CN120504620A

CN120504620A - Improved SF5Cl synthesis method and its synthesis method for preparing β-SF5-ketone compounds and its use

Info

Publication number: CN120504620A
Application number: CN202510632613.5A
Authority: CN
Inventors: 郭硕; 李佳宇; 杨会议; 贾艳媛; 岳帅帅; 章炜; 孙东雷
Original assignee: Inner Mongolia University
Current assignee: Inner Mongolia University
Priority date: 2025-05-16
Filing date: 2025-05-16
Publication date: 2025-08-19

Abstract

The present invention discloses an improved _SF5Cl synthesis method and a synthesis method and use thereof for preparing β- _SF5 -ketone compounds, belonging to the field of pharmaceutical chemistry technology. Its structural formula is as follows: Wherein, the ^R1 group is an alkyl group, an alkene group, a heteroaromatic hydrocarbon or an aryl group, and the ^R2 group is selected from an alkyl group. The preparation method is: a β, γ-unsaturated ketone is added to a solvent together with a high concentration of pentafluorosulfuryl chloride n-hexane solution, and then under light-induced conditions, a free radical 1,2 carbonyl migration is carried out in the β, γ-unsaturated ketone molecule to prepare a β- _SF5 -ketone compound. The present invention prepares a high concentration of pentafluorosulfuryl chloride n-hexane solution by distillation with a yield of up to 67%, and uses it to prepare a variety of valuable β- _SF5 -ketone compounds. This transformation has a wide range of functional group tolerance and can be efficiently used for late modification of complex molecules with a yield of up to 77%. It has excellent chemical and regional selectivity, far exceeding traditional methods, and can overcome the problem that traditional methods are blocked or have poor selectivity for specific functional group reactions.

Description

Improved SF 5 Cl synthesis method, synthesis method for preparing beta-SF 5 -ketone compound and application thereof

Technical Field

The invention belongs to the technical field of pharmaceutical chemistry, and particularly relates to an improved SF ₅ Cl synthesis method, a synthesis method for preparing beta-SF ₅ -ketone compounds and application thereof.

Background

Fluorine has been widely used in the field of drug design and development, and introduction of fluorine atoms into compounds can significantly alter their lipophilicity, dissociation constant (pK _a), and metabolic stability. Common methods of introducing fluorine atoms into compounds include direct fluorination, or the addition of fluorine-containing functional groups. The most common example of the latter method is trifluoromethyl, however, in the field of pharmaceutical chemistry, the search for more fluorine-containing functions has never ceased.

Pentafluorothio (SF ₅) is receiving increasing attention in the pharmaceutical chemistry field as a relatively new class of fluorine-containing building blocks. The unique properties, such as high electronegativity and remarkable lipophilicity, provide novel possibilities for drug design, for example, the electron cloud distribution, lipophilicity, interaction modes with biological targets and the like of drug molecules can be effectively regulated, so that potential application value is shown.

At present, in some existing drug molecular studies, pentafluorosulfanyl shows potential application value. For example, in the study of triazolopyrimidine compound DSM-265, it was the first pentafluorothioyl drug molecule to enter clinical studies. Biochemical and cellular analyses show that its prototype small molecule DSM12 is weak in activity, DSM97 has moderate inhibitory activity when the para position of benzene ring is substituted by methyl, the activity of DSM74 is improved by 15 times by replacing methyl with trifluoromethyl, the activity of DSM280 is improved by 3-5 times again by further introducing ethyl on triazole ring, the IC ₅₀ value of DSM267 can reach 38nM by replacing CH ₂ in ethyl with CF ₂, the EC ₅₀ value of cell can reach 10nM, and the activity of its pentafluorothio analog DSM265 is equivalent to that of DSM267 and in animal model research, DSM265 shows better drug formation, and clinical II research is currently being conducted in the U.S. This case shows the potential of pentafluorothio groups in optimizing pharmaceutical activity and properties.

In addition, when the structure-activity relationship of rimonabant is studied, the activity of the pentafluorosulfanyl analogue is not as good as that of rimonabant (6 times lower), but is twice as strong as that of the trifluoromethyl analogue 10, and the rimonabant has advantages in certain biological properties and deserves intensive study. This further shows that pentafluorosulfanyl can produce unique effects in drug molecular engineering, providing a new direction for drug development. With the development of synthetic methodologies, more and more pentafluorothio compounds are successfully synthesized, and commercially available pentafluorothio synthetic blocks are also significantly increased, which helps to accelerate the application of pentafluorothio as a pharmacophore in pharmaceutical chemistry to a certain extent.

Although pentafluorothio compounds have demonstrated potential in drug development, their development still faces many limitations. From a comprehensive search and analysis of the existing literature, almost all research on bioactive molecules is limited to substituting aromatic ring systems, and is difficult to expand to other structural types. This limitation has led to a significant gap in the research of aliphatic pentafluorothioylated drug molecules.

In addition, the current lack of truly stable and convenient pentafluorothioylation reagents makes the reaction conditions often more severe, and requires high reaction equipment, which also limits the large-scale preparation and application of pentafluorothioyl compounds. Meanwhile, no method for introducing the pentafluorothio group is mild and efficient, so that the pentafluorothio group is difficult to be flexibly and efficiently introduced into molecules with various structures in the design of drug molecules, and the deep research and development of the potential effect of the pentafluorothio group in more types of drug molecules are hindered.

The preparation of pentafluorothiochloride (SF ₅ Cl) encompasses a variety of methods. The conventional preparation method comprises the steps of reacting sulfur powder with chlorine trifluoride gas for 4 hours at the temperature of not more than 105 ℃, reacting disulfide dichloride with fluorine gas for 5 hours at the temperature of-80 ℃ to 20 ℃ but the yield is only 13%, reacting sulfur tetrafluoride, chlorine gas with cesium fluoride for 6 hours at the temperature of 100 ℃ to 150 ℃ and the yield is 75%, reacting sulfur tetrafluoride, chlorine gas and nitrosyl fluoride for 16 hours at room temperature and the like. The traditional methods have the obvious disadvantages that on one hand, extremely toxic gases such as sulfur tetrafluoride, chlorine fluoride and the like are adopted as raw materials, so that the safety risk is extremely high, on the other hand, the reaction conditions are required to be high or low, or the reaction time is required to be extremely long, and the yield of partial reaction is low.

In the aspect of an improved method, the Paeonia suffruticosa team uses sulfur simple substance, potassium fluoride and trichloroisocyanuric acid as raw materials, acetonitrile as a solvent, and the Paeonia suffruticosa can be prepared at room temperature, but the reaction process is protected from light. The method of patent number WO 2009152385 A2 is to react sulfur powder, chlorine gas, liquid bromine and potassium fluoride for 5-14 days at room temperature, and the yield is 95%. WO 2019229103 A1 is prepared by reacting sulfur powder, trichloroisocyanuric acid and potassium fluoride in acetonitrile solvent under the catalysis of trifluoroacetic acid for 14 hours at room temperature. In the presence of N-methyl pyrrolidone as catalyst, sulfur source is reacted with trichloroisocyanuric acid and the mixture is stirred in acetonitrile solvent at room temperature for 48 hr to reach 34% yield. However, these improved processes also suffer from difficulties such as generally long reaction times, unstable yields, specific catalysts or conditions for the partial reactions, and lower product concentrations.

In view of this, development of efficient and practical synthetic methods to construct functional pentafluorothio-based compounds is of vital significance to fill the gap of the current technology and promote the development of the pharmaceutical chemistry field.

Disclosure of Invention

Aiming at the defects in the prior art, the invention provides an improved SF ₅ Cl synthesis method, a synthesis method for preparing beta-SF ₅ -ketone compounds and application thereof, and the invention purifies a high-concentration pentafluorothiochloride-n-hexane solution and uses the solution to prepare a plurality of valuable beta-SF ₅ -ketone compounds. The conversion has wide functional group tolerance, can be effectively used for the later modification of complex molecules, has the yield of up to 77 percent, has excellent chemical and regioselectivity, is far superior to the traditional method, and can overcome the problems of blocked reaction or poor selectivity of the traditional method on specific functional groups.

In order to achieve the above purpose, the technical scheme adopted by the invention for solving the technical problems is as follows:

The invention aims to provide a beta-SF ₅ -ketone compound, which has the following structural formula:

wherein, the R ¹ group is alkyl, olefin, heteroarene, aryl and arene, and the R ² group is alkyl.

Further, the R ¹ group is selected from a variety of substituted alkyl, alkene, heteroarene, aryl or arene such as halogen, alkane, cyano, alkoxy, ether, isobutyryl, trifluoromethyl, trifluoromethylthio, menthol, 2-tetrol, RU 58841, adamantanecarboxylic acid, ibuprofen, 7-hydroxycoumarin, 6-hydroxyflavone, dihydrocholesterol, epiandrosterone, testosterone or sisal sapogenin, and R ² is methyl.

Further, the beta-SF ₅ -ketone compounds are as follows:

the invention also aims to provide a preparation method of the beta-SF ₅ -ketone compound, which comprises the following steps:

(1) Preparing a pentafluorosulfuric chloride n-hexane solution with the concentration of more than 0.4M;

(2) And adding beta, gamma-unsaturated ketone and pentafluorosulfuric n-hexane solution into a solvent, and then carrying out migration of free radicals 1, 2-carbonyl in beta, gamma-unsaturated ketone molecules under the illumination of the wavelength of 360-365 nm at the temperature of 32-35 ℃ to prepare the beta-SF ₅ -/ketone compound. The reaction formula is as follows:

Further, the molar ratio of the beta, gamma-unsaturated ketone to the pentafluorosulfuric chloride is 0.10:0.10-0.12.

Further, the structural formula of the beta, gamma-unsaturated ketone is as follows:

Wherein the R ¹ groups are selected from various substituted alkyl, alkene, heteroarene, aryl or arene, such as halogen, alkane, cyano, alkoxy, ether, isobutyryl, trifluoromethyl, trifluoromethylthio, menthol, 2-tetrol, RU 58841, adamantanecarboxylic acid, ibuprofen, 7-hydroxycoumarin, 6-hydroxyflavone, dihydrocholesterol, epiandrosterone, testosterone or sisalagenin, and the R2 groups are alkyl groups.

Further, the solvent used in the step (2) was 1, 2-dichloroethane at a concentration of 0.1M.

Further, in the step (2), the wavelength was 365nm, the reaction temperature was 35℃and the reaction time was 1h.

Another object of the invention is the use of β -SF ₅ -ones for the late derivatization, comprising the following structural formula:

It is another object of the present invention to provide an improved method for synthesizing SF ₅ Cl, comprising the steps of:

Under the catalysis of trifluoroacetic acid, sulfur powder, trichloroisocyanuric acid and potassium fluoride are used as raw materials to react for 14-16 hours at room temperature in a solvent, and then the pentafluorosulfuric chloride n-hexane solution with the concentration of more than 0.4M is obtained through distillation.

The invention also aims to provide the application of the beta-SF ₅ -ketone compound in preparing antitumor drugs.

Further, the tumor is liver cancer, colon cancer, cervical cancer, prostate cancer, lung cancer, breast cancer or myeloma.

Another object of the present invention is to provide an antitumor drug comprising the above β -SF ₅ -ketone compound and pharmaceutically acceptable adjuvants thereof.

The invention has the beneficial effects that:

the purification mode of SF ₅ Cl is optimized, and the pentafluorosulfuric chloride n-hexane solution with high concentration characteristic is successfully obtained through distillation. The pentafluorosulfuric chloride is in a gaseous state in a standard state, and in actual operation, is usually dissolved by using n-hexane as a solvent for subsequent use. Reviewing previous studies, the concentration of the pentafluorothiolchloro-n-hexane solution prepared by the method used by the former is generally at a low level. This limitation directly results in the need to input a large amount of n-hexane as solvent medium to meet the reaction requirement for the amount of pentafluorosulfuric chloride when carrying out the pentafluorosulfization reaction. In contrast, the high concentration pentafluorothiochlor-n-hexane solution prepared by the invention has the advantage that the use amount of n-hexane is greatly reduced under the condition of achieving the same reaction effect. When other solvents are selected to construct a reaction system, a large amount of n-hexane may cause non-negligible interference to the target reaction process due to dilution effect, competing reaction and other factors. The invention effectively avoids the potential influence, provides more ideal, pure and efficient reaction raw materials for pentafluorosulfurization reaction, and is hopeful to promote the further development of related research and application in the field.

The invention prepares a high-concentration pentafluorothiochloride-n-hexane solution by a distillation mode, and prepares a plurality of valuable beta-SF ₅ -ketone compounds by using the solution. The conversion has wide functional group tolerance, can be effectively used for the later modification of complex molecules, has the yield of up to 77 percent, has excellent chemical and regioselectivity, is far superior to the traditional method, and can overcome the problems of blocked reaction or poor selectivity of the traditional method on specific functional groups. In addition, the obtained beta-SF ₅ -ketone compound can be converted into various structures, which lays a foundation for constructing functional pentafluorothio compounds and developing molecular research of aliphatic pentafluorothio drugs, and has wide application prospect.

Drawings

FIG. 1 is a graph showing the inhibition of PC cells by Compound 5;

FIG. 2 shows the number and size of tumor-inhibiting colonies detected by Compound 5 of the colony formation assay;

FIG. 3 is a scratch assay to detect inhibition of tumor cell invasion by Compound 5;

FIG. 4 is a flow cytometry detection of apoptosis of tumor cells by Compound 5;

FIG. 5 is a compound 5 inducing the production of ROS by tumor cells;

FIG. 6 is a graph showing that Compound 5 causes altered gene expression in sequencing results;

FIG. 7 is the effect of GO assay compound 5 on tumor cell structural and functional changes;

FIG. 8 is a correlation of KEGG analysis compound 5 with cancer suppressing pathway.

Detailed Description

The following description of the embodiments of the present invention is provided to facilitate understanding of the present invention by those skilled in the art, but it should be understood that the present invention is not limited to the scope of the embodiments, and all the inventions which make use of the inventive concept are protected by the spirit and scope of the present invention as defined and defined in the appended claims to those skilled in the art.

Example 1 modification of the Synthesis method of Pentafluorosulfachlor

To a thick-walled pressure-resistant bottle (500 mL) equipped with a magnet and fully wrapped with aluminum foil under N ₂ was added TCCA (33.50 g,144mmol,4.5 eq.), spray-dried potassium fluoride powder (16.70 g,288mmol,9.0 eq.) and sulfur powder (1.02 g,32mmol,1.0 eq.) followed by MeCN (160 mL) sealed with a screw cap. Subsequently, trifluoroacetic acid (73.50. Mu.L, 0.96mmol,0.03 eq.) was added and stirred vigorously at room temperature for 16h in the absence of light. After stopping the reaction, the liquid nitrogen-acetone bath cooled the thick-walled pressure-resistant flask to-78 ℃ and maintained for 20min, then the cock was opened to transfer the reaction solution to a single-neck round bottom flask (500 mL) at low temperature, distillation was performed for 2-4h at 50 ℃ and the gaseous product in the reaction flask was distilled to a receiving flask, which was cooled with the liquid nitrogen-acetone bath. Finally, the distilled fraction was added to 40mL of n-hexane to give a colorless to pale yellow solution of SF ₅ Cl in n-hexane with high concentration, which was used without further purification. After returning to room temperature, the solution concentration was determined by ¹⁹ F NMR using 5 μl of trifluoromethoxybenzene as an internal standard. A0.3 mL volume of anhydrous CDCl ₃ and 0.2mL of SF ₅ Cl stock solution aliquots were added to a 3mm NMR tube that was dried. ¹⁹ F NMR data acquisition pulse angle,90 °; correlation delay,30s; O1P,33ppm. (e.g., 32.0mmol,54mL,0.40M, yield: 68%). The prepared SF ₅ Cl normal hexane solution should be stored in a refrigerator at-30 ℃ in the dark, and is recommended to be used within five days. (note: all steps need to be performed in a well ventilated fume hood.) the equation is as follows:

SF₅Cl:¹⁹F NMR(565MHz,CDCl₃)δ125.94(d,J=149.9Hz),63.72–62.37(m).

EXAMPLE 2 Synthesis of beta-SF ₅ -one 3a

In a glove box, a 20mL vial equipped with a magnetic stirrer was charged with β, γ -unsaturated ketone (104.54 mg,0.6mmol,1.0 eq.) and 1, 2-dichloroethane (DCE, 6.0mL,0.10M). After sealing the vial, it was removed from the glove box. Subsequently, sulfur hexafluoride chloride SF ₅ Cl (1.8 mL,0.72mmol,1.2 eq, 0.40M in n-hexane) was injected into the reaction mixture three times at 10min intervals with the aid of a 1mL syringe, while the reaction mixture was stirred under 30W, 365nm LED light. Thereafter, the reaction mixture was stirred under light from 365nm LEDs at 35℃for a further 30min. After the reaction was completed, the reaction mixture was quenched with water and extracted three times with 1, 2-Dichloromethane (DCM). The organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The crude product was purified rapidly by silica gel column chromatography to give the desired pure product 3a.

R _f = 0.50 (petroleum ether/ethyl acetate = 20:1), white solid, 91% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.11(d,J＝8.2Hz,2H),8.06(d,J＝8.3Hz,2H),4.63(dt,J＝13.0,8.8Hz,2H),4.33–4.15(m,1H),3.62–3.46(m,1H),1.56(s,3H),1.52(s,3H),1.24(d,J＝6.8Hz,6H).¹³C NMR(151MHz,CDCl₃)δ203.8,196.8,140.4,139.8,129.0,128.9,71.5(p,J＝14.3Hz),69.3,53.2,36.1,32.9,28.7,19.1.¹⁹F NMR(565MHz,CDCl₃)δ84.81–83.23(m,1F),67.48(dt,J＝145.7,6.7Hz,4F).

Example 3

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3b.

R _f = 0.50 (petroleum ether/ethyl acetate = 20:1), white solid, yield 57%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.92(d,J＝7.8Hz,2H),7.31(d,J＝7.8Hz,2H),4.63(s,2H),4.38–4.14(m,1H),2.44(s,3H),1.54(s,3H),1.52(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.7,145.2,134.6,129.8,129.0,72.0–71.5(m),70.0,52.8,33.5,28.3,21.8.¹⁹FNMR(565MHz,CDCl₃)δ85.03–83.51(m,1F),67.42(d,J＝145.7Hz,4F).

Example 4

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3c.

R _f = 0.50 (petroleum ether/ethyl acetate = 20:1), white solid, 59% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.96(d,J＝8.2Hz,2H),7.51(d,J＝8.2Hz,2H),4.68–4.58(m,2H),4.33–4.22(m,1H),1.55(s,3H),1.52(s,3H),1.35(s,9H).¹³C NMR(151MHz,CDCl₃)δ196.7,158.1,134.3,128.8,126.1,71.7(p,J＝14.2Hz),70.1,52.8,35.4,33.6,31.2,28.3.¹⁹F NMR(565MHz,CDCl₃)δ85.13–83.43(m,1F),67.45(d,J＝145.5Hz,4F).

Example 5

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3d.

R _f = 0.50 (petroleum ether/ethyl acetate = 20:1), white solid, yield 51%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.93(d,J＝8.1Hz,2H),7.29–7.26(m,2H),4.70–4.54(m,2H),4.31–4.19(m,1H),2.55(d,J＝7.2Hz,2H),1.98–1.85(m,1H),1.54(s,3H),1.52(s,3H),0.92(d,J＝6.6Hz,6H).¹³C NMR(151MHz,CDCl₃)δ196.8,148.9,134.8,129.8,128.8,72.0–71.4(m),70.0,52.8,45.6,33.5,30.2,28.3,22.5.¹⁹F NMR(565MHz,CDCl₃)δ84.39(p,J＝145.4Hz,1F),67.49(d,J＝148.8Hz,4F).

Example 6

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3e.

R _f = 0.40 (petroleum ether/ethyl acetate = 20:1), white solid, 76% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.05(d,J＝8.4Hz,2H),7.78(d,J＝8.2Hz,2H),4.66–4.51(m,2H),4.30–4.15(m,1H),1.56(s,3H),1.52(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.5,138.2,135.8,131.5,129.5,129.3(q,J＝308.5Hz),71.7–71.1(m),69.3,53.0,32.9,28.6.¹⁹F NMR(565MHz,CDCl₃)δ84.84–82.78(m,1F),67.41(d,J＝145.7Hz,4F),-41.39(d,J＝9.0Hz,3F).

Example 7

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3f.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), white solid, 77% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.11(d,J＝7.0Hz,2H),7.74(d,J＝6.9Hz,2H),7.64(d,J＝7.1Hz,2H),7.57–7.46(m,2H),7.43(d,J＝6.8Hz,1H),4.82–4.54(m,2H),4.47–4.20(m,1H),1.58(s,3H),1.57(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.7,146.9,139.7,135.6,129.5,129.2,128.7,127.7,127.5,71.9–71.4(m),69.9,52.9,33.4,28.4.¹⁹F NMR(565MHz,CDCl₃)δ85.04–83.53(m,1F),67.50(d,J＝145.4Hz,4F).

EXAMPLE 8 Synthesis of beta-SF ₅ -one 3g

With reference to the synthesis method of example 2, the substituents of the substrate were changed to give 3g of compound.

R _f = 0.70 (petroleum ether/ethyl acetate = 20:1), white solid, 58% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.12–8.02(m,2H),7.24–7.13(m,2H),δ4.72–4.50(m,2H),4.30–4.18(m,1H),1.55(s,3H),1.52(s,3H).¹³C NMR(151MHz,CDCl₃)δ195.7,166.4(d,J＝257.2Hz),133.4,131.6(d,J＝9.5Hz),116.3(d,J＝22.0Hz),71.6(p,J＝14.4Hz),69.6,52.9,33.1,28.5.¹⁹F NMR(565MHz,CDCl₃)δ84.76–83.57(m,1F),67.41(d,J＝144.0Hz,4F),-103.39(s,1F).

Example 9

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3h.

R _f = 0.70 (petroleum ether/ethyl acetate = 20:1), white solid, 54% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.97(d,J＝8.3Hz,2H),7.49(d,J＝8.3Hz,2H),4.68–4.50(m,2H),4.30–4.17(m,1H),1.55(s,3H),1.51(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.1,140.8,135.3,130.2,129.5,71.8–71.3(m),69.5,52.9,33.1,28.5.¹⁹F NMR(565MHz,CDCl₃)δ85.00–83.34(m,1F),67.39(d,J＝144.0Hz,4F).

Example 10

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3i.

R _f = 0.70 (petroleum ether/ethyl acetate = 20:1), white solid, 61% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.89(d,J＝8.5Hz,2H),7.66(d,J＝8.5Hz,2H),4.63–4.55(m,2H),4.27–4.18(m,1H),1.55(s,3H),1.51(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.3,135.7,132.5,130.3,129.6,71.8–71.2(m),69.5,52.8,33.0,28.5.¹⁹F NMR(565MHz,CDCl₃)δ85.00–83.34(m,1F),67.04(d,J＝145.1Hz,4F).

Example 11

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3j.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), white solid, 75% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.97(d,J＝8.4Hz,2H),7.49(d,J＝8.4Hz,2H),4.78–4.51(m,2H),4.35–4.12(m,1H),1.55(s,3H),1.51(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.2,139.8,132.9,129.1,117.8,117.3,71.3(p,J＝14.4Hz),68.9,53.0,32.3,29.0.¹⁹FNMR(565MHz,CDCl₃)δ84.78–83.17(m,1F),67.43(d,J＝145.6,4F).

Example 12

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3k.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), white solid, 63% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.96(d,J＝7.8Hz,1H),7.85(s,1H),7.61–7.55(m,1H),7.48(d,J＝8.1Hz,1H),4.65–4.55(m,2H),4.29–4.17(m,1H),1.57(s,3H),1.52(s,3H).¹³C NMR(151MHz,CDCl₃)δ195.9,150.0,138.8,130.7,127.0,126.3,121.1,120.7(q,J＝258.5Hz),71.5(p,J＝14.1Hz),69.2,53.1,32.9,28.7.¹⁹F NMR(565MHz,CDCl₃)δ85.06–82.51(m,1F),67.38(d,J＝145.7Hz,4F),-57.98(s,3F).

Example 13

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3l.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), white solid, yield 64%;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.81(d,J＝7.8Hz,1H),7.70(d,J＝9.4Hz,1H),7.55–7.47(m,1H),7.37–7.30(m,1H),4.67–4.50(m,2H),4.33–4.16(m,1H),1.55(s,3H),1.52(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.1,163.2(d,J＝249.2Hz),139.1(d,J＝5.4Hz),130.8(d,J＝7.6Hz),124.6,121.2(d,J＝21.6Hz),115.5(d,J＝22.8Hz),71.7–71.2(m),69.4,53.1,33.0,28.5.¹⁹F NMR(565MHz,CDCl₃)δ84.71–83.30(m,1F),67.45(dt,J＝145.6,7.5Hz,4F),-110.93–-111.04(m,1F).

Example 14

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3m.

R _f =0.50 (petroleum ether/ethyl acetate=20:1), oily liquid, yield 63%;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.91(d,J＝7.8Hz,1H),7.58–7.50(m,1H),7.10–6.99(m,2H),5.26(d,J＝10.6Hz,1H),4.75–4.61(m,1H),4.25–4.14(m,1H),4.00(s,3H),1.59(s,3H),1.53(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.9,159.3,135.2,131.7,127.1,121.2,112.7,71.6–71.0(m),70.4,56.7,55.9,32.5,28.8.¹⁹F NMR(565MHz,CDCl₃)δ85.58–84.07(m,1F),67.26(dt,J＝145.3,7.7Hz,4F).

Example 15

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3n.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), white solid, 61% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.74–7.62(m,2H),4.58–4.48(m,1H),4.44(d,J＝10.8Hz,1H),4.25–4.11(m,1H),1.58(s,3H),1.53(s,3H).¹³C NMR(151MHz,CDCl₃)δ194.2,153.1–149.8(m),145.5–141.9(m),132.6,114.0–112.5(m),72.0–70.8(m),68.8,52.8,32.3,29.0.¹⁹F NMR(565MHz,CDCl₃)δ84.65–82.84(m,1F),67.41(d,J＝145.6Hz,4F),-128.17–-134.05(m,3F).

Example 16

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3o.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), white solid, 63% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ6.88(s,2H),5.03–4.87(m,1H),4.28(d,J＝7.2Hz,1H),4.23–4.10(m,1H),2.36(s,6H),2.29(s,3H),1.58(s,3H),1.43(s,3H).¹³C NMR(151MHz,CDCl₃)δ200.9,140.7,137.8,135.9,130.6,70.3,69.4–69.0(m),60.2,34.0,30.8,21.2.¹⁹F NMR(565MHz,CDCl₃)δ86.58–84.73(m,1F),67.45(dt,J＝145.4,7.8Hz,4F).

Example 17

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3p.

R _f = 0.50 (petroleum ether/ethyl acetate = 20:1), white solid, 83% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.86(d,J＝1.4Hz,2H),7.61(s,1H),4.62–4.50(m,1H),4.47(d,J＝10.9Hz,1H),4.23–4.14(m,1H),1.57(s,3H),1.53(s,3H).¹³C NMR(151MHz,CDCl₃)δ195.1,139.4,136.3,133.8,127.1,71.3(p,J＝14.3Hz),68.9,53.2,32.6,28.9.¹⁹F NMR(565MHz,CDCl₃)δ84.88–82.57(m,1F),67.52(dt,J＝145.5,7.4Hz,4F).

Example 18

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3q.

R _f = 0.450 (petroleum ether/ethyl acetate = 10:1), white solid, 80% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.99(d,J＝8.0Hz,2H),7.94(d,J＝8.0Hz,2H),4.68–4.58(m,2H),4.31–4.20(m,1H),1.54(s,3H),1.50(s,3H),1.36(s,12H).¹³C NMR(151MHz,CDCl₃)δ197.4,138.7,135.4,127.8,84.5,72.2–71.1(m),69.8,52.9,33.4,28.4,25.1,25.0.¹⁹F NMR(565MHz,CDCl₃)δ85.15–83.16(m,1F),67.42(d,J＝146.0Hz,4F).

Example 19

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3r.

R _f = 0.20 (petroleum ether/ethyl acetate = 20:1), white solid, 61% yield;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.05(d,J＝8.6Hz,2H),7.67(d,J＝8.3Hz,2H),7.17(d,J＝8.2Hz,2H),7.09(d,J＝8.6Hz,2H),4.69–4.46(m,2H),4.31–4.16(m,1H),1.57(s,3H),1.54(s,3H).¹³C NMR(151MHz,CDCl₃)δ195.6,161.6,158.4,132.5,131.3,127.7(q,J＝6.9,3.2Hz),127.0(q,J＝32.7Hz),124.1(q,J＝272.0Hz),120.1,118.5,71.7(p,J＝14.1Hz),69.8,52.8,33.2,28.5.¹⁹F NMR(565MHz,CDCl₃)δ85.34–82.81(m,1F),67.43(d,J＝146.1Hz,4F),-62.03(s,3F).

Example 20

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3s.

R _f = 0.70 (petroleum ether/ethyl acetate = 5:1), white solid, 63% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.13(d,J＝8.6Hz,2H),8.03(m,1H),7.87(d,J＝8.6Hz,2H),7.78(s,1H),6.53(s,1H),4.69–4.58(m,2H),4.31–4.20(m,1H),1.57(s,3H),1.54(s,3H).¹³C NMR(151MHz,CDCl₃)δ195.9,144.1,142.5,134.4,130.6,127.0,118.8,109.0,71.9–71.3(m),69.7,52.8,33.2,28.4.¹⁹F NMR(565MHz,CDCl₃)δ84.86–83.40(m,1F),67.45(d,J＝145.5Hz,4F).

Example 21

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3t.

R _f = 0.60 (petroleum ether/ethyl acetate = 20:1), white solid, yield 45%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.18(d,J＝1.6Hz,1H),7.60(d,J＝5.0Hz,1H),7.41–7.33(m,1H),4.65–4.51(m,1H),4.36(d,J＝10.7Hz,1H),4.31–4.14(m,1H),1.57(s,3H),1.56(s,3H).¹³C NMR(151MHz,CDCl₃)δ191.1,142.3,133.8,127.3,127.2,71.4(p,J＝14.3Hz),69.8,55.9–55.3(m),33.4,28.2.¹⁹F NMR(565MHz,CDCl₃)δ84.80–83.36(m,1F),66.97(d,J＝145.4Hz,4F).

Example 22

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3u.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), white solid, 77% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.83(s,1H),8.33(d,J＝7.9Hz,1H),7.78–7.70(m,1H),7.56–7.48(m,2H),5.81(d,J＝11.0Hz,1H),4.63–4.46(m,1H),4.12–3.97(m,1H),1.72(s,3H),1.63(s,3H).¹³C NMR(151MHz,CDCl₃)δ195.9,175.2,164.0,155.8,134.8,126.9,126.8,125.6,121.0,118.4,71.1(p,J＝14.4Hz),69.6,54.3,31.3,29.7.¹⁹F NMR(565MHz,CDCl₃)δ85.69–83.65(m,1F),67.50(d,J＝145.6Hz,4F).

Example 23

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3v.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), white solid, yield 38%;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.50–7.41(m,5H),7.25(d,J＝2.9Hz,1H),4.16–4.03(m,1H),3.85(d,J＝11.1Hz,1H),3.82–3.72(m,1H),1.40(s,3H),1.29(s,3H).¹³C NMR(151MHz,CDCl₃)δ204.2,141.8,132.9,131.4,131.1,130.3,129.5,67.9–67.4(m),61.7,45.5,23.1,17.1.¹⁹F NMR(565MHz,CDCl₃)δ85.21–83.92(m,1F),64.37(d,J＝145.2Hz,4F).

Example 24

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3w.

R _f = 0.70 (petroleum ether/ethyl acetate = 5:1), white solid, 60% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.90–7.87(m,2H),7.77–7.74(m,2H),4.82–4.65(m,2H),4.43–4.26(m,1H),4.25–4.06(m,1H),3.81(d,J＝10.8Hz,1H),1.89(s,3H),1.55(s,3H).¹³C NMR(151MHz,CDCl₃)δ199.8,167.5,134.4,132.2,123.8,71.7–70.4(m),68.7,56.4,48.7,32.4,28.4.¹⁹F NMR(565MHz,CDCl₃)δ85.95–81.43(m,1F),67.23(d,J＝145.3Hz,4F).

Example 25

Referring to the synthetic method of example 2, the substituents of the substrate were changed to give compound 3x.

R _f = 0.60 (petroleum ether/ethyl acetate = 20:1), white solid, yield 68%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ4.68(d,J＝9.1Hz,1H),3.96–3.77(m,2H),2.83–2.70(m,1H),1.84–1.75(m,2H),1.70(d,J＝8.2Hz,2H),1.67–1.62(m,1H),1.50–1.41(m,1H),1.41–1.33(m,1H),1.31(s,3H),1.27(s,3H),1.26–1.19(m,3H).¹³C NMR(151MHz,CDCl₃)δ214.2,74.7(p,J＝14.1Hz),60.1,52.5,45.2,29.1,28.8,24.8,24.7,24.7,21.2,19.1.¹⁹F NMR(565MHz,CDCl₃)δ84.17–82.29(m,1F),65.80(d,J＝146.9Hz,4F).

Example 26

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3y.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), white solid, yield 72%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ4.49–4.33(m,1H),3.97–3.88(m,1H),3.87(d,J＝10.0Hz,1H),2.76(t,J＝11.2Hz,1H),2.27–2.14(m,2H),2.13–2.07(m,1H),2.00–1.93(m,1H),1.92–1.83(m,1H),1.82–1.65(m,2H),1.64–1.62(m,1H),1.61(s,3H),1.59(s,3H).¹³C NMR(151MHz,CDCl₃)δ209.3,122.5(t,J＝240.87Hz),71.5–70.7(m),68.9,57.5(t,J＝3.4Hz),50.4,33.2(t,J＝24.46Hz),32.8(t,J＝24.88Hz),31.0,30.1,25.5(d,J＝9.7Hz),24.5(d,J＝9.4Hz).¹⁹F NMR(565MHz,CDCl₃)δ86.36–81.25(m,1F),67.42–67.06(m,4F),-87.94–-95.89(m,1F),-99.71–-105.47(m,1F).

Example 27

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3z.

R _f = 0.50 (petroleum ether/ethyl acetate = 40:1), white solid, 53% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ4.54–4.31(m,1H),4.10–3.94(m,1H),3.85(d,J＝10.2Hz,1H),3.20–3.08(m,1H),1.98(dd,J＝24.9,14.1Hz,1H),1.93–1.83(m,2H),1.83–1.74(m,2H),1.68(d,J＝14.9Hz,3H),1.66–1.56(m,3H),1.54(s,3H).¹³C NMR(151MHz,CDCl₃)δ212.6,71.5–70.8(m),69.4,59.7,54.3,32.8,32.1,30.8,29.1,26.7,26.0.¹⁹F NMR(565MHz,CDCl₃)δ85.51–83.70(m,1F),67.11(dt,J＝146.2,7.6Hz,4F)

Example 28

Referring to the synthesis of example 2, the substituents of the substrate are changed to give compound 3aa.

R _f = 0.90 (petroleum ether/ethyl acetate = 20:1), white solid, 67% yield;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.06–7.90(m,2H),7.65–7.55(m,1H),7.53–7.46(m,2H),4.77–4.61(m,2H),4.09–4.01(m,1H),1.81–1.73(m,1H),1.73–1.64(m,2H),1.61–1.50(m,2H),1.50–1.35(m,3H),0.85(t,J＝7.2Hz,3H),0.72(t,J＝7.3Hz,3H).¹³C NMR(151MHz,CDCl₃)δ197.9,137.8,133.7,128.9,128.6,72.0–71.4(m),49.3,41.4,41.2,18.0,17.6,14.1,13.9.¹⁹F NMR(565MHz,CDCl₃)δ85.00–83.66(m,1F),67.23(d,J＝145.1Hz,4F).

Example 29

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 3ab.

R _f =0.50 (petroleum ether/ethyl acetate=20:1), white solid, 71% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.03(d,J＝7.7Hz,2H),7.63(s,1H),7.57–7.39(m,2H),4.75–4.56(m,2H),4.41–4.24(m,1H),2.01–1.88(m,1H),1.80–1.55(m,6H),1.52–1.46(m,1H),1.26(t,J＝13.1Hz,1H),1.08–0.95(m,1H).¹³C NMR(151MHz,CDCl₃)δ197.3,137.1,134.0,129.1,128.8,76.5,71.4(p,J＝14.1Hz),53.6,40.1,34.2,24.7,22.1,21.5.¹⁹F NMR(565MHz,CDCl₃)δ85.55–83.64(m,1F),67.49(d,J＝145.7Hz,4F).

Example 30

Referring to the synthetic method of example 2, the substituents of the substrate were changed to give compound 3ac.

R _f = 0.50 (petroleum ether/ethyl acetate = 40:1), white solid, 71% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.01(d,J＝7.5Hz,2H),7.66–7.60(m,1H),7.55–7.44(m,2H),4.81–4.64(m,2H),4.33–4.18(m,1H),2.13–2.05(m,1H),1.99–1.84(m,3H),1.84–1.74(m,1H),1.73–1.55(m,3H).¹³C NMR(151MHz,CDCl₃)δ196.4,136.9,134.1,129.2,128.7,81.3,71.8–71.0(m),51.3,42.4,38.3,22.5,22.2.¹⁹F NMR(565MHz,CDCl₃)δ85.35–83.49(m,1F),66.96(dt,J＝145.3,7.3Hz,4F).

Example 31

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 3ad.

R _f = 0.40 (petroleum ether/ethyl acetate = 5:1), white solid, 58% yield;

Example 32

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4a.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), colorless clear liquid, yield 70%;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.17(d,J＝7.9Hz,2H),8.08(d,J＝8.0Hz,2H),5.02–4.91(m,1H),4.68–4.56(m,2H),4.29–4.19(m,1H),2.13(d,J＝11.9Hz,1H),2.00–1.91(m,1H),1.74(d,J＝11.1Hz,2H),1.56(s,6H),1.51(s,3H),1.19–1.07(m,2H),0.93(t,J＝6.2Hz,6H),0.80(d,J＝6.9Hz,3H).¹³C NMR(151MHz,CDCl₃).δ196.9,165.1,139.9,135.6,130.2,128.7,75.9,71.9–71.7(m),69.4,53.1,47.4,41.1,34.4,33.0,31.6,28.6,26.7,23.8,22.2,20.9,16.7.¹⁹F NMR(565MHz,CDCl₃)δ85.04–83.25(m,1F),67.50(d,J＝145.3Hz,4F).

Example 33

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 4b.

R _f = 0.50 (petroleum ether/ethyl acetate = 20:1), white solid, 58% yield;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.19(d,J＝8.2Hz,2H),8.10(d,J＝8.1Hz,2H),5.14(d,J＝9.6Hz,1H),4.69–4.52(m,2H),4.30–4.13(m,1H),2.54–2.42(m,1H),2.17–2.03(m,1H),1.82(t,J＝11.9Hz,1H),1.76(t,J＝3.8Hz,1H),1.56(s,3H),1.51(s,3H),1.43(t,J＝11.8Hz,1H),1.34–1.27(m,1H),1.14–1.10(m,1H),0.97(s,3H),0.92(s,6H).¹³C NMR(151MHz,CDCl₃)δ196.9,165.8,140.0,135.6,130.2,128.7,81.5,71.7–71.2(m),69.3,53.1,49.3,48.1,45.2,37.1,32.9,28.6,28.2,27.6,19.8,19.0,13.7.¹⁹F NMR(565MHz,CDCl₃)δ85.03–83.26(m,1F),67.43(d,J＝145.5Hz,4F).

Example 34

Referring to the synthetic method of example 2, the substituents of the substrate were changed to give compound 4c.

R _f = 0.30 (petroleum ether/ethyl acetate = 1:1), white solid, 77% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.16(d,J＝8.6Hz,3H),8.08(d,J＝8.2Hz,2H),8.00(d,J＝8.4Hz,1H),7.91(d,J＝8.4Hz,1H),4.68–4.52(m,2H),4.49–4.35(m,2H),4.32–4.13(m,1H),3.45(s,2H),1.89(s,4H),1.56(s,3H),1.55(s,6H),1.50(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.8,174.6,165.5,153.1,140.2,136.6,135.4,134.8,133.8(q,J＝66.5,32.9Hz),130.2,128.7,128.0,123.1(q,J＝9.5,4.7Hz),121.2,115.1,108.5,71.8–71.2(m),69.3,64.8,62.0,53.1,40.1,32.8,28.7,26.5,26.3,23.7.¹⁹F NMR(565MHz,CDCl₃)δ84.74–83.44(m,1F),67.45(d,J＝145.5Hz,4F),-62.04(s,3F).

Example 35

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4d.

R _f = 0.25 (petroleum ether/ethyl acetate = 20:1), white solid, 58% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.05(d,J＝8.4Hz,2H),7.22(d,J＝8.5Hz,2H),4.61(s,2H),4.34–4.16(m,1H),2.10(s,3H),2.06(s,6H),1.85–1.69(m,6H),1.54(s,3H),1.51(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.0,175.5,155.9,134.1,130.4,122.3,71.8–71.5(m),69.8,52.8,41.4,38.8,36.5,33.4,28.3,28.0.¹⁹F NMR(565MHz,CDCl₃)δ85.03–83.50(m,1F),67.43(d,J＝145.6Hz,4F).

Example 36

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4e.

R _f = 0.25 (petroleum ether/ethyl acetate = 20:1), white solid, 55% yield;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.01(d,J＝8.6Hz,2H),7.29(d,J＝7.8Hz,2H),7.19–7.12(m,4H),4.58(s,2H),4.32–4.15(m,1H),4.00–3.89(m,1H),2.47(d,J＝7.2Hz,2H),1.93–1.80(m,1H),1.62(d,J＝7.1Hz,3H),1.53(s,3H),1.49(s,3H),0.91(d,J＝6.6Hz,6H).¹³C NMR(151MHz,CDCl₃)δ195.9,172.6,155.5,141.3,136.9,134.3,130.4,129.8,127.4,122.1,71.9–71.4(m),69.7,52.9,45.5,45.2,33.3,30.3,28.4,22.5,18.5.¹⁹F NMR(565MHz,CDCl₃)δ84.15(p,J＝146.3Hz,1F),67.39(d,J＝146.1Hz,4F).

Example 37

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4f.

R _f = 0.25 (petroleum ether/ethyl acetate = 20:1), white solid, 40% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.34(d,J＝8.4Hz,2H),8.17(d,J＝8.4Hz,2H),7.73(d,J＝9.6Hz,1H),7.57(d,J＝8.4Hz,1H),7.27(d,J＝1.8Hz,1H),7.23–7.15(m,1H),6.44(d,J＝9.6Hz,1H),4.68(d,J＝10.9Hz,1H),4.66–4.56(m,1H),4.30–4.16(m,1H),1.60(s,3H),1.54(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.8,163.6,160.3,154.9,153.3,142.9,140.9,133.4,131.0,128.9,128.9,118.5,117.2,116.5,110.7,71.6–70.9(m),69.2,53.2,32.7,28.8.¹⁹F NMR(565MHz,CDCl₃)δ84.69–83.28(m,1F),67.51(dt,J＝146.5,7.1Hz,4F).

Example 38

With reference to the synthesis method of example 2, the substituents of the substrate were changed to give 4g of compound.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), white solid, yield 50%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.36(d,J＝8.3Hz,2H),8.18(d,J＝8.3Hz,2H),8.08(d,J＝2.7Hz,1H),7.95(d,J＝6.5Hz,2H),7.68(d,J＝9.0Hz,1H),7.63–7.58(m,1H),7.58–7.52(m,3H),6.85(s,1H),4.72–4.67(m,1H),4.67–4.58(m,1H),4.31–4.19(m,1H),1.60(s,3H),1.55(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.8,177.7,164.0,163.9,154.1,147.8,140.8,133.6,132.0,131.7,130.9,129.3,128.9,127.9,126.5,125.0,119.8,118.0,107.4,71.7–71.1(m),69.2,53.2,32.8,28.7.¹⁹F NMR(565MHz,CDCl₃)δ84.78–83.33(m,1F),67.51(d,J＝145.4Hz,4F).

Example 39

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4h.

R _f = 0.50 (petroleum ether/ethyl acetate = 5:1), white solid, yield 70%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.16(d,J＝8.1Hz,2H),8.06(d,J＝8.0Hz,2H),5.03–4.93(m,1H),4.67–4.56(m,2H),4.31–4.17(m,1H),2.44(dd,J＝19.4,8.7Hz,1H),2.15–2.02(m,1H),2.02–1.88(m,2H),1.86–1.74(m,4H),1.73–1.61(m,2H),1.62–1.57(m,2H),1.56(s,3H),1.50(s,3H),1.42–1.32(m,3H),1.32–1.22(m,4H),1.17–1.08(m,1H),1.07–0.96(m,1H),0.91(s,3H),0.87(s,3H),0.80–0.73(m,1H).¹³C NMR(151MHz,CDCl₃)δ196.9,165.1,139.9,135.6,130.2,128.6,75.1,72.0–70.5(m),69.4,54.5,53.1,51.6,47.9,44.9,36.9,36.0,35.9,35.2,34.1,33.0,31.7,31.0,28.6,28.5,27.6,21.9,20.7,14.0,12.4.¹⁹F NMR(565MHz,CDCl₃)δ84.98–83.39(m,1F),67.47(d,J＝145.4Hz,4F).

Example 40

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4i.

R _f = 0.30 (petroleum ether/ethyl acetate = 10:1), white solid, 52% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.16(d,J＝8.0Hz,2H),8.08(d,J＝8.1Hz,2H),5.74(s,1H),4.88(t,J＝8.3Hz,1H),4.70–4.55(m,2H),4.28–4.18(m,1H),2.50–2.38(m,2H),2.37–2.27(m,3H),2.03(d,J＝13.1Hz,1H),1.88(d,J＝11.2Hz,2H),1.79–1.58(m,5H),1.56(s,3H),1.51(s,3H),1.48–1.41(m,2H),1.32–1.24(m,2H),1.21(s,3H),1.19–1.12(m,1H),1.11–1.03(m,1H),0.99(s,3H).¹³C NMR(151MHz,CDCl₃)δ199.5,196.9,170.8,165.4,140.0,135.3,130.2,128.7,124.2,83.8,71.9–70.8(m),69.3,53.9,53.1,50.5,43.1,38.8,36.9,35.9,35.6,34.1,32.9,32.9,31.7,28.6,27.8,23.8,20.7,17.6,12.5.¹⁹F NMR(565MHz,CDCl₃)δ84.77–83.31(m,1F),67.44(d,J＝145.3Hz,4F).

Example 41

Referring to the synthesis of example 2, the substituents of the substrate were changed to give compound 4j.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), white solid, yield 30%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.16(d,J＝8.0Hz,2H),8.06(d,J＝8.0Hz,2H),5.01–4.91(m,1H),4.68–4.55(m,2H),4.31–4.16(m,1H),1.96(t,J＝14.7Hz,2H),1.80(d,J＝14.1Hz,2H),1.73(d,J＝11.7Hz,1H),1.70–1.61(m,2H),1.55(s,5H),1.50(s,5H),1.42–1.20(m,12H),1.18–1.05(m,6H),1.04–0.95(m,3H),0.90(d,J＝6.1Hz,5H),0.88–0.85(m,8H),0.66(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.9,165.1,139.9,135.7,130.2,128.6,75.4,71.8–71.0(m),69.4,56.6,56.5,54.4,53.2,44.9,42.8,40.2,39.7,37.0,36.4,36.0,35.7,34.2,33.0,32.2,28.8,28.6,28.4,28.2,27.7,24.4,24.0,23.0,22.7,21.4,18.8,12.5,12.2.¹⁹FNMR(565MHz,CDCl₃)δ84.84–83.35(m,1F),67.45(d,J＝145.4Hz,4F).

Example 42

Referring to the synthesis of example 2, the substituents of the substrate were varied to give compound 4k.

R _f = 0.30 (petroleum ether/ethyl acetate = 10:1), white solid, 52% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.17(d,J＝8.2Hz,2H),8.08(d,J＝8.2Hz,2H),5.03–4.92(m,1H),4.72–4.58(m,2H),4.47–4.37(m,1H),4.34–4.17(m,1H),3.54–3.43(m,1H),3.40(t,J＝11.0Hz,1H),2.05–1.94(m,2H),1.88(dd,J＝14.0,7.1Hz,1H),1.85–1.72(m,4H),1.72–1.61(m,4H),1.57(s,6H),1.51(s,6H),1.38–1.23(m,6H),1.21–1.08(m,3H),0.99(d,J＝6.9Hz,3H),0.97–0.93(m,1H),0.92(s,3H),0.83–0.79(m,5H),0.77–0.70(m,1H).¹³C NMR(151MHz,CDCl₃)δ196.9,165.1,139.9,135.7,130.2,128.6,109.4,81.0,75.2,71.8–71.0(m),69.4,67.0,62.4,56.4,54.4,53.1,44.9,41.8,40.7,40.2,36.9,35.8,35.3,34.2,33.0,32.3,31.9,31.6,30.5,29.0,28.7,28.6,27.7,21.2,17.3,16.6,14.7,12.5.¹⁹F NMR(565MHz,CDCl₃)84.06(p,J＝145.9Hz,1F),67.44(d,J＝145.8Hz,4F).

Example 43

In a glove box, 3ad (162.4 mg,0.4mmol,1.0 eq.) and tetrahydrofuran (1.5 mL,0.3 m) were added to a 5mL reaction flask equipped with a stirrer, followed by methyl magnesium bromide (0.26 mL,0.80mmol, tetrahydrofuran solution concentration 3.0m,2.0 eq.) at 0 ℃. The reaction mixture was stirred at room temperature for 12 hours. Thereafter, the reaction was quenched with saturated aqueous ammonium chloride and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 5.

R _f = 0.30 (petroleum ether/ethyl acetate = 5:1), white solid, yield 95%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.98(d,J＝8.3Hz,2H),7.56(d,J＝8.2Hz,2H),4.76–4.47(m,2H),4.33–4.17(m,1H),2.13–1.90(m,1H),1.64(s,1H),1.55(s,3H),1.54(s,3H),1.52(s,3H),0.93(d,J＝6.7Hz,3H),0.78(d,J＝6.8Hz,3H).¹³C NMR(151MHz,CDCl₃)δ196.9,154.6,135.1,128.5,126.1,71.9–71.2(m),69.9,52.9,38.6,38.6,33.4,28.2,27.0,17.4,17.1.¹⁹F NMR(565MHz,CDCl₃)δ85.43–83.13(m,1F),67.47(d,J＝145.6Hz,4F).

Example 44

In a glove box, 3ad (162.4 mg,0.4mmol,1.0 eq.) and absolute ethanol (0.7 mL,0.6 m) were added in a 5mL reaction flask equipped with a stirrer, followed by the addition of sodium borohydride (8.2 mg,0.48mmol,1.2 eq.) in portions at 0 ℃. The reaction mixture was stirred at 100 ℃ for 2 hours. After this time, ethanol was concentrated in vacuo to remove it, which was extracted with water and dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 6.

R _f = 0.30 (petroleum ether/ethyl acetate = 5:1), colorless oily liquid, yield 79%;

Example 45

In a glove box, 3ad (162.4 mg,0.4mmol,1.0 eq), m-chloroperoxybenzoic acid (487.26 mg,2.4mmol,4.0equiv., 85%), TFA (91.9 μl,1.2mmol,2.0 equiv.) and anhydrous dichloromethane (6.0 mL,0.10 m) were added to a 5mL reaction flask equipped with a stirrer. The reaction mixture was stirred at room temperature for 24 hours. Thereafter, the reaction was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 7.

R _f =0.30 (petroleum ether/ethyl acetate=20:1), yellow oily liquid, yield 81%;

its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.16(d,J＝8.1Hz,2H),8.07(d,J＝8.0Hz,2H),5.28(dt,J＝12.1,6.1Hz,1H),4.64(s,2H),4.31–4.17(m,1H),1.56(s,3H),1.51(s,3H),1.39(d,J＝6.0Hz,6H).¹³C NMR(151MHz,CDCl₃)δ196.9,165.0,139.9,135.6,130.2,128.6,71.4(p,J＝15.0Hz),69.3,53.1,33.0,28.6,22.0.¹⁹F NMR(565MHz,CDCl₃)δ84.90–83.13(m,1F),67.45(dt,J＝126.1,6.8Hz,4F).

Example 46

In a glove box, 3a (100.81 mg,0.3mmol,1.0 equiv.), phenol (28.23 mg,0.3mmol,1.0 equiv.), cesium carbonate (293.24 mg,0.9mmol,3.0 equiv.) and anhydrous acetonitrile (1.2 mL,0.25 m) were added to a 2mL reaction flask equipped with a stirrer. The reaction mixture was stirred at 40 ℃ for 8 hours. Thereafter, the reaction was quenched with water and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 8.

R _f = 0.30 (petroleum ether/ethyl acetate = 5:1), colorless oily liquid, 75% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.96(d,J＝7.5Hz,2H),7.57–7.51(m,1H),7.47–7.41(m,2H),7.26–7.20(m,2H),6.95–6.89(m,1H),6.85(d,J＝8.2Hz,2H),4.76(s,2H),1.99(s,3H),1.69(s,3H).¹³C NMR(151MHz,CDCl₃)δ199.8,158.8,141.9,138.1,133.2,131.4,129.5,129.5,128.7,121.1,115.0,65.9,23.3,20.9.

Example 47

In a glove box, 3a (100.81 mg,0.3mmol,1.0 equiv.), cesium acetate (230.34 mg,1.2mmol,4.0 equiv.), silver acetate (50.07 mg,0.3mmol,1.0 equiv.) and absolute ethanol (0.6 mL,0.50 m) were added to a 2mL reaction flask equipped with a stirrer. The reaction mixture was stirred at 40 ℃ for 12 hours. Thereafter, the reaction was quenched with water and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator.

Further purification by silica gel column chromatography gave compound 9.

R _f = 0.60 (petroleum ether/ethyl acetate = 5:1), colorless oily liquid, 36% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.86(d,J＝7.4Hz,2H),7.60–7.55(m,1H),7.50–7.45(m,2H),4.89–4.63(m,2H),2.05(s,3H),1.65(s,3H).¹³C NMR(151MHz,CDCl₃)δ197.5,149.1,145.0,137.8,133.4,129.5,128.9,71.7(p,J＝13.4Hz),24.9,22.3.¹⁹FNMR(565MHz,CDCl₃)83.18–81.94(m,1F),65.79(dt,J＝144.3,7.1Hz,4F).

Example 48

In a glove box, 3a (201.62 mg,0.6mmol,1.0 equiv.), tris (trimethylsilyl) silane (0.78 mL,2.52mmol,4.2 equiv.), azobisisobutyronitrile (19.71 mg,0.12mmol,20 mol%) and anhydrous toluene (6.0 mL, 0.10M) were added to a 10mL reaction flask equipped with a stirrer. The reaction mixture was stirred at 80 ℃ for 6 hours. Thereafter, the reaction was quenched with saturated ammonium chloride solution and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 10.

R _f = 0.30 (petroleum ether/ethyl acetate = 20:1), colorless oily liquid, 94% yield;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.01–7.93(m,2H),7.64–7.56(m,1H),7.54–7.46(m,2H),4.69–4.51(m,1H),4.16–4.00(m,1H),3.84–3.63(m,1H),2.16–1.99(m,1H),1.05(d,J＝6.9Hz,3H),0.84(d,J＝6.9Hz,3H).¹³C NMR(151MHz,CDCl₃)δ198.9,136.4,133.6,129.0,128.5,69.8(p,J＝13.1Hz),48.7,30.9,20.9,18.4.¹⁹F NMR(565MHz,CDCl₃)δ86.80–83.71(m,1F),66.19(d,J＝145.0Hz,4F).

Example 49

In a glove box, 3i (124.18 mg,0.3mmol,1.0 equiv.), 4-cyanophenylboronic acid (88.23 mg,0.6mmol,2.0 equiv.), tetrakis triphenylphosphine palladium (34.67 mg,0.03mmol,10 mol%), sodium carbonate (82.67 mg,0.78mmol,2.6 equiv.), and 1, 4-dioxane (2.0 mL,0.15 m) were added to a 5mL reaction flask equipped with a stirrer. The reaction mixture was stirred at 90 ℃ for 8 hours. Thereafter, the reaction was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 11.

R _f = 0.30 (petroleum ether/ethyl acetate = 5:1), colorless oily liquid, yield 85%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ8.14(d,J＝8.3Hz,2H),7.78(d,J＝8.3Hz,2H),7.74(s,2H),7.72(s,2H),4.70–4.58(m,2H),4.26(d,J＝12.4Hz,1H),1.59(s,3H),1.56(s,3H).¹³C NMR(151MHz,CDCl₃)δ196.6,144.6,144.1,136.7,133.0,129.6,128.1,128.0,118.7,112.5,71.9–71.3(m),69.6,53.0,33.1,28.6.¹⁹F NMR(565MHz,CDCl₃)δ87.27–78.70(m,1F),67.50(dt,J＝12.8,6.7Hz,4F).

Example 50

In a glove box, 3i (82.79 mg,0.2mmol,1.0 equiv.) of BrettPhos Pd G3 (18.13 mg,0.02mmol,10 mol%), cesium carbonate (97.70 mg,0.3mmol,1.5 equiv.), aniline (22.8. Mu.L, 0.25mmol,1.3 equiv.) and 1, 4-dioxane (0.8 mL, 0.25M) were added to a 5mL reaction flask equipped with a stirrer. The reaction mixture was stirred at 100 ℃ for 1 hour. Thereafter, the reaction was quenched with saturated sodium bicarbonate solution and extracted with dichloromethane (3×3.0 mL). The organic layers were combined, dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure by rotary evaporator. Further purification by silica gel column chromatography gave compound 12.

R _f =0.50 (petroleum ether/ethyl acetate=5:1), yellow oily liquid, yield 78%;

Its nuclear magnetic data is ：¹H NMR(600MHz,CDCl₃)δ7.93(d,J＝8.3Hz,2H),7.41–7.31(m,2H),7.21(d,J＝7.8Hz,2H),7.17–7.09(m,1H),7.00(d,J＝8.2Hz,2H),6.16(s,1H),4.70–4.59(m,1H),4.56(d,J＝10.6Hz,1H),4.33–4.19(m,1H),1.56(s,6H).¹³C NMR(151MHz,CDCl₃)δ194.6,149.6,140.2,131.4,129.8,128.4,124.2,121.6,114.5,71.9(p,J＝14.1Hz),70.6,52.4,33.6,28.3.¹⁹F NMR(565MHz,CDCl₃)δ85.32–83.69(m,1F),66.95(d,J＝145.4Hz,4F).

Test examples

1. Tumor inhibition activity assay

The inhibition efficacy of the synthesized compounds against different tumor cells was examined by CCK-8 cell activity assay and irinotecan was used as a control, the results of which are shown in fig. 1 and table 1.

TABLE 1 inhibition of different tumor cells by different Compounds

A represents the mean ± Standard Deviation (SD) of three independent experiments;

b served as positive control.

As shown in Table 1, after 48 hours of treatment, the half inhibition concentration (IC ₅₀) of the compound on liver cancer cells HepG2, colon cancer cells HCT116, cervical cancer cells Hela, prostate cancer cells PC3, lung cancer cells A549, breast cancer cells MCF-7 and myeloma cells U266 is generally less than 100 mu M, and a certain antitumor activity is shown. Of these, compound 5 had the strongest inhibitory effect on PC3 cells, IC ₅₀ was 6.3 μm, which was stronger than the positive control drug irinotecan (fig. 1).

2. Inhibition of tumors by Compound 5

(1) The inhibition efficacy of compound 5 on PC3 cells was examined by colony formation assay, the results of which are shown in fig. 2.

As shown in fig. 2, 2.5 μm compound 5 treated PC3 cells for 48 hours, the cell colonies grew for 14 days, the control group colonies were 412, the compound 5 reduced the colony count to 139, and the colony size was significantly reduced, indicating that compound 5 can inhibit the long-term growth of tumor cells.

(2) The inhibition effect of compound 5 on PC3 cells was examined by a scratch test, and the results are shown in fig. 3.

As shown in fig. 3, 2.5 μm compound 5 treated PC3 cells for 48 hours, the tumor cell invasion area decreased, indicating that compound 5 reduced the tumor cell invasion capacity. Tumor cell apoptosis and Reactive Oxygen Species (ROS) production are important strategies for cancer suppression.

(3) The effect of compound 5 on apoptosis of PC3 cells was examined by flow cytometry, while its effect on ROS was examined, the results of which are shown in fig. 4 and 5.

As shown in fig. 4, 2.5 μm compound 5 treated PC3 cells for 48 hours increased the apoptosis rate from 1.2% to 10.7%, indicating that compound 5 was able to cause apoptosis in tumor cells. Whereas in ROS assay, 2.5. Mu.M treatment of PC3 cells with Compound 3b for 48 hours significantly promoted intracellular ROS production, indicating that Compound 5 was able to cause ROS production by tumor cells and thus oxidative stress (FIG. 5)

(4) The change of gene expression in PC3 cells after compound 5 was detected by using a cell transcriptome sequencing technique, and GO analysis and KEGG pathway analysis were performed, and the results are shown in FIGS. 6 to 8.

As shown in FIG. 6, 2.5. Mu.M compound 5 treatment of PC3 cells for 48 hours resulted in an increase in 1306 gene expression and a decrease in 1373 gene expression. The biological function GO analysis of these differential genes showed that compound 5 affected tumor cell structure and function (FIG. 7), and the differential gene KEGG pathway analysis showed that compound 5 was associated with classical cancer-suppressing pathways such as P53, TNF, NF-kappa B, TGF-beta, etc. (FIG. 8).

In summary, the compounds prepared by the invention all show a certain antitumor activity, wherein the inhibition effect of the compound 5 on the prostate cancer cells is most remarkable, and the mechanism is probably to activate cancer inhibition related pathways, induce ROS to generate, cause cancer cell apoptosis and finally inhibit proliferation, survival and migration of tumor cells.

Finally, it should be noted that the above-mentioned embodiments are only for illustrating the technical solution of the present invention, and not for limiting the same, and although the present invention has been described in detail with reference to examples, it should be understood by those skilled in the art that modifications and equivalents may be made to the technical solution of the present invention without departing from the spirit and scope of the technical solution of the present invention, and all such modifications and equivalents are intended to be encompassed in the scope of the claims of the present invention.

Claims

1. A beta-SF ₅ -ketone compound is characterized by having the following structural formula:

wherein the R ¹ group is alkyl, olefin, heteroaromatic or aryl, and the R ² group is alkyl.

2. The β -SF ₅ -one compound according to claim 1, wherein the R ¹ groups are selected from alkyl, alkene, heteroarene, aryl or arene groups containing different substituents, the R ² groups being methyl;

The substituent is one of halogen, alkane, cyano, alkoxy, ether, isobutyryl, trifluoromethyl, trifluoromethylthio, menthol, 2-alcohol, RU 58841, adamantanecarboxylic acid, ibuprofen, 7-hydroxycoumarin, 6-hydroxyflavone, dihydrocholesterol, epiandrosterone, testosterone or sisal sapogenin.

3. The β -SF ₅ -ketone compound according to claim 2, wherein the β -SF ₅ -ketone compound is:

4. a method for preparing the β -SF ₅ -ketone compound according to any one of claims 1 to 3, comprising the following steps:

(1) Preparing a pentafluorosulfuric chloride n-hexane solution with the concentration of more than 0.4M by a distillation mode;

(2) And adding beta, gamma-unsaturated ketone and pentafluorosulfuric n-hexane solution into a solvent, and then carrying out migration of free radicals 1,2 carbonyl in beta, gamma-unsaturated ketone molecules under the illumination of the wavelength of 360-365 nm at the temperature of 32-35 ℃ to prepare the beta-SF ₅ -ketone compound.

5. The method according to claim 4, wherein the molar ratio of the beta, gamma-unsaturated ketone to the pentafluorothiochloride is 0.10:0.10-0.12.

6. The method of claim 4 or 5, wherein the β, γ -unsaturated ketone has the following structural formula:

Wherein the R ¹ group is selected from alkyl, alkene, heteroarene, aryl or arene containing different substituents, the R ² group is methyl, and the substituents are one of halogen, alkane, cyano, alkoxy, ether, isobutyryl, trifluoromethyl, trifluoromethylthio, menthol, 2-alcohol, RU 58841, adamantanecarboxylic acid, ibuprofen, 7-hydroxycoumarin, 6-hydroxyflavone, dihydrocholesterol, epiandrosterone, testosterone or sisalagenin.

7. An improved SF ₅ Cl synthesis method is characterized by comprising the following steps:

8. The use of the beta-SF ₅ -ketone compound according to any one of claims 1 to 3 in the preparation of antitumor drugs.

9. The use according to claim 8, wherein the tumor is liver cancer, colon cancer, cervical cancer, prostate cancer, lung cancer, breast cancer or myeloma.

10. An antitumor drug comprising the β -SF ₅ -one compound of any one of claims 1 to 3 and pharmaceutically acceptable adjuvants thereof.