A pyrrolidinone dihydropyrone compound, a preparation method and application thereof

Abstract

The application provides a pyrrolidinone and dihydropyrone compound, a preparation method and application, and belongs to the technical field of organic synthesis. Specifically, under the catalysis of a Lewis base, a pyrrolidinone and dihydropyrone compound is synthesized from a beta-oxoacrylamide and an alpha-pyrone derivative by a one-step method. The pyrrolidinone and dihydropyrone compound is synthesized by adopting the simple and easily obtained beta-oxoacrylamide and alpha-pyrone derivative as starting raw materials, and by the [3+2]-cycloaddition reaction under the catalysis of a Lewis base. The method has the advantages of simple operation, mild reaction condition, economic and easily obtained reagents and raw materials, high yield of the target product, and wide substrate application range. The method is applied to the preparation of an antitumor drug and has a good application prospect.

Description

Technical Field

[0001] This invention belongs to the field of organic synthesis and application technology, specifically relating to a pyrrolidone dihydropyranone compound, its preparation method, and its application. Background Technology

[0002] Dihydropyranones, as an important class of six-membered oxygen-containing heterocyclic compounds, are important structural units in a variety of natural products and bioactive molecules, and their derivatives have diverse pharmacological activities. For example, targonanthuslactone, containing a dihydropyranone structure, exhibits significant antitumor activity and hypoglycemic effects (Hsu F., et al. Planta Med. 2000, 66, 228); CI-1029 can effectively inhibit HIV protease activity (Hagen SE, et al. J. Med. Chem. 2001, 44, 2319); Leptomycin B is an effective antifungal antibiotic used as a protein nuclear transport inhibitor, which can block the eukaryotic cell cycle (Kikuchi H., et al. Biorg. Med. Chem. 2004, 12, 3203); the natural product Goniodiol shows selective cytotoxicity against human lung adenocarcinoma cells A-549 and murine leukemia cells P-388 (Palakodety RK, et al. Helv. Chim. Acta. 2011, 94, 1102). Therefore, the construction of structurally diverse dihydropyranone derivatives has attracted widespread attention from researchers. Pyrrolidone is also an important pharmacophore, widely used in medicinal chemistry and pesticides, exhibiting antiviral, antibacterial, and antitumor biological activities. For example, Tetflupyrolimet, developed by DuPont, is a highly effective dihydroorotate dehydrogenase inhibitor exhibiting broad-spectrum herbicidal activity; Doxapram is a central nervous system stimulant used to treat acute respiratory depression; and Briviactam is an antiepileptic drug containing a pyrrolidone structure. Based on the pharmacophore fusion strategy, hybridizing pyrrolidone and dihydropyranone functional groups into the same molecular structure holds promise for developing novel lead compounds with potential pharmacological activities. Currently, there are no reported synthetic methods for pyrrolidone-hybrid dihydropyranone derivatives. Therefore, developing an efficient and highly selective synthetic method for pyrrolidone-dihydropyranone derivatives has significant scientific and application value. Summary of the Invention

[0003] To address the lack of existing methods for synthesizing pyrrolidone heterodihydropyranone derivatives, this invention provides a pyrrolidone-dihydropyranone compound, its preparation method, and its applications. Using readily available β-oxoacrylamide and α-pyranone derivatives as starting materials, a [3+2]-cycloaddition reaction is carried out under Lewis base catalysis to synthesize the pyrrolidone-dihydropyranone compound.

[0004] This invention is achieved through the following technical solution:

[0005] This invention provides a pyrrolidone-dihydropyranone compound with the following structural formula:

[0006] ;

[0007] Among them, R 1 It is one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 3-methylphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2-methylphenyl, 2-fluorophenyl, 2-bromophenyl, 2-naphthyl, 2-thienyl, methyl, tert-butyl, and benzyl; R 2 It is one of C1-C5 alkyl, C3-C12 cycloalkyl, allyl, propargyl, benzyl, 4-methylbenzyl, 4-chlorobenzyl, 4-bromobenzyl, 4-trifluorobenzyl, and 2-naphthylmethyl; R 3 It is one of methoxy, ethoxy, benzyloxy, phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 3-methylphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2-methylphenyl, 2-fluorophenyl, 2-bromophenyl, 2-naphthyl, and 2-thiophene.

[0008] This invention provides a method for preparing the aforementioned pyrrolidone dihydropyranone compounds, wherein pyrrolidone dihydropyranone compounds are synthesized from β-oxoacrylamide and α-pyranone derivatives under the catalysis of a Lewis base.

[0009] The structural formula of the β-oxoacrylamide is: ;

[0010] The structural formula of the α-pyranone derivative is as follows: .

[0011] Furthermore, the molar ratio of β-oxoacrylamide, α-pyranone derivative, and Lewis base is 1~1.2:1:0.05~0.2.

[0012] Furthermore, the molar ratio of β-oxoacrylamide, α-pyranone derivative, and Lewis base is 1.2:1:0.1.

[0013] Further, the Lewis base is one or more of triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylenediamine, 1,5,7-trizabicyclo[4.4.0]decen-5-ene, 4-dimethylaminopyridine, pyridine, cesium carbonate, potassium carbonate, and sodium carbonate; the solvent for synthesizing pyrrolidone and dihydropyranone compounds is one of acetonitrile, N,N-dimethylformamide, toluene, p-xylene, dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran, and ethyl acetate.

[0014] Furthermore, the Lewis base is triethylamine; the solvent for synthesizing pyrrolidone and dihydropyranone compounds is acetonitrile.

[0015] Furthermore, the reaction temperature for synthesizing pyrrolidone and dihydropyranone compounds is 0~40℃, and the stirring reaction time is 8~12h.

[0016] Furthermore, after the reaction of synthesizing pyrrolidone and dihydropyranone compounds was completed, the reaction solution was concentrated under vacuum, and the residue was subjected to 200-mesh silica gel column chromatography to obtain pyrrolidone and dihydropyranone compounds.

[0017] Furthermore, silica gel column chromatography uses a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 to 3:1 as the eluent.

[0018] This invention further provides the application of the aforementioned pyrrolidone and dihydropyranone compounds in the preparation of antitumor drugs.

[0019] The beneficial effects achieved by this invention are as follows:

[0020] This invention synthesizes pyrrolidone and dihydropyranone compounds by using readily available β-oxoacrylamide and α-pyranone derivatives as starting materials and conducting a [3+2]-cycloaddition reaction under Lewis base catalysis. This method is simple to operate, has mild reaction conditions, uses economical and readily available reagents and raw materials, has a high yield of the target product, and has a wide range of substrate applicability; it also exhibits good antitumor activity. Attached Figure Description

[0021] Figure 1 For example 1, pyrrolidone and dihydropyranone compound 3aa 1 HNMR spectrum;

[0022] Figure 2 For example 1, pyrrolidone and dihydropyranone compound 3aa 13 CNMR spectrum;

[0023] Figure 3For example 2, pyrrolidone-dihydropyranone compound 3ba 1 HNMR spectrum;

[0024] Figure 4 For example 2, pyrrolidone-dihydropyranone compound 3ba 13 CNMR spectrum;

[0025] Figure 5 For example 3, pyrrolidone and dihydropyranone compounds 3ca 1 HNMR spectrum;

[0026] Figure 6 For example 3, pyrrolidone and dihydropyranone compounds 3ca 13 CNMR spectrum;

[0027] Figure 7 For example 4, pyrrolidone and dihydropyranone compounds 3da 1 HNMR spectrum;

[0028] Figure 8 For example 4, pyrrolidone and dihydropyranone compounds 3da 13 CNMR spectrum;

[0029] Figure 9 For example 5, pyrrolidone and dihydropyranone compounds 3ea 1 HNMR spectrum;

[0030] Figure 10 For example 5, pyrrolidone and dihydropyranone compounds 3ea 13 CNMR spectrum;

[0031] Figure 11 For example 6, pyrrolidone and dihydropyranone compound 3fa 1 HNMR spectrum;

[0032] Figure 12 For example 6, pyrrolidone and dihydropyranone compound 3fa 13 CNMR spectrum;

[0033] Figure 13 For example 7, pyrrolidone and dihydropyranone compounds 3ga 1 HNMR spectrum;

[0034] Figure 14 For example 7, pyrrolidone and dihydropyranone compounds 3ga 13 CNMR spectrum;

[0035] Figure 15For example 8, pyrrolidone and dihydropyranone compounds, 3 ha 1 HNMR spectrum;

[0036] Figure 16 For example 8, pyrrolidone and dihydropyranone compounds, 3 ha 13 CNMR spectrum;

[0037] Figure 17 For example 9, pyrrolidone and dihydropyranone compound 3ia 1 HNMR spectrum;

[0038] Figure 18 For example 9, pyrrolidone and dihydropyranone compound 3ia 13 CNMR spectrum;

[0039] Figure 19 For example 10, pyrrolidone and dihydropyranone compounds 3ja 1 HNMR spectrum;

[0040] Figure 20 For example 10, pyrrolidone and dihydropyranone compounds 3ja 13 CNMR spectrum;

[0041] Figure 21 For example 11, pyrrolidone and dihydropyranone compounds, 3 kDa 1 HNMR spectrum;

[0042] Figure 22 For example 11, pyrrolidone and dihydropyranone compounds, 3 kDa 13 CNMR spectrum;

[0043] Figure 23 This is a single crystal image of a 3ka pyrrolidone-dihydropyranone compound from Example 11;

[0044] Figure 24 For example 12, pyrrolidone and dihydropyranone compound 3la 1 HNMR spectrum;

[0045] Figure 25 For example 12, pyrrolidone and dihydropyranone compound 3la 13 CNMR spectrum;

[0046] Figure 26 For example 13, pyrrolidone and dihydropyranone compound 3ma 1 HNMR spectrum;

[0047] Figure 27 For example 13, pyrrolidone and dihydropyranone compound 3ma13 CNMR spectrum;

[0048] Figure 28 For example 14, pyrrolidone and dihydropyranone compound 3ab 1 HNMR spectrum;

[0049] Figure 29 For example 14, pyrrolidone and dihydropyranone compound 3ab 13 CNMR spectrum

[0050] Figure 30 For example 15, pyrrolidone and dihydropyranone compound 3ac 1 HNMR spectrum;

[0051] Figure 31 For example 15, pyrrolidone and dihydropyranone compound 3ac 1 HNMR spectrum; Detailed Implementation

[0052] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0053] Example 1

[0054] β-(benzoyl)-N-methoxyacrylamide 1a (24.6 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction system, and the mixture was stirred at room temperature for 8 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) (using a 5:1 mixture of petroleum ether and ethyl acetate as eluent) to obtain the product pyrrolidone dihydropyranone compound 3aa, a colorless oil with a yield of 31.7 mg and a yield of 85%. 1 HNMR and 13 CNMR spectra are as follows: Figure 1 and Figure 2 As shown; 1H NMR (500 MHz, CDCl3) δ 7.98-7.92 (m,2H), 7.65-7.60 (m, 1H), 7.52-7.47 (m, 2H), 6.63 (dd, J =10.4, 0.9 Hz, 1H),6.19-6.12 (m, 2H), 4.45 -4.32 (m, 2H), 3.94 (s, 3H), 3.84-3.74 (m, 2H), 3.26-3.17 (m, 1H), 1.36 (t, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 196.26,169.13, 168.66, 159.04, 141.14, 135.39, 134.14, 128.95, 128.15, 121.36,89.71, 65.41, 63.57, 46.06, 43.58, 36.06, 14.01; HRMS (ESI) m / z [M+Na] + calcdfor C 19 H 19 NO7Na: 396.1059, Found: 396.1060.

[0055] Example 2

[0056] β-(4-methylbenzoyl)-N-methoxyacrylamide 1b (26.3 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 11 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3ba, a white solid with a yield of 33.7 mg (87%). 1 HNMR and 13 CNMR spectra are as follows: Figure 3 and Figure 4 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.84 (d, J= 8.0Hz, 2H), 7.29 (d, J =7.4 Hz, 2H), 6.63 (dd, J =10.3, 1.0 Hz, 1H), 6.18-6.11 (m,2H), 4.45- 4.30 (m, 2H), 3.94 (d, J =1.2 Hz, 3H), 3.80 (dd, J =11.3, 2.7 Hz, 1H), 3.74 (ddd, J =18.7, 2.9, 1.1 Hz, 1H), 3.19 (dd, J =18.7, 11.2 Hz, 1H), 2.43 (s,3H), 1.35 (t, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.82, 169.15, 168.76,159.08, 145.17, 141.24, 132.96, 129.60, 128.26, 121.27, 89.71, 65.38, 63.52,46.07, 43.62, 35.93, 21.74, 14.00.HRMS (ESI) m / z [M+Na] + calcd for C 20 H 21 NO7Na:410.1216, Found: 410.1218.

[0057] Example 3

[0058] β-(4-methoxybenzoyl)-N-methoxyacrylamide 1c (28.2 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 9 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3ca, a white solid with a yield of 32.2 mg (80%). 1 HNMR and13 CNMR spectra are as follows: Figure 5 and Figure 6 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.99 -7.88 (m, 2H), 7.02-6.92 (m, 2H), 6.65 (dt, J = 10.3, 1.2 Hz, 1H), 6.22 - 6.07(m, 2H), 4.37 (dqt, J = 13.8, 10.2, 6.8 Hz, 2H), 3.98 – 3.92 (m, 3H), 3.89 (d, J = 2.6 Hz, 3H), 3.79 (dt, J = 11.4, 2.7 Hz, 1H), 3.70 (dt, J = 18.5, 3.1 Hz, 1H),3.17 (ddd, J = 18.6, 11.2, 1.4 Hz, 1H), 1.35 (td, J = 7.2, 2.5 Hz, 3H). 13 C NMR(126 MHz, CDCl3) δ 194.58, 169.15, 168.80, 164.21, 159.10, 141.34, 130.48,128.48, 121.19, 114.04, 89.66, 65.30, 63.45, 55.58, 46.07, 43.64, 35.62,13.97; HRMS (ESI) m / z [M+Na] + calcd for C 20 H 21 NO8Na: 426.1165, Found: 426.1168.

[0059] Example 4

[0060] β-(4-fluorobenzoyl)-N-methoxyacrylamide 1d (26.8 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 10 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) (using a 5:1 mixture of petroleum ether and ethyl acetate as eluent) to obtain the product pyrrolidone and dihydropyranone compound 3da, a white solid with a yield of 29.3 mg and a yield of 75%. 1 HNMR and 13 CNMR spectra are as follows: Figure 7 and Figure 8 As shown; 1 H NMR (500 MHz, CDCl3) δ 8.02 – 7.95 (m,2H), 7.21 – 7.14 (m, 2H), 6.62 (dd, J = 10.3, 0.9 Hz, 1H), 6.17 (d, J = 10.4 Hz, 1H), 6.14 (d, J = 1.0 Hz, 1H), 4.45 – 4.32 (m, 2H), 3.94 (s, 3H), 3.83 – 3.72(m, 2H), 3.17 (dd, J = 18.6, 11.0 Hz, 1H), 1.36 (t, J = 7.1 Hz, 3H); 13 C NMR (126MHz, CDCl3) δ 194.69, 169.06, 168.56, 166.29 (d, J = 256.6 Hz), 158.99, 141.04,131.87 (d, J = 3.1 Hz), 130.90 (d, J = 9.5 Hz), 121.43, 116.15 (d, J = 21.9 Hz),89.64, 65.39, 63.59, 46.05, 43.51, 35.96, 14.00; HRMS (ESI) m / z [M+Na] +calcdfor C 19 H 18 FNO7Na: 414.0965, Found: 414.0966.

[0061] Example 5

[0062] β-(4-trifluoromethylbenzoyl)-N-methoxyacrylamide 1e (32.8 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction system, and the mixture was stirred at room temperature for 12 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) (using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent) to obtain the product pyrrolidone and dihydropyranone compound 3ea, a white solid, with a yield of 22.1 mg and a yield of 50%. 1 HNMR and 13 CNMR spectra are as follows: Figure 9 and Figure 10 As shown; 1 H NMR (500 MHz, CDCl3) δ 8.11 – 8.03 (m, 2H), 7.77 (d, J = 8.2 Hz, 2H), 6.62 (dd, J = 10.3, 1.0Hz, 1H), 6.21 – 6.12 (m, 2H), 4.39 (qq, J = 10.8, 7.1 Hz, 2H), 3.94 (s, 3H), 3.86 – 3.75 (m, 2H), 3.23 (dd, J = 19.4, 11.4 Hz, 1H), 1.37 (t, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.50, 168.95, 168.32, 158.87, 140.79, 137.99,135.32 (q, J = 32.9 Hz), 128.54, 126.03 (q, J = 3.8 Hz), 123.38 (q, J= 273.0 Hz),121.61, 89.53, 65.37, 63.65, 46.03, 43.36, 36.30, 13.99; HRMS (ESI) m / z [M+Na] + calcd for C 20 H 18 F3NO7Na: 464.0933, Found: 464.0935.

[0063] Example 6

[0064] β-(3-methoxybenzoyl)-N-methoxyacrylamide 1f (28.2 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 10 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3fa, a white solid with a yield of 32.2 mg (80%). 1 HNMR and 13 CNMR spectra are as follows: Figure 11 and Figure 12 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.52(dt, J = 7.5, 1.3 Hz, 1H), 7.45 (dd, J = 2.6, 1.6 Hz, 1H), 7.40 (td, J = 8.0, 1.8Hz, 1H), 7.19 – 7.14 (m, 1H), 6.63 (dd, J = 10.2, 1.1 Hz, 1H), 6.20-6.11 (m,2H), 4.38 (dddd, J = 17.8, 12.5, 7.1, 3.5 Hz, 2H), 3.94 (d, J = 2.0 Hz, 3H), 3.86(d, J= 1.8 Hz, 3H), 3.83 – 3.71 (m, 2H), 3.21 (dd, J = 18.8, 11.0 Hz, 1H), 1.36(td, J = 7.1, 1.7 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 196.12, 169.08, 168.61,159.98, 159.01, 141.11, 136.72, 129.94, 121.36, 120.73, 120.51, 112.34,89.62, 65.34, 63.52, 55.50, 46.03, 43.56, 36.13, 13.99; HRMS (ESI) m / z [M+Na] + calcd for C 20 H 21 NO8Na: 426.1165, Found: 426.1168.

[0065] Example 7

[0066] 1 g (28.9 mg, 0.12 mmol, 1.2 equiv.) of β-(3-chlorobenzoyl)-N-methoxyacrylamide and 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) of 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Then, triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was added to the reaction system, and the mixture was stirred at room temperature for 10 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) (using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent) to obtain the product pyrrolidone and dihydropyranone compound 3ga, a white solid with a yield of 34.6 mg (85%). 1 HNMR and 13 CNMR spectra are as follows: Figure 13 and Figure 14 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.92 (t, J = 1.9Hz, 1H), 7.82 (dt, J = 7.8, 1.4 Hz, 1H), 7.60 (ddd, J= 8.0, 2.2, 1.1 Hz, 1H),7.45 (t, J = 7.9 Hz, 1H), 6.62 (dd, J = 10.3, 1.0 Hz, 1H), 6.18 (d, J = 10.3 Hz, 1H), 6.14 (d, J = 1.0 Hz, 1H), 4.38 (qq, J = 10.8, 7.2 Hz, 2H), 3.93 (s, 3H), 3.83 – 3.71 (m, 2H), 3.19 (dd, J = 18.7, 10.8 Hz, 1H), 1.36 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.16, 168.99, 168.36, 158.93, 140.92, 136.88,135.32, 134.02, 130.30, 128.22, 126.25, 121.52, 89.57, 65.38, 63.61, 46.00,43.42, 36.10, 14.00; HRMS (ESI) m / z [M+Na] + calcd for C 19 H 18 ClNO7Na: 430.0669, Found: 430.0670.

[0067] Example 8

[0068] β-(2-bromobenzoyl)-N-methoxyacrylamide 1h (33.8 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 11 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent. The product, pyrrolidone and dihydropyranone compound 3ha, was obtained as a white solid with a yield of 27.1 mg (60%). 1 HNMR and 13CNMR spectra are as follows: Figure 15 and Figure 16 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.65 (dd, J =7.9, 1.2 Hz, 1H), 7.47 (dd, J = 7.6, 1.8 Hz, 1H), 7.41 (td, J = 7.5, 1.3 Hz, 1H), 7.36 (td, J = 7.7, 1.8 Hz, 1H), 6.79 (d, J = 10.3 Hz, 1H), 6.24 (d, J = 10.3 Hz,1H), 6.18 – 6.13 (m, 1H), 4.38 (qd, J = 7.2, 5.7 Hz, 2H), 3.92 (s, 3H), 3.79(dd, J = 10.5, 3.5 Hz, 1H), 3.68 (dd, J = 19.1, 3.5 Hz, 1H), 3.23 (dd, J = 19.1, 10.5 Hz, 1H), 1.37 (t, J = 7.2 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 199.71,168.93, 168.18, 158.97, 141.10, 139.58, 134.14, 132.62, 129.10, 127.78,121.66, 118.86, 89.52, 65.41, 63.71, 46.05, 43.62, 39.64, 14.03; HRMS (ESI) m / z [M+Na] + calcd for C 19 H 18 BrNO7Na: 474.0164, Found: 474.0166.

[0069] Example 9

[0070] β-(1-naphthoyl)-N-methoxyacrylamide 1i (30.6 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction system, and the mixture was stirred at room temperature for 10 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3ia, a white solid with a yield of 29.6 mg (70%). 1 HNMR and 13 CNMR spectra are as follows: Figure 17 and Figure 18 As shown; 1 H NMR (500 MHz, CDCl3) δ 8.73 – 8.67 (m,1H), 8.06 (d, J = 8.2 Hz, 1H), 7.96 (dd, J = 7.3, 1.2 Hz, 1H), 7.90 (dd, J = 8.2, 1.4 Hz, 1H), 7.63 (ddd, J = 8.6, 6.7, 1.5 Hz, 1H), 7.60 – 7.50 (m, 2H), 6.72(dd, J = 10.3, 0.9 Hz, 1H), 6.22 – 6.14 (m, 2H), 4.49 – 4.37 (m, 2H), 3.95 (s,3H), 3.94 – 3.83 (m, 2H), 3.33 (dd, J = 18.4, 10.6 Hz, 1H), 1.39 (t, J = 7.1 Hz, 3H). 13C NMR (126 MHz, CDCl3) δ 199.47, 169.16, 168.68, 159.04, 141.16, 134.25,134.07, 133.29, 130.16, 128.86, 128.70, 128.64, 126.81, 125.49, 124.39,121.49, 89.73, 65.46, 63.67, 46.09, 43.96, 38.87, 14.05; HRMS (ESI) m / z [M+Na] + calcd for C 23 H 21 NO7Na: 446.1216, Found: 446.1218.

[0071] Example 10

[0072] β-(4-methylbenzoyl)-N-benzyloxyacrylamide 1j (35.4 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 8 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3ja, a white solid with a yield of 35.2 mg and a yield of 76%. 1 HNMR and 13 CNMR spectra are as follows: Figure 19 and Figure 20 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.85 – 7.79 (m,2H), 7.51 – 7.45 (m, 2H), 7.42 – 7.35 (m, 3H), 7.27 (d, J = 7.5 Hz, 2H), 6.57 (dd, J = 10.4, 0.8 Hz, 1H), 6.09 (d, J = 10.3 Hz, 1H), 5.95 (d, J = 0.8 Hz, 1H), 5.09 (q, J= 10.2 Hz, 2H), 4.39 – 4.22 (m, 2H), 3.82 (dd, J = 11.3, 2.7 Hz, 1H), 3.69 (dd, J = 18.7, 2.8 Hz, 1H), 3.13 (dd, J = 18.8, 11.4 Hz, 1H), 2.42 (s, 3H), 1.30 (t, J = 7.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.93, 169.45, 169.02,159.12, 145.13, 141.13, 134.27, 133.00, 129.73, 129.60, 129.13, 128.58,128.25, 121.20, 90.02, 79.47, 63.47, 46.29, 43.01, 36.13, 21.75, 13.97; HRMS(ESI) m / z [M+Na] + calcd for C 26 H 25 NO7Na: 486.1529, Found: 486.1530.

[0073] Example 11

[0074] β-(4-methylbenzoyl)-N-(2-naphthylmethoxy)-acrylamide 1k (41.4 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 10 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent. The product, pyrrolidone and dihydropyranone compound 3ka, was obtained as a white solid with a yield of 28.7 mg (56%). 1 HNMR and 13 CNMR spectra are as follows: Figure 21 and Figure 22 As shown, the single crystal diagram is as follows: Figure 23 As shown; 11H NMR (500 MHz, CDCl3) δ 7.86 (dt, J J = 11.9, 5.4 Hz, 4H), 7.78 (d, J J = 8.0 Hz, 2H), 7.65 (dd, J J = 8.4, 1.7 Hz, 1H), 7.54 – 7.47 (m, 2H), 7.25 (d, J J = 6.6 Hz, 2H), 6.53 (d, J J = 10.3 Hz, 1H), 6.05 (d, J J = 10.2 Hz, 1H), 5.91 (s, 1H), 5.25 (q, J J = 10.5 Hz, 2H), 4.19 (dq, J J = 10.6, 7.1 Hz, 1H), 4.02 (dq, J J = 10.7, 7.1 Hz, 1H), 3.83 (dd, J J = 11.3, 2.7 Hz, 1H), 3.65 (dd, J J = 18.7, 2.8 Hz, 1H), 3.10 (dd, J J = 18.8, 11.4 Hz, 1H), 2.40 (d, J J = 1.7 Hz, 3H), 1.16 (t, J J = 7.1 Hz, 3H). 13 13C NMR(126 MHz, CDCl3) δ 195.93, 169.68, 168.90, 159.18, 145.08, 141.14, 133.57, 133.04, 133.02, 131.76, 129.58, 129.33, 128.46, 128.24, 127.76, 126.95, 126.64, 126.35, 121.12, 90.07, 79.51, 63.37, 46.33, 42.80, 36.24, 21.74,13.85;HRMS (ESI) m / z [M+Na] + calcd for C 30 H 27 NO7Na: 536.1685, Found: 536.1688。

[0075] Example 12

[0076] β-(4-methylbenzoyl)-N-cyclododecyloxyacrylamide 1l (44.5 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 12 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) (using a 5:1 mixture of petroleum ether and ethyl acetate as eluent) to obtain the product pyrrolidone and dihydropyranone compound 3la, a white solid, with a yield of 30.2 mg and a yield of 56%. 1 HNMR and 13 CNMR spectra are as follows: Figure 24 and Figure 25 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.83 (d, J = 8.0 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 6.62 (d, J = 10.2 Hz, 1H), 6.14 (d, J = 10.2 Hz, 1H), 6.08 (s, 1H), 4.44 – 4.31 (m, 2H), 4.21 (dq, J =9.4, 5.1 Hz, 1H), 3.82 (dd, J = 11.3, 2.8 Hz, 1H), 3.73 (dd, J = 18.8, 2.9 Hz, 1H), 3.17 (dd, J = 18.7, 11.4 Hz, 1H), 2.42 (s, 3H), 1.80 – 1.67 (m, 2H), 1.64(td, J = 7.4, 6.9, 4.5 Hz, 2H), 1.45 – 1.27 (m, 21H). 13C NMR (126 MHz, CDCl3) δ195.94, 170.34, 169.23, 159.19, 145.08, 141.41, 133.02, 129.57, 128.26,121.36, 90.61, 85.22, 63.43, 46.15, 43.51, 36.08, 29.00, 28.07, 24.02, 24.00,23.92, 23.45, 23.00, 22.87, 21.75, 21.30, 21.03, 14.03; HRMS (ESI) m / z [M+Na] + calcd for C 31 H 41 NO7Na: 562.2781, Found: 562.2783.

[0077] Example 13

[0078] β-(4-methylbenzoyl)-N-allyloxyacrylamide 1m (29.4 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl ester-α-pyranone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 9 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3ma, a white solid with a yield of 27.3 mg (66% yield). 1 HNMR and 13 CNMR spectra are as follows: Figure 26 and Figure 27 As shown; 1 H NMR (500 MHz, CDCl3) δ 7.84(d, J = 8.1 Hz, 2H), 7.28 (d, J = 8.5 Hz, 2H), 6.61 (dd, J = 10.2, 1.0 Hz, 1H), 6.17 – 6.09 (m, 2H), 6.03 (ddtd, J= 17.0, 10.3, 6.7, 1.2 Hz, 1H), 5.39 – 5.29(m, 2H), 4.62 – 4.53 (m, 2H), 4.44 – 4.28 (m, 2H), 3.82 (dd, J = 11.3, 2.8 Hz,1H), 3.72 (ddd, J = 18.8, 2.9, 1.4 Hz, 1H), 3.17 (dd, J = 18.7, 11.3 Hz, 1H), 2.42 (s, 3H), 1.35 (td, J = 7.2, 1.1 Hz, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.85,169.28, 169.13, 159.12, 145.10, 141.23, 133.00, 131.79, 129.57, 128.25,121.66, 121.33, 90.04, 78.46, 63.45, 46.15, 43.52, 35.92, 21.73, 13.99; HRMS(ESI) m / z [M+Na] + calcd for C 22 H 23 NO7Na: 436.1372, Found: 436.1375.

[0079] Example 14

[0080] β-(4-methylbenzoyl)-N-methoxyacrylamide 1a (26.3 mg, 0.12 mmol, 1.2 equiv.) and 5-methyl ester-α-pyranone 2b (15.4 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 10 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent to obtain the product pyrrolidone and dihydropyranone compound 3ab, a white solid with a yield of 33.6 mg (90%). 1 HNMR and 13 CNMR spectra are as follows: Figure 28 and Figure 29 As shown;1 H NMR (500 MHz, CDCl3) δ 7.89 – 7.80 (m,2H), 7.28 (d, J = 7.6 Hz, 2H), 6.62 (dd, J = 10.4, 1.0 Hz, 1H), 6.20 – 6.10 (m,2H), 3.93 (d, J = 6.3 Hz, 6H), 3.83 – 3.71 (m, 2H), 3.19 (dd, J = 18.4, 11.0 Hz,1H), 2.43 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.96, 169.74, 168.61, 158.99,145.20, 141.05, 132.93, 129.59, 128.27, 121.38, 89.68, 65.39, 54.10, 46.07,43.74, 35.84, 21.75; HRMS (ESI) m / z [M+Na] + calcd for C 19 H 19 NO7Na: 396.1059, Found: 396.1060.

[0081] Example 15

[0082] β-(4-methylbenzoyl)-N-methoxyacrylamide 1a (26.3 mg, 0.12 mmol, 1.2 equiv.) and 5-benzyl ester-α-pyranone 2c (23 mg, 0.1 mmol, 1.0 equiv.) were added to a 10 mL reaction tube, followed by 1 mL of dry acetonitrile (0.1 M). The mixture was stirred at room temperature until the solid was completely dissolved. Triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) was then added to the reaction mixture, and the mixture was stirred at room temperature for 13 h. After the reaction was complete, the acetonitrile was removed under reduced pressure, and the product was separated by column chromatography (200 mesh silica gel column chromatography) using a 5:1 mixture of petroleum ether and ethyl acetate as the eluent. The product, pyrrolidone and dihydropyranone compound 3ac, was obtained as a white solid with a yield of 38.2 mg, representing a yield of 85%. 1 HNMR and 13 CNMR spectra are as follows: Figure 30 and Figure 31 As shown; 1H NMR (500 MHz, CDCl3) δ 7.86 – 7.79 (m,2H), 7.36 (d, J = 3.0 Hz, 5H), 7.27 (d, J = 8.4 Hz, 2H), 6.62 (dd, J = 10.4, 1.0Hz, 1H), 6.17 – 6.08 (m, 2H), 5.39 – 5.27 (m, 2H), 3.87 (s, 3H), 3.82 (dd, J =11.3, 2.9 Hz, 1H), 3.73 (dd, J = 18.8, 2.8 Hz, 1H), 3.18 (dd, J = 18.8, 11.3 Hz,1H), 2.42 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ 195.86, 169.06, 168.68, 159.01,145.17, 141.01, 134.43, 132.96, 129.59, 128.85, 128.77, 128.53, 128.29,121.43, 89.60, 69.05, 65.30, 46.17, 43.65, 35.90, 21.75; HRMS (ESI) m / z [M+Na] + calcd for C 25 H 23 NO7Na: 472.1372, Found: 472.1375.

[0083] Examples 16-23

[0084] According to the correspondence shown in Table 1, taking Example 1 as an example, the catalyst triethylamine was replaced with other Lewis base catalysts of the same molar amount, and other operations were the same. The product yields are shown in Table 1.

[0085] Table 1 Product yield under different catalysts

[0086]

[0087] As shown in Table 1, the corresponding products can be obtained under different Lewis base catalysis. Triethylenediamine has a better catalytic effect on the reaction, second only to the optimal catalyst triethylamine. Without catalyst, the yield is 0.

[0088] Examples 24-30

[0089] According to the correspondence shown in Table 2, taking Example 1 as an example, the solvent acetonitrile in Example 1 was replaced with the same volume of other solvents, and other operations were the same. The product yields are shown in Table 2.

[0090] Table 2. Product yields under different solvents

[0091]

[0092] As shown in Table 2, the solvent also has a certain impact on the final results. Dichloromethane and ethyl acetate showed better results, while the yields of other solvents decreased to varying degrees.

[0093] Examples 31-33

[0094] According to the correspondence shown in Table 3, taking Example 1 as an example, the reaction temperature of Example 1 was replaced with other temperatures, and other operations remained the same. The product yields obtained are shown in Table 3:

[0095] Table 3. Product yields at different reaction temperatures

[0096]

[0097] As can be seen from Table 3 and Example 1, temperature also has a certain impact on the final result. Room temperature is the optimal reaction temperature. Increasing or decreasing the temperature will reduce the reaction yield.

[0098] Application Examples

[0099] Antitumor activity test

[0100] Human cervical cancer cell line (HeLa) and human breast cancer cell line (MCF-7) were selected as research subjects (Table 1) to evaluate the in vitro antitumor activity of pyrrolidone dihydropyranone compounds.

[0101] The counted HeLa or MCF-7 cell suspensions were added dropwise to 96-well plates at a density of 3000-5000 cells per well, with the liquid volume added to each well to a final volume of 100 μL. The plates were then incubated in a cell culture incubator. Different compounds were added to the wells at a final concentration of 100 μM, and the plates were incubated for 24 h. After incubation, 10 μL of MTT solution (5 mg / mL, i.e., 0.5% MTT) was added to each well, and the plates were incubated for another 4 h. The culture was then terminated, and the culture medium was aspirated from the wells. 100 μL of dimethyl sulfoxide was added to each well, and the plates were shaken at low speed for 30 min to fully dissolve the crystals. The absorbance of each well was measured at OD 490 nm using an ELISA reader, and the inhibition rate was calculated. The results are shown in Table 4 below.

[0102] Table 4. In vitro antitumor activity (inhibition rate %) of pyrrolidone and dihydropyranone compounds

[0103]

[0104] As shown in Table 4, pyrrolidone and dihydropyranone compounds exhibited good cytotoxicity against human cervical cancer cell lines and human breast cancer cell lines, with maximum inhibition rates of 95.67% and 98.17% (3ea), respectively.

[0105] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A pyrrolidinonodihydropyranyl ketone compound, characterized by, The structural formula of the pyrrolidinone dihydropyrone compound is as follows: ； wherein R 1 is one of phenyl, 4-methylphenyl, 4-methoxyphenyl, 4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-trifluoromethylphenyl, 3-methylphenyl, 3-methoxyphenyl, 3-chlorophenyl, 2-methylphenyl, 2-fluorophenyl, 2-bromophenyl, 2-naphthyl, 2-thienyl, methyl, tert-butyl, benzyl; R 2 is one of C1-C5 alkyl, C3-C12 cycloalkyl, allyl, propargyl, benzyl, 4-methylbenzyl, 4-chlorobenzyl, 4-bromobenzyl, 2-naphthylmethyl; R 3 is methyl, ethyl or benzyl.

2. A method of preparing the pyrrolidinone dihydropyrone compound according to claim 1, characterized by, The pyrrolidinone dihydropyrone compound is synthesized from β-oxoacrylamide and α-pyrone derivative under catalysis of a Lewis base. The structural formula of the β-oxoacrylamide is: ; The structural formula of the α-pyrone derivative is: ; The Lewis base is triethylamine, and the solvent for synthesizing the pyrrolidinone dihydropyrone compound is acetonitrile.

3. The method for preparing pyrrolidone-dihydropyranone compounds according to claim 2, characterized in that, The molar ratio of the β-oxoacrylamide, the α-pyrone derivative and the Lewis base is 1-1.2:1:0.05-0.

2.

4. The method for preparing pyrrolidone-dihydropyranone compounds according to claim 3, characterized in that, The molar ratio of the β-oxoacrylamide, the α-pyrone derivative and the Lewis base is 1.2:1:0.

1.

5. The method for preparing pyrrolidone-dihydropyranone compounds according to claim 1, characterized in that, The reaction temperature for synthesizing the pyrrolidinone dihydropyrone compound is 0-40℃, and the stirring reaction time is 8-12h.

6. The method for preparing pyrrolidone-dihydropyranone compounds according to claim 1, characterized in that, After the reaction of synthesizing the pyrrolidinone dihydropyrone compound is completed, the reaction solution is concentrated under vacuum, and the residue is subjected to silica gel column chromatography to obtain the pyrrolidinone dihydropyrone compound.

7. The method of claim 6, wherein the pyrrolidinone dihydropyrone compound is prepared by the reaction of a compound of formula (II) with a compound of formula (III) in the presence of a base. The silica gel column chromatography adopts a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1-3:1 as an eluent.

8. Use of the pyrrolidinone dihydropyrone compound of claim 1 in the preparation of an antitumor drug.

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