2-aryl-3-acyloxy tetrahydrofuran compound as well as preparation method and application thereof

Abstract

The invention discloses a 2-aryl-3-acyloxy tetrahydrofuran compound in the technical field of organic synthesis, and the structural formula of the 2-aryl-3-acyloxy tetrahydrofuran compound is as follows: # imgabs0 #. The compound is prepared by the following steps: taking 4-aryl-3-butenol and alkyl or aryl carboxylic acid as raw materials, and reacting in an electrolytic tank in a constant-current electric reaction mode; and further separating and purifying to obtain the 2-aryl-3-acyloxy tetrahydrofuran compound. The method is mild in condition, does not need to add an oxidizing agent, provides a green and efficient preparation method for the alkoxy modified tetrahydrofuran compound, and further promotes the biological activity research of related compounds.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and specifically relates to a 2-aryl-3-acyloxytetrahydrofuran compound, a preparation method and application thereof. Background Art

[0002] Oxygen-containing functional group-modified tetrahydrofuran is widely present in natural products and bioactive molecules, such as the natural product (+)-Varitriol with antitumor activity, the selective respiratory syncytial virus (RSV) polymerase inhibitor ALS-8122, and the drugs such as afatinib for the treatment of advanced non-small cell lung cancer all contain this type of heterocyclic structure. Therefore, the development of tetrahydrofuran compounds substituted with oxygen-containing functional groups with various structures is of great significance to promote the biological activity research of related molecules and the discovery of lead compounds. At present, there are relatively few studies on the direct one-step synthesis of tetrahydrofuran modified with oxygen-containing functional groups, which are mainly synthesized by the two step-by-step steps of epoxidation reaction of unsaturated alcohol double bonds and subsequent nucleophilic ring-opening reaction of alcohol hydroxyl molecules (J.Org.Chem.2002,67,3479; Tetrahedron Lett.2002,43,1495).

[0003] The olefin epoxidation part often requires the use of an excess of chemical oxidant, which results in the production of equivalent by-products and also affects the compatibility of the substrate functional groups. Summary of the invention

[0004] In view of the deficiencies of the prior art, the present invention designs a method for preparing 2-aryl-3-acyloxytetrahydrofuran compounds in one step under organic electrochemical synthesis conditions.

[0005] One of the purposes of the present invention is to provide a 2-aryl-3-acyloxytetrahydrofuran compound, the structural formula of which is as follows:

[0006]

[0007] wherein Ar is 4-methylphenyl, biphenyl, 2-naphthyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-n-propoxyphenyl, 4-isopropoxyphenyl, 4-butoxyphenyl, 4-phenoxyphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3,5-dimethyl-4-methoxyphenyl, 3-methyl-4-methoxyphenyl or 2,3-dihydrobenzofuran-5-yl; and R is hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, phenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-n-propoxyphenyl, 4-butoxyphenyl, 4-phenoxyphenyl, 4-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, biphenyl, 2-naphthyl, 2-thienyl, 2-furyl or 2-benzofuranyl.

[0008] 3. The second object of the present invention is to provide a method for preparing 2-aryl-3-acyloxytetrahydrofuran compounds, the reaction formula of which is as follows:

[0009]

[0010] 4-aryl-3-butenol, carboxylic acid, electrolyte and solvent are sequentially added into an electrolytic cell equipped with cathode and anode electrode materials, reacted in the electrolytic cell under constant current conditions, and 2-aryl-3-acyloxytetrahydrofuran compounds are subsequently separated and purified; the carboxylic acid is an alkyl carboxylic acid or an aryl carboxylic acid.

[0011] Working principle and beneficial effects of the present invention: The present invention innovatively uses 4-aryl-3-butenol and alkyl or aryl carboxylic acid as raw materials, and obtains 2-aryl-3-acyloxytetrahydrofuran compounds through organic electrochemical synthesis conditions and subsequent purification processes. The reaction makes full use of the characteristics of organic electrochemical technology and develops a new reaction mode to synthesize novel and diverse 2-aryl-3-acyloxytetrahydrofuran compounds.

[0012] The invention has mild conditions, simple raw materials, convenient operation, and the product is easy to be further hydrolyzed, thereby providing a green and efficient preparation method for 2-aryl-3-acyloxytetrahydrofuran compounds and derivatives thereof.

[0013] Furthermore, the molar ratio of each substance in the reaction is: 4-aryl-3-butenol: electrolyte: carboxylic acid = 1:0.5-5:1-100.

[0014] Furthermore, when the carboxylic acid is a solid or a high-boiling point liquid, 4-aryl-3-butenol: electrolyte: carboxylic acid = 1:3:2; when the carboxylic acid is a low-boiling point liquid, 4-aryl-3-butenol: electrolyte: carboxylic acid = 1:1:30-100.

[0015] Furthermore, the electrolyte is selected from tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium hexafluorophosphate, tetra-n-butylammonium tetrafluoroborate or lithium perchlorate, preferably tetra-n-butylammonium acetate.

[0016] Furthermore, the solvent is selected from one or more of acetonitrile, dimethyl sulfoxide, dichloromethane, water, methanol or N,N-dimethylformamide, preferably acetonitrile.

[0017] Furthermore, the electrode material includes an anode electrode material and a cathode electrode material. The anode electrode material is selected from carbon rods, carbon felt, carbon cloth, platinum sheets or nickel sheets, preferably carbon rod electrodes; the cathode electrode material is selected from carbon rods, platinum sheets, nickel sheets, copper sheets, iron sheets or zinc sheets, preferably platinum sheets.

[0018] Further, the current is 1-30 mA, preferably 6 mA; the temperature used is 0°C-60°C, preferably 25°C; the reaction time is 0.5-20 hours, preferably 4 hours; the gas atmosphere is selected from air, argon, nitrogen and oxygen, preferably argon, wherein when the gas atmosphere is air, the electrolytic cell is not evacuated. The separation and purification method is selected from column chromatography and recrystallization, preferably column chromatography.

[0019] Furthermore, the electrolytic cell is selected from a diaphragmless electrolytic cell and a separation electrolytic cell, and is preferably a diaphragmless electrolytic cell.

[0020] The third object of the present invention is to provide the use of 2-aryl-3-acyloxytetrahydrofuran compounds in the preparation of anti-cancer drugs, specifically, the cancer is human breast cancer.

[0021] It has been verified that the 2-aryl-3-acyloxytetrahydrofuran compounds have drug activity against human breast cancer MCF-7 cells. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a single crystal diagram of compound 1h prepared in Example 8;

[0023] Figure 2 Compound 1a prepared in Example 1 1 H NMR spectrum;

[0024] Figure 3 Compound 1a prepared in Example 1 13 C NMR spectrum;

[0025] Figure 4 Compound 1b prepared in Example 2 1 H NMR spectrum;

[0026] Figure 5 Compound 1b prepared in Example 2 13 C NMR spectrum;

[0027] Figure 6 The compound 1c prepared in Example 3 1 H NMR spectrum;

[0028] Figure 7 The compound 1c prepared in Example 3 13 C NMR spectrum;

[0029] Figure 8 Compound 1d prepared in Example 4 1 H NMR spectrum;

[0030] Fig. 9 Compound 1d prepared in Example 4 13 C NMR spectrum;

[0031] Fig.10 The compound 1e prepared in Example 5 1 H NMR spectrum;

[0032] Fig.11 The compound 1e prepared in Example 5 13 C NMR spectrum;

[0033] Fig.12 The compound 1e prepared in Example 5 19 F NMR spectrum;

[0034] Fig.13 The compound 1f prepared in Example 6 1 H NMR spectrum;

[0035] Fig.14 The compound 1f prepared in Example 6 13 C NMR spectrum;

[0036] Fig.15 1g of the compound prepared in Example 7 1 H NMR spectrum;

[0037] Fig.16 1g of the compound prepared in Example 7 13 C NMR spectrum;

[0038] Fig.17 Compound 1h prepared in Example 8 1 H NMR spectrum;

[0039] Fig.18 Compound 1h prepared in Example 8 13 C NMR spectrum;

[0040] Fig.19 The compound 1i prepared in Example 91 H NMR spectrum;

[0041] Fig. 20 The compound 1i prepared in Example 9 13 C NMR spectrum;

[0042] Fig.21 Compound 1j prepared in Example 10 1 H NMR spectrum;

[0043] Fig. 22 Compound 1j prepared in Example 10 13 C NMR spectrum;

[0044] Fig.23 Compound 1k prepared in Example 11 1 H NMR spectrum;

[0045] Fig.24 Compound 1k prepared in Example 11 13 C NMR spectrum;

[0046] Fig.25 Schematic diagram of the inhibitory effect of some compounds on the proliferation of human breast cancer cells (MCF-7 cells). DETAILED DESCRIPTION

[0047] The following is further described in detail through specific implementation methods:

[0048] Example 1: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and acetic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1a was prepared (Reaction Formula 1)

[0049]

[0050] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), n Bu4NOAc (0.2mmol, 1.0equiv.) and MeCN (12mL), acetic acid (2.0mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1a (dr>20:1, 41.8mg, 75%).

[0051] The test data of product 1a are as follows:

[0052] 1 H NMR (400MHz, CDCl3) δ7.29(d,J=8.3Hz,2H),6.86(d,J=8.7Hz,2H),5.12(d,J=5.7Hz,1H),4.95(s,1H),4.27–4.21(m,1H),4.10–4.03(m,1 H),3.94(t,J=6.5Hz,2H),2.25–2.15(m,1H),2.11(s,3H),2.01–1.94(m,1H),1.78–1.71(m,2H),1.53–1.43(m,2H),0.96(t,J=7.4Hz,3H).

[0053] 13 C NMR (101MHz, CDCl3) δ170.9,158.7,132.0,126.8,114.4,85.2,81.0,67.72,67.66,31.4,31.2,21.3,19.3,14.0.

[0054] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 16 H 23 O4,279.1591;Found:279.1592.

[0055] Example 2: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and formic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1b was prepared (Reaction Formula 2)

[0056]

[0057] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), nBu4NOAc (0.2mmol, 1.0equiv.) and MeCN (12mL), formic acid (2.0mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1b (dr>20:1, 34.4mg, 65%).

[0058] The test data of product 1b are as follows:

[0059] 1 H NMR (400MHz, CDCl3) δ8.09(s,1H),7.28(d,J=8.5Hz,2H),6.87(d,J=8.6Hz,2H),5.23(d,J=5.2Hz,1H),4.96(s,1H),4.28–4.21(m,1H),4. 10–4.03(m,1H),3.93(t,J=6.5Hz,2H),2.27–2.18(m,1H),2.03–1.97(m,1H),1.78–1.71(m,2H),1.51–1.44(m,2H),0.96(t,J=7.4Hz,3H).

[0060] 13 C NMR (101MHz, CDCl3) δ160.7,158.8,131.7,126.8,114.5,85.1,80.6,67.7,67.6,31.4,31.2,19.3,13.9.

[0061] HRMS (ESI, Q-TOF) m / z: [M+Na + ]Calcd for C 15 H 20 O4Na,287.1254; Found:287.1259.

[0062] Example 3: Using 4-(4-butoxy)phenyl-3-butene-1-ol as a substrate and cyclopropylcarboxylic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1c was prepared (Reaction Formula 3)

[0063]

[0064] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), n Bu4NOAc (0.2mmol, 1.0equiv.) and MeCN (12mL), cyclopropylcarboxylic acid (2.0mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1c (dr>20:1, 41.4mg, 68%).

[0065] The test data of product 1c are as follows:

[0066] 1 H NMR (400MHz, CD3OD) δ7.24(d,J=8.7Hz,2H),6.84(d,J=8.7Hz,2H),5.05–5.00(m,1H),4.84(s,1H),4.24–4.18(m,1H),4.07–3.9 8(m,1H),3.92(t,J=6.4Hz,2H),2.23–2.12(m,1H),2.00–1.93(m,1H),1.75–1.64(m,3H),1.51–1.42(m,2H),0.98–0.88(m,7H).

[0067] 13 C NMR (101MHz, CD3OD) δ176.3,160.1,133.3,127.9,115.3,86.6,82.4,68.64,68.61,32.5,32.0,20.3,14.2,13.7,9.1,9.0.

[0068] HRMS ESI, Q-TOF) m / z: [M+H + ]Calcd for C 18 H 25 O4,305.1747;Found:305.1744.

[0069] Example 4: Using 4-(4-butoxy)phenyl-3-butene-1-ol as a substrate and benzoic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1d was prepared (Reaction Formula 4)

[0070]

[0071] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), benzoic acid (0.4 mmol, 2.0 equiv), n Bu4NOAc (0.2mmol, 1.0equiv.), MeCN (12mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1d (dr>20:1, 36.8mg, 54%).

[0072] The test data of product 1d are as follows:

[0073] 1 H NMR (400MHz, CDCl3) δ8.10(d,J=7.4Hz,2H),7.59(t,J=7.4Hz,1H),7.47(t,J=7.7H z,2H),7.38(d,J=8.6Hz,2H),6.91(d,J=8.7Hz,2H),5.39(d,J=5.6Hz,1H),5.14(s ,1H),4.37–4.30(m,1H),4.23–4.16(m,1H),3.96(t,J=6.5Hz,2H),2.38–2.28(m,1 H),2.19–2.12(m,1H),1.81–1.73(m,2H),1.54–1.45(m,2H),0.98(t,J=7.4Hz,3H).

[0074] 13 C NMR (101MHz, CDCl3) δ166.3,158.7,133.3,132.1,130.0,129.7,128.5,126.8,114.4,85.3,81.6,67.8,67.7,31.37,31.35,19.3,14.0.

[0075] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 21 H 25 O4,341.1747;Found:341.1746.

[0076] Example 5: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and p-fluorobenzoic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1e was prepared (Reaction Formula 5)

[0077]

[0078] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), p-fluorobenzoic acid (0.4 mmol, 2.0 equiv), n Bu4NOAc (0.6mmol, 1.0equiv.), MeCN (12mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1e (dr>20:1, 43.0mg, 60%).

[0079] The test data of product 1e are as follows:

[0080] 1 H NMR (400MHz, CDCl3) δ8.14–8.05(m,2H),7.35(d,J=8.4Hz,2H),7.13(t,J=8. 5Hz,2H),6.90(d,J=8.4Hz,2H),5.37(d,J=5.1Hz,1H),5.11(s,1H),4.32(t,J =7.6Hz,1H),4.21–4.14(m,1H),3.96(t,J=6.4Hz,2H),2.37–2.27(m,1H),2. 17–2.10(m,1H),1.80–1.74(m,2H),1.54–1.46(m,2H),0.97(t,J=7.3Hz,3H).

[0081] 13C NMR(101MHz, CDCl3)δ166.0(d,J=254.4Hz),165.4,158.8,132.3(d,J=9.4Hz),132.0,126.8,126 .4(d,J=2.9Hz),115.7(d,J=22.0Hz),114.5,85.3,81.8,67.83,67.78,31.42,31.39,19.4,14.0.

[0082] 19 F NMR (376MHz,CDCl3)δ-105.14.

[0083] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 21 H 24 FO4,359.1653; Found:359.1657.

[0084] Example 6: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and p-bromobenzoic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1f was prepared (Reaction Formula 6)

[0085]

[0086] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), p-bromobenzoic acid (0.4 mmol, 2.0 equiv), n Bu4NOAc (0.6mmol, 1.0equiv.), MeCN (12mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 4 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1f (dr>20:1, 40.3mg, 48%).

[0087] The test data of product 1f are as follows:

[0088] 1H NMR (400MHz, CDCl3) δ7.94(d,J=8.5Hz,2H),7.60(d,J=8.5Hz,2H),7.35(d,J =8.5Hz,2H),6.89(d,J=8.6Hz,2H),5.36(d,J=5.6Hz,1H),5.11(s,1H),4.35– 4.29(m,1H),4.21–4.14(m,1H),3.95(t,J=6.5Hz,2H),2.37–2.27(m,1H),2. 17–2.10(m,1H),1.79–1.73(m,2H),1.52–1.46(m,2H),0.97(t,J=7.3Hz,3H).

[0089] 13 C NMR (101MHz, CDCl3) δ165.7,158.8,132.0,131.9,131.3,129.0,128.5,126.8,114.5,85.3,81.9,67.84,67.80,31.43,31.37,19.4,14.0.

[0090] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 21 H 24 BrO4,419.0852; Found:419.0846.

[0091] Example 7: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and 2-furancarboxylic acid as an acidifying agent, 1 g of 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule was prepared (Reaction Formula 7)

[0092]

[0093] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), 2-furancarboxylic acid (0.4 mmol, 2.0 equiv), nBu4NOAc (0.6mmol, 1.0equiv.), MeCN (12mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 4 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1g (dr>20:1, 45.6mg, 69%).

[0094] The test data of 1g of product are as follows:

[0095] 1 H NMR (400MHz, CDCl3) δ7.60(d,J=0.8Hz,1H),7.34(d,J=8.4Hz,2H),7.23(d,J=2.9H z,1H),6.88(d,J=8.6Hz,2H),6.55–6.49(m,1H),5.34(d,J=5.6Hz,1H),5.12–5.08( m,1H),4.33–4.26(m,1H),4.19–4.11(m,1H),3.94(t,J=6.5Hz,2H),2.34–2.24(m,1 H),2.15–2.10(m,1H),1.79–1.73(m,2H),1.52–1.45(m,2H),0.96(t,J=7.4Hz,3H).

[0096] 13 C NMR (101MHz, CDCl3) δ158.8,158.4,146.7,144.5,131.9,126.8,118.4,114.5,112.0,85.2,81.6,67.7,31.4,31.3,21.3,19.3,13.9.

[0097] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 19 H 23 O5, 331.1540; Found: 331.1538.

[0098] Example 8: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and benzofuran-2-carboxylic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1h was prepared (Reaction Formula 8)

[0099]

[0100] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), benzofuran-2-carboxylic acid (0.4 mmol, 2.0 equiv), n Bu4NOAc (0.6mmol, 1.0equiv.), MeCN (12mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid product 1h (dr>20:1, 50.2mg, 66%).

[0101] The product 1h detection data is as follows:

[0102] 1 H NMR(400MHz, CDCl3)δ7.70(d,J=7.9Hz,1H),7.64–7.57(m,2H),7.50–7.45(m,1H) ),7.39–7.30(m,3H),6.90(d,J=8.7Hz,2H),5.42(d,J=5.7Hz,1H),5.15(s,1H), 4.36–4.31(m,1H),4.24–4.17(m,1H),3.96(t,J=6.5Hz,2H),2.40–2.29(m,1H), 2.22–2.15(m,1H),1.80–1.72(m,2H),1.54–1.44(m,2H),0.97(t,J=7.4Hz,3H).

[0103] 13 C NMR (101MHz, CDCl3) δ159.4,158.9,156.0,145.4,131.9,128.0,127.0,126 .9,124.0,123.0,114.6,114.5,112.5,85.2,82.2,67.8,31.4,19.4,14.0.

[0104] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 23 H 25O5, 381.1697; Found: 381.1698.

[0105] The product 1h single crystal is as follows Figure 1 As shown, the specific data are shown in Table 1:

[0106]

[0107]

[0108] Example 9: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and 2,5-dichlorophenylacetic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1i was prepared (Reaction Formula 9)

[0109]

[0110] 4-(4-Butoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), 2,5-dichlorophenylacetic acid (0.4 mmol, 2.0 equiv.), n Bu4NOAc (0.6mmol, 1.0equiv.), MeCN (12mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, electrolysis was performed with a constant current (direct current, output by a constant current potentiometer) for 4 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography (petroleum ether and ethyl acetate as eluents, petroleum ether / ethyl acetate = 10:1-5:1) to obtain a colorless oily liquid 1i (dr>20:1, 32.2mg, 38%).

[0111] The test data of product 1i are as follows:

[0112] 1H NMR (400MHz, CDCl3) δ7.35–7.30 (m, 2H), 7.29 (s, 1H), 7.26 (d, J = 2.5Hz, 1H), 7.25 –7.20(m,1H),6.86(d,J=8.7Hz,2H),5.16(d,J=5.6Hz,1H),4.97(s,1H),4.28–4.2 1(m,1H),4.08–4.01(m,1H),3.94(t,J=6.5Hz,2H),3.79(s,2H),2.26–2.16(m,1H ),2.04–1.97(m,1H),1.78–1.71(m,2H),1.52–1.44(m,2H),0.97(t,J=7.4Hz,3H).

[0113] 13 C{ 1 H}NMR(101MHz,CDCl3)δ169.9,158.8,133.9,133.0,132.8,131.9,131.5,130 .7,129.0,126.8,114.4,85.1,82.0,67.8,67.7,39.3,31.4,31.1,19.4,14.0.

[0114] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 22 H 25 Cl2O4,423.1124; Found:423.1121.

[0115] Example 10: Using (3,4-dimethoxy)phenyl-3-butene-1-ol as an olefin substrate and acetic acid as an acidifying agent, a 2-aryl-3-ester carbonyl-substituted tetrahydrofuran molecule 1j was prepared (Reaction Formula 10)

[0116]

[0117] (3,4-dimethoxy)phenyl-3-butene-1-ol substrate (0.2 mmol, 1.0 equiv.), nBu4NOAc (0.2mmol, 1.0equiv.) and MeCN (12mL), acetic acid (2.0mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, constant current (direct current, output by a constant current potentiometer) was used for electrolysis for 3 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography using a mixture of petroleum ether and ethyl acetate (PE / EA=10:1-5:1) to obtain a colorless oily liquid product 1j (dr>20:1, 33.5mg, 63%).

[0118] The test data of product 1j are as follows:

[0119] 1 H NMR (400MHz, CDCl3) δ6.93–6.87(m,2H),6.80(d,J=8.1Hz,1H),5.10(d,J=5.7Hz,1H),4.91(s,1H),4.24–4. 19(m,1H),4.08–4.01(m,1H),3.86(s,3H),3.82(s,3H),2.21–2.12(m,1H),2.08(s,3H),1.98–1.91(m,1H).

[0120] 13 C NMR (101MHz, CDCl3) δ170.9,148.9,148.4,132.7,117.6,110.9,108.7,85.2,81.0,67.7,55.9,55.8,31.0,21.2.

[0121] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 14 H 19 O5, 267.1227; Found: 267.1225.

[0122] Example 11: Using 4-(4-butoxy)phenyl-3-butene-1-ol as an olefin substrate and acetic acid as an acidifying agent, a 2-aryl-3-hydroxy substituted tetrahydrofuran molecule 1k is prepared (Reaction Formula 11)

[0123]

[0124] (3,4-dimethoxy)phenyl-3-butene-1-ol (0.2 mmol, 1.0 equiv.), nBu4NOAc (0.2mmol, 1.0equiv.) and MeCN (12mL), acetic acid (2.0mL) and a stirrer were added to a three-necked flask in sequence, and the reaction flask was sealed with a rubber stopper equipped with a carbon rod and a platinum electrode. Subsequently, an oil pump was used to evacuate the system, and argon gas was injected into the reaction system for protection (this operation was repeated three times). Under stirring at room temperature, constant current (direct current, output by a constant current potentiometer) was used for electrolysis for 5 hours. After the reaction was completed, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude product was dissolved in MeOH (10mL), and then K2CO3 (2.0equiv.) was added and stirred at room temperature for reaction). After 2 hours, the reaction solution was extracted, dried, filtered and concentrated to obtain a crude reaction product. The crude reaction product was purified by column chromatography using a mixture of petroleum ether and ethyl acetate (PE / EA=3:1-1:1) to obtain a colorless oily liquid product 1k (dr>20:1, 31.2mg, 66%).

[0125] The test data of product 1l are as follows:

[0126] 1 H NMR (400MHz, DMSO-d6) δ7.04(d,J=8.2Hz,2H),6.72(d,J=8.2Hz,2H),5.10(d,J=3.9Hz,1H),4.37(d,J=2.4Hz,1H),3.91–3.82 (m,2H),3.80–3.72(m,3H),1.91–1.81(m,1H),1.67–1.60(m,1H),1.56–1.48(m,2H),1.32–1.22(m,2H),0.77(t,J=7.3Hz,3H).

[0127] 13 C NMR (101MHz, DMSO-d6) δ157.9,133.8,126.9,114.1,86.8,77.7,67.2,66.7,34.2,30.9,18.9,13.8.

[0128] HRMS (ESI, Q-TOF) m / z: [M+H + ]Calcd for C 14 H 21 O3,237.1485;Found:237.1486.

[0129] Anti-tumor activity verification experiment:

[0130] The 2-aryl-3-acyloxytetrahydrofuran compounds prepared in the examples were selected, and human breast cancer cells (MCF-7 cells) were used as receptors, and the CCK-8 method was used to test their in vitro antitumor activities.

[0131] The activity test process of compound 1e in Example 5 is described as follows: (1) Collect cells in the logarithmic phase, adjust the concentration of the cell suspension, add 100 μL to each well, and plate the cells to be tested to a density of 5000 cells / well; (2) Incubate at 5% CO2 and 37°C until the cell monolayer covers the bottom of a 96-well flat-bottom plate, and then add compound 1e with a concentration gradient (0.015 μM, 0.045 μM, 0.137 μM, 0.411 μM, 1.234 μM, 3.703 μM, 11.111 μM, 33.333 μM, 100.000 μM), respectively, with 3 replicate wells; (3) Incubate at 5% CO2 and 37°C for 48 hours and observe under an inverted microscope; (4) Add 10 μL to each well. CCK-8 solution, and continue to culture for 1-4h; (4) when the color of the solution in the 96-well plate gradually turns orange-red, when a significant color change occurs, measure the absorbance of each well at OD450nm on an automatic microplate reader; (5) simultaneously set a zeroing well (culture medium, CCK-8 solution), a positive control well (cells, cisplatin dissolution medium of the same concentration, culture medium, CCK-8 solution), and a blank control well (no drug, only cells, culture medium and CCK-8 solution); (6) plot the cell survival rate (%) against the logarithmic-transformed drug concentration (such as log (drug concentration)), and use a nonlinear regression curve to fit the data (GraphPad Prism) to obtain the IC50 value of compound 1e; (7) The tumor inhibition experiment of 2-aryl-3-acyloxytetrahydrofuran compounds and cisplatin prepared in other embodiments was performed in a similar manner as above.

[0132] Table 2 shows the inhibitory effects of some compounds in the examples on the proliferation of human breast cancer cells (MCF-7 cells).

[0133] Compound Human breast cancer cells (MCF-7 cells) [IC50 (μM)] Example 5 Compound 1e 67.09 Example 6 Compound 1f 54.00 Example 8 Compound 1h 42.97 Example 9 Compound 1i 18.18 Cisplatin 7.62

[0134] like Fig.25 As shown, the results show that the 2-aryl-3-acyloxytetrahydrofuran compounds prepared by the present invention have a certain inhibitory effect on human breast cancer cells.

[0135] The above is only an embodiment of the present invention, and the common knowledge such as the known specific structure and characteristics in the scheme is not described in detail here. It should be pointed out that for those skilled in the art, several deformations and improvements can be made without departing from the structure of the present invention, which should also be regarded as the protection scope of the present invention, and these will not affect the effect of the implementation of the present invention and the practicality of the patent. The scope of protection required by this application shall be based on the content of its claims, and the specific implementation methods and other records in the specification can be used to interpret the content of the claims.

Claims

1. A 2-aryl-3-acyloxytetrahydrofuran compound, characterized in that: Its structural formula is as follows: Wherein: Ar is p-4-methylphenyl, biphenyl, 2-naphthyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-n-propoxyphenyl, 4-isopropoxyphenyl, 4-butoxyphenyl, 4-phenoxyphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, 3,5-dimethyl-4-methoxyphenyl, 3-methyl-4-methoxyphenyl or 2,3-dihydrobenzofuran-5-yl; R is hydrogen, methyl, ethyl, propyl, cyclopropyl, butyl, phenyl, 4-methoxyphenyl, 4-ethoxyphenyl, 4-n-propoxyphenyl, 4-butoxyphenyl, 4-phenoxyphenyl, 4-methylphenyl, 4-fluorophenyl, 4-bromophenyl, 4-iodophenyl, 4-cyanophenyl, 4-trifluoromethylphenyl, 3,4-dimethoxyphenyl, 3,4,5-trimethoxyphenyl, biphenyl, 2-naphthyl, 2-thienyl, 2-furyl or 2-benzofuranyl.

2. The method for preparing 2-aryl-3-acyloxytetrahydrofuran compounds according to claim 1, characterized in that: The reaction formula is as follows: 4-aryl-3-butenol, carboxylic acid, electrolyte and solvent are sequentially added into an electrolytic cell equipped with cathode and anode electrode materials, reacted in the electrolytic cell under constant current conditions, and 2-aryl-3-acyloxytetrahydrofuran compounds are subsequently separated and purified.

3. The preparation method according to claim 2, characterized in that: The molar ratio of each substance in the reaction: 4-aryl-3-butenol: electrolyte: carboxylic acid = 1: 0.5~5: 1~100.

4. The preparation method according to claim 3, characterized in that: When the carboxylic acid is a solid or a high-boiling point liquid, 4-aryl-3-butenol: electrolyte: carboxylic acid = 1:1:2; when the carboxylic acid is a low-boiling point liquid, 4-aryl-3-butenol: electrolyte: carboxylic acid = 1:1:30-100.

5. The preparation method according to claim 2, characterized in that: The electrolyte is selected from tetra-n-butylammonium tetrafluoroborate, tetra-n-butylammonium hexafluorophosphate, tetra-n-butylammonium tetrafluoroborate or lithium perchlorate.

6. The preparation method according to claim 2, characterized in that: The solvent is selected from one or more of acetonitrile, dimethyl sulfoxide, dichloromethane, water, methanol or N,N-dimethylformamide.

7. The preparation method according to claim 2, characterized in that: The electrode materials include anode electrode materials and cathode electrode materials. The anode electrode materials are selected from carbon rods, carbon felt, carbon cloth, platinum sheets or nickel sheets; the cathode electrode materials are selected from carbon rods, platinum sheets, nickel sheets, copper sheets, iron sheets or zinc sheets.

8. The preparation method according to claim 2, characterized in that: The current is 1 mA to 30 mA; the temperature is 0° C. to 60° C.; the reaction time is 0.5 h to 20 h; the gas atmosphere is selected from air, argon, nitrogen and oxygen; and the separation and purification method is selected from column chromatography or recrystallization.

9. Use of the compound according to claim 1 and / or the compound prepared by the method according to any one of claims 2 to 8 in the preparation of anticancer drugs.

10. The use according to claim 9, characterized in that: The cancer is human breast cancer.

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