Preparation method of methylsulfonamido chalcone derivatives

Abstract

The present invention provides a method for preparing a sulfonamido chalcone derivative. Under gold catalysis, a p-toluenesulfonyl structure containing a nitrogen element is used to replace the A-ring structure in chalcone. Under mild reaction conditions, a series of chalcone derivatives containing a sulfonyl structure and having the α-position substituted by a benzene ring or other heterocyclic groups are synthesized through a one-step reaction.

Description

Technical Field

[0001] The present invention relates to a chalcone derivative, a preparation method thereof, and an application thereof in anti-tumor drugs. Background Art

[0002] Chalcone compounds exist in most natural compounds, and chalcones serve as important intermediates in the biosynthesis of flavones and flavonoid compounds. Chalcones are polyphenols of plant origin and have good biological activities. They have received extensive attention due to their biological activities and relatively easy structural manipulation and synthesis of new compounds. Some chalcone derivatives have been proven to have a wide range of biological activities.

[0003] In the chemical synthesis of chalcones, the relatively classical one is the Claisen-Schmidt reaction, in which benzaldehyde and methyl ketone are condensed into chalcone through alkali or acid catalysis. This synthesis method can be divided into two cases according to the type of catalyst. Under alkali catalysis, chalcone is dehydrated from the aldol product through the enolate mechanism. If it is acid catalyzed, chalcone is generated through the enol mechanism. However, this method has a long reaction time, incomplete reaction, and is prone to produce by-products, resulting in difficult separation of the products. In addition to the Claisen-Schmidt reaction, there is also a method of synthesizing chalcone by using cross-coupling. This method was first reported in 1979 and was first applied to chalcone in 2003. Its synthesis method is divided into the coupling of cinnamoyl chloride and phenylboronic acid or the coupling of benzoyl chloride and styrylboronic acid. The research on synthesizing chalcone by using cross-coupling methods is not limited to this, and also includes Suzuki-Miyaura coupling, Heck coupling and carbonyl Heck coupling, Wittig reaction, Julia-Kocienski olefination reaction, etc.; in addition to the synthesis methods of cross-coupling, chalcone can also be synthesized by acylation reaction and Photo-Fries rearrangement reaction. In addition, chalcone synthase can be used to synthesize chalcone and its different derivatives through a biosynthetic method.

[0004] The basic skeleton of chalcone is 1,3-diphenylpropenone. The benzene ring usually connected to the ketone group is called the A ring, and the one connected to the double-bonded alkene is the B ring. The structure between the two benzene rings is an acryloyl ketone structure, which can combine with different receptors, thus having diverse biological activities. Chalcone is an important part of flavonoid compounds. It can inhibit a series of enzymes in the body, including monooxygenase, xanthine oxidase, and cyclooxygenase, through its antioxidant activity of scavenging free radicals. By adjusting the compound structure and then modifying different compounds, target compounds with higher bioavailability and stronger in vivo tolerance can be synthesized. Many naturally occurring chalcone derivatives have various biological activities. For example, isoliquiritigenin, 2',3,4,4'-tetrahydroxychalcone, and taxusin have anti-cancer activities; sappanchalcone has anti-inflammatory effects; psoralen has antioxidant effects; and bavachalcone has antibacterial properties.

[0005] Most organic chemists use chalcone as a lead compound and introduce other active groups on its basis to improve the biological activity of chalcone. In recent years, significant results have been achieved in the research on improving the biological activity of chalcone by modifying its basic skeleton. In 2010, during the research on the pharmacological potential of chalcone compounds, Daniela Ilieva Batovska found that by introducing α-substituents and using heterocycles to replace the A ring, the synthesized chalcone derivatives have significant effects in aspects such as antioxidant and anti-inflammatory. In 2023, Shaimaa M. Aboukhatwa and his team designed and synthesized 15 chalcone-sulfonamide compounds by replacing the benzene ring in the chalcone structure with an aromatic ring with a sulfonamide substituent, and the research shows that they have good anti-tumor activity.

[0006] This invention uses gold catalysis, replaces the A ring structure in chalcone with a p-toluenesulfonyl structure containing nitrogen elements, and through a one-step reaction under mild reaction conditions, synthesizes a series of chalcone derivatives containing a toluenesulfonyl structure and with the α-position substituted by a benzene ring or other heterocyclic groups, which are detected to have anti-tumor activity. Summary of the Invention

[0007] The purpose of this invention is to provide a chalcone derivative containing a toluenesulfonyl structure and with the α-position substituted by a benzene ring or other heterocyclic groups, its preparation method, and the application of this kind of compound in anti-tumor drugs. The synthesis process of this kind of compound is simple, the reaction conditions are mild, the reaction is rapid, and the product is easy to separate, which is beneficial to industrial production. This kind of compound has a significant inhibitory effect on cervical cancer cells and low toxicity to normal cells, and has good application prospects in anti-tumor drugs.

[0008] Technical Solution Adopted in This Invention

[0009] In a first aspect, the present invention provides the use of a sulfonylamino chalcone derivative represented by formula (I) in the preparation of an anti-tumor drug:

[0010]

[0011] In formula (I), R1 is cyclohexenyl, naphthyl or phenyl in which H on the benzene ring is substituted by halogen, C1-C3 alkyl or C1-C3 alkoxy;

[0012] R2 is thienyl, C1-C7 alkyl or phenyl in which H on the benzene ring is substituted by halogen or C1-C3 alkyl.

[0013] Further, R1 is cyclohexenyl, naphthyl or phenyl in which one H on the benzene ring is substituted by fluorine, chlorine, methyl or methoxy;

[0014] R2 is thienyl, octyl or phenyl in which one H on the benzene ring is substituted by fluorine, chlorine or methyl.

[0015] Furthermore, the sulfonylamino chalcone derivative is one of the following:

[0016]

[0017] Preferably, the sulfonylamino chalcone derivative is compound (I-1), (I-3), (I-4), (I-7), (I-9), (I-10), (I-11), (I-12), (I-13), (I-14), (I-15), (I-16) or (I-18); more preferably, it is compound (I-4), (I-7), (I-9), (I-10), (I-12), (I-13), (I-14), (I-16) or (I-18), and most preferably it is compound (I-18).

[0018] Preferably, the cells of the tumor are cervical cancer cells.

[0019] Further, the anti-tumor drug is composed of the sulfonylamino chalcone derivative represented by formula (I) or its pharmaceutically acceptable salt, stereoisomer, solvate and a pharmaceutically acceptable carrier.

[0020] The pharmaceutically acceptable carrier is one or more of a diluent, a filler, a binder, a wetting agent, a disintegrant, an absorption promoter, a surfactant, an adsorption carrier, a lubricant, and a thickening agent. When necessary, flavoring agents, sweetening agents, etc. may also be added. The pharmaceutically acceptable carrier refers to a conventional pharmaceutical carrier in the pharmaceutical field, including conventional diluents in the pharmaceutical field such as water, fillers such as starch, binders such as cellulose derivatives and gelatin, wetting agents such as glycerol, disintegrants such as agar and calcium carbonate, absorption promoters such as quaternary ammonium compounds, surfactants such as cetyl alcohol, adsorption carriers such as kaolin and saponite clay, lubricants such as talc powder, and thickening agents such as sodium carboxymethyl cellulose, etc.

[0021] The pharmaceutical preparation is suitable for administration by any appropriate route, such as oral (including buccal or sublingual administration), rectal administration, nasal administration, topical administration (including buccal, sublingual or transdermal administration) or parenteral administration (including subcutaneous injection, intramuscular injection, intravenous injection or intradermal injection) routes. These preparations can be prepared by any method known in the pharmaceutical field. For example, by mixing the active ingredient with a carrier or excipient.

[0022] In a third aspect, the present invention provides a preparation method of the above-mentioned methylsulfonamido chalcone derivative, and the method is as follows:

[0023] Dissolve catalyst A and catalyst B in an organic solvent, add reactant 2.1 and reactant 2.2, and stir and react at 5 - 80 °C under a protective atmosphere (generally for 2 - 12 h, preferably stir and react at 40 °C for 8 h). After the reaction is complete, the obtained reaction solution is post-treated to obtain the methylsulfonamido chalcone derivative shown in formula (I); the molar ratio of catalyst A, catalyst B, reactant 2.1 to reactant 2.2 is 0.005 - 0.015:0.02 - 0.05:1:1 - 3 (preferably 0.015:0.02:1:2);

[0024] The catalyst A is one or more of IPrAuCl, WangPhosAuCl, JhonPhosAuCl, PPh3AuCl, (PhO)3PAuCl (preferably PPh3AuCl); the catalyst B is one or more of AgSbF6, NaBARF, AgOTf, AgOAc (preferably AgSbF6);

[0025]

[0026] In formulas 2.1, 2.2, and (I), R1 is cyclohexenyl, naphthyl, or a phenyl group in which H on the benzene ring is substituted by a halogen, a C1 - C3 alkyl group, or a C1 - C3 alkoxy group;

[0027] R2 is a thienyl group, an alkyl group having 1 to 7 carbon atoms, or a phenyl group in which H on the benzene ring is substituted by a halogen or an alkyl group having 1 to 3 carbon atoms.

[0028] Preferably, the methanesulfonamido chalcone derivative represented by formula (I) is one of compounds (I-1) to (I-18).

[0029] Note that the reaction of the present invention is carried out under anhydrous conditions.

[0030]

[0031] Furthermore, the post-treatment is as follows: filtering the reaction solution, rinsing the filter cake with dichloromethane, combining the filtrates, concentrating, performing silica gel column separation and purification using petroleum ether as an eluent, collecting the eluate containing the target compound, and evaporating the solvent under reduced pressure to obtain the methanesulfonamido chalcone derivative represented by formula (I). Even further, the filtering is: filtering using diatomaceous earth as a filler, aiming to separate catalysts and the like.

[0032] In one embodiment of the present invention, the protective atmosphere is a nitrogen atmosphere.

[0033] Furthermore, the organic solvent is one or more of dichloroethane (DCE), toluene, and tetrahydrofuran (THF), and preferably dichloroethane.

[0034] Even further, the volume of the organic solvent is 15 to 30 mL / mmol (preferably 20 mL / mmol) based on the amount of substance of reactant 2.1.

[0035] Compared with the prior art, the beneficial effects of the present invention are mainly reflected in:

[0036] (1) The present invention provides a new chalcone derivative containing a methanesulfonyl structure and having an α-position substituted by a benzene ring or other heterocyclic groups;

[0037] (2) This type of compound is a compound with significant anti-tumor activity, providing a research basis for the screening of new anti-tumor drugs;

[0038] (3) The present invention provides a new synthesis method for chalcone-derived compounds. The greatest advantage of this method is that under gold catalysis, a p-methanesulfonyl structure containing a nitrogen element is used to replace the A-ring structure in chalcone, and a series of chalcone derivatives containing a methanesulfonyl structure and having an α-position substituted by a benzene ring or other heterocyclic groups are synthesized through a one-step reaction under mild reaction conditions.

[0039] This synthesis method has simple synthesis steps, no by-products are generated, the separation method is simple, the reaction time is short, and the yield is high. The synthesis process of the compound of the present invention is convenient to operate. By changing different liquid-phase reactants (i.e., small molecule reaction substrates), different chalcone-derived compounds can be synthesized. Therefore, it is easy to be applied to the synthesis of new compounds for high-throughput compound screening. Detailed implementation mode

[0040] The present invention will be further described below in conjunction with specific embodiments, but the protection scope of the present invention is not limited thereto:

[0041] Example 1: Synthesis of Sample I-1

[0042] The reaction formula is as follows

[0043]

[0044] 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added to an anhydrous and dry small reaction flask. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.1 was completely reacted as detected by thin layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth (diatomaceous earth 535 adamas, the same hereinafter), the filter cake was washed with dichloromethane (DCM) for several times, the filtrates were combined, the combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0269 g of white solid (I-1), with a yield of 85.2% and a purity > 99%.

[0045] I-1, white solid. 1 H NMR (500 MHz, Chloroform-d) δ 7.37 - 7.35 (m, 3H), 7.33 - 7.30 (m, 2H), 7.28 (s, 1H), 7.24 - 7.21 (m, 3H), 7.16 - 7.14 (m, 2H), 3.16 (s, 3H), 3.14 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 172.35, 136.25, 135.93, 134.29, 134.02, 129.88, 129.50, 129.01, 128.90, 128.68, 128.31, 40.89, 34.35. GC-MS (EI): m / z 315.09 [M + .

[0046] Example 2: Synthesis of Sample I-2

[0047] The reaction formula is as follows

[0048]

[0049] 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added to an anhydrous and dry small reaction flask. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0223 g of reaction substrate 2.3 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of reaction substrate 2.3 was complete as detected by thin layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined, concentrated under a vacuum rotary evaporator, passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0303 g of white solid (I-2), with a yield of 92.3% and a purity > 99%.

[0050] I-2, white solid,. 1 H NMR (500 MHz, Chloroform-d) δ 7.23 (dddd, J = 13.6, 8.7, 7.4, 1.5 Hz, 5H), 7.18 - 7.15 (m, 3H), 7.10 (d, J = 5.2 Hz, 2H), 3.17 (d, J = 16.3 Hz, 6H), 2.32 (s, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 172.43, 138.78, 136.31, 135.57, 134.36, 133.87, 129.44, 128.85, 128.69, 128.58, 128.25, 128.12, 126.57, 40.93, 34.38, 21.37. GC-MS (EI): m / z 329.41 [M + .

[0051] Example 3: Synthesis of Sample I-3

[0052] The reaction formula is as follows

[0053]

[0054] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0245 g of reaction substrate 2.4 (0.1 mmol) and 0.0281 g of reaction substrate 2.5 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.4 was completely reacted as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was rinsed several times with dichloromethane (DCM). The filtrates were collected and combined, and the combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column. It was rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0322 g of a white solid (Ⅰ-3), with a yield of 83.3% and a purity > 99%.

[0055] Ⅰ-3, white solid. 1 H NMR (500 MHz, Chloroform-d) δ 7.47 - 7.42 (m, 1H), 7.32 - 7.30 (m, 3H), 6.89 (d, J = 1.2 Hz, 1H), 3.44 (s, 3H), 3.37 (s, 3H), 2.47 - 2.43 (m, 2H), 1.44 (p, J = 7.3 Hz, 2H), 1.36 (d, J = 6.9 Hz, 2H), 1.27 (d, J = 3.9 Hz, 2H), 1.23 - 1.20 (m, 6H), 0.87 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, Chloroform-d) δ 173.09, 139.09, 133.90, 133.43, 130.81, 130.08, 129.85, 129.62, 129.52, 126.69, 41.14, 34.90, 31.76, 29.40, 29.11, 28.78, 27.99, 22.60, 14.07. GC-MS (EI): m / z 385.15 [M + .

[0056] Example 4: Synthesis of Sample Ⅰ-4

[0057] The reaction formula is as follows

[0058]

[0059] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0227 g of reaction substrate 2.6 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.6 was completely reacted as detected by thin-layer chromatography (TLC), the reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, and the eluate was collected. The solvent was removed by evaporation under reduced pressure to obtain 0.0291 g of a white solid (Ⅰ-4), with a yield of 87.6% and a purity > 99%.

[0060] Ⅰ-4, white solid. 1 H NMR (500 MHz, Chloroform-d) δ 7.31 - 7.25 (m, 3H), 7.24 - 7.21 (m, 2H), 7.14 - 7.12 (m, 3H), 7.08 - 7.04 (m, 2H), 3.18 (d, J = 20.2 Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 172.17, 136.13, 135.17, 134.06, 131.42, 131.36, 129.79, 129.04, 128.43, 116.25, 116.08, 41.01, 34.38. GC-MS (EI): m / z 333.08 [M + .

[0061] Example 5: Synthesis of Sample Ⅰ-5

[0062] The reaction formula is as follows

[0063]

[0064] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0223 g of reaction substrate 2.7 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of the reaction substrate 2.7 was detected to be complete by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was rinsed with dichloromethane (DCM) multiple times. The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0298 g of a white solid (Ⅰ-5), with a yield of 90.5% and a purity > 99%.

[0065] Ⅰ-5, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.23 - 7.19 (m, 5H), 7.16 (d, J = 1.8 Hz, 3H), 7.09 (s, 1H), 7.01 (s, 1H), 3.17 (s, 3H), 3.12 (s, 3H), 2.37 (s, 3H). 13 13C NMR (126 MHz, Chloroform-d) δ 172.58, 138.70, 136.29, 135.29, 134.49, 130.94, 129.84, 129.74, 129.31, 128.78, 128.29, 40.92, 34.35, 21.34. GC-MS (EI): m / z 329.11 [M + .

[0066] Example 6: Synthesis of Sample Ⅰ-6

[0067] The reaction formula is as follows

[0068]

[0069] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0227 g of reaction substrate 2.8 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.8 was completely reacted as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was rinsed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0289 g of a white solid (Ⅰ-6), with a yield of 86.8% and a purity > 99%.

[0070] Ⅰ-6, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.34 (tdd, J = 7.6, 6.0, 1.4 Hz, 1H), 7.26 - 7.17 (m, 4H), 7.14 - 7.10 (m, 3H), 7.07 - 7.03 (m, 2H), 3.19 (d, J = 13.2 Hz, 6H), 2.94 (s, 1H). 13 13C NMR (126 MHz, Chloroform-d) δ 171.81, 136.68, 133.77, 130.70, 130.64, 129.83, 129.59, 129.23, 128.47, 128.30, 127.19, 125.29, 125.27, 40.96, 34.46. GC-MS (EI): m / z 333.08 [M + .

[0071] Example 7: Synthesis of Sample Ⅰ-7

[0072] The reaction formula is as follows

[0073]

[0074] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0215 g of reaction substrate 2.9 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.9 was completely reacted as detected by thin-layer chromatography (TLC), the reaction solution was filtered through diatomaceous earth. The filter cake was washed with dichloromethane (DCM) multiple times, and the filtrates were collected and combined. The filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0258 g of white solid (Ⅰ-7), with a yield of 80.2% and a purity > 99%.

[0075] Ⅰ-7, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.35 - 7.28 (m, 6H), 7.08 - 7.00 (m, 3H), 3.28 (s, 3H), 3.24 (s, 3H). 13 13C NMR (126 MHz, Chloroform-d) δ 171.33, 134.98, 134.69, 134.15, 130.10, 129.53, 129.10, 128.87, 128.52, 127.79, 127.28, 41.12, 34.29. GC-MS (EI): m / z 321.05 [M + .

[0076] Example 8: Synthesis of Sample Ⅰ-8

[0077] The reaction formula is as follows

[0078]

[0079] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0243 g of reaction substrate 2.10 (0.1 mmol) and 0.0212 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.10 was completely reacted as detected by thin-layer chromatography (TLC), the reaction solution was filtered through diatomaceous earth. The filter cake was washed with dichloromethane (DCM) multiple times, and the filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column. It was washed with petroleum ether (PET), monitored by TLC, and the eluate was collected. The solvent was removed by evaporation under reduced pressure to obtain 0.0298 g of a white solid (Ⅰ-8), with a yield of 85.2% and a purity > 99%.

[0080] Ⅰ-8, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.35 - 7.32 (m, 2H), 7.28 - 7.23 (m, 5H), 7.15 - 7.12 (m, 3H), 3.18 (d, J = 24.6 Hz, 6H). 13 13C NMR (126 MHz, Chloroform-d) δ 171.97, 136.38, 135.04, 134.75, 133.92, 132.49, 130.86, 129.80, 129.31, 129.14, 128.48, 41.02, 34.39. GC-MS (EI): m / z 349.05 [M + .

[0081] Example 9: Synthesis of Sample Ⅰ-9

[0082] The reaction formula is as follows

[0083]

[0084] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0272 g of reaction substrate 2.11 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.1 was completely reacted as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0308 g of a white solid (Ⅰ-9), with a yield of 89.2% and a purity >99%.

[0085] Ⅰ-9, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.38 - 7.32 (m, 5H), 7.17 - 7.10 (m, 2H), 6.82 - 6.74 (m, 2H), 6.63 (t, J = 2.1 Hz, 1H), 3.56 (s, 3H), 3.15 (d, J = 5.7 Hz, 6H). 13 13C NMR (126 MHz, Chloroform-d) δ 172.27, 159.21, 136.36, 135.89, 135.49, 134.09, 129.56, 129.34, 129.00, 128.69, 122.73, 115.45, 114.31, 54.93, 40.88, 34.40. GC-MS (EI): m / z 345.10 [M + .

[0086] Example 10: Synthesis of Sample Ⅰ-10

[0087] The reaction formula is as follows

[0088]

[0089] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0281 g of reaction substrate 2.12 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.1 was completely reacted as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0287 g of a white solid (Ⅰ-10), with a yield of 82.0% and a purity > 99%.

[0090] Ⅰ-10, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.41 (dd, J = 8.1, 1.1 Hz, 1H), 7.31 - 7.29 (m, 2H), 7.28 (t, J = 2.4 Hz, 1H), 7.25 - 7.22 (m, 2H), 7.22 - 7.17 (m, 2H), 7.00 - 6.89 (m, 2H), 3.25 (s, 3H), 3.16 (s, 3H). 13 13C NMR (126 MHz, Chloroform-d) δ 171.72, 138.29, 134.48, 133.33, 133.01, 131.60, 130.97, 129.73, 129.50, 129.24, 128.89, 128.81, 126.42, 41.19, 34.26. GC-MS (EI): m / z 349.05 [M + .

[0091] Example 11: Synthesis of Sample Ⅰ-11

[0092] The reaction formula is as follows

[0093]

[0094] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0240 g of reaction substrate 2.13 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of the reaction substrate 2.1 was detected to be complete by thin layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, and the eluate was collected. The solvent was removed by evaporation under reduced pressure to obtain 0.0305 g of a white solid (Ⅰ-11), with a yield of 92.5% and a purity > 99%.

[0095] Ⅰ-11, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.30 - 7.23 (m, 3H), 7.21 - 7.13 (m, 5H), 6.97 - 6.88 (m, 2H), 3.13 (s, 3H), 3.12 (s, 3H), 2.34 (s, 3H). 13 13C NMR (126 MHz, Chloroform-d) δ 172.23, 137.33, 137.05, 134.53, 130.17, 129.39, 129.34, 128.75, 128.49, 128.45, 125.57, 40.89, 34.18, 20.02. GC-MS (EI): m / z 329.11 [M + .

[0096] Example 12: Synthesis of Sample Ⅰ-12

[0097] The reaction formula is as follows

[0098]

[0099] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.14 (0.1 mmol) and 0.0312 g of reaction substrate 2.2 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of the reaction substrate 2.1 was complete as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0327 g of a white solid (Ⅰ-12), with a yield of 89.6% and a purity > 99%.

[0100] Ⅰ-12, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.76 (dd, J = 7.4, 1.8 Hz, 1H), 7.72 (s, 1H), 7.70 (d, J = 1.9 Hz, 1H), 7.61 (d, J = 8.6 Hz, 1H), 7.50 - 7.44 (m, 3H), 7.36 (d, J = 1.6 Hz, 3H), 7.32 (s, 1H), 7.14 (dd, J = 8.6, 1.8 Hz, 1H), 5.31 (s, 1H), 3.17 (d, J = 6.8 Hz, 6H). 13 13C NMR (126 MHz, Chloroform-d) δ 172.40, 136.42, 136.04, 134.11, 133.26, 133.05, 131.94, 130.44, 129.65, 129.22, 129.04, 128.88, 128.78, 128.29, 127.69, 127.62, 126.96, 126.55, 126.41, 40.90, 34.40. GC-MS (EI): m / z 319.12 [M + .

[0101] Example 13: Synthesis of Sample Ⅰ-13

[0102] The reaction formula is as follows

[0103]

[0104] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0280 g of reaction substrate 2.15 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.1 was completely reacted as detected by thin layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was rinsed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0293 g of a white solid (Ⅰ-10), with a yield of 83.9% and a purity > 99%.

[0105] Ⅰ-13, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.38 - 7.36 (m, 3H), 7.30 - 7.28 (m, 2H), 7.21 (dd, J = 2.1, 1.1 Hz, 1H), 7.14 - 7.11 (m, 2H), 7.05 - 6.97 (m, 2H), 3.13 (s, 3H), 3.10 (s, 3H). 13 13C NMR (126 MHz, Chloroform-d) δ 171.81, 137.81, 136.17, 134.22, 133.85, 133.40, 129.66, 129.53, 129.38, 129.12, 129.02, 128.79, 127.85, 40.81, 34.20. GC-MS (EI): m / z 349.05 [M + .

[0106] Example 14: Synthesis of Sample Ⅰ-14

[0107] The reaction formula is as follows

[0108]

[0109] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0240 g of reaction substrate 2.16 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.1 was completely reacted as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0315 g of a white solid (Ⅰ-14), with a yield of 95.7% and a purity > 99%.

[0110] Ⅰ-14, white solid. 1 H NMR(500MHz,Chloroform-d)δ7.38-7.35(m,3H),7.34-7.32(m,2H),7.13(s,1H),7.05-7.00(m,4H),3.28(s,0H),3.17(s,3H),3.12(s,3H),2.88(s,0H),2.31(s,3H). 13 C NMR(126MHz,Chloroform-d)δ172.58,143.72,139.25,136.45,135.20,134.32,131.38,129.95,129.54,129.05,129.01,128.57,127.17,40.88,34.47,21.34.GC-MS(EI):m / z 329.11[M + .

[0111] Example 15: Synthesis of Sample Ⅰ-15

[0112] The reaction formula is as follows

[0113]

[0114] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0248 g of reaction substrate 2.17 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of the reaction substrate 2.1 was detected to be complete by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0290 g of a white solid (Ⅰ-15), with a yield of 87.1% and a purity > 99%.

[0115] Ⅰ-15, white solid. 1 H NMR (500 MHz, Chloroform-d) δ 7.38 - 7.35 (m, 3H), 7.31 - 7.29 (m, 2H), 7.13 - 7.08 (m, 3H), 6.92 - 6.87 (m, 2H), 3.12 (d, J = 0.8 Hz, 6H). 13 C NMR (126 MHz, Chloroform-d) δ 172.19, 136.16, 134.83, 133.83, 131.82, 131.75, 130.39, 129.49, 129.13, 128.80, 115.36, 40.79, 34.33. GC-MS (EI): m / z 333.08 [M + .

[0116] Example 16: Synthesis of Sample Ⅰ-16

[0117] The reaction formula is as follows

[0118]

[0119] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0280 g of reaction substrate 2.18 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction substrate 2.1 was completely reacted as detected by thin-layer chromatography (TLC). The reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined. The combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0324 g of a white solid (Ⅰ-16), with a yield of 92.8% and a purity > 99%.

[0120] Ⅰ-16, white solid. 1 H NMR(500MHz,Chloroform-d)δ7.36(ddt,J=5.6,3.9,2.1Hz,3H),7.30-7.27(m,2H),7.19-7.15(m,2H),7.08-7.04(m,3H),3.11(d,J=5.3Hz,6H). 13 C NMR(126MHz,Chloroform-d)δ172.01,136.97,134.72,134.40,133.68,132.81,131.11,129.43,129.15,128.91,128.59,40.79,34.28.GC-MS(EI):m / z 349.05[M + .

[0121] Example 17: Synthesis of Sample Ⅰ-17

[0122] The reaction formula is as follows

[0123]

[0124] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0240 g of reaction substrate 2.19 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of the reaction substrate 2.1 was complete as detected by thin-layer chromatography (TLC), the reaction solution was filtered through diatomaceous earth, and the filter cake was washed several times with dichloromethane (DCM). The filtrates were collected and combined, and the combined filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0308 g of a white solid (Ⅰ-17), with a yield of 93.7% and a purity > 99%.

[0125] Ⅰ-17, white solid. 1 H NMR(500MHz,Chloroform-d)δ7.52 - 7.49(m,1H),7.46 - 7.42(m,1H),7.35(d,J=2.9Hz,2H),7.33 - 7.31(m,2H),7.11(s,1H),7.07(d,J=1.5Hz,1H),6.97(d,J=1.4Hz,1H),6.92(dt,J=7.2,1.9Hz,1H),3.17(s,3H),3.14(s,3H),2.23(s,3H). 13 C NMR(126MHz,Chloroform-d)δ172.44,137.93,136.22,134.18,130.72,129.70,129.49,129.21,128.94,128.84,128.62,128.14,126.89,40.89,34.40,21.25.GC-MS(EI):m / z 329.11[M + .

[0126] Example 18: Synthesis of Sample Ⅰ-18

[0127] The reaction formula is as follows

[0128]

[0129] To an anhydrous and dry small reaction flask, 0.0007 g of PPh3AuCl (1.5 μmol) and 0.0007 g of AgSbF6 (2 μmol) were successively added. After dissolving in 2 mL of anhydrous dichloroethane (DCE), 0.0209 g of reaction substrate 2.1 (0.1 mmol) and 0.0220 g of reaction substrate 2.20 (0.2 mmol) were successively added to the reaction flask. The reaction was stirred at 40 °C under a nitrogen atmosphere. After the reaction of reaction substrate 2.1 was complete as detected by thin-layer chromatography (TLC), the reaction solution was filtered through diatomaceous earth. The filter cake was washed several times with dichloromethane (DCM), and the filtrates were collected and combined. The filtrate was concentrated under a vacuum rotary evaporator and then passed through a silica gel column, rinsed with petroleum ether (PET), monitored by TLC, the eluate was collected, and the solvent was removed by evaporation under reduced pressure to obtain 0.0244 g of a white solid (Ⅰ-18), with a yield of 76.4% and a purity > 99%.

[0130] Ⅰ-18, white solid. 1 1H NMR (500 MHz, Chloroform-d) δ 7.39 - 7.34 (m, 5H), 6.08 (d, J = 10.3 Hz, 1H), 5.74 - 5.68 (m, 2H), 3.26 (d, J = 2.2 Hz, 3H), 3.15 (s, 3H), 3.00 - 2.92 (m, 1H), 2.55 (dddd, J = 15.8, 10.5, 5.2, 3.2 Hz, 1H), 2.02 - 1.81 (m, 4H), 1.59 - 1.54 (m, 1H). 13 13C NMR (126 MHz, Chloroform-d) δ 170.66, 137.48, 135.50, 134.81, 129.14, 128.46, 126.99, 125.62, 125.11, 41.47, 35.23, 33.29, 30.93, 28.29, 24.01. GC-MS (EI): m / z 319.12 [M + .

[0131] Example 19: Antitumor Activity Test

[0132] (1) Hela cells stored in the laboratory were transferred to a T25 cell culture dish and incubated at a constant temperature of 37 °C in a culture environment containing 5% CO2. After the cells grew to the logarithmic phase, the supernatant was aspirated, and 1 ml of trypsin-EDTA digestion solution was added to the flask. After digestion for 90 s, the digestion solution was aspirated, and 1 ml of complete medium was added to blow down the cells from the flask

[0133] (2) The cell suspension was centrifuged at 1200 rpm for 3 min, the supernatant was carefully aspirated, and the precipitate was suspended with the culture medium to make the cell density 1×10 4 / mL, evenly add the cell suspension into a 96-well plate, adding 100 μL of the cell suspension to each well. Place the 96-well plate containing the cell suspension in a culture environment with 5% CO2 at a constant temperature of 37 °C for incubation. (3) Dissolve the sample in dimethyl sulfoxide (DMSO) and dilute it with complete medium to make the drug concentrations 320, 160, 80, 40, 20, 10 μmol / L.

[0134] When the cell density reaches 80%, add 100 μL of the culture medium containing different concentrations of the drug solution, so that the dosing concentrations are 160, 80, 40, 20, 10, 5 μmol / L. Set three replicate experiments for each group of experiments, and place the 96-well plate in a cell culture incubator for culture. The blank control is 100 μL of the culture medium without the drug solution, and the positive control is the licorice chalcone A compound.

[0135] (4) After adding the drug for 36 h, add 20 μL of 5 mg / ml thiazolyl blue DMSO solution to each well, continue to culture for 4 - 6 hours and then terminate the culture. Carefully aspirate the remaining liquid in each well, add 150 μL of DMSO to each well, and shake gently on a shaker at low speed for 10 min to fully dissolve the crystals. Finally, place the 96-well plate at 490 nm to measure the absorbance value (OD).

[0136] (5) Use Excel spreadsheet to calculate the inhibition rate. Cell viability = (OD of the experimental group / OD of the control group) × 100%; Cell inhibition rate = (1 - cell viability) × 100%. Use Graphpad prism to calculate the IC50.

[0137] Table 1: Inhibitory effects of chalcone-derived compounds on Hela cells

[0138] Sample IC50 (μmol / L) Sample IC50 (μmol / L) Ⅰ-1 192.7 Ⅰ-12 99.54 Ⅰ-3 232.2 Ⅰ-13 72.18 Ⅰ-4 82.45 Ⅰ-14 74.45 Ⅰ-7 31.9 Ⅰ-15 119.2 Ⅰ-9 72.74 Ⅰ-16 68.65 Ⅰ-10 69.74 Ⅰ-18 13.44 Ⅰ-11 172.7 Licochalcone A 116

[0139] It can be seen from Table 1 that compounds I-1, I-3, I-4, I-7, I-9, I-10, I-11, I-12, I-13, I-14, I-15, I-16 and I-18 all have inhibitory effects on Hela cells. Among them, the inhibitory abilities of compounds I-4, I-7, I-9, I-10, I-12, I-13, I-14, I-16 and I-18 on Hela cells are higher than that of licorice chalcone A; the compound with the strongest inhibitory ability on Hela cells is I-18.

Claims

1. Preparation method of the methylsulfonamido chalcone derivative shown in formula (I), characterized in that The method described is as follows: Catalyst A and catalyst B are dissolved in an organic solvent, and reactants 2.1 and 2.2 are added. The reaction is stirred at 5 - 80 °C under a protective atmosphere. After the reaction is complete, the obtained reaction solution is post-treated to obtain the methylsulfonamido chalcone derivative shown in formula (I); the molar ratio of catalyst A, catalyst B, reactant 2.1 to reactant 2.2 is 0.005 - 0.015:0.02 - 0.05:1:1 - 3; The catalyst A is PPh3AuCl; the catalyst B is AgSbF6; In formulae 2.1, 2.2, and (I), R1 is cyclohexenyl, naphthyl, or phenyl in which H on the benzene ring is substituted by halogen, C1 - C3 alkyl, or C1 - C3 alkoxy; R2 is thienyl, C1 - C7 alkyl, or phenyl in which H on the benzene ring is substituted by halogen or C1 - C3 alkyl.

2. The preparation method of the methanesulfonamido chalcone derivative shown by formula (I) according to claim 1, characterized in that The post-treatment is as follows: The reaction solution is filtered, the filter cake is rinsed with dichloromethane, the filtrates are combined, concentrated, and subjected to silica gel column separation and purification using petroleum ether as the eluent. The eluate containing the target compound is collected, and the solvent is removed by distillation under reduced pressure to obtain the methylsulfonamido chalcone derivative shown in formula (I).

3. The preparation method of the methylsulfonamido chalcone derivative shown in formula (I) as described in claim 1, characterized in that: The protective atmosphere is a nitrogen atmosphere.

4. The preparation method of the methanesulfonamido chalcone derivative shown by formula (I) as described in claim 1, characterized in that: The organic solvent is one or more of dichloroethane, toluene, and tetrahydrofuran.

5. The preparation method of the methanesulfonamido chalcone derivative shown in formula (I) according to claim 4, characterized in that: The organic solvent is dichloroethane.

6. The preparation method of the sulfonylamino chalcone derivative shown by formula (I) as claimed in claim 4, characterized in that: The volume of the organic solvent is 15 - 30 mL / mmol based on the amount of substance of reactant 2.

1.

7. The preparation method of the methanesulfonamido chalcone derivative represented by formula (I) according to claim 1, characterized in that: The temperature of the stirring reaction is 40 °C.

8. The preparation method of the methylsulfonamido chalcone derivative shown by formula (I) as described in claim 1, characterized in that: The methylsulfonamido chalcone derivative shown in formula (I) is one of the following: 。

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