drug varieties, but also effectively promotes the rapid development of the pharmaceutical industry. Its main research contents include extraction of natural products, structure identification, biological activity research, structure-activity relationship research, and new drug development, etc. However, this direction also faces great challenges and developments. For example, the structures of natural products are complex, and the extraction and separation are difficult; some natural resources are scarce and need to be solved through chemical synthesis. In short, natural product chemistry plays an important role in drug research. With the continuous development of technology and instruments, it is expected to discover more new drugs with high efficiency and low toxicity in the future.

[0003] Adunctin B is a monoterpene-substituted dihydrochalcone compound extracted and isolated from the plant Piper arboreum of the Piperaceae family. This natural product can exhibit antibacterial activity against Micrococcus luteus at a low concentration of 3.5 μg / mL, showing good potential medicinal value and drug activity. At the same time, more biological activities and pharmacological activities remain to be further explored and studied. However, the plant source of this natural product is very limited, and only 4.8 mg of adunctin B can be extracted from 1.55 kg of dry Piper arboreum leaves, with a yield of only 0.0003%. It is very difficult to achieve large-scale extraction from plants at present, and it may have a greater impact on the natural ecological environment. Therefore, based on the protection of the natural ecological environment and the limitations of the source of this natural product, it is necessary to prepare this natural product by means of synthetic organic chemistry from the perspective of new drug research and drug lead compounds. Summary of the Invention

[0004] The present invention mainly overcomes the deficiencies in the prior art and provides a new method for preparing monoterpene-substituted dihydrochalcone adunctin B. It discloses that using commercially available phloroglucinol as a raw material, dihydrochalcone is obtained through phenolic hydroxyl methylation reaction and Friedel-Crafts reaction; utilizing the dual catalytic action of iodobenzene diacetate and silver carbonate; connecting the two fragment compounds of dihydrochalcone and α-phellandrene through an intermolecular oxidative [3+2] cycloaddition reaction, thereby efficiently preparing monoterpene-substituted dihydrochalcone adunctin B; the present invention uses synthetic organic chemistry as a means, with four major characteristics: short route, high yield, low cost, and simple operation; realizing the total synthesis of the medicinally active natural product monoterpene-substituted dihydrochalcone adunctin B; having excellent prospects for popularization and application.

[0005] To achieve the above technical objectives, the technical solution adopted by the present invention is as follows: A new method for preparing monoterpene-substituted dihydrochalcone adunctin B, and the reaction process of the preparation method is as follows: ; The synthesis method includes Step 1 to Step 3: Specifically: Step 1: Using phloroglucinol and dimethyl carbonate as raw materials, compound 1 is obtained through phenolic hydroxyl methylation reaction; that is, methoxydiphenol; Step 2: Compound 1 and 3-phenylpropionic acid undergo a Friedel-Crafts reaction to obtain compound 2; that is, dihydrochalcone; Step 3: Using iodobenzene diacetate and silver carbonate as dual catalysts; through an intermolecular oxidative [3+2] cycloaddition reaction, two fragment compounds of compound 2 and α-phellandrene are connected to prepare the monoterpene-substituted dihydrochalcone adunctin B.

[0006] Furthermore, the structural formulas of phloroglucinol, compound 1, compound 2, α-phellandrene, and monoterpene-substituted dihydrochalcone adunctin B are: .

[0007] Furthermore, Step 1 is as follows: Dewater the reaction vessel, set the atmosphere in the reaction vessel to an inert gas environment, add phloroglucinol and anhydrous potassium carbonate in sequence, then add acetone and dimethyl carbonate, gradually raise the temperature for reaction. After the reaction ends, cool the reaction solution to 25°C, distill off the excess solvent acetone, then extract multiple times, wash with water and saturated brine in sequence, dry with anhydrous magnesium sulfate, distill the extraction solvent, and separate after concentration to obtain compound 1, that is, light brown oily liquid methoxydiphenol.

[0008] Furthermore, Step 2 is as follows: Dewater the reaction vessel, set the atmosphere in the reaction vessel to an inert gas environment, add dichloromethane and 3-phenylpropionic acid in sequence, place the reaction vessel in a low-temperature reactor at 0°C for precooling, then dropwise add oxalyl chloride within 5 minutes, then add N,N-dimethylformamide, gradually raise the temperature to 25°C. After the reaction ends, distill off the excess dichloromethane solvent and oxalyl chloride reagent, and concentrate to form solution a for standby; Dewater another reaction vessel, set the atmosphere in the reaction vessel to an inert gas environment. After adding the light brown oily liquid methoxydiphenol synthesized in Step 1 and dichloromethane solvent, place the reaction vessel in a low-temperature reactor at 0 °C for precooling, and then add aluminum trichloride. Subsequently, dropwise add Solution a prepared above within 10 minutes, gradually heat up to 25 °C. After the reaction ends, add ice water to quench the reaction, extract, distill the extraction solvent, and concentrate to separate to obtain Compound 2, which is the light yellow solid dihydrochalcone.

[0009] Further, Step 3 is as follows: Add Compound 2 and α-phellandrene to the reaction vessel. Under the dual catalysis of iodobenzene diacetate and silver carbonate, add a mixed solvent of toluene and acetonitrile, heat up to 35 °C and react for 30 - 35 minutes. Distill the solvent, concentrate, and separate and purify the generated adunctin B to finally obtain the monoterpene-substituted dihydrochalcone adunctin B.

[0010] Further, the specific synthesis method of Step 1 is as follows: The reaction vessel is a two-necked round-bottom flask, and the water removal method is to preheat with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace with nitrogen 3 - 4 times; after adding anhydrous potassium carbonate, set the atmosphere in the reaction vessel to an inert gas environment again, and the method is to displace with argon 2 - 3 times; the molar ratio of phloroglucinol, anhydrous potassium carbonate, and dimethyl carbonate is 160 - 162:240 - 242:76.8 - 78.8; acetone does not need to be dried, and when phloroglucinol is 160 mmol, the amount of acetone used is 250 mL; the temperature is 60 °C - 63 °C, and the reaction time is 6 - 7 h; the extraction solvent for multiple extractions is ethyl acetate, and the number of extractions is 3 - 4 times; the separation means is column chromatography, and column chromatography is carried out 2 times. The first eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 10:1. The second eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 5:1.

[0011] Further, the specific synthesis method of Step 2 is as follows: The reaction vessel is a single-necked round-bottom flask, and the water removal method is to preheat with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace with nitrogen 3 - 4 times; the precooling time is 2 - 3 min; the reaction temperature is room temperature, and the reaction time is 2 h; the method for distilling the excessive oxalyl chloride and dichloromethane solvent is rotary evaporation; the molar ratio of 3-phenylpropionic acid to oxalyl chloride is 1 - 2:4 - 5; when 3-phenylpropionic acid is 100 mmol, the amount of dichloromethane used is 120 mL; the amount of N,N-dimethylformamide used is 5 drops. Another reaction vessel is a two-necked round-bottom flask, and the water removal method is to preheat it with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace it with nitrogen 3 - 4 times; the pre-cooling time is 5 - 6 min; the reaction time is 20 - 22 h; after the reaction ends, ice water is added to quench the reaction within 6 - 7 minutes at 0 o °C; extraction is carried out with ethyl acetate, and the separation means is column chromatography, and column chromatography separation is carried out 2 times. The first eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 16:1. The second eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 4:1.

[0012] Further, the specific synthesis method of step three is as follows: The reaction vessel is a two-necked round-bottom flask, and the water removal method is to preheat it with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace it with nitrogen 3 - 4 times; after adding compound 2 and α-phellandrene, argon is displaced again 2 - 3 times; the molar ratio of ketodihydrochalcone, β-phellandrene, iodobenzene diacetate, and silver carbonate is 1 - 1.2:2 - 2.2:0.2 - 0.23:0.2 - 0.23; when the amount of dihydrochalcone added is 10 mmol, the mixed solvent of toluene and acetonitrile is 25 mL; the method for distilling the solvent is rotary evaporation; the method for separation and purification is column chromatography 2 times; the first eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 30:1. The second eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 15:1.

[0013] Beneficial effects Compared with the prior art, the present invention has the following advantages: The present invention discloses a new method for preparing monoterpene-substituted dihydrochalcone adunctin B, which uses a biomimetic [3 + 2] cycloaddition as the key reaction and can quickly prepare monoterpene-substituted dihydrochalcone adunctin B in only three steps, enriching the new methods for synthesizing such natural products. This method not only has the advantages of simple operation, cheap raw materials, high yield, and short steps, greatly breaking through the limitations of the source of this natural product; at the same time, this reaction plays an important role in the development of both organic chemistry and medicinal chemistry. Especially when this method is applied to the synthesis of natural product molecules with important physiological and pharmacological activities, its value can be maximally reflected.

[0014] Compared with the previous preparation methods of predecessors, there are three innovations in the present invention: First, under the dual catalytic action of iodobenzene diacetate and silver carbonate, the product adunctin B can be obtained, while other methods require a large amount of oxidant, even a greatly excessive amount to achieve the purpose; Second, our method can obtain the product adunctin B in only 30 minutes, while the previous similar reactions took 8 - 24 hours, greatly shortening the reaction time; Third, under the catalytic conditions of our invention, the yield of the reaction product adunctin B is 87%, while that of the previous researchers was only about 50%, greatly improving the yield. Brief Description of the Drawings

[0015] Figure 1 It is the synthetic route diagram of adunctin B in the embodiments of the present invention; Figure 2 They are the structural formulas of mesitylene triol, compound 1, compound 2, α - phellandrene, and the monoterpene - substituted dihydrochalcone adunctin B in the embodiments. Detailed Embodiments

[0016] In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0017] According to Figure 1 the synthetic route diagram shown, the compounds in the following embodiments are synthesized, and the structural formulas of each compound involved are Figure 2 shown as follows.

[0018] Example 1: Step 1: Take a 500 mL two - neck round - bottom flask and pre - heat it with an alcohol lamp to remove water for 3 minutes, and displace nitrogen 3 times. Weigh mesitylene triol (purity 97%, 20.78 g, 160 mmol) and anhydrous potassium carbonate (purity 97%, 34.20 g, 240 mmol, 1.5 equiv), and then displace nitrogen twice again; then, add acetone (250 mL); finally, dropwise add dimethyl carbonate (purity 97%, 6.7 ml, 76.8 mmol, 0.48 equiv), and gradually raise the reaction temperature to 60 °C and react for six hours. After the reaction is completed, cool it to 25 °C, and distill acetone with a rotary evaporator. Extract with ethyl acetate (3 × 150 mL), wash successively with water (50 mL) and saturated brine (40 mL), dry with anhydrous magnesium sulfate, and distill the extraction solvent ethyl acetate under reduced pressure. After concentration, separate by column chromatography twice. The volume ratio of the first eluent is petroleum ether:ethyl acetate = 10:1, and the volume ratio of the second eluent is petroleum ether:ethyl acetate = 5:1, to obtain a light - brown oily liquid, methoxydiphenol. 15.90 g of methoxydiphenol is obtained, and the yield is 71%. Rf = 0.5 (petroleum ether:ethyl acetate = 2:1).

[0019] Step 2: Take a 500 mL single-necked round-bottom flask and preheat it with an alcohol lamp to remove water for 3 minutes, and displace nitrogen 3 times. First, weigh 3-phenylpropionic acid (purity 95%, 15.79 g, 100 mmol, 2.0 equiv) and dichloromethane (120 mL). Place it in an ice-salt bath at 0 °C and pre-cool for 2 minutes; then, dropwise add oxalyl chloride (purity 96%, 35.5 ml, 400 mmol, 4.0 equiv) within 5 minutes; finally, add 5 drops of N,N-dimethylformamide to the reaction. Gradually raise the temperature to 25 °C and react for 2 hours. After the reaction is completed, distill the excess dichloromethane solvent and oxalyl chloride using a rotary evaporator, and concentrate to obtain solution a for standby.

[0020] During this period, take another 500 mL two-necked round-bottom flask and preheat it with an alcohol lamp to remove water for 3 minutes, and displace nitrogen 3 times. First, weigh the methoxydiphenol compound prepared in Step 1 (7.00 g, 50 mmol) and aluminum trichloride (purity 95%, 10.53 g, 75 mmol, 2.5 equiv); then, after adding dichloromethane (150 mL), pre-cool in an ice-salt bath at 0 °C for 5 minutes; finally, dropwise add the solution a from the previous step within 10 minutes, and gradually raise the temperature to 25 °C and react for 20 hours. After the reaction is completed, add ice water (30 mL) to quench the reaction within 6 minutes at 0 °C. Extract with ethyl acetate (3 × 80 mL), wash with water (40 mL) and saturated brine (30 mL), dry with anhydrous magnesium sulfate, distill the extraction solvent ethyl acetate under reduced pressure, and concentrate and separate by column chromatography 2 times. The volume ratio of the first eluent is petroleum ether:ethyl acetate = 16:1, and the volume ratio of the second eluent is petroleum ether:ethyl acetate = 4:1 to obtain 9.11 g of white solid dihydrochalcone 2, with a total yield of 67%. Rf = 0.4 (petroleum ether:ethyl acetate = 2:1).

[0021] Step 3: Take a 100 mL two-necked round-bottom flask and preheat it with an alcohol lamp to remove water for 3 minutes, and displace nitrogen 3 times. First, add the dihydrochalcone compound 2 (2.72 g, 10 mmol) prepared in the previous step and α-phellandrene (purity 85%, 3.20 g, 20 mmol, 2.0 equiv), and displace argon 2 times again. Then, add a mixed solvent of toluene and acetonitrile (25 mL) and dissolve it. Finally, add iodobenzene diacetate (97%, 0.664 g, 2 mmol, 0.2 equiv) and silver carbonate (97%, 0.569 g, 2 mmol, 0.2 equiv). Gradually raise the temperature to 35 °C and react for 30 minutes. After the reaction is completed, cool it to room temperature. Distill the solvent toluene under reduced pressure using a rotary evaporator, and after concentration, perform column chromatography separation 2 times. The volume ratio of the eluent for the first time is petroleum ether:ethyl acetate = 30:1, and the volume ratio of the eluent for the second time is petroleum ether:ethyl acetate = 15:1, to obtain 3.53 g of a light yellow solid adunctin B, with a total yield of 87%. Rf = 0.70 (petroleum ether:ethyl acetate = 2:1).

[0022] Its structure was characterized by TLC thin layer chromatography and NMR data as follows: Data for adunctin B, Rf = 0.70 (petroleum ether / EtOAc = 2 : 1); 1H NMR (300 MHz, CDCl3): δ = 13.38(s, 1H), 7.30 7.20 (m, 5H), 6.02 (s, 1H), 5.88 (dd, J = 11.4, 2.8 Hz, 1H),5.62 (dd, J = 11.4, 2.4 Hz, 1H), 3.82 (s, 3H), 3.41 (t, J = 4.8 Hz, 1H), 3.28(dt, 14.8, 7.6 Hz, 1H), 3.24 (dt, 14.8, 7.6 Hz, 1H), 3.01 2.95 (m, 2H), 2.272.26 (m, 1H), 1.88 (s, 1H), 1.60 1.58 (m, 2H), 1.58 (s, 3H), 0.91 (d, J = 2.7Hz, 3H), 0.89 (d, J = 2.7 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ = 203.4,165.9, 161.8, 161.6, 141.3, 135.1, 128.9, 128.1, 125.6, 107.5, 102.1, 91.9,88.7, 55.2, 44.0, 43.8, 37.7, 31.3, 30.6, 26.1, 25.8, 19.5, 9.3 ppm. The structural formulas of the compounds described in this factual example are respectively as follows Figure 2 shown. For the target natural product adunctin B, we designed the above synthetic scheme.

[0023] Starting from commercially available phloroglucinol (663 yuan / 500 g, CAS: 108-73-6), reacting with dimethyl carbonate (192 yuan / 2.5 kg, CAS: 616-38-6), monomethylated diphenol 1 was prepared. Subsequently, it was further reacted with easily prepared phenylpropionyl chloride {prepared by reacting commercially available 3-phenylpropionic acid (169 yuan / 500 g, CAS: 501-52-0) and oxalyl chloride (179 yuan / 500 g, CAS:79-37-8)}, and an intermolecular Friedel-Crafts reaction occurred to prepare a large amount of dihydrochalcone 2.

[0024] After mixing the two fragments of dihydrochalcone 2 prepared in the previous step and commercially available α-phellandrene (88 yuan / 100 g, CAS: 99-83-2), the intermolecular oxidative [3+2] cycloaddition reaction catalyzed by iodobenzene diacetate and silver carbonate was used as the key reaction to effectively connect the two fragment compounds and rapidly construct the tricyclic skeleton of the natural product, thereby obtaining the natural product adunctin B. After the accumulation of the natural product in terms of quantity, more in-depth bioactivity tests can be carried out. Therefore, relying on synthetic chemical means, more natural product samples can be prepared for activity test research.

[0025] Comparative Example 1: The synthesis method in Comparative Example 1 was the same as that in Example 1, except that 4 mmol of iodobenzene diacetate was added as the catalyst in Step 3, and the others remained unchanged.

[0026] The total yield of the final light yellow solid adunctin B was 43%.

[0027] Comparative Example 2: The synthesis method in Comparative Example 1 was the same as that in Example 1, except that 4 mmol of silver carbonate was added as the catalyst in Step 3, and the others remained unchanged.

[0028] The total yield of the final light yellow solid adunctin B was 11%.

[0029] Comparative Example 3: The synthesis method in Comparative Example 1 was the same as that in Example 1, except that 4 mmol of iodobenzene diacetate was added as the catalyst in Step 3 and the reaction time was extended to 10 h; the others remained unchanged.

[0030] The total yield of the final light yellow solid adunctin B was 56%.

[0031] Comparative Example 4: The synthesis method in Comparative Example 1 was the same as that in Example 1, except that 4 mmol of silver carbonate was added as the catalyst in Step 3 and the reaction time was extended to 10 h; the others remained unchanged.

[0032] The total yield of the final light yellow solid adunctin B was 51%.

[0033] In summary, the present invention discloses a new method for preparing monoterpene-substituted dihydrochalcone adunctin B. It discloses that using commercially available phloroglucinol and α-phellandrene as raw materials, dihydrochalcone 2 is synthesized through Friedel-Crafts reaction. Then, it reacts with α-phellandrene under the dual catalysis of iodobenzene diacetate and silver carbonate, and the two fragment compounds are connected through a [3+2] cycloaddition reaction to efficiently prepare the natural product adunctin B with a yield of 87%. The present invention develops a new method for preparing the natural product adunctin B with important physiological and pharmacological activities through synthetic organic chemical means. This method has the advantages of simple operation, cheap raw materials, high yield, and short steps, greatly breaking through the limitations of the source of this natural product.

[0034] Finally, it should also be noted that the term "comprising", "including" or any other variation thereof is intended to cover non-exclusive inclusion, so that a process, method, article or device comprising a series of elements not only includes those elements but also other elements not expressly listed, or elements inherent to such process, method, article or device.

[0035] Although the preferred embodiments of the present invention have been described, those skilled in the art can make additional changes and modifications to these embodiments once they learn the basic creative concept. Therefore, the appended claims are intended to be construed as including the preferred embodiments and all changes and modifications falling within the scope of the present invention.

[0036] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalent technologies, the present invention also intends to include these changes and modifications.

Claims

1. A new method for preparing monoterpene-substituted dihydrochalcone adunctin B, characterized in that, The reaction process of the preparation method is as follows: ； The synthesis method includes Step 1 to Step 3: Specifically: Step 1: Using phloroglucinol and dimethyl carbonate as raw materials, compound 1 is obtained through phenolic hydroxyl methylation reaction; that is, methoxydiphenol; Step 2: Compound 1 and 3-phenylpropionic acid undergo a Friedel-Crafts reaction to obtain compound 2; that is, dihydrochalcone; Step 3: Using the dual catalysis of iodobenzene diacetate and silver carbonate; the two fragment compounds of compound 2 and α-phellandrene are connected through an intermolecular oxidative [3+2] cycloaddition reaction to prepare the monoterpene-substituted dihydrochalcone adunctin B.

2. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 1, characterized in that, The structural formulas of the phloroglucinol, compound 1, compound 2, α-phellandrene, and the monoterpene-substituted dihydrochalcone adunctin B are: 。 3. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 1, characterized in that, The specific content of Step 1 is: The reaction vessel is dehydrated, and the atmosphere in the reaction vessel is set to an inert gas environment. Phloroglucinol and anhydrous potassium carbonate are added in sequence, then acetone and dimethyl carbonate are added, and the temperature is gradually increased for reaction. After the reaction is completed, the reaction solution is cooled to 25°C. After distilling off the excess solvent acetone, it is extracted multiple times, washed successively with water and saturated brine, dried with anhydrous magnesium sulfate, the extraction solvent is distilled, and after concentration, compound 1 is separated to obtain methoxydiphenol, which is a light brown oily liquid.

4. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 1, characterized in that, The specific content of Step 2 is: The reaction vessel is dehydrated, and the atmosphere in the reaction vessel is set to an inert gas environment. Dichloromethane and 3-phenylpropionic acid are added in sequence. The reaction vessel is placed in a low-temperature reactor at 0°C for precooling, then oxalyl chloride is added dropwise within 5 minutes, and then N,N-dimethylformamide is added. The temperature is gradually increased to 25°C. After the reaction is completed, the excess dichloromethane solvent and oxalyl chloride reagent are distilled, and after concentration into solution a, it is reserved for later use; Another reaction vessel is dehydrated, and the atmosphere in the reaction vessel is set to an inert gas environment. After adding the light brown oily liquid methoxydiphenol synthesized in Step 1 and dichloromethane solvent, the reaction vessel is placed in a low-temperature reactor at 0°C for precooling, and then aluminum trichloride is added; subsequently, solution a prepared above is added dropwise within 10 minutes, and the temperature is gradually increased to 25°C. After the reaction is completed, the reaction is quenched with ice water, extracted, the extraction solvent is distilled, and after concentration, compound 2 is separated to obtain dihydrochalcone, which is a light yellow solid.

5. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 1, characterized in that, The specific content of Step 3 is: Compound 2 and α-phellandrene are added to the reaction vessel. Under the dual catalysis of iodobenzene diacetate and silver carbonate, a mixed solvent of toluene and acetonitrile is added, and the temperature is raised to 35°C for reaction for 30 - 35 minutes. The solvent is distilled, and after concentration, the generated adunctin B is separated and purified to finally obtain the monoterpene-substituted dihydrochalcone adunctin B.

6. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 3, characterized in that, The specific synthesis method of Step 1 is: The reaction vessel is a two-neck round-bottom flask, and the water removal method is to preheat it with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace it with nitrogen 3 - 4 times; after adding anhydrous potassium carbonate, the atmosphere in the reaction vessel is set to an inert gas environment again, and the method is to displace it with argon 2 - 3 times; the molar ratio of phloroglucinol, anhydrous potassium carbonate, and dimethyl carbonate is 160 - 162:240 - 242:76.8 - 78.8; acetone does not need to be dried, and when the amount of phloroglucinol is 160 mmol, the amount of acetone used is 250 mL; the temperature is 60°C - 63°C, and the reaction time is 6 - 7 h; the extractant for multiple extractions is ethyl acetate, and the number of extractions is 3 - 4 times; the separation method is column chromatography, and column chromatography is carried out 2 times. The first eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 10:

1. The second eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 5:

1.

7. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 4, characterized in that, The specific synthesis method of Step 2 is as follows: The reaction vessel is a single-neck round-bottom flask, and the water removal method is to preheat it with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace it with nitrogen 3 - 4 times; the pre-cooling time is 2 - 3 min; the reaction temperature is room temperature, and the reaction time is 2 h; the method for distilling the excessive oxalyl chloride and dichloromethane solvent is distillation with a rotary evaporator; the molar ratio of 3-phenylpropionic acid to oxalyl chloride is 1 - 2:4 - 5; when the amount of 3-phenylpropionic acid is 100 mmol, the amount of dichloromethane used is 120 mL; the amount of N,N-dimethylformamide used is 5 drops. Another reaction vessel is a two-necked round-bottom flask, and the water removal method is to preheat it with an alcohol lamp for 3 to 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace it with nitrogen 3 to 4 times; the pre-cooling time is 5 to 6 min; the reaction time is 20 to 22 h; after the reaction is completed, ice water is added to quench the reaction within 6 to 7 minutes at 0 o °C; extraction is carried out with ethyl acetate, the separation means is column chromatography, and column chromatography is carried out 2 times. The first eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 16:

1. The second eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 4:

1.

8. The novel method for preparing monoterpene-substituted dihydrochalcone adunctin B as described in claim 5, characterized in that, The specific synthesis method of Step 3 is as follows: The reaction vessel is a two-neck round-bottom flask, and the water removal method is to preheat it with an alcohol lamp for 3 - 5 minutes; the method for setting the atmosphere in the reaction vessel to an inert gas environment is to displace it with nitrogen 3 - 4 times; after adding Compound 2 and α-phellandrene, argon is displaced 2 - 3 times again; the molar ratio of ketodihydrochalcone, β-phellandrene, iodobenzene diacetate, and silver carbonate is 1 - 1.2:2 - 2.2:0.2 - 0.23:0.2 - 0.23; when the amount of dihydrochalcone added is 10 mmol, the mixed solvent of toluene and acetonitrile is 25 mL; the method for distilling the solvent is distillation with a rotary evaporator; the separation and purification method is column chromatography 2 times; the first eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 30:

1. The second eluent is petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is 15:1.

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