Composition containing turmeric analogue and application of composition in insecticide

Abstract

The invention discloses a composition containing a turmeric analogue and application of the composition in an insecticide. The structural formula of the turmeric analogue is (E)-3-((1H-indole-3-yl) methylene)-5-((E)-4-mercaptobenzylidene)-1-methylpiperidine-4-thioketone. The turmeric analogue is synthesized through multi-step reaction, including aldehyde acylation, cyclization, thiolation reaction and condensation reaction. Insecticidal experiments show that the composition has good inhibitory activity on beet armyworms and can be used as a potential pesticide for preventing and treating beet armyworms.

Description

Technical Field

[0001] This invention belongs to the field of medicinal chemistry, specifically relating to a composition containing a curcumin analogue and its application in insecticides. Background Technology

[0002] The beet armyworm (Spodoptera exigua) is a highly damaging polyphagous agricultural pest. Its larvae are voracious eaters with overlapping generations. The main damage manifests as follows: newly hatched larvae congregate on the underside of leaves, weaving webs and feeding on the leaf tissue, creating transparent window spots; after the third instar, they disperse and voraciously feed on leaves, creating holes and notches, sometimes completely consuming the leaves except for the veins, leading to seedling death; after the fourth instar, they bore into the fruits of peppers, tomatoes, and corn ears, causing fruit drop, rot, and contamination, resulting in yield reductions of 30%-70%. This insect has 4-9 generations per year, with peak outbreaks from July to September. It is nocturnal, exhibits feigning death, and migrates; adults are strongly attracted to light, and the control window is only 3-5 days. The current control of the beet armyworm faces multiple challenges: the insect has developed resistance to mainstream pesticides such as pyrethroids and spinosads by 50-200 times; the camouflage habits of third-instar larvae, which involve boring into fruits or hiding in soil crevices, make it difficult for contact pesticides to penetrate effectively, while biopesticides suffer from degradation due to ultraviolet radiation, resulting in a residual effect of less than 5 days; at the same time, broad-spectrum insecticides such as organophosphates kill over 70% of natural enemies, disrupting the ecological balance; and the high cost of highly effective pesticides (over 50 yuan per mu) and the need to precisely grasp the 3-5 day application window have led to a vicious cycle of "increasing pesticide dosage—intensified resistance—decreased efficacy." Therefore, there is an urgent need to develop novel compounds with novel mechanisms of action, environmental friendliness, and controllable costs.

[0003] Studies have shown that the natural product curcumin has a variety of pharmacological effects in vitro, including anti-inflammatory, antioxidant, anticoagulant, anti-aging, lipid-lowering, anti-atherosclerotic, and anti-tumor effects, which have attracted widespread attention and research both domestically and internationally.

[0004]

[0005] Inspired by the structure of curcumin, we designed and synthesized a curcumin analog with a cyclic ketone monocarbonyl group. Subsequent biological experiments showed that it has good inhibitory activity against beet armyworm and can be used as a potential pesticide for the control of beet armyworm. Summary of the Invention

[0006] To address the problems existing in the prior art, this invention modifies the structure of turmeric and, through repeated experiments, discovers a turmeric analogue with good inhibitory activity against the beet armyworm. The structure of the analogue is as follows:

[0007]

[0008] This turmeric analog can be used alone for the control of beet armyworm, or it can be added to an agronomically acceptable adjuvant to form a composition containing the turmeric analog for the control of beet armyworm, or it can be combined with other insecticides for the control of beet armyworm.

[0009] More preferably, the composition containing a turmeric analog may contain a salt of the turmeric analog, wherein the salt is a sodium salt, citrate, phosphate, or acetate.

[0010] Furthermore, the turmeric analog in the composition containing the turmeric analog of the present invention is obtained by the following method:

[0011]

[0012] Step 1: React 3-indolecarboxaldehyde with benzoyl chloride to generate intermediate compound 2;

[0013] Step 2: Compound 2 is condensed with piperidine and N-methyl-4-piperidinone in tetrahydrofuran to generate intermediate compound 3;

[0014] Step 3: Under nitrogen protection, compound 3 reacts with Lawson's reagent to generate thiointermediate compound 4;

[0015] Step 4: Compound 4 is condensed with p-mercaptobenzaldehyde under the catalysis of trifluoroacetic acid to obtain the target turmeric analog.

[0016] More preferably, in step one, the reaction temperature is 0-5℃ and the reaction time is 1-3 hours; in step two, the reaction temperature is 40-60℃ and the reaction time is 2-5 hours; in step three, the molar ratio of Lawson's reagent to compound 3 is 1-1.5:1; and in step four, the molar ratio of trifluoroacetic acid to compound 4 is 3-5:1.

[0017] More preferably, the composition of the present invention containing a turmeric analogue is used in the prevention and control of beet armyworm.

[0018] Furthermore, compositions containing curcumin analogues can be prepared into wettable powders, water-dispersible granules, suspensions, emulsions, and water-in-oil emulsions. These compositions can be used to prepare pesticides against beet armyworm, wherein the weight content of the curcumin analogue is 2% to 90%.

[0019] Furthermore, the turmeric analogue of the present invention can be used alone to control the beet armyworm, wherein the structural formula of the turmeric analogue is as follows:

[0020]

[0021] The beneficial effects of this invention are:

[0022] 1) The composition or turmeric analog provided by the present invention has significant insecticidal effect, especially against beet armyworm. Its insecticidal effect at low concentrations is significantly better than that of the existing beet leafminer insecticide flufenoxuron. The turmeric analog of the present invention has good insecticidal effect and low dosage, making it very suitable for the control of beet leafminer.

[0023] 2) The preparation process of the turmeric analog provided by the present invention is simple, and no fluorine-containing substances are used in the reaction process. It is environmentally friendly and suitable for large-scale industrial promotion. Attached Figure Description

[0024] Figure 1 The first image shows the hydrogen NMR spectrum of the turmeric analog obtained in Example 1 of this invention.

[0025] Figure 2 The carbon NMR spectrum of the turmeric analog obtained in Example 2 of this invention;

[0026] Figure 3 This is the mass spectrum of the turmeric analog obtained in Example 3 of the present invention; Detailed Implementation

[0027] The technical solutions of this application will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are merely some embodiments of this application, and not all embodiments. The components of this application described and shown in the accompanying drawings can generally be arranged and designed in various different configurations. Therefore, the following detailed description of the embodiments of this application provided in the accompanying drawings is not intended to limit the scope of the claimed application, but merely to illustrate selected embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application without inventive effort are within the scope of protection of this application.

[0028] Example 1: Preparation of Curcuma analogues

[0029] The raw materials 3-indolecarboxaldehyde, benzoyl chloride, and Lawson reagent were purchased from Anhui Zesheng Technology Co., Ltd., and 4-mercaptobenzaldehyde was purchased from Beijing Bailingwei Technology Co., Ltd.

[0030] Step 1:

[0031]

[0032] The starting material 3-indolecarboxaldehyde (10 mmol) was dissolved in a solution of dichloromethane (10 mL), and triethylamine (12 mmol) was added. Benzoyl chloride (10 mmol) was slowly added to the mixture at 0 °C. After reacting for 1 h, the solvent was directly evaporated to obtain compound 2 with a yield of 95%.

[0033] Step 2:

[0034]

[0035] Compound 2 (5 mmol) was dissolved in a solution of tetrahydrofuran (10 mL), and piperidine (7.5 mmol) and N-methyl-4-piperidinone (7.5 mmol) were added. The mixture was reacted at 50 °C for 4 hours. TLC was monitored until the reaction of the starting material was complete. The reaction was quenched by adding 10 mL of ammonium chloride aqueous solution, and extracted with 50 mL × 3 ethyl acetate. The organic phase was dried over anhydrous sodium sulfate, and after vacuum distillation, silica gel column chromatography (EA:MeOH = 8:1) gave product compound 3 in 76% yield.

[0036] Step 3:

[0037]

[0038] Under nitrogen protection, compound 3 (3 mmol) was dissolved in 5 mL of tetrahydrofuran, and Lawson's reagent (4 mmol) was added at 30 °C. The reaction was carried out at this temperature for 12 hours. TLC monitoring was performed until the reaction of the starting material was complete. The reaction was quenched by adding 10 mL of ammonium chloride aqueous solution, extracted with 50 mL × 3 ethyl acetate, dried over anhydrous sodium sulfate, and purified by silica gel column chromatography (EA:MeOH = 6:1) under reduced pressure to give compound 4 in 89.2% yield.

[0039] Step 4:

[0040]

[0041] Compound 4 (1 mmol) was dissolved in 3 ml of acetic acid, and trifluoroacetic acid (5 mmol) and p-mercaptobenzaldehyde (2.5 mmol) were added. The mixture was reacted at 80 °C for 5 hours. The solvent was then directly evaporated, and silica gel column chromatography (EA:MeOH = 7:1) was performed to give the curcumin analog (compound 5) with a yield of 85% and a purity of 99.2%. 1 H NMR(400MHz,MeOD)δ8.25(s,1H),7.83(d,J=7.6Hz,1H),7.79(s,1H),7.63(s,1H),7.46(d,J=7.7Hz,1H ),7.35(d,J=8.5Hz,2H),7.28–7.17(m,2H),6.88(d,J=8.5Hz,2H),3.86(d,J=10.3Hz,4H),2.59(s,3H). 13C10 NMR (150MHz, DMSO) δ 174.91, 147.46, 142.47, 139.47, 136.21, 131.26, 131.17, 131.07, 129.43, 129.21, 128.68, 127.06, 124.86, 122.72, 122.64, 119.79, 117.91, 112.44, 58.85, 33.96. HRMS (m / z): 377.1624. The 1H NMR spectrum, 1C NMR spectrum, and mass spectrum are shown below. Figure 1 , Figure 2 , Figure 3 .

[0042] Example 2: Insecticide Experiment

[0043] This includes experimental materials and consumables (including solvents, labeled ligands, and unlabeled ligands), the specific source of the cells, and the name, model, and manufacturer of the main instruments used.

[0044] Instrument Name model Manufacturer One-millionth electronic balance TP50121 Beijing Yuping Scientific Instruments Co., Ltd. TLC silicone plate MPGJ254 Yantai Muping Chemical Silica Gel Co., Ltd. Rotary evaporator Xz-zf-2024A Zhengzhou Xintai Instrument Technology Co., Ltd. Heated magnetic stirrer MGS-01 Beijing Chuangyu Technology Co., Ltd. Nuclear magnetic resonance spectrometer VANCEIII400 Bruckbeyspin GmbH, Switzerland

[0045] After synthesizing the target compound curcumin analog compound 5, its insecticidal activity against the beet armyworm was tested using flubendiamide as a positive control. The specific method was as follows: equal amounts of compound 5 and flubendiamide were dissolved in dimethyl sulfoxide (DMSO) and diluted to the desired concentration with distilled water containing 0.1% (v / v) Tween-80. Leaf discs with a diameter of 1.8 cm were cut from fresh cabbage grown in a greenhouse, immersed in the test solution for 30 seconds, and then air-dried. Distilled water containing 0.1% (v / v) Tween-80 and 0.01% (v / v) dimethyl sulfoxide was used as a negative control. The treated leaf discs were placed in 9 cm diameter petri dishes lined with filter paper, and each petri dish contained 10 second-instar larvae of the beet armyworm reared in the laboratory. The petri dishes were then incubated at 26±1℃, 85% relative humidity, and a photoperiod of 16 hours light / 8 hours darkness. Each experiment was conducted in triplicate, with different concentrations of compound 5, flubendiamide, applied to the beet armyworm. Mortality rates (%) were measured 48 hours after treatment. The experiment found that distilled water containing 0.1% (v / v) Tween-80 and 0.01% (v / v) dimethyl sulfoxide had no control effect on the second instar larvae of the beet armyworm. Therefore, the experimental results of different concentrations of curcumin analog compound 5 and flubendiamide were analyzed.

[0046] Table 1. Toxicity tests of compound 5 and the positive control flubendiamide on beet armyworm at different concentrations.

[0047]

[0048] We can see that at a high concentration (80 mg / L), both compound 5 and the positive control flubendiamide showed a 100% kill rate against beet armyworm larvae. As the concentration decreased, the insecticidal effect of compound 5 became increasingly significant. When the concentration decreased to 20 mg / L, the LC5 of compound 5 against larvae... 50 It was significantly superior to the positive control flubendiamide, demonstrating its potential advantages as a novel insecticide.

[0049] The turmeric analogue (compound 5) obtained in Example 1 was compounded with an agronomically acceptable adjuvant, and the above insecticidal experiment was repeated. The results were similar to those in Table 1.

[0050] While the specific embodiments of the present invention have been described above, they are not intended to limit the scope of protection of the present invention. Those skilled in the art should understand that various modifications or variations that can be made by those skilled in the art without creative effort based on the technical solutions of the present invention are still within the scope of protection of the present invention.

Claims

1. A composition containing a turmeric analogue, characterized in that, The structural formula of the turmeric analogue is shown below:

2. The composition containing a turmeric analogue according to claim 1, characterized in that, The composition is in the form of wettable powder, water-dispersible granules, suspension, emulsion, or water-in-oil emulsion.

3. The composition containing a turmeric analogue according to claim 2, characterized in that, The weight content of the turmeric analogue is 2% to 90%.

4. The application of the composition containing a turmeric analogue according to claim 2 for the control of beet armyworm.

5. The application of a turmeric analog in the control of beet armyworm, characterized in that, The structural formula of the turmeric analogue is shown below:

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