A method for preparing a cyclopenta[b]chromenone compound

Abstract

The application discloses a preparation method and application of a cyclopentano[b]chromone compound, and belongs to the technical field of organic synthesis. The cyclopentano[b]chromone compound is synthesized through a [2+2+1] cascade reaction of 3-iodochromone and norbornene as raw materials, cheap and easily obtained methyl iodide or deuterated methyl iodide as a methylene source, under the action of a palladium catalyst and alkali in an organic solvent. The chromone skeleton contained in the compound has various potential biological activities, can provide a compound source for biological activity screening, and has important significance for drug research and development and the pharmaceutical industry. Meanwhile, the application performs tumor growth inhibition activity screening on human myelomonocytic leukemia cells (MV4-11) around the compound, finds that the compound has certain tumor cell growth inhibition activity, and has potential for application in development and preparation of antitumor drugs.

Description

Technical Field

[0001] This invention relates to a method for preparing cyclopentanoid[b]chromone compounds, belonging to the field of organic synthesis. Background Technology

[0002] Chromone skeletons, as a class of oxygen-containing units, are widely present in drug molecules. These skeletons are important structural units in many natural products and active pharmaceutical molecules. Compounds containing these skeletons have attracted much attention due to their significant biological and pharmaceutical activities, including antitumor, antibacterial, antioxidant, anti-inflammatory, and kinase inhibitory effects. Chemical transformation of specific skeletons is one of the important methods in drug research and development; therefore, developing new synthetic strategies to construct novel polycyclic compounds containing chromone skeletons is of great research significance.

[0003] However, many relatively simple chromone skeleton compounds still require complex functionalized chromone or o-hydroxyacetophenone derivatives as raw materials. Furthermore, there are few reported methods for constructing complex chromone skeleton polycyclic compounds, and the methods are often cumbersome and lack atom economy. Therefore, exploring efficient, simple, and atom-economical new methods for preparing chromone skeleton polycyclic compounds is of great significance. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a method for preparing cyclopentanoid[b]chromone compounds. This method uses inexpensive and readily available iodomethane as the methylene unit, and has the advantages of simple operation and good substrate universality. It also enriches the organic synthesis methodology of chromone skeleton polycyclic compounds.

[0005] This invention utilizes readily available 3-iodochrome ketones as raw materials and commercially available iodomethane as the methylene unit to prepare cyclopentanop[b]chrome ketones in an organic solvent under the action of a palladium catalyst and a base. The invention is characterized by: adding a 3-iodochrome ketone, an iodoalkane or a deuterated iodoalkane, a palladium catalyst, and a base to an organic solvent, stirring at a reaction temperature of 100°C for 12 hours under an argon atmosphere, and then purifying the mixture by column chromatography to obtain the cyclopentanop[b]chrome ketone.

[0006] The 3-iodochromone compounds have the structure shown in Formula I, R 1 The groups are H, methyl, methoxy, isopropyl, nitro, halogen, and ester.

[0007]

[0008] In this invention, the palladium catalyst is at least one of tetra(triphenylphosphine)palladium, palladium acetate, palladium bromide, palladium trifluoroacetate, tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium neopentanoate, and cinnamyl palladium chloride dimer.

[0009] In this invention, the phosphine ligand is at least one selected from the following: triisopropylidene acetone phosphine, 2-(di-tert-butylphosphine)biphenyl, 2-dicyclohexylphosphine-2′,6′-dimethoxy-biphenyl, tris(2-methoxyphenyl)phosphine, tris(4-methylphenyl)phosphine, tris[3,5-di(trifluoromethyl)phenyl]phosphine, tris(4-trifluorotolyl)phosphine, tris(3-fluorophenyl)phosphine, tetrafluoropropanol, and triphenylphosphine.

[0010] In this invention, the alkali is at least one selected from cesium carbonate, potassium phosphate, potassium carbonate, sodium acetate, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and sodium neopentanoate.

[0011] In this invention, the organic solvent is at least one selected from toluene, trifluorotoluene, o-xylene, m-xylene, p-xylene, mesitylene, 1,4-dioxane, 1,2-dichloroethane, and N,N-dimethylformamide.

[0012] This invention also provides the application of chromone skeleton polycyclic compounds having the structure shown in Formula I in the preparation of antitumor drugs. Attached Figure Description

[0013] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0014] Figure 1 Single-crystal X-ray diffraction structure of compound 4a obtained in Example 1;

[0015] Figure 2 The proton NMR spectrum of compound 4a obtained in Example 1;

[0016] Figure 3 The carbon NMR spectrum of compound 4a obtained in Example 1. Detailed Implementation

[0017] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0018] It should be understood that the terminology used herein is merely for describing particular embodiments and is not intended to limit the invention. Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0019] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0020] Example 1

[0021] Taking the preparation of cyclopentano[b]chromone compound 4a with the following structural formula as an example, the raw materials and preparation method are as follows:

[0022]

[0023] 3-Iodochrome (0.2 mmol), norbornene (0.4 mmol), iodomethane (0.3 mmol), Cs₂CO₃ (0.4 mmol, 130.4 mg), Pd(OAc)₂ (0.02 mmol, 4.5 mg), PPh₃ (0.04 mmol, 10.5 mg), and 2.0 mL of toluene were added to a 4 mL reaction flask. The reaction was carried out at 100 °C for 12 hours under an argon atmosphere. After the reaction was completed, the mixture was cooled to room temperature, and the reaction solution was subjected to column chromatography (ethyl acetate / petroleum ether = 40:1–10:1). The solvent was removed from the column chromatography solution to obtain a yellow solid with a yield of 46.2 mg (92%) and a melting point of 131.2–133.0 °C. The yellow solid was characterized by single-crystal X-ray diffraction, and the results are as follows: Figure 1 As shown.

[0024] The above-mentioned yellow solid was characterized by NMR, and the results are as follows: Figures 2-3 As shown, where Figure 2 This is the proton NMR spectrum. Figure 3 The carbon NMR spectrum is shown below.

[0025] 1H-NMR(CDCl3,400MHz)δ8.16(dd,J=8.0,1.7Hz,1H),7.53(ddd,J=8.6,7.1,1.7Hz,1H),7.37–7.27(m,2H),3.16–3.01(m,2H),2.55–2.43 (m,2H),2.29–2.20(m,1H),2.00(d,J=4.1Hz,1H),1.60–1.41(m,2H),1.39–1.30(m,1H),1.24–1.12(m,2H),1.04(dt,J=10.3,1.6Hz,1H);

[0026] 13 C-NMR (CDCl3, 100MHz) δ176.2,169.7,156.8,132.7,125.7,124.7,124.3,122.2,117.9,49.8,42.8,40.4,39.2,38.4,32.3,28.8,28.5;

[0027] HRMS(ESI-TOF):calcd.for[C 17 H 17 O2] + [M+H] + 253.1223; found 253.1230.

[0028] Example 2

[0029]

[0030] In Example 1, 3-iodochromone was replaced with 3-iodo-5-methoxychromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 43.6 mg, a yield of 77%, and a melting point of 179.8–180.8 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0031] 1 H-NMR(CDCl3,400MHz)δ7.45(t,J=8.3Hz,1H),6.95(d,J=8.4Hz,1H),6.75(d,J=8.2Hz,1H),3.94(s,3H),3.15–3.02(m,2H),2.58(d,J=4.0Hz, 1H),2.53–2.41(m,1H),2.30–2.21(m,1H),2.03(d,J=4.1Hz,1H),1.63 –1.44(m,2H),1.41–1.32(m,1H),1.29–1.14(m,2H),1.10–1.02(m,1H);

[0032] 13 C-NMR (CDCl3, 100MHz) δ176.6,167.2,160.2,159.3,132.8,123.6,115.0,110.3,106.3,56.5,50.1,42.9,40.7,39.1,38.1,32.4,28.8,28.7;

[0033] HRMS(ESI-TOF):calcd.for[C 18 H 19 O3] + [M+H] + 283.1329; found 283.1338.

[0034] Example 3

[0035]

[0036] In Example 1, 3-iodochromene was replaced with 3-iodo-5-fluorochromene, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 44.9 mg, a yield of 83%, and a melting point of 146.2–148.3 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0037] 1 H-NMR (CDCl3, 400MHz) δ7.49(td,J=8.3,5.4Hz,1H),7.18(d,J=8.5Hz,1H),6.98(dd,J=10.8,8.2Hz,1H),3.19–3.03(m,2H),2.59–2.45( m,2H),2.34–2.23(m,1H),2.05(d,J=4.1Hz,1H),1.63–1.45(m,2H),1.41–1.33(m,1H),1.27–1.17(m,2H),1.09(dt,J=10.4,1.7Hz,1H);

[0038] 13 C-NMR (CDCl3, 100MHz) δ174.9, 168.6, 161.2 (d, J = 263.8Hz), 158.2 (d, J = 3.9Hz), 132.7 (d, J = 10.9Hz), 123.3, 114.9(d,J=10.0Hz), 114.0(d,J=4.5Hz), 111.9(d,J=21.2Hz), 49.9, 42.9, 40.5, 39.1, 38.2, 32.4, 28.8, 28.6;

[0039] HRMS(ESI-TOF):calcd.for[C 17 H 15 [FNaO2] + [M+Na] + 293.0948; found 293.0958.

[0040] Example 4

[0041]

[0042] In Example 1, 3-iodochromone was replaced with 3-iodo-5-chlorochromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 48.1 mg, a yield of 84%, and a melting point of 174.0–175.1 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0043] 1 H-NMR(CDCl3,400MHz)δ7.42(t,J=8.1Hz,1H),7.30(t,J=7.6Hz,2H),3.19–2.99(m,2H),2.61–2.44(m,2H),2.29(td,J=9.9,9 .4,3.8Hz,1H),2.05(d,J=4.1Hz,1H),1.62–1.47(m,2H),1.39–1.32(m,1H),1.27–1.17(m,2H),1.09(dt,J=10.4,1.6Hz,1H);

[0044] 13 C-NMR (CDCl3, 100MHz) δ175.3,168.1,158.7,133.7,131.9,128.0,123.5,121.3,117.4,50.1,42.9,40.7,39.1,38.2,32.4,28.8,28.6;

[0045] HRMS(ESI-TOF):calcd.for[C 17 H 15 ClNaO2] + [M+Na] + 309.0653; found 309.0658.

[0046] Example 5

[0047]

[0048] In Example 1, 3-iodochromene was replaced with 3-iodo-6-methylchromene, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 46.2 mg, a yield of 87%, and a melting point of 136.6–137.4 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0049] 1 H-NMR(CDCl3,400MHz)δ7.97(d,J=2.3Hz,1H),7.37(dd,J=8.5,2.2Hz,1H),7.27(d,J=8.8Hz,1H),3.17–3.05(m,2H),2.56–2.46(m,2H),2.40(s ,3H),2.28(td,J=10.2,9.8,3.7Hz,1H),2.03(d,J=4.1Hz,1H),1.63–1. 45(m,2H),1.42–1.34(m,1H),1.27–1.16(m,2H),1.07(d,J=9.8Hz,1H);

[0050] 13 C-NMR (CDCl3, 100MHz) δ176.5,169.7,155.2,134.6,134.0,125.3,124.1,122.2,117.7,49.9,43.0,40.6,39.3,38.5,32.4,28.9,28.7,21.0;

[0051] HRMS(ESI-TOF):calcd.for[C 18 H 19 O2][M+H] + 267.1380; found 267.1392.

[0052] Example 6

[0053]

[0054] In Example 1, 3-iodochromone was replaced with 3-iodo-5-methoxychromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 46.7 mg, a yield of 83%, and a melting point of 124.5–126.3 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0055] 1H-NMR (400MHz, CDCl3) δ7.57(d,J=3.1Hz,1H),7.31(d,J=9.1Hz,1H),7.16(dd,J=9.1,2.9Hz,1H),3.86(s,3H),3.21–3.05(m,2H),2.60–2.46(m ,2H),2.29(td,J=10.7,9.8,3.6Hz,1H),2.04(d,J=4.1Hz,1H),1.64–1. 45(m,2H),1.43–1.35(m,1H),1.27–1.17(m,2H),1.07(d,J=10.2Hz,1H);

[0056] 13 C-NMR (CDCl3, 100MHz) δ176.1,169.7,156.7,151.8,125.0,122.6,121.7,119.3,105.2,55.9,49.9,43.0,40.6,39.3,38.4,32.4,28.9,28.7;

[0057] HRMS(ESI-TOF):calcd.for[C 18 H 19 O3] + [M+H] + 283.1329; found 283.1337.

[0058] Example 7

[0059]

[0060] In Example 1, 3-iodochromone was replaced with 3-iodo-6-isopropylchromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 50.1 mg, a yield of 85%, and a melting point of 151.6–153.2 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0061] 1H-NMR (400MHz, CDCl3) δ8.05(d,J=2.3Hz,1H),7.45(dd,J=8.6,2.3Hz,1H),7.31(d,J=8.6Hz,1H),3.29–3.06(m,2H),3.01(h,J=6.9Hz,1H),2.64– 2.44(m,2H),2.38–2.22(m,1H),2.03(d,J=4.1Hz,1H),1.69–1.44(m,2H) ,1.39(td,J=10.0,8.3,2.5Hz,1H),1.32–1.14(m,8H),1.12–1.00(m,1H);

[0062] 13 C-NMR(CDCl3,100MHz)δ176.6,169.7,155.4,145.6,131.6,124.1,122.6,12 2.2,117.8,49.9,43.0,40.5,39.3,38.5,33.8,32.4,28.9,28.7,24.1,24.0;

[0063] HRMS(ESI-TOF):calcd.for[C 20 H 23 O2] + [M+H] + 295.1693; found 295.1692.

[0064] Example 8

[0065]

[0066] In Example 1, 3-iodochromene was replaced with 3-iodo-6-fluorochromene, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 44.6 mg, a yield of 83%, and a melting point of 157.6–159.8 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0067] 1H-NMR (400MHz, CDCl3) δ7.83(dd,J=8.5,3.1Hz,1H),7.39(dd,J=9.1,4.2Hz,1H),7.33–7.27(m,1H),3.21–3.05(m,2H),2.58–2.48 (m,2H),2.37–2.26(m,1H),2.06(d,J=4.1Hz,1H),1.63–1.47(m,2H),1.42–1.34(m,1H),1.27–1.18(m,2H),1.09(d,J=10.4Hz,1H);

[0068] 13 C-NMR (CDCl3, 100MHz) δ175.5 (d, J = 2.1Hz), 170.4, 159.7 (d, J = 245.7Hz), 153.1 (d, J = 1.8Hz), 125.7 (d, J = 7.1Hz), 121.9, 120 .9(d,J=25.5Hz),119.9(d,J=8.0Hz),110.8(dd,J=23.6,2.1Hz),49.8,43.0,40.6,39.3(d,J=1.6Hz),38.5,32.4,28.8,28.6;

[0069] HRMS(ESI-TOF):calcd.for[C 17 H 15 [FNaO2] + [M+Na] + 293.0948; found 293.0954.

[0070] Example 9

[0071]

[0072] In Example 1, 3-iodochromone was replaced with 3-iodo-6-chlorochromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 44.5 mg, a yield of 78%, and a melting point of 181.5–183.0 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0073] 1H-NMR (400MHz, CDCl3) δ8.16(d,J=2.4Hz,1H),7.52(dt,J=8.9,1.9Hz,1H),7.35(d,J=8.9Hz,1H),3.23–3.06(m,2H),2.60–2.48(m,2H) ,2.36–2.25(m,1H),2.07(d,J=4.1Hz,1H),1.64–1.47(m,2H),1.39(td,J=10.1,8.7,2.5Hz,1H),1.28–1.18(m,2H),1.13–1.06(m,1H);

[0074] 13 C-NMR (CDCl3, 100MHz) δ175.1,170.2,155.3,133.0,130.8,125.5,125.4,122.5,119.7,49.9,43.0,40.6,39.3,38.5,32.5,28.9,28.6;

[0075] HRMS(ESI-TOF):calcd.for[C 17 H 15 ClNaO2] + [M+Na] + 309.0653; found 309.0659.

[0076] Example 10

[0077]

[0078] In Example 1, 3-iodochromone was replaced with 3-iodo-6-bromochromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 49.2 mg, a yield of 74%, and a melting point of 202.0–203.9 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0079] 1 H-NMR (400MHz, CDCl3) δ8.32(d,J=2.5Hz,1H),7.66(d,J=6.3Hz,1H),7.29(d,J=8.8Hz,1H),3.24–3.04(m,2H),2.62–2.47( m,2H),2.37–2.27(m,1H),2.08(s,1H),1.66–1.47(m,2H),1.39(t,J=9.8Hz,1H),1.29–1.21(m,2H),1.11(d,J=10.4Hz,1H);

[0080] 13 C-NMR (CDCl3, 100MHz) δ175.0,170.2,155.8,135.8,128.6,125.9,122.6,120.0,118.3,49.9,43.0,40.6,39.3,38.5,32.5,28.9,28.6;

[0081] HRMS(ESI-TOF):calcd.for[C 17 H 15 BrNaO2] + [M+Na] + 353.0148; found 353.0150.

[0082] Example 11

[0083]

[0084] In Example 1, 3-iodochromone was replaced with 3-iodo-6-cyanochromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 22.6 mg, a yield of 41%, and a melting point of 180.6–182.2 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0085] 1 H-NMR (400MHz, CDCl3) δ8.54(s,1H),7.82(dd,J=8.7,2.1Hz,1H),7.52(d,J=8.7Hz,1H),3.31–3.04(m,2H),2.68–2.47(m,2H),2.4 3–2.30(m,1H),2.10(d,J=4.1Hz,1H),1.66–1.49(m,2H),1.40(td,J=11.4,3.0Hz,1H),1.28–1.20(m,2H),1.13(d,J=10.4Hz,1H);

[0086] 13 C-NMR (CDCl3, 100MHz) δ174.4,170.5,158.7,135.3,131.7,125.0,123.5,119.7,117.9,109.0,49.8,42.9,40.5,39.3,38.5,32.5,28.8,28.6;

[0087] HRMS(ESI-TOF):calcd.for[C 18 H 16 NO2] + [M+H] +278.1176; found 278.1187.

[0088] Example 12

[0089]

[0090] In Example 1, 3-iodochromone was replaced with 3-iodo-6-esterochromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 54.0 mg, a yield of 87%, and a melting point of 195.8–197.1 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0091] 1 H-NMR (400MHz, CDCl3) δ8.93–8.85(m,1H),8.24(dd,J=8.8,2.2Hz,1H),7.44(d,J=8.7Hz,1H),3.94(s,3H),3.26–3.08(m,2H),2.62 –2.52(m,2H),2.39–2.29(m,1H),2.08(d,J=4.1Hz,1H),1.65–1.49(m,2H),1.44–1.37(m,1H),1.26–1.21(m,2H),1.15–1.09(m,1H);

[0092] 13 C-NMR(CDCl3,100MHz)δ175.7,170.1,166.1,159.5,133.6,128.5,126.9, 124.2,123.0,118.5,52.5,49.9,43.0,40.6,39.3,38.5,32.5,28.9,28.6;

[0093] HRMS(ESI-TOF):calcd.for[C 19 H 19 O4] + [M+H] + 311.1278; found 311.1277.

[0094] Example 13

[0095]

[0096] In Example 1, 3-iodochromone was replaced with 3-iodo-7-methylchromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 46.5 mg, a yield of 87%, and a melting point of 144.6–146.4 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0097] 1 H-NMR (400MHz, CDCl3) δ8.08(d,J=8.0Hz,1H),7.15(d,J=9.0Hz,2H),3.20–3.00(m,2H),2.60–2.47(m,2H),2.43(s,3H),2 .33–2.22(m,1H),2.04(d,J=4.1Hz,1H),1.63–1.46(m,2H),1.43–1.34(m,1H),1.28–1.17(m,2H),1.08(d,J=10.3Hz,1H);

[0098] 13 C-NMR (CDCl3, 100MHz) δ176.4,169.5,157.1,144.0,126.3,125.6,122.2,122.1,117.8,49.9,43.0,40.5,39.3,38.5,32.4,28.9,28.7,21.8;

[0099] HRMS(ESI-TOF):calcd.for[C 18 H 19 O2] + [M+H] + 267.1380; found 267.1389.

[0100] Example 14

[0101]

[0102] In Example 1, 3-iodochromone was replaced with 3-iodo-7-methoxychromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 47.4 mg, a yield of 84%, and a melting point of 128.8–130.5 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0103] 1 H-NMR (400MHz, CDCl3) δ8.08(d,J=8.8Hz,1H),6.89(d,J=8.6Hz,1H),6.77(s,1H),3.84(s,3H),3.16–3.00(m,2H),2.58–2.41(m,2 H),2.32–2.22(m,1H),2.03(d,J=4.1Hz,1H),1.61–1.44(m,2H),1.37(t,J=10.4Hz,1H),1.28–1.15(m,2H),1.06(d,J=10.3Hz,1H);

[0104] 13 C-NMR (CDCl3, 100MHz) δ176.0,169.2,163.4,158.7,127.1,122.1,118.3,113.7,100.5,55.8,49.8,43.0,40.6,39.3,38.4,32.4,28.9,28.7;

[0105] HRMS(ESI-TOF):calcd.for[C 18 H 19 O3] + [M+H] + 283.1329; found 283.1336.

[0106] Example 15

[0107]

[0108] In Example 1, 3-iodochromone was replaced with 3-iodo-7-fluorochromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 45.2 mg, a yield of 84%, and a melting point of 125.5–126.7 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0109] 1 H-NMR(400MHz, CDCl3)δ8.21(dd,J=9.2,6.4Hz,1H),7.13–6.99(m,2H),3.21–3.05(m,2H),2.60–2.47(m,2H),2.37– 2.26(m,1H),2.06(d,J=4.1Hz,1H),1.65–1.45(m,2H),1.44–1.33(m,1H),1.29–1.16(m,2H),1.10(d,J=10.4Hz,1H);

[0110] 13 C-NMR (CDCl3, 100MHz) δ175.5, 170.0, 165.1 (d, J = 253.4Hz), 157.9 (d, J = 13.0Hz), 128.2 (d, J = 10.6Hz), 122.5, 121.3(d,J=2.4Hz),113.4(d,J=22.6Hz),104.7(d,J=25.4Hz),49.8,42.9,40.6,39.3,38.4,32.4,28.9,28.6;

[0111] HRMS(ESI-TOF):calcd.for[C 17H 15 [FNaO2] + [M+Na] + 293.0948; found 293.0956.

[0112] Example 16

[0113]

[0114] In Example 1, 3-iodochromone was replaced with 3-iodo-7-bromochromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 51.6 mg, a yield of 78%, and a melting point of 180.7–182.0 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0115] 1 H-NMR (400MHz, CDCl3) δ8.04(d,J=8.4Hz,1H),7.55(s,1H),7.44(d,J=8.4Hz,1H),3.21–2.96(m,2H),2.59–2.45(m,2H),2.3 6–2.24(m,1H),2.05(d,J=4.1Hz,1H),1.64–1.44(m,2H),1.37(t,J=10.7Hz,1H),1.27–1.15(m,2H),1.09(d,J=10.4Hz,1H);

[0116] 13 C-NMR (CDCl3, 100MHz) δ175.6,169.9,157.0,128.4,127.3,126.9,123.4,122.7,121.1,49.8,42.9,40.5,39.3,38.4,32.4,28.8,28.6;

[0117] HRMS(ESI-TOF):calcd.for[C 17 H 15 BrNaO2] + [M+Na] + 353.0148; found 353.0154.

[0118] Example 17

[0119]

[0120] In Example 1, 3-iodochromene was replaced with 3-iodo-8-methylchromene, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 48.9 mg, a yield of 92%, and a melting point of 126.3–120 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0121] 1 H-NMR (400MHz, CDCl3) δ8.04(d,J=7.9Hz,1H),7.39(d,J=7.2Hz,1H),7.21(t,J=7.7Hz,1H),3.21–3.06(m,2H),2.59–2.50(m,2H),2. 42(s,3H),2.33–2.23(m,1H),2.05(d,J=4.0Hz,1H),1.61–1.46(m,2H),1.42–1.34(m,1H),1.29–1.18(m,2H),1.07(d,J=10.4Hz,1H);

[0122] 13 C-NMR (CDCl3, 100MHz) δ176.7,169.7,155.5,133.8,127.3,124.3,124.2,123.4,122.1,49.9,43.0,40.5,39.3,38.5,32.4,28.8,28.6,15.7;

[0123] HRMS(ESI-TOF):calcd.for[C 18 H 18 NaO2] + [M+Na] + 289.1199; found 289.1205.

[0124] Example 18

[0125]

[0126] In Example 1, 3-iodochromone was replaced with 3-iodo-8-chlorochromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 49.0 mg, a yield of 86%, and a melting point of 142.9–144.1 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0127] 1H-NMR (400MHz, CDCl3) δ8.11(d,J=8.0Hz,1H),7.64(d,J=7.7Hz,1H),7.28(t,J=7.8Hz,1H),3.22(dd,J=18.9,10.3Hz,1H),3.11(d,J=7.7Hz,1H ),2.67–2.51(m,2H),2.39–2.28(m,1H),2.08(d,J=4.1Hz,1H),1.65–1. 47(m,2H),1.44–1.35(m,1H),1.30–1.19(m,2H),1.11(d,J=10.4Hz,1H);

[0128] 13 C-NMR (CDCl3, 100MHz) δ175.5,169.9,152.6,133.2,125.9,124.9,124.6,122.9,122.7,49.8,43.0,40.6,39.2,38.5,32.4,28.8,28.6;

[0129] HRMS(ESI-TOF):calcd.for[C 17 H 15 ClNaO2] + [M+Na] + 309.0653; found 309.0656.

[0130] Example 19

[0131]

[0132] In Example 1, 3-iodochromone was replaced with 3-iodo-8-nitrochromone, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 29.8 mg, a yield of 50%, and a melting point of 158.9–160.3 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0133] 1H-NMR (400MHz, CDCl3) δ8.50(dd,J=7.9,1.8Hz,1H),8.22(dd,J=7.9,1.7Hz,1H),7.48(t,J=7.9Hz,1H),3.24(dd,J=19.1,10.2Hz,1H),3.13( d,J=7.7Hz,1H),2.70–2.53(m,2H),2.40–2.33(m,1H),1.67–1.50(m,2 H),1.45–1.37(m,1H),1.29–1.22(m,2H),1.14(dt,J=10.4,1.5Hz,1H);

[0134] 13 C-NMR (CDCl3, 100MHz) δ174.2,170.2,149.1,139.2,131.8,128.9,126.4,124.1,123.5,49.8,43.0,40.6,39.3,38.5,32.5,28.9,28.6;

[0135] HRMS(ESI-TOF):calcd.for[C 17 H 16 NO4] + [M+H] + 298.1074; found 298.1082.

[0136] Example 20

[0137]

[0138] In Example 1, 3-iodochromene was replaced with 3-iodo-6,7-dimethylchromene, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 47.5 mg, a yield of 85%, and a melting point of 168.0–169.2 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0139] 1 H-NMR (400MHz, CDCl3) δ7.91(s,1H),7.12(s,1H),3.16–3.03(m,2H),2.56–2.45(m,2H),2.31(d,J=7.7Hz,7 H),2.03(d,J=4.1Hz,1H),1.62–1.45(m,2H),1.42–1.34(m,1H),1.27–1.17(m,2H),1.06(d,J=10.3Hz,1H);

[0140] 13C-NMR(CDCl3,100MHz)δ176.4,169.3,155.5,143.0,133.9,125.5,122.2, 122.0,118.1,49.9,43.0,40.5,39.3,38.4,32.4,28.9,28.7,20.4,19.3;

[0141] HRMS(ESI-TOF):calcd.for[C 19 H 21 O2] + [M+H] + 281.1536; found 281.1546.

[0142] Example 21

[0143]

[0144] In Example 1, 3-iodochromene was replaced with 3-iodo-6,8-dimethylchromene, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 44.6 mg, a yield of 80%, and a melting point of 214.8–215.5 °C. The above yellow solid was characterized by NMR, and the specific results are as follows:

[0145] 1 H-NMR (400MHz, CDCl3) δ7.82(s,1H),7.21(s,1H),3.20–3.04(m,2H),2.57–2.48(m,2H),2.37(d,J=7.5Hz,6H),2.31– 2.24(m,1H),2.04(d,J=3.9Hz,1H),1.62–1.45(m,2H),1.42–1.34(m,1H),1.27–1.17(m,2H),1.06(d,J=10.3Hz,1H);

[0146] 13 C-NMR(CDCl3,100MHz)δ176.7,169.4,153.8,135.1,134.0,126.9,123.9, 122.8,121.9,49.9,43.0,40.6,39.3,38.5,32.4,28.9,28.6,20.9,15.6;

[0147] HRMS(ESI-TOF):calcd.for[C 19 H 21 O2] + [M+H] + 281.1536; found 281.1546.

[0148] Example 22

[0149]

[0150] In Example 1, 3-iodochromone was replaced with 3-iodo-6-chloro-7-methylchromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 53.9 mg, a yield of 74%, and a melting point of 143.4–145.1 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0151] 1 H-NMR (400MHz, CDCl3) δ8.12(s,1H),7.25(s,1H),3.23–3.01(m,2H),2.61–2.39(m,5H),2.30(d,J=9.2Hz,1 H),2.05(s,1H),1.63–1.46(m,2H),1.37(t,J=10.5Hz,1H),1.23(d,J=10.5Hz,2H),1.08(d,J=10.5Hz,1H);

[0152] 13 C-NMR (CDCl3, 100MHz) δ175.2,169.9,155.2,141.8,131.4,125.6,123.6,122.3,119.8,49.9,43.0,40.6,39.3,38.5,32.4,28.9,28.6,20.8;

[0153] HRMS(ESI-TOF):calcd.for[C 18 H 18 ClO2] + [M+H] + 301.0990; found 301.1003

[0154] Example 23

[0155]

[0156] In Example 1, 3-iodochromone was replaced with 3-iodo-6-chloro-8-bromochromone, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 53.9 mg, a yield of 74%, and a melting point of 143.4–145.1 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0157] 1H-NMR (400MHz, CDCl3) δ8.11(d,J=2.5Hz,1H),7.78(d,J=2.4Hz,1H),3.22(dd,J=19.0,10.1Hz,1H),3.10(d,J=7.7Hz,1H),2.67–2.50 (m,2H),2.39–2.30(m,1H),2.09(d,J=4.1Hz,1H),1.65–1.48(m,2H),1.39(t,J=9.9Hz,1H),1.29–1.19(m,2H),1.12(d,J=10.5Hz,1H);

[0158] 13 C-NMR (CDCl3, 100MHz) δ174.3,170.4,152.2,136.0,130.9,126.3,124.9,122.7,112.5,49.8,43.0,40.6,39.3,38.5,32.5,28.8,28.6;

[0159] HRMS(ESI-TOF):calcd.for[C17H14BrClNaO2] + [M+Na] + 386.9758; found 386.9767.

[0160] Example 24

[0161]

[0162] In Example 1, 3-iodochromone was replaced with 2-iodo-1H-benzo[f]chromone-1-one, and other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 35.5 mg, a yield of 55%, and a melting point of 205.2–206.2 °C. The above yellow solid was characterized by NMR, and the specific results are as follows:

[0163] 1H-NMR (400MHz, CDCl3) δ10.14(d,J=8.7Hz,1H),7.97(d,J=9.0Hz,1H),7.85(d, J=8.0Hz,1H),7.71(t,J=8.0Hz1H),7.56(t,J=7.5Hz,1H),7.42(d,J=9.0Hz,1H ),3.21–3.10(m,2H),2.68–2.50(m,2H),2.37–2.27(m,1H),2.07(d,J=4.1Hz,1 H),1.68–1.47(m,2H),1.48–1.38(m,1H),1.29–1.18(m,2H),1.14–1.07(m,1H);

[0164] 13 C-NMR(CDCl3,100MHz)δ178.7,166.9,158.1,134.5,131.1,130.7,128.9,128.1,1 27.2,126.3,125.1,117.8,117.4,50.2,43.0,41.0,39.3,38.0,32.5,28.9,28.7;

[0165] HRMS(ESI-TOF):calcd.for[C 21 H 19 O2] + [M+H] + 303.1380; found 303.1390

[0166] Example 25

[0167]

[0168] In Example 1, 3-iodochromone was replaced with 3-iodo-4H-benzo[h]chromone-4-one, and other conditions were the same as in Example 1. A yellow solid was finally obtained with a yield of 50.5 mg, a yield of 84%, and a melting point of 181.9–183.7 °C. The above yellow solid was characterized by NMR, and the specific results are as follows:

[0169] 1H-NMR (400MHz, CDCl3) δ8.43(d,J=8.9Hz,1H),8.17(d,J=8.7Hz,1H),7.88(dd,J=7.5, 1.8Hz,1H),7.71(d,J=8.7Hz,1H),7.62(pd,J=7.1,1.5Hz,2H),3.26(dd,J=18.4,10.1 Hz,1H),3.17(d,J=7.7Hz,1H),2.73–2.57(m,2H),2.41–2.30(m,1H),2.10(d,J=4.2Hz ,1H),1.68–1.50(m,2H),1.47–1.39(m,1H),1.31–1.21(m,2H),1.12(d,J=10.4Hz,1H);

[0170] 13 C-NMR(CDCl3,100MHz)δ176.4,168.9,154.2,135.6,128.9,128.1,126.9,124.9,1 24.2,123.7,122.2,121.2,120.6,50.0,43.0,40.8,39.3,38.4,32.5,28.9,28.7;

[0171] HRMS(ESI-TOF):calcd.for[C 21 H 19 O2] + [M+H] + 303.1380; found 303.1387.

[0172] Example 26

[0173]

[0174] In Example 1, iodomethane was replaced with iodoethane, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 32.9 mg, a yield of 62%, and a melting point of 142.6–144.3 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0175] 1H-NMR (400MHz, CDCl3) δ8.22 (dd, J=8.0, 1.8Hz, 1H), 7.59 (ddd, J=8.6, 7.1, 1.8Hz, 1H), 7.43(dd,J=8.5,1.2Hz,1H),7.36(ddd,J=8.2,7.1,1.2Hz,1H),3.42(dq,J=10.1,7.5Hz, 1H),3.18(d,J=7.7Hz,1H),2.62–2.57(m,1H),2.33–2.19(m,2H),1.66–1.49(m,2H),1. 42–1.35(m,1H),1.31(d,J=7.5Hz,3H),1.19–1.12(m,2H),1.07(dt,J=10.0,1.7Hz,1H);

[0176] 13 C-NMR (CDCl3, 100MHz) δ176.6,172.5,157.0,132.8,125.9,124.8,124.6,120.8,118.1,49.7,44.4,40.9,37.6,37.1,34.0,29.4,28.6,12.0;

[0177] HRMS(ESI-TOF):calcd.for[C 18 H 19 O2] + [M+H] + 267.1380; found 267.1377.

[0178] Example 27

[0179]

[0180] In Example 1, iodomethane was replaced with iodopropane, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 35.0 mg, a yield of 62%, and a melting point of 99.8–101.6 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0181] 1H-NMR (400MHz, CDCl3) δ8.22(dd,J=7.9,1.7Hz,1H),7.59(ddd,J=8.7,7.1,1.8Hz,1H),7.44–7.40(m,1H),7.40–7.32(m,1H),3.25–3.10(m,2H ),2.60(d,J=3.8Hz,1H),2.36–2.26(m,2H),1.99–1.89(m,1H),1.70–1. 53(m,3H),1.43–1.35(m,1H),1.18(t,J=7.4Hz,5H),1.09–1.03(m,1H);

[0182] 13 C-NMR(CDCl3,100MHz)δ176.6,172.0,157.0,132.8,125.9,124.9,124.6, 121.0,118.1,49.4,48.5,43.7,37.8,36.9,34.0,29.6,28.5,20.3,13.9;

[0183] HRMS(ESI-TOF):calcd.for[C 19 H 21 O2] + [M+H] + 281.1536; found 281.1537.

[0184] Example 28

[0185]

[0186] In Example 1, iodomethane was replaced with iodobutane, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 18.0 mg, a yield of 31%, and a melting point of 115.3–116.8 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0187] 1H-NMR (400MHz, CDCl3) δ8.22(dd,J=7.9,1.8Hz,1H),7.59(ddd,J=8.7,7.0,1.8Hz,1H),7.42(d,J=8.4Hz,1H),7.36(t,J=7.5Hz,1H),3.26(td,J=9.4,4 .4Hz,1H),3.18(d,J=7.6Hz,1H),2.61(d,J=3.9Hz,1H),2.33–2.22(m,2H), 1.70–1.47(m,5H),1.44–1.35(m,1H),1.21–1.13(m,2H),1.10–1.00(m,4H);

[0188] 13 C-NMR(CDCl3,100MHz)δ176.5,172.0,157.0,132.8,125.9,124.8,124.6,12 1.0,118.1,49.5,46.5,43.8,37.7,37.0,34.0,29.6,29.3,28.5,22.4,14.5;

[0189] HRMS(ESI-TOF):calcd.for[C 20 H 23 O2] + [M+H] + 295.1693; found 295.1692.

[0190] Example 29

[0191]

[0192] In Example 1, iodomethane was replaced with deuterated iodomethane, and other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 45.8 mg, a yield of 90%, a deuteration rate of 92%, and a melting point of 139.7–141.0 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0193] 1H-NMR (400MHz, CDCl3) δ8.22(dd,J=8.0,1.8Hz,1H),7.59(ddd,J=8.6,7.1,1.8Hz,1H),7.43–7.30(m,2H),3.11(d,J=7.8Hz,1H),2.56(d,J=4. 1Hz,1H),2.29(d,J=7.7Hz,1H),2.06(d,J=4.2Hz,1H),1.64–1.47(m,2H),1.44–1.36(m,1H),1.28–1.19(m,2H),1.09(dt,J=10.3,1.6Hz,1H);

[0194] 13 C-NMR (CDCl3, 100MHz) δ176.4,169.8,157.0,132.8,125.9,124.8,124.4,122.5,118.0,49.9,42.9,40.4,39.3,38.6–36.9(m),32.4,28.9,28.7;

[0195] HRMS(ESI-TOF):calcd.for[C 17 H 15 D2O2] + [M+H] + 255.1349; found 255.1345.

[0196] Example 30

[0197]

[0198] In Example 1, 3-iodochromene was replaced with 3-iodo-5-chlorochromene, and iodomethane was replaced with deuterated iodomethane. All other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 40.4 mg, a yield of 70%, a deuteration rate of 76%, and a melting point of 173.0–172.4 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0199] 1H-NMR (400MHz, CDCl3) δ7.43(t,J=8.1Hz,1H),7.31(td,J=7.8,1.3Hz,2H),3.06(d,J=7.7Hz,1H),2.62–2.47(m,1H),2.28(d ,J=7.7Hz,1H),2.05(d,J=4.0Hz,1H),1.65–1.45(m,2H),1.41–1.32(m,1H),1.27–1.17(m,2H),1.09(dt,J=10.3,1.5Hz,1H);

[0200] 13 C-NMR (CDCl3, 100MHz) δ175.4,168.1,158.8,133.8,131.9,128.1,123.6,121.4,117.4,50.1,42.8,40.5,39.2,38.4–37.3(m),32.5,28.8,28.6;

[0201] HRMS(ESI-TOF):calcd.for[C 17 H 14 D2ClO2] + [M+H] + 289.0959; found 289.0957.

[0202] Example 31

[0203]

[0204] In Example 1, 3-iodochromene was replaced with 3-iodo-6-methylchromene, and iodomethane was replaced with deuterated iodomethane. All other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 42.0 mg, a yield of 78%, a deuteration rate of 86%, and a melting point of 142.1–144.0 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0205] 1H-NMR (400MHz, CDCl3) δ7.99(d,J=1.6Hz,1H),7.39(dd,J=8.5,2.3Hz,1H),7.28(d,J=8.5Hz,1H),3.10(d,J=7.6Hz,1H),2.56(d,J=4.1Hz,1H),2 .42(s,3H),2.28(d,J=7.7Hz,1H),2.05(d,J=4.1Hz,1H),1.64–1.47(m, 2H),1.43–1.36(m,1H),1.26–1.15(m,2H),1.08(dt,J=10.3,1.5Hz,1H);

[0206] 13 C-NMR(CDCl3,100MHz)δ176.5,169.7,155.3,134.7,134.0,125.3,124.1,1 22.3,117.7,49.9,42.9,40.4,39.3,38.7–37.2(m),32.4,28.9,28.7,21.0;

[0207] HRMS(ESI-TOF):calcd.for[C 18 H 17 D2O2] + [M+H] + 269.1505; found 269.1503.

[0208] Example 32

[0209]

[0210] In Example 1, 3-iodochromene was replaced with 3-iodo-7-methylchromene, and iodomethane was replaced with deuterated iodomethane. All other conditions remained the same as in Example 1. A yellow solid was finally obtained with a yield of 44.9 mg, a yield of 84%, a deuteration rate of 89%, and a melting point of 147.3–148.4 °C. The above yellow solid was characterized by NMR, and the specific results are as follows:

[0211] 1H-NMR (400MHz, CDCl3) δ8.08(d,J=8.0Hz,1H),7.16(d,J=8.7Hz,2H),3.09(d,J=7.6Hz,1H),2.57–2.48(m,1H),2.44(s,3H),2.2 7(d,J=7.7Hz,1H),2.05(d,J=4.1Hz,1H),1.63–1.47(m,2H),1.43–1.35(m,1H),1.26–1.17(m,2H),1.08(dt,J=10.3,1.6Hz,1H);

[0212] 13 C-NMR(CDCl3,100MHz)δ176.4,169.5,157.2,144.0,126.3,125.7,122.3,1 22.2,117.8,49.9,42.9,40.6,39.3,38.7–36.8(m),32.4,28.9,28.7,21.8;

[0213] HRMS(ESI-TOF):calcd.for[C 18 H 17 D2O2] + [M+H] + 269.1505; found 269.1505.

[0214] Example 33

[0215]

[0216] In Example 1, 3-iodochromene was replaced with 3-iodo-8-methylchromene, and iodomethane was replaced with deuterated iodomethane. All other conditions remained the same as in Example 1. A yellow solid was obtained with a yield of 43.5 mg, a yield of 81%, a deuteration rate of 90%, and a melting point of 121.9–123.8 °C. The yellow solid was characterized by NMR, and the specific results are as follows:

[0217] 1H-NMR (400MHz, CDCl3) δ8.10(dd,J=8.0,1.8Hz,1H),7.55–7.38(m,1H),7.31–7.27(m,1H),3.15(d,J=7.7Hz,1H),2.61(d,J=4.1Hz,1H),2.48 (s,3H),2.34(d,J=7.7Hz,1H),2.11(d,J=4.1Hz,1H),1.69–1.52(m,2H),1.48–1.40(m,1H),1.32–1.23(m,2H),1.14(dd,J=10.3,1.5Hz,1H);

[0218] 13 C-NMR(CDCl3,100MHz)δ176.7,169.5,155.5,133.9,127.3,124.3,124.3,1 23.5,122.2,49.9,42.9,40.4,39.3,38.8–37.0(m),32.4,28.9,28.7,15.8;

[0219] HRMS(ESI-TOF):calcd.for[C 18 H 17 D2O2] + [M+H] + 269.1505; found 269.1503.

[0220] Application Example 1

[0221] Cytotoxicity test of the chromone-containing polycyclic aromatic hydrocarbons obtained in the examples against human myeloid monocytic leukemia cells: MV4-11 cells:

[0222] A suitable amount of logarithmic growth phase cell suspension was evenly seeded into 96-well plates and pre-cultured for 24 hours in an incubator (at 37℃ and 5% CO2). The compound was dissolved in DMSO to prepare a 10mM stock solution, which was then diluted with culture medium. Different concentrations of the compound were added to the culture plates, and the plates were incubated for another 24 hours (at 37℃ and 5% CO2). 10 μL of LCK-8 solution was added to each well (avoiding air bubbles as they will affect OD readings), and the plates were incubated for 3-4 hours. The OD value at 450 nm was measured using a microplate reader. The inhibition rate of the compound was calculated using the following formulas: Cell viability = [(As-Ab) / (Ac-Ab)] × 100%; Inhibition rate = [(Ac-As) / (Ac-Ab)] * 100%. As: Absorbance of experimental wells (containing cells, culture medium, CCK-8 solution, and drug solution); Ac: Absorbance of control wells (containing cells, culture medium, and CCK-8 solution, but without drug); Ab: Absorbance of blank wells (containing culture medium and CCK-8 solution, but without cells and drug). The IC50 of each compound was calculated using Graphpad Prism software. 50 value.

[0223] The above method was used to test the half-maximal inhibitory concentration (IC50) of compounds 4c, 4e, 4o, and 4q on MV4-11 cells. 50 The results were 2.861 μmol / L, 10.570 μmol / L, 2.739 μmol / L, and 13.210 μmol / L, respectively. This demonstrates that the chromone-containing polycyclic compounds provided by this invention possess excellent antitumor activity.

[0224] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing cyclopentanoid[b]chromone compounds, characterized in that, The method involves a [2+2+1] tandem reaction of a 3-iodochrome ketone compound of formula I, norbornene, and iodomethane or deuterated iodomethane as a C1 methylene or deuterated C1 methylene source in an organic solvent, under the action of a palladium catalyst, a phosphine ligand, and a base, to obtain a cyclopentano[b]chrome ketone compound of formula II; wherein, R 1 Selected from H, methyl, methoxy, isopropyl, nitro, halogen, ester group, R 2 For H, R 3 For H or deuterium; Formula I, Formula II.

2. The method for preparing cyclopentano[b]chromone compounds according to claim 1, characterized in that, The palladium catalyst is any one of tetra(triphenylphosphine)palladium, palladium acetate, palladium bromide, palladium trifluoroacetate, tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium neopentanoate, and cinnamyl palladium chloride dimer.

3. The method for preparing cyclopentanoid [b]chromone compounds according to claim 1, characterized in that, The phosphine ligand is any one of triisopropylidene acetone phosphine, 2-(di-tert-butylphosphine)biphenyl, 2-dicyclohexylphosphine-2′,6′-dimethoxy-biphenyl, tris(2-methoxyphenyl)phosphine, tris(4-methylphenyl)phosphine, tris[3,5-di(trifluoromethyl)phenyl]phosphine, tris(4-trifluorotolyl)phosphine, tris(3-fluorophenyl)phosphine, tetrafluoropropanol, and triphenylphosphine.

4. The method for preparing cyclopentano[b]chromone compounds according to claim 1, characterized in that, The alkali is any one of cesium carbonate, potassium phosphate, potassium carbonate, sodium acetate, potassium acetate, sodium tert-butoxide, potassium tert-butoxide, and sodium neopentanoate.

5. The method for preparing cyclopentanoid [b]chromone compounds according to claim 1, characterized in that, The organic solvent is any one of toluene, trifluorotoluene, o-xylene, m-xylene, p-xylene, mesitylene, 1,4-dioxane, 1,2-dichloroethane, and N,N-dimethylformamide.

6. The method for preparing cyclopentano[b]chromone compounds according to claim 1, characterized in that, The molar ratio of the 3-iodochrome compound, norbornene, iodomethane or deuterated iodomethane, base, palladium catalyst and phosphine ligand is 1:1~5:1~5:1~3:0.02~0.2:0.05~0.

25.

7. The method according to claim 1, characterized in that, 3-iodochrome ketone compounds, norbornene, iodomethane or deuterated iodomethane, palladium catalyst, phosphine ligand and base are dispersed in an organic solvent and reacted at 100°C under an argon or nitrogen atmosphere.

8. The method according to claim 7, characterized in that, The reaction time was 12 hours; after the reaction was completed, the mixture was cooled to room temperature and separated by column chromatography to obtain the target product.

9. The use of the cyclopentano[b]chromone compound of formula II in claim 1 in the preparation of a drug for inhibiting the proliferation of human myeloid monocytic leukemia cells MV4-11.

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