Pyrrolidone dihydropyrone compound as well as preparation method and application thereof

Abstract

The invention provides a pyrrolidone dihydropyrone compound as well as a preparation method and application thereof, and belongs to the technical field of organic synthesis. Specifically, under the catalytic action of Lewis base, beta-oxoacrylamide and an alpha-pyrone derivative serve as raw materials, and the pyrrolidone dihydropyrone compound is synthesized through a one-step method. Beta-oxoacrylamide and alpha-pyrone derivatives which are simple and easy to obtain are adopted as starting raw materials, [3 + 2]-cycloaddition reaction is carried out under the catalysis of Lewis base, the pyrrolidone dihydropyrone compound is synthesized, the method is easy and convenient to operate, the reaction condition is mild, the used reagents and raw materials are economical and easy to obtain, and the method is suitable for industrial production. The target product yield is high, and the substrate application range is wide; the compound is applied to preparation of anti-tumor drugs and has a good application prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis and applications, and particularly relates to a pyrrolidinone-fused dihydropyranone compound, a preparation method thereof, and applications thereof. Background Art

[0002] As an important class of six-membered oxygen-containing heterocyclic compounds, dihydropyranones are important structural units in a variety of natural products and bioactive molecules, and their derivatives have diverse pharmacological activities. For example, Tarchonanthus lactone containing a dihydropyranone structure exhibits significant anti-tumor activity and hypoglycemic effects (Hsu F., et al. Planta Med. 2000, 66, 228); CI-1029 can effectively inhibit the activity of HIV protease (Hagen S. E., et al. J. Med. Chem. 2001, 44, 2319); Leptomycin B is an effective antifungal antibiotic used as a protein nuclear export 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 R. K., et al. Helv. Chim. Acta. 2011, 94, 1102). Therefore, the construction of structurally diverse dihydropyranone derivatives has attracted extensive attention from researchers. Pyrrolidinone is also an important pharmacophore, which is widely used in the fields of medicinal chemistry and pesticides, and has biological activities such as antiviral, antibacterial, and anti-tumor. For example, Tetflupyrolimet developed by DuPont, as a highly efficient dihydroorotate dehydrogenase inhibitor, exhibits broad-spectrum herbicidal activity; Doxapram is a central nervous stimulant used to treat acute respiratory depression; Briviactam is an anti-epileptic drug containing a pyrrolidinone structure. Based on the pharmacophore fusion strategy, hybridizing pyrrolidinone and dihydropyranone two functional groups in the same molecular structure is expected to develop novel lead compounds with potential pharmacological activities. Currently, there is still no report on the synthesis method of pyrrolidinone-fused dihydropyranone derivatives. Therefore, developing an efficient and highly selective synthesis of pyrrolidinone-fused dihydropyranone derivatives has important scientific significance and application value. Summary of the Invention

[0003] In view of the problem that there is a lack of a synthetic method for pyrrolidone hybridized dihydropyranone derivatives in the prior art, the present invention provides a pyrrolidone-fused dihydropyranone compound, a preparation method and an application thereof. Using easily available β-oxoacrylamide and α-pyranone derivative as starting materials, a [3+2]-cycloaddition reaction occurs under the catalysis of a Lewis base to synthesize a pyrrolidone-fused dihydropyranone compound.

[0004] The present invention is achieved through the following technical solutions: The present invention provides a pyrrolidone-fused dihydropyranone compound, and its structural formula is as follows: ; Among them, 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, 4-trifluorobenzyl, 2-naphthylmethyl; R 3 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, 2-thienyl.

[0005] In the present invention, a preparation method of the pyrrolidone-fused dihydropyranone compound is provided. Under the catalysis of a Lewis base, a pyrrolidone-fused dihydropyranone compound is synthesized using β-oxoacrylamide and α-pyranone derivative as raw materials; The structural formula of the said β-oxoacrylamide is: ; The structural formula of the said α-pyranone derivative is: .

[0006] Furthermore, the molar ratio of β-oxoacrylamide, α-pyranone derivative, and Lewis base is 1~1.2:1:0.05~0.2.

[0007] Furthermore, the molar ratio of β-oxoacrylamide, α-pyranone derivative, and Lewis base is 1.2:1:0.1.

[0008] 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-triazabicyclo[4.4.0]dec-5-ene, 4-dimethylaminopyridine, pyridine, cesium carbonate, potassium carbonate, and sodium carbonate; the solvent for synthesizing pyrrolidone-fused dihydropyranone compounds is one of acetonitrile, N,N-dimethylformamide, toluene, p-xylene, dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran, and ethyl acetate.

[0009] Further, the Lewis base is triethylamine; the solvent for synthesizing pyrrolidone-fused dihydropyranone compounds is acetonitrile.

[0010] Further, the reaction temperature for synthesizing pyrrolidone-fused dihydropyranone compounds is 0-40 °C, and the stirring reaction time is 8-12 h.

[0011] Further, after the reaction for synthesizing pyrrolidone-fused dihydropyranone compounds is completed, the reaction solution is concentrated under vacuum, and the residue is passed through a silica gel column chromatography with 200 meshes to obtain pyrrolidone-fused dihydropyranone compounds.

[0012] Further, the silica gel column chromatography uses a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 to 3:1 as the eluent.

[0013] In the present invention, the application of the pyrrolidone-fused dihydropyranone compounds in the preparation of anti-tumor drugs is further provided.

[0014] The beneficial effects achieved by the present invention are as follows: By using easily available β-oxoacrylamide and α-pyrone derivatives as starting materials, the present invention synthesizes pyrrolidone-fused dihydropyranone compounds through a [3+2]-cycloaddition reaction catalyzed by a Lewis base. This method is simple to operate, has mild reaction conditions, uses economically available reagents and raw materials, has a high yield of the target product, and a wide substrate scope; it has good anti-tumor activity. Description of the Drawings

[0015] Figure 1 For the 1 HNMR spectrum of the pyrrolidone-fused dihydropyranone compound 3aa in Example 1; Figure 2 For the 13 CNMR spectrum of the pyrrolidone-fused dihydropyranone compound 3aa in Example 1; Figure 3 For the 1 HNMR spectrum of the pyrrolidone-fused dihydropyranone compound 3ba in Example 2; Figure 4For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ba in Example 2; Figure 5 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ca in Example 3; Figure 6 For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ca in Example 3; Figure 7 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3da in Example 4; Figure 8 For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3da in Example 4; Figure 9 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ea in Example 5; Figure 10 For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ea in Example 5; Figure 11 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3fa in Example 6; Figure 12 For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3fa in Example 6; Figure 13 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ga in Example 7; Figure 14 For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ga in Example 7; Figure 15 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ha in Example 8; Figure 16 For the 13 13 CNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ha in Example 8; Figure 17 For the 1 1 HNMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ia in Example 9; Figure 18 For the 13 13CNMR spectrum; Figure 19 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ja in Example 10; 1 1H NMR spectrum; Figure 20 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ja in Example 10; 13 CNMR spectrum; Figure 21 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ka in Example 11; 1 1H NMR spectrum; Figure 22 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ka in Example 11; 13 CNMR spectrum; Figure 23 Single crystal diagram of pyrrolidinone-fused dihydropyranone compound 3ka in Example 11; Figure 24 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3la in Example 12; 1 1H NMR spectrum; Figure 25 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3la in Example 12; 13 CNMR spectrum; Figure 26 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ma in Example 13; 1 1H NMR spectrum; Figure 27 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ma in Example 13; 13 CNMR spectrum; Figure 28 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ab in Example 14; 1 1H NMR spectrum; Figure 29 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ab in Example 14; 13 CNMR spectrum Figure 30 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ac in Example 15; 1 1H NMR spectrum; Figure 31 1H NMR spectrum of pyrrolidinone-fused dihydropyranone compound 3ac in Example 15; 1 HNMR spectrum; Detailed implementation method Next, in combination with the embodiments of the present invention, the technical solutions of the present invention will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0016] Example 1 Add β-(benzoyl)-N-methoxyacrylamide 1a (24.6 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) into a 10 mL reaction test tube, add 1 mL of dry acetonitrile (0.1 M), and stir at room temperature until the solid is completely dissolved; then add triethylamine (1.01 mg, 0.01 mmol, 0.1 equiv.) into the reaction system, stir at room temperature for 8 h. After the reaction is completed, remove acetonitrile under reduced pressure, and then perform column chromatography (200-mesh silica gel column chromatography) separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone and dihydropyrone compound 3aa, a colorless oil. The separated yield is 31.7 mg, and the yield is 85%. The 1 1H NMR and 13 13C NMR spectra are respectively as Figure 1 and Figure 2 shown; 1 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 13C 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] + calcd for C19 H 19 NO7Na: 396.1059, Found: 396.1060。 Example 2 β-(4-Methylbenzoyl)-N-methoxyacrylamide 1b (26.3 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 11 h. After the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ba, a white solid. The isolated yield was 33.7 mg, and the yield was 87%. The 1 1H NMR and 13 13C NMR spectra are shown as Figure 3 and Figure 4 shown; 1 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J J = 8.0 Hz, 2H), 7.29 (d, J J = 7.4 Hz, 2H), 6.63 (dd, J J = 10.3, 1.0 Hz, 1H), 6.18 - 6.11 (m, 2H), 4.45 - 4.30 (m, 2H), 3.94 (d, J J = 1.2 Hz, 3H), 3.80 (dd, J J = 11.3, 2.7 Hz, 1H), 3.74 (ddd, J J = 18.7, 2.9, 1.1 Hz, 1H), 3.19 (dd, J J = 18.7, 11.2 Hz, 1H), 2.43 (s, 3H), 1.35 (t, J J = 7.2 Hz, 3H). 1313C 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。

[0017] Example 3 β-(4-Methoxybenzoyl)-N-methoxyacrylamide 1c (28.2 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. 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 9 h; after the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was carried out for separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ca, a white solid. The isolated yield was 32.2 mg and the yield was 80%. The 1 1H NMR and 13 13C NMR spectra are shown as Figure 5 and Figure 6 shown; 1 1H NMR (500 MHz, CDCl3) δ 7.99 - 7.88 (m, 2H), 7.02 - 6.92 (m, 2H), 6.65 (dt, J J = 10.3, 1.2 Hz, 1H), 6.22 - 6.07 (m, 2H), 4.37 (dqt, J J = 13.8, 10.2, 6.8 Hz, 2H), 3.98 – 3.92 (m, 3H), 3.89 (d, J J = 2.6 Hz, 3H), 3.79 (dt, J 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。

[0018] Example 4 β-(4-Fluorobenzoyl)-N-methoxyacrylamide 1d (26.8 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. 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 completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was performed for separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3da, a white solid. The isolated yield was 29.3 mg, and the yield was 75%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 7 and Figure 8 as follows; 1 1H 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。

[0019] Example 5 β-(4-Trifluoromethylbenzoyl)-N-methoxyacrylamide 1e (32.8 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 12 h. After the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out for separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ea, a white solid. The isolated yield was 22.1 mg, and the yield was 50%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 9 and Figure 10 respectively; 11H NMR (500 MHz, CDCl3) δ 8.11 – 8.03 (m, 2H), 7.77 (d, J J = 8.2 Hz, 2H), 6.62 (dd, J J = 10.3, 1.0 Hz, 1H), 6.21 – 6.12 (m, 2H), 4.39 (qq, J J = 10.8, 7.1 Hz, 2H), 3.94 (s, 3H), 3.86 – 3.75 (m, 2H), 3.23 (dd, J J = 19.4, 11.4 Hz, 1H), 1.37 (t, J J = 7.2 Hz, 3H). 13 13C NMR (126 MHz, CDCl3) δ 195.50, 168.95, 168.32, 158.87, 140.79, 137.99, 135.32 (q, J J = 32.9 Hz), 128.54, 126.03 (q, J J = 3.8 Hz), 123.38 (q, J 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。

[0020] Example 6 β-(3-Methoxybenzoyl)-N-methoxyacrylamide 1f (28.2 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube. 1 mL of dry acetonitrile (0.1 M) was added and the mixture was stirred at room temperature until the solids were completely dissolved. Subsequently, 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 completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3fa, a white solid. The isolated yield was 32.2 mg and the yield was 80%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 11 and Figure 12 respectively; 1 1H NMR (500 MHz, CDCl3) δ 7.52 (dt, J J = 7.5, 1.3 Hz, 1H), 7.45 (dd, J J = 2.6, 1.6 Hz, 1H), 7.40 (td, J J = 8.0, 1.8 Hz, 1H), 7.19 – 7.14 (m, 1H), 6.63 (dd, J J = 10.2, 1.1 Hz, 1H), 6.20 - 6.11 (m, 2H), 4.38 (dddd, J J = 17.8, 12.5, 7.1, 3.5 Hz, 2H), 3.94 (d, J J = 2.0 Hz, 3H), 3.86 (d, J J = 1.8 Hz, 3H), 3.83 – 3.71 (m, 2H), 3.21 (dd, J J = 18.8, 11.0 Hz, 1H), 1.36 (td, J J = 7.1, 1.7 Hz, 3H). 1313C 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。

[0021] Example 7 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-α-pyrone were added into a 10 mL reaction test tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ga, a white solid. The isolated yield was 34.6 mg, and the yield was 85%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 13 and Figure 14 as follows; 1 1H NMR (500 MHz, CDCl3) δ 7.92 (t, J J = 1.9 Hz, 1H), 7.82 (dt, J J = 7.8, 1.4 Hz, 1H), 7.60 (ddd, J J = 8.0, 2.2, 1.1 Hz, 1H), 7.45 (t, J J = 7.9 Hz, 1H), 6.62 (dd, J J = 10.3, 1.0 Hz, 1H), 6.18 (d, J 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。

[0022] Example 8 β-(2-Bromobenzoyl)-N-methoxyacrylamide 1h (33.8 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, 1 mL of dry acetonitrile (0.1 M) was added, and 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 11 h; after the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out for separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ha, a white solid, with a separated yield of 27.1 mg and a yield of 60%. The 1 1H NMR and 13 13C NMR spectra are shown as Figure 15 and Figure 16 shown; 1 1H 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。

[0023] Example 9 β-(1-Naphthoyl)-N-methoxyacrylamide 1i (30.6 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solids were completely dissolved. Subsequently, 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 completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ia, a white solid. The isolated yield was 29.6 mg, and the yield was 70%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 17 and Figure 18 respectively; 1 1H NMR (500 MHz, CDCl3) δ 8.73 – 8.67 (m, 1H), 8.06 (d, J J = 8.2 Hz, 1H), 7.96 (dd, J J = 7.3, 1.2 Hz, 1H), 7.90 (dd, J J = 8.2, 1.4 Hz, 1H), 7.63 (ddd, J J = 8.6, 6.7, 1.5 Hz, 1H), 7.60 – 7.50 (m, 2H), 6.72 (dd, J 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 J = 18.4, 10.6 Hz, 1H), 1.39 (t, J J = 7.1 Hz, 3H). 1313C 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。

[0024] Example 10 β-(4-Methylbenzoyl)-N-benzyloxyacrylamide 1j (35.4 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 8 h. After the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ja, a white solid. The isolated yield was 35.2 mg, and the yield was 76%. The 1 1H NMR and 13 13C NMR spectra are shown as Figure 19 and Figure 20 shown below; 1 1H 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 J = 7.5 Hz, 2H), 6.57(dd, J J = 10.4, 0.8 Hz, 1H), 6.09 (d, J J = 10.3 Hz, 1H), 5.95 (d, J 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。

[0025] Example 11 β-(4-Methylbenzoyl)-N-(2-naphthalenemethoxy)-acrylamide 1k (41.4 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ka, a white solid. The isolated yield was 28.7 mg, and the yield was 56%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 21 and Figure 22 respectively, and the single crystal diagram is shown in 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 = 10.३ 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: 536.५६८५, Found: 536.1688。

[0026] Example 12 It should be noted that there may be some inaccuracies in the original text, such as the symbol "३" which might be a typo. The above translation tries to maintain the original content as much as possible while making the necessary language conversions.β-(4-Methylbenzoyl)-N-cyclododecyloxyacrylamide 1l (44.5 mg, 0.12 mmol, 1.2 equiv.) and 5-ethyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solids were completely dissolved. Subsequently, 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 12 h. After the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3la, a white solid. The isolated yield was 30.2 mg, and the yield was 56%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 24 and Figure 25 respectively; 1 1H NMR (500 MHz, CDCl3) δ 7.83 (d, J J = 8.0 Hz, 2H), 7.28 (d, J J = 8.1 Hz, 2H), 6.62 (d, J J = 10.2 Hz, 1H), 6.14 (d, J J = 10.2 Hz, 1H), 6.08 (s, 1H), 4.44 – 4.31 (m, 2H), 4.21 (dq, J J = 9.4, 5.1 Hz, 1H), 3.82 (dd, J J = 11.3, 2.8 Hz, 1H), 3.73 (dd, J J = 18.8, 2.9 Hz, 1H), 3.17 (dd, J J = 18.7, 11.4 Hz, 1H), 2.42 (s, 3H), 1.80 – 1.67 (m, 2H), 1.64 (td, J J = 7.4, 6.9, 4.5 Hz, 2H), 1.45 – 1.27 (m, 21H). 1313C 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。

[0027] Example 13 β-(4-Methylbenzoyl)-N-allyloxyacrylamide 1m (29.4 mg, 0.12 mmol, 1.2 equiv.) and 5-ethoxycarbonyl-α-pyrone 2a (16.8 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 9 h. After the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out for separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ma, a white solid. The isolated yield was 27.3 mg, and the yield was 66%. The 1 1H NMR and 13 13C NMR spectra are shown as Figure 26 and Figure 27 shown respectively; 1 1H NMR (500 MHz, CDCl3) δ 7.84 (d, J J = 8. Hz, 2H), 7.28 (d, J J = 8.5 Hz, 2H), 6.61 (dd, J 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。

[0028] Example 14 β-(4-Methylbenzoyl)-N-methoxyacrylamide 1a (26.3 mg, 0.12 mmol, 1.2 equiv.) and 5-methyl ester-α-pyrone 2b (15.4 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solid was completely dissolved. Subsequently, 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 completed, acetonitrile was removed under reduced pressure, and then column chromatography (silica gel column chromatography with 200 mesh) was carried out (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ab, a white solid. The isolated yield was 33.6 mg, and the yield was 90%. The 1 HNMR and 13 CNMR spectra are shown in Figure 28 and Figure 29 respectively; 11H NMR (500 MHz, CDCl3) δ 7.89 – 7.80 (m, 2H), 7.28 (d, J J = 7.6 Hz, 2H), 6.62 (dd, J J = 10.4, 1.0 Hz, 1H), 6.20 – 6.10 (m, 2H), 3.93 (d, J J = 6.3 Hz, 6H), 3.83 – 3.71 (m, 2H), 3.19 (dd, J J = 18.4, 11.0 Hz, 1H), 2.43 (s, 3H). 13 13C 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。

[0029] Example 15 β-(4-Methylbenzoyl)-N-methoxyacrylamide 1a (26.3 mg, 0.12 mmol, 1.2 equiv.) and 5-benzyl-α-pyrone 2c (23 mg, 0.1 mmol, 1.0 equiv.) were added into a 10 mL reaction tube, and 1 mL of dry acetonitrile (0.1 M) was added. The mixture was stirred at room temperature until the solids were completely dissolved. Subsequently, 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 13 h. After the reaction was completed, acetonitrile was removed under reduced pressure, and then column chromatography (200-mesh silica gel column chromatography) was performed for separation (using a mixture of petroleum ether and ethyl acetate with a volume ratio of 5:1 as the eluent) to obtain the product pyrrolidone-fused dihydropyrone compound 3ac, a white solid. The isolated yield was 38.2 mg, and the yield was 85%. The 1 1H NMR and 13 13C NMR spectra are shown in Figure 30 and Figure 31 as follows; 11H NMR (500 MHz, CDCl3) δ 7.86 – 7.79 (m, 2H), 7.36 (d, J J = 3.0 Hz, 5H), 7.27 (d, J J = 8.4 Hz, 2H), 6.62 (dd, J J = 10.4, 1.0 Hz, 1H), 6.17 – 6.08 (m, 2H), 5.39 – 5.27 (m, 2H), 3.87 (s, 3H), 3.82 (dd, J J = 11.3, 2.9 Hz, 1H), 3.73 (dd, J J = 18.8, 2.8 Hz, 1H), 3.18 (dd, J J = 18.8, 11.3 Hz, 1H), 2.42 (s, 3H). 13 13C 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。

[0030] Examples 16 - 23 According to the corresponding relationship 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 obtained are shown in Table 1.

[0031] Table 1 Product Yields under Different Catalysts As can be seen from Table 1, corresponding products can be obtained under the catalysis of different Lewis bases. Among them, triethylenediamine has a relatively good catalytic effect on the reaction, second only to the catalytic effect of the optimal catalyst triethylamine; when no catalyst is added, the yield is 0.

[0032] Examples 24 - 30 According to the corresponding relationship shown in Table 2, taking Example 1 as an example, the acetonitrile solvent in Example 1 was replaced with other solvents of the same volume, and other operations were the same. The product yields obtained are shown in Table 2.

[0033] Table 2. Product yields under different solvents As can be seen from Table 2, the solvent also has a certain influence on the final result. Among them, dichloromethane and ethyl acetate show better effects, and the yields of other solvents all decrease to varying degrees.

[0034] Examples 31 - 33 According to the corresponding relationship shown in Table 3, taking Example 1 as an example, the reaction temperature in Example 1 was replaced with other temperatures, and other operations were the same. The product yields obtained are shown in Table 3: Table 3. Product yields under different reaction temperatures As can be seen from Table 3 in combination with Example 1, the temperature also has a certain influence on the final result. Among them, room temperature is the optimal reaction temperature. When the temperature is increased or decreased, the reaction yield will decrease.

[0035] Application examples Antitumor activity test The human cervical cancer cell line (HeLa) and human breast cancer cell line (MCF - 7) were selected as the research objects (Table 1) to evaluate the in vitro antitumor activity of pyrrolidinone - fused dihydropyranone compounds.

[0036] The counted HeLa or MCF - 7 cell suspension was dropped into a 96 - well plate, seeded at 3000 - 5000 cells per well, and the liquid in each well was added to 100 μL, and then placed in a cell culture incubator for culture; different compounds were added to the wells at a final concentration of 100 μM and incubated in the incubator for 24 h. After incubation, 10 μL of MTT solution (5 mg / mL, i.e., 0.5% MTT) was added to each well and cultured for another 4 h. The culture was terminated, and the culture medium in the wells was aspirated. 100 μL of dimethyl sulfoxide was added to each well, and the plate was shaken on a shaker at low speed for 30 min to fully dissolve the crystals; the absorbance of each well was measured at 490 nm using an enzyme - linked immunosorbent assay detector, and the inhibition rate was calculated. The results are shown in Table 4 below: Table 4 In vitro antitumor activity of pyrrolidinone - fused dihydropyranone compounds (inhibition rate %) As can be seen from Table 1, pyrrolidinone - fused dihydropyranone compounds show good cytotoxicity against the human cervical cancer cell line and human breast cancer cell line, and their highest inhibition rates are 95.67% and 98.17% (3ea), respectively.

[0037] The above are only the preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A pyrrolidone-fused dihydropyranone compound, characterized in that, The structural formula of the pyrrolidone and dihydropyrone compounds is as follows: ； Among them, 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, 4-trifluorobenzyl, 2-naphthylmethyl; R 3 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, 2-thienyl.

2. A method for preparing the pyrrolidinone-fused dihydropyranone compound according to claim 1, characterized in that, Pyrrolidone and dihydropyrone compounds were synthesized from β-oxyacrylamide and α-pyrone derivatives under the catalysis of Lewis base. The structural formula of the β-oxopropenamide described is as follows: ; The structural formula of the α-pyrone derivative described is as follows: .

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

2.

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

1.

5. The preparation method of the pyrrolidone and dihydropyranone compounds according to claim 1, characterized in that, The Lewis base is one or more of triethylamine, diisopropylethylamine, tributylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, triethylenediamine, 1,5,7-triazabicyclo[4.4.0]decene-5-ene, 4-dimethylaminopyridine, pyridine, cesium carbonate, potassium carbonate, and sodium carbonate; and the solvent for synthesizing pyrrolidone and dihydropyrone compounds is one of acetonitrile, N,N-dimethylformamide, toluene, p-xylene, dichloromethane, chloroform, 1,2-dichloroethane, tetrahydrofuran, and ethyl acetate.

6. The method for preparing pyrrolidone and dihydropyranone compounds according to claim 5, characterized in that, The Lewis base is triethylamine; and the solvent for synthesizing pyrrolidone and dihydropyrone compounds is acetonitrile.

7. The preparation method of the pyrrolidone-fused dihydropyranone compound according to claim 1, characterized in that, The reaction temperature for synthesizing pyrrolidone and dihydropyrone compounds is 0-40°C, and the stirring reaction time is 8-12 hours.

8. The method for preparing the pyrrolidone and dihydropyranone compounds according to claim 1, characterized in that, After the reaction for synthesizing pyrrolidone and dihydropyrone compounds is completed, the reaction solution is concentrated in vacuo, and the residue is chromatographed on a 200-mesh silica gel column to obtain pyrrolidone and dihydropyrone compounds.

9. The method for preparing pyrrolidone and dihydropyranone compounds according to claim 8, characterized in that, Silica gel column chromatography used a mixture of petroleum ether and ethyl acetate in a volume ratio of 5:1 to 3:1 as the eluent.

10. Use of the pyrrolidone dihydropyrone compound according to claim 1 in the preparation of anti-tumor drugs.

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