Monofluoroolefins containing indole skeleton, their synthesis and anticancer activity

Abstract

The application discloses a single-fluoro olefin compound containing an indole skeleton, a synthesis method and anticancer activity thereof, and belongs to the technical field of organic synthesis. The single-fluoro olefin compound 3 containing the indole skeleton is obtained by using o-alkynyl aniline compounds 1 and gem-difluoro olefin compounds 2 as raw materials, and by carrying out a reaction in an organic solvent under the presence of a palladium catalyst, a ligand, an additive and a base and by heating. Then, screening is carried out on compounds with various substituents, and verification is carried out through an anticancer cell activity test. Research finds that the compound 3u disclosed by the application can effectively inhibit HCT-116 cancer cell proliferation. Meanwhile, the synthesis method is simple and efficient, and has the advantages of simple and easily obtained raw materials, simple operation, mild conditions, wide substrate application range, good functional group tolerance, high yield and high regioselectivity.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis technology, specifically relating to monofluoroolefin compounds containing an indole skeleton, their synthesis methods, and their anticancer activities. Background Technology

[0002] Monofluoroolefins, as an important class of organofluorine compounds, play a crucial role in organic synthesis, medicinal chemistry, and peptide chemistry. This is because monofluoroolefins are isosteric amide bonds and enol mimics; introducing monofluoroolefins into drug molecules can enhance the bioactivity of the parent molecule. Simultaneously, monofluoroolefins are also highly valuable fluorinated synthons in organic synthesis, capable of further conversion into other fluorine-containing compounds. Therefore, developing universal and efficient synthetic methods to obtain monofluoroolefins is of great significance.

[0003] On the other hand, nitrogen-containing heterocycles (such as indole rings) are widely found in natural products and drug molecules, and are an important structural unit with biological activity. For example, commonly used clinical drugs such as indomethacin and reserpine contain indole skeletons. In organic synthesis, o-alkynylaniline is an readily available building block for constructing indole skeletons, but its coupling reaction with gem-difluoroolefins has not yet been reported in the literature.

[0004] Therefore, researching and developing a green and sustainable new method for synthesizing monofluoroolefins containing an indole skeleton from inexpensive and readily available substrates through a simple operation process, and further studying their biological activities, is not only of great theoretical significance, but also has certain application prospects. Summary of the Invention

[0005] In order to address the problems existing in the prior art, one of the objectives of this invention is to provide a new class of monofluoroolefin compounds containing an indole skeleton, which studies have shown to have anticancer activity.

[0006] The monofluoroolefin compound containing an indole skeleton described in this invention has the following general structural formula: , Where: R 1 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, trifluoromethyl, halogen, ester group; R 2 Selected from phenyl, substituted phenyl, naphthyl, heteroaryl, cycloalkyl, alkyl; R 3 Selected from p-toluenesulfonyl and methanesulfonyl; R 4 Selected from phenyl or substituted phenyl, cycloalkyl; R 5 Selected from alkyl groups; the substituents in the aforementioned substituted phenyl groups are C. 1-4 Alkyl, C 1-4 Alkoxy or halogen.

[0007] The second objective of this invention is to provide the application of monofluoroolefin compounds 3u containing an indole skeleton in the preparation of anticancer drugs.

[0008] Furthermore, in the above technical solution, the anti-cancer treatment is for colon cancer. Specifically, it targets HCT-116 cells.

[0009] A third objective of this invention is to provide a pharmaceutical composition for treating colon cancer, wherein the active ingredient is the aforementioned monofluoroolefin compound 3u containing an indole skeleton.

[0010] The experimental design of this invention verifies that the compound 3u described in this invention has a certain inhibitory activity on the proliferation of HCT-116 cancer cells, suggesting that the compound 3u of this invention can be used as an active ingredient in anti-colon cancer drugs, and has the effects of prevention, treatment and inhibition of the progression of colon cancer.

[0011] The fourth objective of this invention is to provide a method for synthesizing monofluoroolefin compounds containing an indole skeleton, including preparation from o-alkynyl aniline compounds and gemini difluoroolefin compounds.

[0012] The method for synthesizing monofluoroolefin compounds containing an indole skeleton according to the present invention includes the following steps: Using o-alkynyl aniline compound 1 and gemini difluoroolefin compound 2 as starting materials, a reaction was carried out in an organic solvent in the presence of a palladium catalyst, ligand, additive, and base, with heating, to obtain monofluoroolefin compound 3 containing an indole skeleton; the reaction equation is shown below: , Where: R 1 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, trifluoromethyl, halogen, ester group; R 2 Selected from phenyl, substituted phenyl, naphthyl, heteroaryl, cycloalkyl, alkyl; R 3 Selected from p-toluenesulfonyl and methanesulfonyl; R 4 Selected from phenyl or substituted phenyl, cycloalkyl; R 5 Selected from alkyl groups; the substituents in the aforementioned substituted phenyl groups are C. 1-4 Alkyl, C 1-4 Alkoxy or halogen.

[0013] Furthermore, in the above technical solution, the palladium catalyst is selected from Pd(dba)2; the ligand is selected from 1,2-bis(diphenylphosphine)ethane or 1,3-bis(diphenylphosphine)propane; the base is selected from sodium carbonate or sodium bicarbonate; and the additive is selected from chromium trioxide.

[0014] Furthermore, in the above technical solution, the molar ratio of the o-alkynyl aniline compound 1, gemini difluoroolefin compound 2, palladium catalyst, ligand, base and additive is 1:1:0.05-0.1:0.05-0.1:1:0.3.

[0015] Furthermore, in the above technical solution, the organic solvent is selected from methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and 1,2-dimethoxyethane.

[0016] Furthermore, in the above technical solution, the reaction temperature is 50 ℃; the reaction is carried out in an argon atmosphere.

[0017] Compared with the prior art, the present invention has the following advantages: (1) The monofluoroolefin compounds containing indole skeletons provided by the present invention have potential medicinal value. By screening compounds with various substituents and verifying them through anti-cancer cell activity tests, the compound 3u provided by the present invention can effectively inhibit the proliferation of HCT-116 cancer cells, suggesting that the compound 3u of the present invention has certain anti-cancer activity against colon cancer and has potential medicinal value; (2) The synthesis method provided by this invention is simple and efficient. Monofluoroolefin compounds containing an indole skeleton can be synthesized through a one-pot tandem reaction of o-alkynyl aniline compounds and gemini difluoroolefin compounds; (3) The synthesis method provided by the present invention has the advantages of cheap and readily available raw materials, simple operation, high atom economy, wide range of substrates, and good functional group tolerance. Attached Figure Description

[0018] Figure 1 This is the X-ray single-crystal diffraction pattern of compound 3a in Example 3. Detailed Implementation

[0019] The following examples further illustrate the above-described content of the present invention, but it should not be construed as limiting the scope of the subject matter of the present invention to the following examples. All technologies implemented based on the above-described content of the present invention fall within the scope of the present invention. Example 1

[0020] , General experimental procedure: Under an argon atmosphere, add the catalyst, ligand, and solvent sequentially to a 25 mL sealed tube, and incubate the mixture at 50°C. o Stir at C for 30 minutes; add o-alkynyl aniline compound 1a, gemini difluoroolefin compound 2a, base and additive in sequence to the reaction mixture; seal the tube and place it at 50°C. oThe mixture was stirred in a metal bath for 24 hours. The reaction mixture was then filtered through diatomaceous earth, concentrated under reduced pressure by rotary evaporation, and purified by silica gel chromatography (PE:EA = 10:1) to finally obtain monofluoroolefin product 3a. The reaction conditions, including catalyst, ligand, base, additives, and solvent, were varied, and the results are shown in the table below. . Example 2

[0021] , In an argon-filled glove box, Pd(dba)₂ (2.9 mg, 0.005 mmol, 0.05 equiv), L₂ (2.0 mg, 0.005 mmol, 0.05 equiv), and DME (1 mL) were added sequentially to a 25 mL sealed tube, and the mixture was stirred at room temperature for 30 minutes. Then, 1a (0.1 mmol, 1.0 equiv), 2a (0.1 mmol, 1.0 equiv), NaHCO₃ (8.4 mg, 0.1 mmol, 1.0 equiv), and CrO₃ (3.0 mg, 0.03 mmol, 0.3 equiv) were added sequentially to the reaction mixture. The tube was sealed and stirred in a 50 °C metal bath for 24 hours. The reaction mixture was then purified sequentially by diatomaceous earth filtration, vacuum rotary evaporation, and silica gel chromatography to finally obtain monofluoroolefin product 3a (49.7 mg, (93% yield), and the structure of product 3a was also confirmed by X-ray single crystal diffraction. 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J =8.4 Hz, 1H), 7.51 – 7.36 (m, 7H), 7.34 – 7.28 (m, 6H), 7.25 – 7.23 (m, 2H),7.10 (d, J = 8.4 Hz, 2H), 3.70 (q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 0.57 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.4 (d, J = 14.3 Hz), 157.0 (d, J = 265.7 Hz), 145.2, 141.3 (d, J= 5.1 Hz), 136.7, 135.3, 132.1, 131.2 (d, J =1.6 Hz), 130.1 (d, J = 1.0 Hz), 129.6, 129.5, 128.9, 128.2, 128.1, 127.6,127.1, 125.7, 124.7, 120.7 (d, J = 21.3 Hz), 119.7, 117.1 (d, J = 28.0 Hz)116.3, 61.1, 21.7, 13.3. 19 F NMR (377 MHz, CDCl3) δ -79.96 (s). HRMS (ESI, m / z): calcd for C 32 H 26 FNNaO4S + [M + Na] + : 562.1459, found 562.1458. . Example 3

[0022] According to the method and steps of Example 2 a,b By changing reactant 1 and reactant 2, various monofluoroolefin compounds 3 containing indole skeletons were synthesized. The specific results are as follows: , .

[0023] The representative product characterization data are as follows: 3a: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 1H), 7.51 – 7.36(m, 7H), 7.34 – 7.28 (m, 6H), 7.25 – 7.23 (m, 2H), 7.10 (d, J = 8.4 Hz, 2H), 3.70 (q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 0.57 (t, J = 7.2 Hz, 3H). 13 C NMR (101MHz, CDCl3) δ 166.4 (d, J = 14.3 Hz), 157.0 (d,J = 265.7 Hz), 145.2, 141.3(d, J = 5.1 Hz), 136.7, 135.3, 132.1, 131.2 (d, J = 1.6 Hz), 130.1 (d, J =1.0 Hz), 129.6, 129.5, 128.9, 128.2, 128.1, 127.6, 127.1, 125.7, 124.7, 120.7(d, J = 21.3 Hz), 119.7, 117.1 (d, J = 28.0 Hz) 116.3, 61.1, 21.7, 13.3. 19 FNMR (377 MHz, CDCl3) δ -79.96 (s). HRMS (ESI, m / z): calcd for C 32 H 26 FNNaO4S + [M+ Na] + : 562.1459, found 562.1458. 。

[0024] 3b: 1 H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.6 Hz, 1H), 7.47 – 7.38(m, 5H), 7.34 – 7.27 (m, 6H), 7.24 – 7.22 (m, 3H), 7.08 (d, J = 8.2 Hz, 2H),3.71 (q, J = 7.2 Hz, 2H), 2.43 (s, 3H), 2.30 (s, 3H), 0.62 (t, J = 7.2 Hz,3H). 13 C NMR (101 MHz, CDCl3) δ 166.4 (d, J = 14.2 Hz), 157.2 (d, J = 265.5Hz), 145.1, 141.4 (d, J = 5.4 Hz), 135.3, 135.0, 134.5, 132.2, 131.2 (d, J=1.0 Hz), 130.2 (d, J = 1.0 Hz), 129.6, 129.5, 129.2, 128.2, 128.1, 127.6,127.1, 127.0, 120.6 (d, J = 21.4 Hz), 119.5, 117.0 (d, J = 28.0 Hz), 116.0,61.0, 21.7, 21.4, 13.4. 19 F NMR (377 MHz, CDCl3) δ -80.03 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO4S + [M + Na] + : 576.1615, found 576.1614.。

[0025] 3c: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 1H), 7.48 (d, J =7.8 Hz, 1H), 7.43 – 7.38 (m, 3H), 7.36 – 7.30 (m, 5H), 7.29 – 7.25 (m, 3H),7.09 (d, J = 8.2 Hz, 2H), 6.94 (d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 3.70 (q, J = 7.2 Hz, 2H), 2.31 (s, 3H), 0.56 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz,CDCl3) δ 166.4 (d, J = 14.1 Hz), 160.7, 157.1 (d, J = 265.9 Hz), 145.1, 141.4(d, J = 5.0 Hz), 136.7, 135.4, 132.6 (d, J= 1.4 Hz), 132.2, 129.6, 129.6,129.5, 129.0, 128.2, 128.1, 127.1, 125.5, 124.7, 122.2, 120.6 (d, J = 21.2Hz), 119.5, 116.7 (d, J = 27.7 Hz) 116.3, 113.1, 61.0, 55.4, 21.7, 13.3. 19 FNMR (377 MHz, CDCl3) δ -80.30 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO5S + [M+ Na] + : 592.1564, found 592.1563.。

[0026] 3d: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 1H), 7.50 (d, J =7.8 Hz, 1H), 7.45 – 7.41 (m, 3H), 7.36 – 7.29 (m, 6H), 7.25 (d, J = 6.4 Hz,2H), 7.13 – 7.09 (m, 4H), 3.71 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.59 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 14.1 Hz), 163.6 (d, J = 250.0 Hz), 156.6 (d, J = 265.9 Hz), 145.4, 140.1 (d, J = 4.8 Hz), 136.7,135.3, 133.2 (d, J = 1.3 Hz), 133.1 (d, J= 1.6 Hz), 132.0, 129.7, 129.5,129.5, 128.8, 128.3, 127.0, 126.1 (d, J = 2.3 Hz), 125.8, 124.8, 120.9 (d, J = 21.0 Hz), 119.7, 117.3 (d, J = 28.0 Hz), 116.3, 114.9 (d, J = 21.9 Hz),61.1, 21.7, 13.3. 19 F NMR (377 MHz, CDCl3) δ -80.64 (s, 1F), -110.86 – -110.98(m, 1F). HRMS (ESI, m / z): calcd for C 32 H 25 F2NNaO4S + [M + Na] + : 580.1365, found580.1364.。

[0027] 3e: 1 H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.4 Hz, 1H), 7.50 (d, J =7.8 Hz, 1H), 7.46 – 7.38 (m, 5H), 7.36 – 7.30 (m, 6H), 7.26 – 7.25 (m, 2H),7.12 (d, J = 8.2 Hz, 2H), 3.70 (q, J = 7.2 Hz, 2H), 3.01 (s, 3H), 0.58 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 14.3 Hz), 156.4 (d, J = 265.8 Hz), 145.4, 139.9 (d, J = 4.9 Hz), 136.8, 135.9, 135.2, 132.5 (d, J=1.3 Hz), 131.9, 129.7, 129.5, 129.5, 128.8, 128.6 (d, J = 1.0 Hz), 128.4,128.3, 128.0, 127.0, 126.0, 124.9, 121.0 (d, J = 20.9 Hz), 119.8, 117.5 (d, J = 27.7 Hz) 116.3, 61.2, 21.7, 13.3. 19 F NMR (377 MHz, CDCl3) δ -80.88 (s).HRMS (ESI, m / z): calcd for C 32 H 25 ClFNNaO4S + [M + Na] + : 596.1069, found596.1068.。

[0028] 3f: 1 H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.4 Hz, 1H), 7.50 (d, J =7.8 Hz, 1H), 7.43 – 7.39 (m, 1H), 7.36 – 7.21 (m, 12H), 7.09 (d, J = 8.2 Hz,2H), 3.71 (q, J = 7.2 Hz, 2H), 2.38 (s, 3H), 2.31 (s, 3H), 0.60 (t, J = 7.2Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 14.3 Hz), 157.2 (d, J =265.7 Hz), 145.1, 141.5 (d, J = 5.3 Hz), 137.0, 136.8, 135.4, 132.2, 131.9(d, J = 1.2 Hz), 130.4, 129.9 (d, J= 1.1 Hz), 129.6, 129.5, 129.5, 128.9,128.3, 128.3, 128.2, 128.1, 127.5, 127.2, 125.6, 124.7, 120.6 (d, J = 21.3Hz), 119.7, 116.9 (d, J = 28.2 Hz), 116.2, 61.0, 21.7, 21.5, 13.3. 19 F NMR(377 MHz, CDCl3) δ -79.78 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO4S + [M +Na] + : 576.1615, found 576.1614.。

[0029] 3g: 1 H NMR (400 MHz, CDCl3) δ 8.39 (d, J = 8.4 Hz, 1H), 7.52 (d, J =7.8 Hz, 1H), 7.45 – 7.41 (m, 3H), 7.38 – 7.34 (m, 2H), 7.32 – 7.26 (m, 4H),7.22 – 7.13 (m, 5H), 7.10 (d, J = 7.4 Hz, 1H), 3.79 – 3.68 (m, 2H), 2.34 (s,3H), 2.21 (s, 3H), 0.50 (t, J = 7.0 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.7(d, J = 14.1 Hz), 157.0 (d, J = 266.9 Hz), 145.3, 140.3 (d, J = 2.8 Hz),140.0 (d, J = 1.0 Hz), 136.2, 135.8, 132.3, 131.2, 129.9, 129.8, 129.7,129.7, 129.6, 128.5 (d, J= 1.2 Hz), 128.2, 128.1, 127.3, 125.5, 124.7,124.4, 120.4 (d, J = 21.2 Hz), 119.6, 116.5 (d, J = 26.6 Hz), 115.6, 61.1,21.7, 20.3, 13.2. 19 F NMR (377 MHz, CDCl3) δ -80.64 (s). HRMS (ESI, m / z):calcd for C 33 H 28 FNNaO4S + [M + Na] + : 576.1615, found 576.1616.。

[0030] 3h: 1 H NMR (400 MHz, CDCl3) δ 8.46 (d, J = 8.4 Hz, 1H), 7.94 (t, J =4.8 Hz, 1H), 7.84 (d, J = 8.2 Hz, 1H), 7.57 (t, J = 7.2 Hz, 2H), 7.53 – 7.36(m, 5H), 7.30 – 7.23 (m, 3H), 7.20 – 7.16 (m, 3H), 7.00 – 6.98 (m, 2H), 6.94(d, J = 8.2 Hz, 2H), 3.77 – 3.60 (m, 2H), 2.24 (s, 3H), 0.59 (t, J = 7.2 Hz,3H). 13 C NMR (101 MHz, CDCl3) δ 166.5 (d, J = 14.3 Hz), 157.0 (d, J = 266.0Hz), 145.2, 138.9 (d, J= 3.6 Hz), 136.7, 135.4, 133.3, 133.1, 132.2, 130.4,129.6, 129.5, 129.4, 128.4, 128.2, 128.1, 128.0, 127.4, 127.2, 126.4, 126.1,125.9, 125.7, 124.5, 124.4, 120.3 (d, J = 21.2 Hz), 119.7, 117.7 (d, J = 27.4Hz), 115.9, 61.1, 21.6, 13.3. 19 F NMR (377 MHz, CDCl3) δ -80.64 (s). HRMS(ESI, m / z): calcd for C 36 H 28 FNNaO4S + [M + Na] + : 612.1615, found 612.1614.。

[0031] 3i: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 1H), 7.52 – 7.50(m, 2H), 7.45 – 7.40 (m, 3H), 7.36 – 7.24 (m, 7H), 7.12 – 7.10 (m, 3H), 3.75(q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.62 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz,CDCl3) δ 166.3 (d, J = 14.1 Hz), 156.5 (d, J = 265.5 Hz), 145.3, 137.0,135.3, 133.5 (d, J = 5.5 Hz), 132.4 (d, J = 1.0 Hz), 132.1, 129.7, 129.6,129.6, 129.3, 129.2 (d, J= 1.3 Hz), 128.5, 128.3, 127.1, 126.8, 126.1,124.7, 121.0 (d, J = 20.8 Hz), 119.8, 118.6 (d, J = 28.1 Hz) 116.2, 61.1,21.7, 13.4. 19 F NMR (377 MHz, CDCl3) δ -80.14 (s). HRMS (ESI, m / z): calcd forC 30 H 24 FNNaO4S2 + [M + Na] + : 568.1023, found 568.1022.。

[0032] 3j: 1 H NMR (400 MHz, CDCl3) δ 8.74 (d, J = 4.8 Hz, 1H), 8.21 (d, J =8.4 Hz, 1H), 7.82 – 7.75 (m, 3H), 7.67 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 7.8Hz, 1H), 7.43 – 7.39 (m, 1H), 7.38 – 7.27 (m, 7H), 7.20 (d, J = 8.2 Hz, 2H),3.75 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.54 (t, J = 7.2 Hz, 3H). 13 C NMR (101MHz, CDCl3) δ 166.5 (d, J = 14.0 Hz), 156.8 (d, J = 265.8 Hz), 150.0, 149.1,145.2, 139.8 (d, J = 4.6 Hz), 136.2, 135.6, 135.0, 132.2, 129.7, 129.7,129.6, 128.8, 128.2, 127.6, 126.8 (d, J= 0.9 Hz), 126.0, 124.7, 123.8, 120.6(d, J = 20.7 Hz), 120.2, 117.9 (d, J = 28.5 Hz), 115.8, 61.2, 21.7, 13.2. 19 FNMR (377 MHz, CDCl3) δ -80.99 (s). HRMS (ESI, m / z): calcd for C 31 H 25 FN2NaO4S + [M+ Na] + : 563.1411, found 563.1410.。

[0033] 3k: 1 H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.4 Hz, 1H), 7.76 (d, J =8.4 Hz, 2H), 7.49 – 7.41 (m, 5H), 7.38 – 7.32 (m, 2H), 7.28 – 7.24 (m, 3H),3.84 (q, J = 7.0 Hz, 2H), 2.37 (s, 3H), 2.24 – 2.19 (m, 1H), 1.26 – 0.80 (m,2H), 0.83 – 0.75 (m, 2H), 0.70 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ166.9 (d, J = 14.3 Hz), 156.8 (d, J = 265.3 Hz), 145.2, 142.8 (d, J = 5.6Hz), 136.6, 136.2, 132.4 (d, J = 0.9 Hz), 129.9, 129.6, 129.5, 128.4, 128.3,128.0, 126.9, 125.2, 124.0, 120.5 (d, J = 21.3 Hz), 119.3, 114.7, 114.1 (d, J= 29.2 Hz), 61.2, 21.7, 13.5, 9.8. 19 F NMR (377 MHz, CDCl3) δ -80.41 (s). HRMS(ESI, m / z): calcd for C 29 H 26 FNNaO4S + [M + Na] + : 526.1459, found 526.1458.。

[0034] 3l: 1 H NMR (400 MHz, CDCl3) δ 8.18 (d, J = 8.2 Hz, 1H), 7.67 (d, J =8.4 Hz, 2H), 7.48 – 7.35 (m, 6H), 7.32 – 7.24 (m, 2H), 7.21 (d, J = 8.4 Hz,2H), 3.71 (q, J = 7.2 Hz, 2H), 3.12 (t, J = 6.8 Hz, 2H), 2.34 (s, 3H), 1.82 –1.74 (m, 2H), 1.47 – 1.38 (m, 2H), 0.94 (t, J = 7.4 Hz, 3H), 0.52 (t, J = 7.2Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.8 (d, J = 14.4 Hz), 156.9 (d, J =266.5 Hz), 145.2, 143.8 (d, J = 3.3 Hz), 136.2, 136.0, 132.3, 130.0, 129.7,129.6, 128.6, 128.4, 128.3, 126.6, 124.8, 124.2, 120.7 (d, J = 21.3 Hz),119.1, 115.2, 114.9 (d, J = 27.5 Hz), 61.1, 33.1, 27.8, 22.8, 21.7, 13.9,13.3. 19F NMR (377 MHz, CDCl3) δ -81.97 (s). HRMS (ESI, m / z): calcd forC 30 H 30 FNNaO4S + [M + Na] + : 542.1772, found 542.1771.。

[0035] 3m: 1 H NMR (400 MHz, CDCl3) δ 8.23 (d, J = 8.6 Hz, 1H), 7.47 – 7.38(m, 5H), 7.34 – 7.32 (m, 3H), 7.30 – 7.26 (m, 3H), 7.25 – 7.21 (m, 3H), 7.08(d, J = 8.0 Hz, 2H), 3.71 (q, J = 7.2 Hz, 2H), 2.43 (s, 3H), 2.30 (s, 3H),0.62 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 14.1 Hz),157.2 (d, J = 265.4 Hz), 145.1, 141.4 (d, J = 5.5 Hz), 135.3, 135.0, 134.5,132.2, 131.7, 131.2 (d, J = 1.2 Hz), 130.2, 129.7, 129.6, 129.5, 129.2,128.7, 128.2, 128.1, 127.6, 127.4, 127.1, 120.6 (d, J = 21.3 Hz), 119.5,117.0 (d, J = 28.2 Hz) 116.0, 61.0, 21.7, 21.4, 13.4. 19 F NMR (377 MHz, CDCl3)δ -80.03 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO4S+ [M + Na] + : 576.1615,found 576.1614.。

[0036] 3n: 1 H NMR (400 MHz, CDCl3) δ 8.25 (d, J = 9.2 Hz, 1H), 7.47 – 7.40(m, 5H), 7.34 – 7.28 (m, 5H), 7.26 – 7.23 (m, 2H), 7.09 (d, J = 8.0 Hz, 2H),7.03 – 7.00 (m, 1H), 6.90 (d, J = 2.4 Hz, 1H), 3.82 (s, 3H), 3.71 (q, J = 7.2Hz, 2H), 2.32 (s, 3H), 0.63 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ166.5 (d, J = 14.3 Hz), 157.5, 157.0 (d, J = 265.3 Hz), 145.1, 142.1 (d, J =5.3 Hz), 135.2, 132.2 (d, J = 1.0 Hz), 131.2, 130.1, 130.0, 129.6, 129.5,129.5, 128.3, 128.2, 127.6, 127.1, 120.6 (d, J = 20.9 Hz), 117.4, 117.2 (d, J = 28.3 Hz), 114.9, 101.7, 61.1, 55.8, 21.7, 13.4. 19 F NMR (377 MHz, CDCl3) δ -81.19 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO5S + [M + Na] + : 592.1564, found592.1563.。

[0037] 3o:1 H NMR (400 MHz, CDCl3) δ 8.34 – 8.31 (m, 1H), 7.48 – 7.39 (m,5H), 7.32 – 7.28 (m, 5H), 7.22 – 7.20 (m, 2H), 7.18 – 7.10 (m, 4H), 3.75 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.67 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz,CDCl3) δ 166.1 (d, J = 14.2 Hz), 160.4 (d, J = 242.6 Hz), 156.4 (d, J = 265.1Hz), 145.4, 143.1 (d, J = 5.2 Hz), 135.0, 133.0, 131.9, 131.2 (d, J = 1.1Hz), 130.1 (d, J = 10.1 Hz), 129.9, 129.7, 129.5, 129.5, 128.3, 128.2, 127.7,127.1, 121.0 (d, J = 21.1 Hz), 117.6 (d, J = 9.1 Hz), 116.8 (dd, J = 28.9,3.9 Hz), 113.6 (d, J = 25.1 Hz), 105.5 (d, J = 24.6 Hz), 61.1, 21.7, 13.4. 19 FNMR (377 MHz, CDCl3) δ -80.76 (s, 1F), -117.55 – -117.66 (m, 1F). HRMS (ESI,m / z): calcd for C 32 H 25 F2NNaO4S + [M + Na] + : 580.1365, found 580.1364.。

[0038] 3p: 1H NMR (400 MHz, CDCl3) δ 8.30 (d, J = 9.0 Hz, 1H), 7.49 – 7.37(m, 7H), 7.34 – 7.28 (m, 5H), 7.22 – 7.20 (m, 2H), 7.11 (d, J = 8.2 Hz, 2H),3.77 (q, J = 7.2 Hz, 2H), 2.33 (s, 3H), 0.70 (t, J = 7.2 Hz, 3H). 13 C NMR (101MHz, CDCl3) δ 166.0 (d, J = 13.9 Hz), 156.2 (d, J = 264.9 Hz), 145.5, 142.7(d, J = 5.5 Hz), 135.1, 135.0, 131.9, 131.2 (d, J = 0.9 Hz), 130.6, 130.1,129.9, 129.7, 129.5, 129.5, 128.3, 128.2, 127.7, 127.1, 125.9, 121.2 (d, J =21.1 Hz), 119.4, 117.4, 116.3 (d, J = 28.6 Hz), 61.2, 21.7, 13.5. 19 F NMR (377MHz, CDCl3) δ -80.70 (s). HRMS (ESI, m / z): calcd for C 32 H 25 ClFNNaO4S + [M + Na] + :596.1069, found 596.1068.。

[0039] 3q: 1 H NMR (400 MHz, CDCl3) δ 8.50 (d, J = 8.8 Hz, 1H), 7.80 (s, 1H),7.69 – 7.66 (m, 1H), 7.50 – 7.46 (m, 1H), 7.42 (d, J= 4.4 Hz, 4H), 7.35 –7.29 (m, 5H), 7.22 (d, J = 7.0 Hz, 2H), 7.12 (d, J = 8.2 Hz, 2H), 3.76 (q, J = 7.2 Hz, 2H), 2.34 (s, 3H), 0.69 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz,CDCl3) δ 166.0 (d, J = 13.9 Hz), 155.9 (d, J = 264.6 Hz), 145.7, 143.0 (d, J = 5.2 Hz), 138.3, 135.1, 131.8, 131.3 (d, J = 1.0 Hz), 130.0, 129.8, 129.5,129.5, 129.3 (d, J = 1.0 Hz), 128.5, 128.4, 128.3, 127.7, 127.2, 127.0 (d, J = 32.4 Hz), 124.5 (q, J = 272.1 Hz), 122.3 (q, J = 3.3 Hz), 121.5 (d, J =21.0 Hz), 117.3 (q, J = 4.1 Hz), 116.6 (d, J = 28.8 Hz), 116.6, 61.2, 21.8,13.4. 19 F NMR (377 MHz, CDCl3) δ -61.35 (s, 3F), -80.97 (s, 1F). HRMS (ESI, m / z): calcd for C 33 H 25 F4NNaO4S + [M + Na] + : 630.1333, found 630.1332.。

[0040] 3r: 1H NMR (400 MHz, CDCl3) δ 8.18 (s, 1H), 7.46 – 7.41 (m, 4H), 7.40– 7.34 (m, 3H), 7.33 – 7.31 (m, 2H), 7.30 – 7.27 (m, 2H), 7.24 – 7.22 (m,2H), 7.17 – 7.15 (m, 1H), 7.10 (d, J = 8.0 Hz, 2H), 3.71 (q, J = 7.2 Hz, 2H),2.55 (s, 3H), 2.32 (s, 3H), 0.62 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3)δ 166.4 (d, J = 14.1 Hz), 157.2 (d, J = 265.8 Hz), 145.1, 140.6 (d, J = 5.2Hz), 137.2, 135.9, 135.5, 132.2, 131.3 (d, J = 1.4 Hz), 130.2 (d, J = 1.1Hz), 129.6, 129.5, 129.4, 128.2, 128.1, 127.5, 127.1, 126.7, 126.2, 120.6 (d, J = 21.2 Hz), 119.3, 117.1 (d, J = 27.7 Hz), 116.3, 61.0, 22.3, 21.7, 13.4. 19 F NMR (377 MHz, CDCl3) δ -79.99 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO4S + [M + Na] + : 576.1615, found 576.1614.。

[0041] 3s: 1 H NMR (400 MHz, CDCl3) δ 7.92 (d, J= 2.2 Hz, 1H), 7.45 – 7.41(m, 4H), 7.40 – 7.35 (m, 3H), 7.33 – 7.31 (m, 2H), 7.30 – 7.22 (m, 4H), 7.10(d, J = 8.0 Hz, 2H), 6.96 (dd, J = 8.6, 2.2 Hz, 1H), 3.94 (s, 3H), 3.72 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.63 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz,CDCl3) δ 166.4 (d, J = 14.1 Hz), 158.6, 157.0 (d, J = 265.8 Hz), 145.2, 140.1(d, J = 5.5 Hz), 137.9, 135.3, 132.2, 131.2 (d, J = 1.6 Hz), 130.3 (d, J =1.0 Hz), 129.6, 129.5, 129.5, 129.4, 128.2, 128.1, 127.6, 127.1, 122.8, 120.6(d, J = 21.1 Hz), 120.2, 117.0 (d, J = 27.8 Hz), 113.9, 100.5, 61.1, 56.0,21.7, 13.4. 19 F NMR (377 MHz, CDCl3) δ -80.42 (s). HRMS (ESI, m / z): calcd forC 33 H 28 FNNaO5S + [M + Na] + : 592.1564, found 592.1563.。

[0042] 3t: 1 H NMR (400 MHz, CDCl3) δ 9.08 (d, J = 0.6 Hz, 1H), 8.05 (dd, J=8.2, 1.4 Hz, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.49 – 7.41 (m, 5H), 7.36 – 7.28(m, 5H), 7.23 – 7.21 (m, 2H), 7.11 (d, J = 8.2 Hz, 2H), 4.01 (s, 3H), 3.72(q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.60 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz,CDCl3) δ 167.3, 166.1 (d, J = 14.3 Hz), 156.3 (d, J = 265.6 Hz), 145.6, 144.1(d, J = 4.5 Hz), 136.2, 135.1, 132.4, 131.9, 131.2 (d, J = 1.0 Hz), 130.0,129.8, 129.5, 129.5, 128.3, 128.2, 127.7, 127.4, 127.2, 125.8, 121.2 (d, J =20.9 Hz), 119.5, 118.0, 116.8 (d, J = 28.5 Hz), 61.1, 52.5, 21.7, 13.4. 19 FNMR (377 MHz, CDCl3) δ -80.32 (s). HRMS (ESI, m / z): calcd for C 34 H 28 FNNaO6S + [M+ Na] + : 620.1514, found 620.1515.。

[0043] 3u: 1 H NMR (400 MHz, CDCl3) δ 8.22 (d, J = 8.4 Hz, 1H), 7.50 – 7.40(m, 4H), 7.36 (d, J= 8.4 Hz, 2H), 7.32 – 7.24 (m, 5H), 7.10 - 7.08 (m, 5H),3.80 – 3.72 (m, 2H), 2.56 (s, 3H), 2.30 (s, 3H), 0.66 (t, J = 7.2 Hz, 3H). 13 CNMR (101 MHz, CDCl3) δ 165.9 (d, J = 13.7 Hz), 158.1 (d, J = 264.9 Hz),145.1, 141.2 (d, J = 7.5 Hz), 136.9, 135.3, 132.0, 131.1, 130.4 (d, J = 3.1Hz), 130.1 (d, J = 2.2 Hz), 129.6, 129.5, 129.2, 129.1, 128.2, 128.1, 127.5,127.1, 126.1, 125.5, 120.9 (d, J = 22.6 Hz), 117.0 (d, J = 29.5 Hz), 113.8,60.9, 21.7, 18.8 (d, J = 1.9 Hz), 13.4. 19 F NMR (377 MHz, CDCl3) δ -69.25 (s).HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO4S + [M + Na] + : 576.1615, found 576.1614.。

[0044] 3v: 1 H NMR (400 MHz, CDCl3) δ 8.13 (s, 1H), 7.45 – 7.38 (m, 5H), 7.33– 7.27 (m, 5H), 7.25 – 7.22 (m, 3H), 7.09 (d, J = 8.2 Hz, 2H), 3.72 (q, J=7.2 Hz, 2H), 2.44 (s, 3H), 2.33 (s, 3H), 2.31 (s, 3H), 0.66 (t, J = 7.2 Hz,3H). 13 C NMR (101 MHz, CDCl3) δ 166.4 (d, J = 14.4 Hz), 157.4 (d, J = 265.3Hz), 145.0, 140.5 (d, J = 5.7 Hz), 135.6, 135.4, 135.0, 133.7, 132.3, 131.3(d, J = 1.5 Hz), 130.3 (d, J = 1.1 Hz), 129.6, 129.6, 129.5, 129.4, 128.2,128.1, 127.5, 127.2, 127.0, 120.4 (d, J = 21.1 Hz), 119.8, 117.0 (d, J = 27.9Hz), 116.7, 61.0, 21.7, 21.0, 20.1, 13.5. 19 F NMR (377 MHz, CDCl3) δ -80.05(s). HRMS (ESI, m / z): calcd for C 34 H 30 FNNaO4S + [M + Na] + : 590.1772, found590.1771.。

[0045] 3w: 1 H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 7.4 Hz, 1H), 7.63 (d, J =7.4 Hz, 1H), 7.58 – 7.56 (m, 2H), 7.47 – 7.40 (m, 5H), 7.39 – 7.31 (m, 3H),7.27 (d, J = 7.4 Hz, 2H), 3.86 (q, J = 7.2 Hz, 2H), 2.89 (s, 3H), 0.82 (t, J= 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.3 (d, J = 14.0 Hz), 157.0 (d, J = 265.3 Hz), 141.1 (d, J = 5.4 Hz), 136.6, 132.1, 130.9 (d, J = 1.3 Hz),129.9, 129.6, 129.5, 128.8, 128.3, 127.9, 126.0, 125.0, 121.1 (d, J = 21.2Hz), 119.9, 117.0 (d, J = 28.3 Hz) 115.7, 61.2, 41.1, 13.7. 19 F NMR (377 MHz,CDCl3) δ -79.68 (s). HRMS (ESI, m / z): calcd for C 26 H 22 FNNaO4S + [M + Na] + :486.1146, found 486.1145.。

[0046] 3aa: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 1H), 7.50 (d, J =7.8 Hz, 1H), 7.47 – 7.39 (m, 6H), 7.35 – 7.28 (m, 6H), 7.21 (d, J = 7.4 Hz,2H), 7.09 (d, J = 8.2 Hz, 2H), 3.23 (s, 3H), 2.31 (s, 3H). 13 C NMR (101 MHz,CDCl3) δ 166.7 (d, J = 14.3 Hz), 157.5 (d, J = 264.9 Hz), 145.2, 141.5 (d, J= 6.2 Hz), 136.9, 135.3, 132.1, 131.3, 130.0, 129.6, 129.6, 129.5, 129.5,128.8, 128.3, 128.2, 127.6, 127.0, 125.7, 124.8, 120.4(d, J (d = 22.0 Hz), 119.6, 116.8 J = 28.4 Hz), 116.4, 52.0, 21.7. 19 F NMR (377 MHz, CDCl3) δ -80.40 (s). HRMS (ESI, m / z): calcd for C 31 H 24 FNNaO4S + [M + Na] + : 548.1302, found548.1301.。

[0047] 3ab: 1 H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.4 Hz, 1H), 7.50 – 7.40(m, 7H), 7.36 – 7.30 (m, 3H), 7.18 (d, J = 8.6 Hz, 2H), 7.09 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 3.78 (s, 3H), 3.69 (q, J = 7.0 Hz, 2H), 2.31(s, 3H), 0.56 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.7 (d, J =14.3 Hz), 159.4, 156.3 (d, J (d = 264.7 Hz), 145.2, 141.2 J= 4.9 Hz, 1H),136.7, 135.3, 131.2, 131.2, 130.9, 130.8, 130.1, 129.6, 129.5, 129.0, 127.6,127.1, 125.6, 124.7, 124.4 (d, J = 1.0 Hz), 120.3 (d, J = 21.1 Hz), 119.7,117.3 (d, J = 28.0 Hz, 1H), 116.2, 113.7, 61.0, 55.4, 21.7, 13.3. 19 F NMR (377MHz, CDCl3) δ -81.59 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO5S + [M + Na] + :592.1564, found 592.1563.。

[0048] 3ac: 1 H NMR (400 MHz, CDCl3) δ 8.36 (d, J = 8.4 Hz, 1H), 7.50 (d, J =7.8 Hz, 1H), 7.46 – 7.38 (m, 6H), 7.35 – 7.31 (m, 3H), 7.17 – 7.13 (m, 4H),7.09 (d, J = 8.2 Hz, 2H), 3.70 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 2.31 (s,3H), 0.58 (t, J = 7.2 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.5 (d, J = 14.0Hz), 156.6 (d, J = 265.0 Hz), 145.2, 141.2 (d, J = 5.0 Hz), 138.1, 136.7,135.3, 131.3, 131.2, 130.1 (d, J= 1.0 Hz), 129.6, 129.5, 129.4, 129.4,129.2, 129.0, 129.0, 127.6, 127.1, 125.6, 124.7, 120.7 (d, J = 21.1 Hz),119.7, 117.3 (d, J = 28.2 Hz), 116.3, 61.0, 21.7, 21.4, 13.3. 19 F NMR (377MHz, CDCl3) δ -80.72 (s). HRMS (ESI, m / z): calcd for C 33 H 28 FNNaO4S + [M + Na] + :576.1615, found 576.1614.。

[0049] 3ad: 1 H NMR (400 MHz, CDCl3) δ 8.37 (d, J = 8.4 Hz, 1H), 7.50 – 7.40(m, 7H), 7.37 – 7.33 (m, 3H), 7.22 – 7.18 (m, 2H), 7.10 (d, J = 8.2 Hz, 2H),7.04 – 6.97 (m, 2H), 3.70 (q, J = 7.2 Hz, 2H), 2.32 (s, 3H), 0.56 (t, J = 7.2Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.2 (d, J = 14.0 Hz), 162.5 (d, J =248.0 Hz), 157.4 (d, J = 266.2 Hz), 145.2, 141.3 (d, J = 5.1 Hz), 136.7,135.3, 131.5 (d, J = 3.3 Hz), 131.4 (d, J = 3.4 Hz), 131.2, 131.2, 130.1 (d, J= 0.9 Hz), 129.7, 129.6, 128.8, 128.0 (d, J = 3.5 Hz), 127.6, 127.1, 125.7,124.8, 119.7 (d, J = 22.6 Hz), 119.6, 117.0 (d, J = 27.8 Hz) , 116.3, 115.3(d, J = 21.7 Hz), 61.2, 21.7, 13.3. 19 F NMR (377 MHz, CDCl3) δ -79.04 (s, 1F),-113.32 - -113.39 (m, 1F). HRMS (ESI, m / z): calcd for C 32 H 25 F2NNaO4S + [M + Na] + :580.1365, found 580.1364.。

[0050] 3ae: 1 H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 8.2 Hz, 1H), 7.77 – 7.61(m, 1H), 7.45 – 7.37 (m, 6H), 7.33 – 7.27 (m, 3H), 7.08 – 7.06 (m, 2H), 3.57(q, J = 7.2 Hz, 2H), 2.66 – 2.60 (m, 1H), 2.30 (s, 3H), 1.72 - 1.68 (m, 2H),1.63 – 1.47 (m, 6H), 1.28 – 1.22 (m, 2H), 0.46 (t, J = 7.2 Hz, 3H). 13 C NMR(101 MHz, CDCl3) δ 167.0 (d, J = 16.6 Hz), 155.0 (d, J = 260.0 Hz), 145.0,143.5, 140.7 (d, J = 4.7 Hz), 136.6, 135.3, 131.2, 131.1, 130.7, 130.1 (d,J = 1.1 Hz), 129.5, 129.4, 129.3, 129.1, 128.5, 127.5, 127.1, 125.6, 125.5,124.9 (d, J = 21.3 Hz), 124.6, 119.8, 117.8 (d, J = 28.9 Hz), 116.2, 60.4,37.5, 30.6 (d, J = 2.1 Hz), 26.8, 25.9, 21.7, 13.2. 19 F NMR (377 MHz, CDCl3) δ-85.96 (s). HRMS (ESI, m / z): calcd for C 32 H 32 FNNaO4S + [M + Na] + : 568.1928, found 568.1927. Example 4

[0051] The anticancer activity of the compounds provided in this invention was evaluated using the CCK-8 assay through studies on their antiproliferative activity against cancer cells.

[0052] The specific method is as follows: First, HCT-116 cells were seeded at a density of 4000 cells per well into 96-well plates containing 100 μL of culture medium per well, and incubated overnight at 37 ℃ and 5% CO2. The next day, according to the plate plot, 100 μL of different concentrations of the test compound prepared in culture medium were added to each well, with three replicates for each concentration. Then, the cells were incubated at 37 ℃ and 5% CO2 for 48 hours. After the 96-well plate equilibrated to room temperature, 10 µL of CCK-8 was added to each well, and the plates were mixed by shaking on an orbital oscillator for 2 minutes. After incubation at 37 ℃ and 5% CO2 for 1.5 hours, the absorbance at 450 nm was measured using a PerkinElmer microplate reader. The inhibition rate (%) was calculated using the formula: (1 - (OD value of drug group - OD value of blank) / (OD value of control group - OD value of blank) * 100%). The blank wells contained only culture medium, no cells or drugs, and were used to subtract the basic absorbance of the culture medium. The control wells contained cells and culture medium with an equal volume of solvent, but no test compound. The drug wells contained cells, culture medium, and the corresponding concentration of the test compound. Each experiment was performed in triplicate, with two independent replicates. 5-Fluorouracil (5-FU) was used as a positive control, and the same treatment procedure as the test compound was followed.

[0053] The anticancer activity results of some compounds are as follows: , The activity results indicate that, at a test concentration of 50 μM, the o-alkynyl aniline compound 3u provided by this invention can inhibit the in vitro proliferation of HCT-116 colon cancer cells.

[0054] The above embodiments describe the basic principles, main features, and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments. The embodiments and descriptions in the specification are merely illustrative of the principles of the present invention. Various changes and modifications can be made to the present invention without departing from its principles, and all such changes and modifications fall within the scope of protection of the present invention.

Claims

1. A method for synthesizing monofluoroolefin compounds containing an indole skeleton, characterized in that, Includes the following steps: ， Using o-alkynylaniline compound 1 and gemini difluoroolefin compound 2 as raw materials, a reaction was carried out in an organic solvent in the presence of a palladium catalyst, ligand, additive, and base, with heating, to obtain monofluoroolefin compound 3 containing an indole skeleton; wherein: R 1 Selected from hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, trifluoromethyl, halogen, ester group; R 2 Selected from phenyl, substituted phenyl, naphthyl, heteroaryl, cycloalkyl, alkyl; R 3 Selected from p-toluenesulfonyl and methanesulfonyl; R 4 Selected from phenyl or substituted phenyl, cycloalkyl; R 5 Selected from alkyl groups; the substituents in the aforementioned substituted phenyl groups are C. 1-4 Alkyl, C 1-4 Alkoxy or halogen.

2. The method for synthesizing monofluoroolefin compounds containing an indole skeleton according to claim 1, characterized in that: The palladium catalyst is selected from Pd(dba)2; the ligand is selected from 1,2-bis(diphenylphosphine)ethane or 1,3-bis(diphenylphosphine)propane; the base is selected from sodium carbonate or sodium bicarbonate; and the additive is selected from chromium trioxide.

3. The method for synthesizing monofluoroolefin compounds containing an indole skeleton according to claim 1, characterized in that: The molar ratio of the o-alkynyl aniline compound 1, gemini difluoroolefin compound 2, palladium catalyst, ligand, base and additive is 1 : 1 : 0.05-0.1 : 0.05-0.1 : 1 : 0.

3.

4. The method for synthesizing monofluoroolefin compounds containing an indole skeleton according to claim 1, characterized in that: The organic solvent is selected from methyl tert-butyl ether, tetrahydrofuran, 1,4-dioxane, and 1,2-dimethoxyethane.

5. The method for synthesizing monofluoroolefin compounds containing an indole skeleton according to claim 1, characterized in that: The reaction temperature was 50 °C; the reaction was carried out in an argon atmosphere.

6. The chemical structural formula of 3u, a monofluoroolefin compound containing an indole skeleton, is as follows: 。 7. The use of the monofluoroolefin compound 3u containing an indole skeleton as described in claim 6 in the preparation of anticancer drugs.

8. The application of the monofluoroolefin compound 3u containing an indole skeleton according to claim 7 in the preparation of an anticancer drug, wherein the anticancer is for colon cancer.

9. The use of the monofluoroolefin compound 3u containing an indole skeleton according to claim 8 in the preparation of an anticancer drug, wherein the colon cancer is targeted at HCT-116 cells.

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