Derivatives of 3-aryl-1-(2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl) propyl-2-ene-1-one and preparation and application thereof

Abstract

The invention relates to a novel compound as well as a preparation method and application thereof, in particular to a derivative of (E)-3-aryl-1-(2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl) propan-2-ene-1-one as well as a preparation method and application of the derivative of (E)-3-aryl-1-(2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl) propan-2-ene-1-one. The structural formula of the (E)-3-aryl-1-(2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl) prop-2-ene-1-one is shown as a formula I, and R is selected from chlorine, bromine, methyl, methoxyl, 2, 3, 4-trimethoxy, ethyoxyl, nitryl and 2, 4-dichloro, and the structural formula of the (E)-3-aryl-1-(2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl) prop-2-ene-1-one is shown as a formula I. The invention further discloses a preparation method of the (E)-3-aryl-1-(2, 2-dimethyl-2, 3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl) prop-2-ene-1-one. Experiments show that the compound disclosed by the invention especially shows relatively good antifungal activity on botryosphaeria dothidea and pythium aphanidermatum, and the activity of a part of drugs is equivalent to that of the drug fluxapyroxad on the market. The compound provided by the invention can provide more choices for research and development of antifungal drugs, and has a wide application prospect. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to a new class of compounds and a preparation method and application thereof, and in particular to a derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one and a preparation method and application thereof. Background Art

[0002] Chalcone has a wide range of pharmacological activities, such as antibacterial, antimalarial, antiprotozoal, antituberculosis, anticancer and antifungal. Studies have found that the reactive α, β-unsaturated ketone group in chalcone is the reason for its biological activity. Deepa Gupta et al. described the antifungal activity of newly synthesized chalcone derivatives against the fungus Microsporumgypseum, and the results were better than ketoconazole. Among them, 4-chloro derivatives (1) and unsubstituted derivatives of chalcone (2) showed antifungal activity better than ketoconazole (J. Adv. Pharm. Technol. Res., 2015, 6, 114-7). Aimei et al. evaluated the in vitro and in vivo antifungal activity of quinoline derivatives related to the chalcone part against Candida albicans. Mechanistic studies demonstrated that PK-10 combined with FLC could inhibit the formation of Candida albicans hyphae, induce the accumulation of reactive oxygen species (ROS), the destruction of mitochondrial membrane potential and the decrease of intracellular ATP content, thereby leading to mitochondrial dysfunction, indicating that they are new drugs for the treatment of drug-resistant Candida albicans infections (Eur. J. Med. Chem., 2023, 260).

[0003]

[0004] In addition, the structure of chalcone also has high potential value in drug synthesis and its application in anti-plant fungi. Chinese patent CN116478032A discloses 2',3,4',5,6'-pentahydroxy-3'-isopentenyl chalcone analogs and their applications, indicating that 2',3,4',5,6'-pentahydroxy-3'-isopentenyl chalcone can significantly inhibit the main post-harvest pathogens of citrus green mold, citrus penicillium and citrus acid rot fungi; Chinese patent CN118490668A discloses the application of 2,6,2',4'-tetrahydroxy-6'-methoxy chalcone in the preparation of antibacterial and / or anti-inflammatory drugs; Chinese patent CN110655464A discloses a chalcone compound containing an oxyacetic acid structure and its use in antibacterial aspects, indicating that the compound has certain anti-Escherichia coli, Staphylococcus aureus, and Salmonella activities, and has high potential value in the research and development of antibacterial drugs.

[0005] Therefore, it is of great significance to develop a new derivative containing a chalcone skeleton and explore its antibacterial uses. Summary of the invention

[0006] One of the purposes of the present invention is to provide a novel derivative containing a chalcone skeleton: a derivative of 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone.

[0007] The second object of the present invention is to provide a method for preparing the derivatives of the above-mentioned 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone.

[0008] The second object of the present invention is to provide the application of the derivatives of the above-mentioned 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone.

[0009] In order to achieve the above object, the present invention adopts the following technical solutions:

[0010] The derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one represented by chemical structural formula I is:

[0011]

[0012] Wherein, R is selected from the group consisting of: chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro.

[0013] Preferably, the derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from: compounds E1, E2, E3, E4, E5, E6, E7, E8 or E9; wherein E1 is (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0014] E2 is (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0015] E3 is (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0016] E4 is (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0017] E5 is (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E6 is (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0018] E7 is (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E8 is (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E9 is (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one.

[0019] The preparation method of the above-mentioned (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivative is as follows:

[0020]

[0021] Wherein, R is selected from the group consisting of chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro.

[0022] The present invention also provides the use of the above-mentioned (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivatives in the preparation of antifungal preparations.

[0023] Preferably, the plant fungus is Botryosphaeria dothidea or Pythium aphanidermatum.

[0024] Preferably, the (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from compounds E1, E3, E4, E5, E6, E7 or E8, wherein:

[0025] E1 is (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0026] E3 is (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0027] E4 is (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0028] E5 is (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E6 is (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one;

[0029] E7 is (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E8 is (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one.

[0030] The beneficial effects of the present invention are:

[0031] The present invention provides a new class of derivatives containing a chalcone skeleton: derivatives of 3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone, and preparation methods and applications thereof. Tests show that the compounds of the present invention show good antifungal activity, especially against Botryosphaeria dothidea and Pythiumaphanidermatum, and some drugs have comparable activity to the marketed drug fluopyrabacterium. The compounds of the present invention will provide more options for the research and development of antifungal drugs and have broad application prospects. DETAILED DESCRIPTION

[0032] The present invention is further described below in conjunction with examples. The following examples are only for illustration and are not intended to limit the scope of protection of the present invention in any way.

[0033] The processes and methods not described in detail in the following examples are conventional methods known in the art, and the reagents used in the examples are all analytically pure or chemically pure, and can be purchased commercially or prepared by methods well known to those of ordinary skill in the art. The following examples all achieve the purpose of the present invention.

[0034] Example 1

[0035] Synthesis of 7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran (B):

[0036]

[0037] In a single-mouth bottle, add 6.0 g (37 mmol) of furanol, 0.24 g (1.5 mmol) of potassium iodide, 7.58 g (55 mmol) of potassium carbonate, and anhydrous ethanol as solvent. Stir at 45°C for about 30 min, then add 7.79 g (55 mmol) of methyl iodide. Monitor by TLC until the reaction is complete. The reaction solution is evaporated to remove the solvent, redissolved with dichloromethane, and filtered to remove potassium carbonate. Pour into ice water to precipitate a large amount of solids. After filtration and drying, brown crystals B are obtained with a yield of 80.7%.

[0038] Example 2

[0039] Synthesis of 1-(7-methoxy-2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-1-ethanone (C):

[0040]

[0041] Under ice bath conditions, 1,2-dichloroethane was added as a reaction solvent in a three-necked flask, 5.86 g (44 mmol) of anhydrous zinc chloride was added, and then 3.68 g (47 mmol) of acetyl chloride was added dropwise with a dropping funnel. After the addition, the reaction was continued by stirring for about 30 min. 6 g (34 mmol) of compound B fully dissolved in 1,2-dichloroethane was added dropwise with a dropping funnel. The color of the initial reaction solution was light blue, and the solution gradually turned dark purple after adding compound B. The reaction time was about 6 h, and the reaction was completed by TLC detection. After the reaction was completed, the mixed solution was poured into 0.1 mol / L glacial hydrochloric acid while stirring, the liquid was separated, the organic phase was collected, dried, and the solvent was removed and then recrystallized with anhydrous ethanol or purified by chromatographic column to obtain a white solid C with a yield of 57.2%.

[0042] Example 3

[0043] Synthesis of (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D1):

[0044]

[0045] Add 0.4 g (1.8 mol) of compound C to a single-necked flask, add 0.33 g (2.4 mmol) of p-chlorobenzaldehyde and an appropriate amount of sodium hydroxide, use a mixture of water and anhydrous ethanol as solvent (the volume ratio of water to anhydrous ethanol is about 1:3), stir at room temperature for 3 hours, and monitor the reaction by TLC. A yellow precipitate appears in the solution during the reaction, which is the obtained product. Filter, wash the filter cake with water and a small amount of anhydrous ethanol, dry and weigh to obtain a light yellow solid, namely D1, with a yield of 50.6%.

[0046] Example 4

[0047] Synthesis of (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D2):

[0048]

[0049] Add 0.2g (0.9mmol) of compound C to a single-necked flask, add 0.2g (1.0mmol) of o-chlorobenzaldehyde and an appropriate proportion of sodium hydroxide, use a mixture of water and anhydrous ethanol as solvent (the volume ratio of water to anhydrous ethanol is about 1:3), stir at room temperature for 3h, and monitor the reaction by TLC. After the reaction, the solution is yellow-green. Adjust the pH to neutral and extract with ethyl acetate. Take the upper organic phase, remove the solvent and purify it with a chromatographic column, dry and weigh it to obtain a green oily substance, namely D2, with a yield of 49.1%.

[0050] Example 5

[0051] Synthesis of (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D3):

[0052]

[0053] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D3 with a total yield of 51.1%.

[0054] Example 6

[0055] Synthesis of (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propene-1-one (D4):

[0056]

[0057] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D4 with a total yield of 76.7%.

[0058] Example 7

[0059] Synthesis of (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propene-1-one (D5):

[0060]

[0061] The preparation method was the same as that of Example 4. The reaction was carried out at room temperature for 3 h to obtain D5 with a total yield of 69.1%.

[0062] Example 8

[0063] Synthesis of (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D6):

[0064]

[0065] The preparation method was the same as that of Example 4. The reaction was carried out at room temperature for 3 h to obtain D6 with a total yield of 88.9%.

[0066] Example 9

[0067] Synthesis of (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D7):

[0068]

[0069] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D7 with a total yield of 90.8%.

[0070] Example 10

[0071] Synthesis of (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propene-1-one (D8):

[0072] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D8 with a total yield of 31.2%.

[0073] Embodiment 11

[0074] Synthesis of (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-propen-1-one (D9):

[0075]

[0076] The preparation method was the same as that in Example 3. The reaction was carried out at room temperature for 3 h to obtain D9 with a total yield of 69.6%.

[0077] Example 12

[0078] Synthesis of (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E1):

[0079]

[0080] Add 0.3 g (0.88 mmol) of compound D1 to a single-necked flask, then add 0.42 g (1.3 mmol) of Toogni reagent and 0.0835 g (0.62 mmol) of CuI, add an appropriate amount of DMF as solvent, evacuate the air in the bottle, use nitrogen as protective gas, react at 80 ° C for 3 days, and TLC detects the end of the reaction. After the reaction is completed, extract with water to remove DMF in the system, use ethyl acetate as an extractant, and take the organic layer. After the solvent is removed, purify with a chromatographic column, dry and weigh to obtain a light yellow oily substance, namely E1, with a yield of 24.6%.

[0081] E1: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.45(s,6H,2×CH3),2.92(s,2H,CH2),3.81(s,3H,CH3),7.16(q,J=8.3Hz,4H,C6H4 2,3,5,6-H),7.26(s,2H,C6H2 2,6-H),7.35(s,1H,C=CH).HRMS:HR-MS(ESI):m / z calcd for C 21 H 18 ClF3O3([M+Na] + )433.0789,found433.0796.

[0082] Embodiment 13

[0083] Synthesis of (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E2):

[0084]

[0085] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E2 with a total yield of 19.3%.

[0086] E2: yellow oily substance, 1H NMR (600MHz, CDCl3) δ1.47(s,6H,2×CH3),2.95(s,2H,CH2),3.84(s,3H,CH3),7.04(t,J=7.6Hz,1H,C6H4 4-H),7.17(t,J=7.8Hz,1H,C6H4 5-H),7.22(d,J=7.6Hz,1H,C6H4 3-H),7.26(s,2H,C6H4 5-H,C6H2 6-H),7.31(s,1H,C6H2 2-H),7.72(s,1H,C=CH).HRMS: HR-MS(ESI):m / z calcd for C 21 H 18 ClF3O3([M+H] + )411.0969,found411.0979.

[0087] Embodiment 14

[0088] Synthesis of (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E3):

[0089]

[0090] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E3 with a total yield of 17.9%.

[0091] E3: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.50(s,6H,2×CH3),2.98(s,2H,CH2),3.87(s,3H,CH3),7.16(d,J=8.5Hz,2H,C6H4 2,6-H),7.31(m,2H,C6H2 2,6-H),7.36(d,J=8.5Hz,2H,C6H4 3,5-H),7.41(s,1H,C=CH).HRMS:HR-MS(ESI):m / z calcd for C 21 H 18 BrF3O3([M+H] + )455.0464, found 455.0474.

[0092] Embodiment 15

[0093] Synthesis of (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E4):

[0094]

[0095] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E4 with a total yield of 19.8%.

[0096] E4: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.41(s,6H,2×CH3),2.18(s,3H,C6H4-CH3),2.88(s,2H,CH2),3.77(s,3H,CH3),6.94(d,J=8.0Hz,2H,C6H4 3,5-H),7.09(d,J=8.1Hz,2H,C6H4 2,6-H),7.27(d,J=11.3Hz,2H,C6H2 2,6-H),7.35(s,1H,C=CH).HRMS: HR-MS(ESI):m / z calcd for C 22 H 21 F3O3([M+H] + )391.1516, found 391.1526.

[0097] Example 16

[0098] Synthesis of (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E5):

[0099]

[0100] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E5 with a total yield of 49.9%.

[0101] E5: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.47(s,6H,2×CH3),2.93(s,2H,CH2),3.82(s,3H,CH3),3.83(s,3H,C6H4-OCH3),6.71(t,J=7.5Hz,1H,C6H4-H),6.78(d,J=8 .3Hz, 1H, C6H4-H), 7.13 (d, J=7.5Hz, 1H, C6H4-H), 7.21 (t, J=7.9Hz, 1H, C6H4-H), 7.33 (d, J=3.4Hz, 2H), 7.74 (s, 1H, C=CH). HRMS: HR-MS (ESI): m / z calcd for C 22 H 21 F3O4([M+H]+ )407.1465, found 407.1475.

[0102] Embodiment 17

[0103] Synthesis of (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E6):

[0104]

[0105] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E6 with an overall yield of 33.5%.

[0106] E6: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.48(s,6H,2×CH3),2.95(s,2H,CH2),3.77(d,J=4.0Hz,6H,C6H2 OCH3,C6H4 4-OCH3),3.84(s,3H,C6H4 3-OCH3),3.92(s,3H,C6H42-OCH3),6.41(d,J=8.8Hz,1H,C6H4 5-H),6.87(d,J=8.8Hz,1H,C6H4 6-H),7.35(d,J=23.6Hz,2H,C6H2 2,6-H),7.62(s,1H,C=CH).HRMS:HR-MS(ESI):m / z calcd for C 24 H 25 F3O6([M+H] + )467.1676, found 467.1684.

[0107] Embodiment 18

[0108] Synthesis of (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E7):

[0109]

[0110] The preparation method was the same as compound E1, and the reaction was carried out at room temperature for 3 hours to obtain E7 with an overall yield of 32.7%.

[0111] E7: yellow oily substance, 1H NMR(600MHz, CDCl3)δ1.36(t,J=7.0Hz,3H,C6H4-CH3),1.50(s,6H,2×CH3),2.97(s,2 H,CH2),3.85(s,3H,CH3),3.96(q,J=7.0Hz,2H,C6H4-CH2),6.72(d,J=8.7Hz,2H,C6H4 3,5-H),7.21(d,J=8.6Hz,2H,C6H4 2,6-H),7.30(s,1H,C6H2 6-H),7.37(s,1H,C6H2 2-H),7.43(s,1H,C=CH).HRMS: HR-MS(ESI):m / z calcd for C 23 H 23 F3O4([M+H] + )421.1627, found 421.1632.

[0112] Embodiment 19

[0113] Synthesis of (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E8):

[0114]

[0115] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E8 with an overall yield of 23.5%.

[0116] E8: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.43(s,6H,2×CH3),2.91(s,2H,CH2),3.81(s,3H,CH3),7.23(s,1H,C6H2 6-H),7.34(d,J=8.9Hz,2H,C=CH,C6H2 2-H),7.41(d,J=8.7Hz,2H,C6H4 2,6-H),8.03(d,J=8.7Hz,2H,C6H4 3,5-H).HRMS: HR-MS(ESI):m / zcalcd for C 21 H 18 F3NO5([M+H] + )422.1210, found 422.1219.

[0117] Embodiment 20

[0118] Synthesis of (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one (E9):

[0119]

[0120] The preparation method is the same as compound E1, and the reaction is carried out at room temperature for 3 hours to obtain E9 with a total yield of 11.6%.

[0121] E9: yellow oily substance, 1 H NMR (600MHz, CDCl3) δ1.49(s,6H,2×CH3),2.97(s,2H,CH2),3.85(s,3H,CH3),7.03(dd,J=8.4,1.9Hz,1H,C6H4 5-H),7.17(d,J=8.4Hz,1H,C6H4 3-H), 7.26 (s, 1H, C6H2 6-H), 7.29 (s, 1H, C6H24 2-H), 7.35 (d, J=1.9Hz, 1H, C6H4 6-H), 7.61 (s, 1H, C=CH). HRMS: HR-MS (ESI): m / z calcd for C 21 H 17 Cl2F3O3([M+H] + )445.0580,found445.0590.

[0122] Embodiment 21

[0123] Determination of Antifungal Activity of 3-Aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-trifluoromethylpropenone Derivatives

[0124] 1. Antifungal activity test method

[0125] The plant fungi used in this experiment are strains preserved at 4℃ in the laboratory, including Botryosphaeria dothidea and Pythium aphanidermatum. The culture medium used is potato agar glucose culture medium (PDA for short). PDA culture medium formula: 200g potato, 20g glucose, 15g agar, 1000mL distilled water. Preparation method: Wash and peel the potato, weigh 200g, cut into small pieces, add water and boil until soft (boil for 20-30min, until it can be pierced by a glass rod), filter into a beaker with eight layers of gauze, add 15-20g agar according to the experimental needs, add 20g glucose, stir evenly, cool slightly after fully dissolved, add water to 1000mL, sterilize at 121℃ for 30min after aliquoting, and set aside after cooling.

[0126] 2. Bactericidal activity (in vitro) experimental method: The growth rate method is used, including the following steps:

[0127] (1) First, culture the above-mentioned plant fungi on a PDA plate at 25°C for about 3-6 days for use;

[0128] (2) Heat and melt the PDA medium, cool it to 45-50°C, add 10 μl of 20 mg / mL concentration of the test compound to prepare a medium containing 100 μg / mL of the drug solution, and pour it into culture dishes to cool. Furazolidone is used as a positive control;

[0129] (3) Using aseptic operation procedures, use a cork puncher to punch a round bacterial cake (0.50 cm in diameter) at the edge of the hyphae of each strain after 6 days of culture (the growth conditions should be as consistent as possible), then use an inoculation needle to pick it to the center of the drug-containing plate, and then place the culture dish upside down in the incubator for culture;

[0130] (4) Observe and measure the growth of mycelium at different times after treatment, measure the diameter using the cross method, process the data, and calculate the inhibition rate;

[0131]

[0132] Each treatment was repeated 3 times.

[0133] Sample: Derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one:

[0134]

[0135] Wherein, R is selected from: chlorine, bromine, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, and nitro.

[0136] Table 1 Inhibition rate of some compounds of the present invention on grape spore fungus and aphanidermatus fungus (%)

[0137]

[0138] The results in Table 1 show that when the concentration of the test compound is 100 μg / mL, the compounds of the present invention exhibit different degrees of inhibitory activity against Botrytis cinerea and have general inhibitory activity against the pathogen. The compounds of the present invention have potential significance for inhibiting plant pathogenic fungi.

Claims

1. The derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one represented by chemical formula I: in, R is selected from the group consisting of chloro, bromo, methyl, methoxy, 2,3,4-trimethoxy, ethoxy, nitro, and 2,4-dichloro.

2. The (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one derivative according to claim 1, characterized in that: The derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from: compounds E1, E2, E3, E4, E5, E6, E7, E8 or E9; wherein E1 is (E)-3-(4-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E2 is (E)-3-(2-chlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E3 is (E)-3-(4-bromophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E4 is (E)-3-(4-methylphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E5 is (E)-3-(2-methoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E6 is (E)-3-(2,3,4-trimethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E7 is (E)-3-(4-ethoxyphenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E8 is (E)-3-(4-nitrophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one; E9 is (E)-3-(2,4-dichlorophenyl)-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one.

3. The method for preparing the derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one according to claim 1, characterized in that: The reaction formula is as follows: In the formula, R is as defined in claim 1.

4. Use of the derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one according to claim 1 or 2 in the preparation of antifungal preparations.

5. The use according to claim 4, characterized in that: The plant fungus is Botryosphaeria dothidea.

6. The use according to claim 4, characterized in that: The plant fungus is Pythium aphanidermatum.

7. The use according to claim 4, characterized in that: The derivative of (E)-3-aryl-1-(2,2-dimethyl-2,3-dihydrobenzofuran-5-yl)-2-(trifluoromethyl)prop-2-en-1-one is selected from compounds E1, E3, E4, E5, E6, E7 or E8, wherein the definitions of E1, E3, E4, E5, E6, E7 and E8 are as described in claim 2.

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