CN110759883B - Genipin derivatives containing ester, oxime and hydrazone fragments and preparation and application thereof - Google Patents
Genipin derivatives containing ester, oxime and hydrazone fragments and preparation and application thereof Download PDFInfo
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Abstract
The invention relates to genipin derivatives containing ester, oxime and hydrazone fragments, a preparation method thereof and application of the genipin derivatives as pesticides. The general formulas (I-a and I-b) of the invention have excellent insecticidal activity on tetranychus cinnabarinus adults, and the genipin acylhydrazone I-b-5 can reach 80% even at the concentration of 200mg/L, so that the harm of tetranychus cinnabarinus to various crops can be effectively prevented and treated. In addition, the general formulas (I-a and I-b) have excellent insecticidal activity on lepidoptera pests, wherein the compound I-a-14 is insecticidal LC for diamondback moth 50 The value was 40.4mg/L (95% confidence interval 23.5-69.7 mg/L), showing excellent diamondback moth killing activity. The general formulas (I-a and I-b) have excellent bacteriostatic activity on common 14 plant pathogenic bacteria, and can effectively prevent and treat fungi of various cropsAnd (4) disease.
Description
Technical Field
The invention relates to genipin derivatives containing ester, oxime and hydrazone fragments, a preparation method thereof and application of the genipin derivatives as pesticides.
Background
The oxime compound contains functional groups such as oxime, oxime ether or oxime ester and the like, has excellent insecticidal, bactericidal, herbicidal and plant virus resistant activities, and has the advantages of low toxicity, low residue and the like in many varieties. Since the development of the first oxime ester pesticide gossypol in 1963, a large number of pesticide varieties such as oxime carbamate pesticides such as aldicarb and methomyl, oxime phosphate pesticides phoxim, methyl phoxim and chlorphoxim, and pesticide phoshoria with a double structure of organophosphorus and oxime carbamate, such as foscarnet, have appeared in succession (organic chemistry, 2005, 05, 507-525- +479). A series of pyrazole oxime ether compounds are designed and synthesized by a Zhongkai Zhonghua Zhouyi Zhonghua woolly subject group (Chin.J. org.chem.,2015, 35, 100), and the bioassay result shows that the compounds have good mosquito-killing, bean aphid-killing and mite-killing activities. The Xue Wei topic group (Chin. J. Org. Chem.,2014, 34, 1662) of Guizhou university designs and synthesizes a series of 1-aryl-5-heterocycle 1, 4-pentadiene-3-ketoxime ether compounds, and the bioassay result shows certain anti-TMV activity. Pyrazole oxime ether series derivatives synthesized by Park et al (bioorg.med.chem.lett., 2005, 15, 3307-3312) showed potent inhibitory activity against human colon cancer cells (HCT 15) and human central nervous system tumor cells (xf-498).
The hydrazone compound is a compound having a molecular structure containing a substructure of-NHN = C-. The compound has wide biological activity, strong coordination capacity and various coordination forms, and can derive compounds with various physiological activities such as antibiosis, disinsection, weeding, HIV resistance, antivirus, anticancer and the like, so the compound has wide attention in the aspects of medicine, pesticide, material, detection and the like. At present, the commercialized varieties comprise herbicide diflufenzopyr, insecticide pymetrozine, cyhalothrin hydrazone and the like. The Wang Qingmin subject group of southern Kai university designs and synthesizes tetrahydro-beta-carboline compounds containing acylhydrazone structures, the anti-TMV activity of most derivatives is better than that of commercial varieties of ribavirin, and the activity of individual compounds is better than that of the efficient plant virosis control medicament NK-007 created by the subject group. The group also designs and synthesizes a series of gossypol hydrazone Schiff base derivatives, and finds that most compounds show better solubility than gossypol aromatic amine Schiff bases and better anti-TMV activity than the parent compound gossypol.
In previous work (j.agric.food chem.,2018, 66, 1341-1348), we found that the bioactivity of glycosyl-10-genipin derivative is significantly higher than glycosyl-1-genipin derivative. The hemiacetal structure at 1-position of genipin is presumed to be a key functional group for biological activity, so that the derivatization research on the 10-position hydroxyl group is expected on the basis of retaining the 1-position hemiacetal structure. In order to change the physicochemical properties of genipin, the hydroxyl at the 10 th position of genipin is expected to be further derivatized, and a series of genipin derivatives containing ester, oxime and hydrazone fragments are synthesized. It is hoped that genipin ester, oxime or hydrazone derivative leads with high biological activity can be obtained through screening of biological activity.
Disclosure of Invention
The invention aims to provide a genipin derivative containing ester, oxime and hydrazone fragments, and preparation and application thereof. Compared with the reported compounds, the compounds have the advantages of novel structure, wide biological activity range, high activity and the like.
The genipin derivative containing ester, oxime and hydrazone fragments is characterized by having a structure shown as the following general formula (I) and specifically comprising two forms (I-a) and (I-b):
the genipin derivatives (I-a-1-13) containing ester fragments can be prepared by the following method (method one): dissolving the substrate 1 and various acyl chloride substrates in dichloromethane, adding triethylamine and dimethylamino pyridine, and reacting at room temperature until the reaction is finished. After post-treatment, the crude product is dissolved in tetrahydrofuran, glacial acetic acid and tetrabutylammonium fluoride are added under ice bath, and the target product (I-a-1-13) is obtained after room temperature reaction.
The method comprises the following steps:
the genipin derivatives (I-a-14-15) containing ester fragments can be prepared by the following method (method II): dissolving the substrate 1 and triethylamine in dichloromethane, dropwise adding an isocyanate substrate, and reacting at room temperature until the reaction is finished. After post-treatment, the crude product is dissolved in tetrahydrofuran, glacial acetic acid and tetrabutylammonium fluoride are added under ice bath, and the target product (I-a-14-15) is obtained by room temperature reaction.
The second method comprises the following steps:
the genipin derivatives (I-a-16-19) containing ester fragments can be prepared by the following method (method III): dissolving the substrate 1 and sodium hydride in tetrahydrofuran, dropwise adding an isothiocyanate or dimethylcarbamoyl chloride or phenyl thiocarbamate substrate under ice bath, and reacting at room temperature until the reaction is finished. After post-treatment, the crude product is dissolved in tetrahydrofuran, glacial acetic acid and tetrabutylammonium fluoride are added under ice bath, and the target product (I-a-16-19) is obtained after room temperature reaction.
The third method comprises the following steps:
the genipin derivatives (I-b-1-6) containing hydrazone fragments can be prepared by the following method (method IV): and dissolving the substrate 2 and the organic amine in absolute ethyl alcohol, and carrying out reflux reaction until the reaction is finished. After post-treatment, the crude product is dissolved in tetrahydrofuran, glacial acetic acid and tetrabutylammonium fluoride are added under ice bath, and the target product (I-b-1-6) is obtained after room temperature reaction.
The method four comprises the following steps:
the genipin derivative (I-b-7) containing oxime fragment can be prepared by the following method (method five): and dissolving the substrate 3 in tetrahydrofuran, adding glacial acetic acid and tetrabutylammonium fluoride under ice bath, and reacting at room temperature to obtain the target product (I-b-7).
The method five comprises the following steps:
the genipin derivative (I-b-8) containing oxime fragment can be prepared by the following method (method six): and dissolving the substrate 3, triethylamine and m-chlorobenzene isocyanate in dichloromethane, and reacting at room temperature until the reaction is finished. And (3) dissolving the post-treated crude product in tetrahydrofuran, adding glacial acetic acid and tetrabutylammonium fluoride under ice bath, and reacting at room temperature to obtain the target product (I-b-8).
The method six:
the genipin derivative (I-b-9) containing the oxime fragment can be prepared by the following method (method seven): and dissolving the substrate 3, methyl carbamyl chloride, dimethylamino pyridine and triethylamine in dichloromethane, and carrying out reflux reaction until the reaction is finished. And (3) dissolving the post-treated crude product in tetrahydrofuran, adding glacial acetic acid and tetrabutylammonium fluoride under ice bath, and reacting at room temperature to obtain the target product (I-b-9).
The method comprises the following steps:
part of the compounds in the general formula (I) of the invention show excellent insecticidal activity to tetranychus cinnabarinus adults, and genipin acylhydrazone I-b-5 even reaches 80% at the concentration of 200mg/L, so that the harm of tetranychus cinnabarinus to various crops can be effectively prevented and treated.
The compound in the general formula (I) has excellent insecticidal activity on lepidoptera pests such as diamondback moth, armyworm, corn borer and cotton bollworm, wherein the compound I-a-12 is insecticidal LC for the diamondback moth 50 The value is 40.4mg/L (the 95% confidence interval is 23.5-69.7 mg/L), the diamondback moth killing activity is excellent, and the method has great prospect for developing diamondback moth killing prodrugs.
Part of the compounds in the general formula (I) have excellent bacteriostatic activity on common 14 plant pathogenic bacteria, and can effectively prevent and treat fungal diseases of various crops.
Detailed Description
The invention is further illustrated by the following examples in which the melting points are uncorrected and the yields are not optimized.
Example 1: synthesis of I-a-1 to 13
Target Compound (I-a-1): a50 mL round-bottom flask was charged with 10mL of dichloromethane, substrate 1 (1 mmol), triethylamine (3 mmol) and 4-dimethylaminopyridine (0.2 mmol), and the acid chloride (1.5 mmol) was added dropwise with stirring at room temperature. After the addition was completed, the reaction was carried out at room temperature until completion of the TLC monitoring. Adding water to quench and react, extracting an organic phase for three times by using dichloromethane, combining the organic phases, washing the organic phases by using saturated saline solution, drying the organic phases by using anhydrous sodium sulfate, and performing desolventizing to obtain a crude product which directly enters the next reaction without purification. The crude product from the previous step was dissolved in tetrahydrofuran, glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) were added under ice bath, warmed to room temperature for reaction, and the reaction was monitored by TLC. When the reaction is complete, rotary evaporation is carried out for desolventizing, silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) is carried out to obtain the target product I-a-1 as light yellow oil, the yield is 63 percent, and d.r. = 10: 1. 1 H NMR(400MHz，CDCl 3 )δ7.48(d，J＝1.2Hz，1H)，5.99-5.78(m，2H)，5.24(d，J＝7.2Hz，1H)，5.15(ddq，J＝13.4，3.1，1.5Hz，2H)，4.91-4.81(m，1H)，4.81-4.69(m，2H)，3.69(s，3H)，3.21-3.05(m，3H)，2.85(ddt，J＝16.7，8.7，2.1Hz，1H)，2.49(td，J＝8.2，2.0Hz，1H)，2.01(ddq，J＝14.4，9.3，1.9Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ172.3，168.1，152.9，138.2，131.8，129.9，119.0，110.5，96.5，63.4，51.4，47.1，39.2，38.9，36.2.HRMS(ESI)calcd for C 15 H 19 O 6 [M+H] + 295.1176，found 295.1170.
The target compounds I-a-2 to 13 can be synthesized by referring to I-a-1.
Target compound I-a-2: silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) gave the target product I-a-2 as a colorless oil in a yield of 57%, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.49(d，J＝1.3Hz，1H)，6.42(dd，J＝17.3，1.4Hz，1H)，6.13(dd，J＝17.3，10.4Hz，1H)，5.98-5.89(m，1H)，5.85(dd，J＝10.4，1.4Hz，1H)，5.29(d，J＝7.4Hz，1H)，5.00-4.89(m，1H)，4.88-4.68(m，2H)，3.69(s，3H)，3.22-3.13(m，1H)，2.87(ddt，J＝16.8，8.6，2.1Hz，1H)，2.52(td，J＝8.2，2.0Hz，1H)，2.03(dddt，J＝16.6，9.3，3.3，1.9Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，166.8，152.9，138.2，132.0，131.8，128.1，110.5，96.6，63.3，51.4，47.1，38.9，36.3.HRMS(ESI)calcd for C 14 H 16 NaO 6 [M+Na] + 303.0839，found 303.0836.
Target compound I-a-3: silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) is carried out to obtain the target product I-a-3 colorless oily substance with the yield of 90 percent and the d.r. = 11: 1. 1 H NMR(400MHz，CDCl 3 )δ7.46(d，J＝1.2Hz，1H)，5.82(s，1H)，5.76-5.52(m，1H)，4.94-4.54(m，3H)，3.67(s，3H)，3.18-3.07(m，1H)，2.83(ddt，J＝15.8，7.3，2.7Hz，1H)，2.53-2.42(m，1H)，2.29(tt，J＝11.2，3.7Hz，1H)，2.05-1.94(m，2H)，1.86(dd，J＝13.4，3.8Hz，2H)，1.69(dt，J＝12.6，3.8Hz，2H)，1.63-1.53(m，1H)，1.39(qd，J＝11.8，3.3Hz，2H)，1.30-1.20(m，2H). 13 C NMR(100MHz，CDCl 3 )δ176.6，168.1，152.9，138.6，130.8，110.3，96.4，62.8，51.3，47.0，43.2，38.8，36.1，29.0，28.9，25.6，25.3.HRMS(ESI)calcd for C 18 H 24 NaO 6 [M+Na] + 359.1465，found 359.1463.
Target compound I-a-4: silica gel column chromatography (petroleum ether: ethyl acetate = 3: 1) gave the target product I-a-4 as a colorless oil in 41% yield, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.48(d，J＝1.4Hz，1H)，6.06-5.93(m，2H)，5.00-4.94(m，2H)，4.80(d，J＝8.6Hz，2H)，3.70(s，3H)，3.23-3.15(m，1H)，2.89(dddt，J＝16.9，8.7，2.9，1.4Hz，1H)，2.55(td，J＝8.2，2.0Hz，1H)，2.12-1.98(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.2，164.6，152.8，136.9，132.7，110.5，96.3，65.7，64.4，51.5，47.1，39.1，36.0.HRMS(ESI)calcd for C 13 H 14 Cl 2 NaO 6 [M+Na] + 359.0060，found 359.0055.
Target compound I-a-5: silica gel column chromatography (petroleum ether: ethyl acetate = 10: 1) to obtain the target product I-a-5 as a white solid, the melting point is 59-61 ℃, the yield is 70%, and d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.93(td，J＝7.6，1.8Hz，1H)，7.57-7.46(m，2H)，7.18(td，J＝7.6，1.1Hz，1H)，7.11(ddd，J＝10.9，8.3，1.1Hz，1H)，6.05-5.95(m，1H)，5.14-5.05(m，2H)，5.00(d，J＝13.6Hz，1H)，4.85(dd，J＝8.5，5.1Hz，1H)，3.70(s，3H)，3.20(q，J＝8.6，8.0Hz，1H)，2.89(ddt，J＝16.4，8.5，2.0Hz，1H)，2.66-2.57(m，1H)，2.11-2.02(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，164.9(d，J＝3.6Hz)，162.1(d，J＝260.0Hz)，152.9，138.1，134.9(d，J＝9.0Hz)，132.3，131.9，124.1(d，J＝4.3Hz)，118.4(d，J＝9.8Hz)，117.1(d，J＝22.6Hz)，110.6，96.6，64.0，51.4，47.3，39.0，36.2.HRMS(ESI)calcd for C 18 H 21 FNO 6 [M+NH 4 ] + 366.1347，found 366.1343.
Target compound I-a-6: silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) gave the target product I-a-6 as a colorless oil in 66% yield, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.91(d，J＝8.1Hz，2H)，7.50(d，J＝1.2Hz，1H)，7.19(d，J＝8.1Hz，2H)，5.95(d，J＝2.7Hz，1H)，5.12-4.92(m，2H)，4.85(d，J＝8.5Hz，1H)，3.68(s，3H)，3.23-3.14(m，1H)，2.88(ddt，J＝16.4，8.5，2.0Hz，1H)，2.60(td，J＝8.1，1.9Hz，1H)，2.36(s，3H)，2.10-1.99(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，167.2，153.0，144.0，138.5，131.5，129.8，129.1，127.0，110.4，96.5，63.5，51.3，47.1，38.9，36.2，21.6.HRMS(ESI)calcd for C 19 H 20 NaO 6 [M+Na] + 367.1152，found 367.1146.
Target compound I-a-7: silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) gave the target product I-a-7 as a colorless oil in 67% yield, d.r. = 8: 1. 1 H NMR(400MHz，CDCl 3 )δ7.47(d，J＝1.3Hz，1H)，5.98(t，J＝2.2Hz，1H)，5.06-4.84(m，3H)，4.79(d，J＝8.5Hz，1H)，3.88(s，3H)，3.69(s，3H)，3.24-3.14(m，1H)，2.88(dddd，J＝17.0，9.8，2.9，1.5Hz，1H)，2.63-2.54(m，1H)，2.05(ddd，J＝9.7，4.7，2.2Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，158.2，157.5，152.8，136.8，133.3，110.5，96.4，65.3，53.8，51.5，47.1，39.1，36.0.HRMS(ESI)calcd for C 14 H 20 NO 8 [M+NH 4 ] + 330.1183，found 330.1177.
Target compound I-a-8: silica gel column chromatography (petroleum ether: ethyl acetate = 3: 1) gave the desired product I-a-8 as a colorless oil in 84% yield, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.48(d，J＝1.4Hz，1H)，5.99(d，J＝2.7Hz，1H)，5.06-4.92(m，2H)，4.80(d，J＝9.7Hz，2H)，4.33(q，J＝7.2Hz，2H)，3.70(s，3H)，3.19(q，J＝9.2，8.7Hz，1H)，2.97-2.84(m，1H)，2.63-2.52(m，1H)，2.10-2.03(m，1H)，1.35(t，J＝7.1Hz，3H). 13 C NMR(100MHz，CDCl 3 )δ168.0，157.8，157.8，152.7，136.8，133.3，110.5，96.4，65.2，63.5，51.5，47.2，39.1，36.1，14.0.HRMS(ESI)calcd for C 15 H 22 NO 8 [M+NH 4 ] + 344.1340，found 344.1332.
Target compound I-a-9: silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) gave the desired product I-a-9 as a colorless oil in 81% yield, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.70(d，J＝16.0Hz，1H)，7.55-7.45(m，3H)，7.39-7.31(m，3H)，6.44(d，J＝16.0Hz，1H)，6.02-5.90(m，1H)，5.68-5.50(m，1H)，5.09-4.97(m，1H)，4.93-4.75(m，2H)，3.69(s，3H)，3.20(q，J＝8.5Hz，1H)，2.89(ddd，J＝17.2，8.9，2.4Hz，1H)，2.59(td，J＝8.2，1.9Hz，1H)，2.11-2.01(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，167.5，152.9，145.7，138.4，134.1，131.7，130.5，128.9，128.2，117.5，110.4，96.5，63.2，51.3，47.0，38.9，36.2.HRMS(ESI)calcd for C 20 H 20 NaO 6 [M+Na] + 379.1152，found 379.1146.
Target compound I-a-10: silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) to obtain the target product I-a-10 white solid with a melting point of 99-101 ℃, a yield of 75% and a d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ8.92(d，J＝2.5Hz，1H)，8.21(dd，J＝8.4，2.3Hz，1H)，7.45(s，1H)，7.37(d，J＝8.5Hz，1H)，5.93(s，1H)，5.78(s，1H)，5.02(t，J＝10.4Hz，2H)，4.85(d，J＝8.5Hz，1H)，3.65(s，3H)，3.17(q，J＝8.6Hz，1H)，2.85(dd，J＝16.9，8.7Hz，1H)，2.59(t，J＝8.2Hz，1H)，2.09-1.98(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.0，164.4，155.6，152.8，151.1，139.8，137.8，132.0，125.0，124.3，110.4，96.3，64.1，51.4，47.2，39.0，36.0.HRMS(ESI)calcd for C 17 H 17 ClNO 6 [M+H] + 366.0739，found 366.0740.
Target compound I-a-11: silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) gave the target product I-a-11 as a colorless oil in a yield of 43%, d.r. = 6: 1. 1 H NMR(400MHz，CDCl 3 )δ7.49(d，J＝1.3Hz，1H)，5.99(t，J＝2.2Hz，1H)，4.98-4.87(m，2H)，4.87-4.77(m，2H)，4.76(s，2H)，3.70(s，3H)，3.19(q，J＝8.6，8.0Hz，1H)，2.94-2.83(m，1H)，2.63-2.53(m，1H)，2.10-1.99(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，154.3，152.8，137.2，133.0，110.6，96.4，94.4，76.9，67.3，51.5，47.0，39.1，36.1.HRMS(ESI)calcd for C 14 H 15 Cl 3 NaO 7 [M+Na] + 422.9776，found 422.9774.
Target compound I-a-12: silica gel column chromatography (petroleum ether: ethyl acetate = 7: 1) is carried out to obtain the target product I-a-12 colorless oily substance with the yield of 55 percent and the d.r. = 6: 1. 1 H NMR(400MHz，CDCl 3 )δ7.50(s，1H)，7.15(d，J＝8.2Hz，2H)，7.03(d，J＝8.5Hz，2H)，5.99(s，1H)，4.97-4.86(m，2H)，4.76(d，J＝8.6Hz，1H)，3.71(s，3H)，3.20(q，J＝8.6Hz，1H)，2.96-2.84(m，1H)，2.57(t，J＝8.2Hz，1H)，2.32(s，3H)，2.12-1.99(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，154.2，152.8，148.9，137.6，135.9，132.6，130.0，120.7，110.5，96.4，66.9，51.4，47.0，39.0，36.1，20.8.HRMS(ESI)calcd for C 19 H 24 NO 7 [M+NH 4 ] + 378.1547，found 378.1543.
Target compound I-a-13: silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) gave the target product I-a-13 as a colorless oil in 74% yield, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.45(s，1H)，6.33(s，1H)，5.81(s，1H)，5.33-5.12(m，1H)，4.83(d，J＝14.0Hz，1H)，4.70(d，J＝8.7Hz，1H)，4.59(d，J＝13.5Hz，1H)，3.65(s，3H)，3.09(q，J＝8.7Hz，1H)，2.80(dd，J＝16.8，8.8Hz，1H)，2.72(d，J＝4.8Hz，3H)，2.47(t，J＝8.3Hz，1H)，2.05-1.87(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.1，158.0，153.1，139.1，131.4，110.3，96.6，63.5，51.2，46.6，38.8，36.3，27.5.HRMS(ESI)calcd for C 13 H 17 NNaO 6 [M+Na] + 306.0948，found 306.0944.
Example 2: synthesis of I-a-14 to 15
Target compound I-a-14: a50 mL round-bottom flask was charged with 10mL of dichloromethane, substrate 1 (1 mmol) and triethylamine (3 mmol) at room temperatureThe isocyanate (1.5 mmol) was added dropwise with stirring. After the addition was completed, the reaction was carried out at room temperature until completion of the TLC monitoring. Adding water to quench and react, extracting an organic phase with dichloromethane for three times, combining the organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, desolventizing to obtain a crude product, and directly carrying out the next reaction without purification. The crude product from the previous step was dissolved in tetrahydrofuran, glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) were added under ice-bath, warmed to room temperature for reaction, and monitored by TLC. When the reaction is complete, rotary evaporation is carried out for desolventizing, silica gel column chromatography (petroleum ether: ethyl acetate = 4: 1) is carried out to obtain the target product I-a-14 colorless oily substance with the yield of 73 percent and the d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.65-7.57(m，2H)，7.54(d，J＝5.0Hz，1H)，7.39-7.24(m，2H)，7.11(d，J＝7.8Hz，1H)，6.03(s，1H)，5.84-5.66(m，1H)，5.08(d，J＝13.5Hz，1H)，4.93-4.81(m，2H)，3.81(s，3H)，3.27(q，J＝8.7Hz，1H)，3.05-2.91(m，1H)，2.67(t，J＝8.3Hz，1H)，2.20-2.06(m，1H). 13 C NMR(100MHz，CDCl 3 )δ168.3，154.2，153.1，139.0，138.5，134.8，132.6，130.1，123.7，119.0，117.0，110.5，96.7，64.1，51.5，46.9，39.0，36.4.HRMS(ESI)calcd for C 18 H 18 ClNNaO 6 [M+Na] + 402.0715，found 402.0711.
The target compound I-a-15 can be synthesized by referring to I-a-14.
Target compound I-a-15: silica gel column chromatography (petroleum ether: ethyl acetate = 3: 1) to obtain the target product I-a-15 gray solid, the melting point is 128-130 ℃, the yield is 65%, and d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.50(d，J＝1.3Hz，1H)，6.39(s，1H)，5.87(s，1H)，5.10-4.80(m，2H)，4.73(d，J＝8.8Hz，1H)，4.55(d，J＝13.5Hz，1H)，3.68(s，3H)，3.52-3.33(m，1H)，3.14(q，J＝8.6Hz，1H)，2.91-2.78(m，1H)，2.49(td，J＝8.8，8.4，2.0Hz，1H)，2.08-1.95(m，1H)，1.95-1.82(m，2H)，1.67(dt，J＝13.4，4.1Hz，2H)，1.57(dt，J＝12.6，3.6Hz，1H)，1.38-1.23(m，2H)，1.19-1.07(m，3H). 13 C NMR(100MHz，CDCl 3 )δ168.1，156.7，153.2，139.3，132.2，110.4，96.8，63.5，51.3，50.1，46.7，38.9，36.7，33.3，25.5，24.8.HRMS(ESI)calcd for C 18 H 15 NNaO 6 [M+Na] + 374.1574，found 374.1570.
Example 3: synthesis of I-a-16 to 19
Target compound I-a-16: a50 mL round-bottom flask was charged with 10mL of tetrahydrofuran, 1 (1 mmol) and sodium hydride (1.5 mmol), reacted in ice bath for 30min, and then isothiocyanate (1.5 mmol) was added dropwise. After the dropwise addition was completed, the reaction was warmed to room temperature until the completion of the TLC monitoring. Adding ice water to quench the reaction, extracting the organic phase with ethyl acetate for three times, combining the organic phases, washing with saturated saline solution, drying with anhydrous sodium sulfate, desolventizing to obtain a crude product, and directly entering the next reaction without purification. The crude product from the previous step was dissolved in tetrahydrofuran, glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) were added under ice-bath, warmed to room temperature for reaction, and monitored by TLC. When the reaction is complete, rotary evaporation is carried out for desolventizing, silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) is carried out to obtain the target product I-a-16 white crystals, the melting point is 106-108 ℃, the yield is 71%, and d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.45(d，J＝1.2Hz，1H)，6.53(s，1H)，5.87-5.77(m，1H)，4.85(d，J＝13.8Hz，1H)，4.70(d，J＝8.7Hz，1H)，4.62(d，J＝13.9Hz，1H)，3.64(s，3H)，3.18-3.04(m，1H)，2.86(d，J＝3.1Hz，6H)，2.83-2.74(m，1H)，2.52-2.42(m，1H)，1.97(dddd，J＝16.8，9.3，3.6，1.9Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ168.0，157.2，153.1，139.2，131.1，110.2，96.7，64.2，51.2，46.7，38.8，36.5，36.4，35.9.HRMS(ESI)calcd for C 14 H 19 NNaO 6 [M+Na] + 320.1105，found 320.1100.
The target compounds I-a-17 to 19 can be synthesized by referring to I-a-16.
Target compound I-a-17: silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) gave the desired product I-a-17 as a colorless oil in 49% yield, d.r. = 9: 1. 1 H NMR(400MHz，CDCl 3 )δ7.49(d，J＝3.3Hz，1H)，6.83(d，J＝7.8Hz，1H)，5.92(d，J＝10.6Hz，1H)，5.29(dd，J＝30.3，13.3Hz，1H)，5.15-4.95(m，2H)，4.81(t，J＝8.2Hz，1H)，4.39-4.24(m，1H)，3.70(s，3H)，3.23-3.11(m，1H)，2.87(dt，J＝16.8，8.8Hz，1H)，2.67-2.55(m，1H)，2.12-1.95(m，1H)，1.21(d，J＝6.5Hz，6H). 13 C NMR(100MHz，CDCl 3 )δ188.9，168.2，152.9，138.5，132.4，110.6，96.6，68.0，51.4，47.4，45.8，39.0，36.3，22.5，21.9.HRMS(ESI)calcd for C 15 H 21 NNaO 5 S[M+Na] + 350.1033，found 350.1025.
Target compound I-a-18: silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) gave the desired product I-a-18 as a colorless oil in 74% yield, d.r. = 6: 1. 1 H NMR(400MHz，CDCl 3 )δ9.04(s，1H)，7.66-7.24(m，5H)，7.22-7.12(m，1H)，5.93(s，1H)，5.49-5.07(m，3H)，4.86(d，J＝8.5Hz，1H)，3.72(s，3H)，3.20(q，J＝8.6Hz，1H)，2.96-2.82(m，1H)，2.63(s，1H)，2.09-2.01(m，1H). 13 C NMR(100MHz，CDCl 3 )δ188.4，168.2，152.9，137.6，136.8，132.3，129.1，125.7，122.0，110.5，96.4，70.7，51.5，47.1，39.0，36.0.HRMS(ESI)calcd for C 18 H 19 NNaO 5 S[M+Na] + 384.0876，found 384.0871.
Target compound I-a-19: silica gel column chromatography (petroleum ether: ethyl acetate = 5: 1) gave the desired product I-a-19 as a colorless oil in 37% yield, d.r. = 6: 1. 1 H NMR(400MHz，CDCl 3 )δ7.53(d，J＝1.3Hz，1H)，7.45-7.34(m，2H)，7.33-7.21(m，1H)，7.18-7.05(m，2H)，6.04(d，J＝2.3Hz，1H)，5.60-5.16(m，2H)，4.85(dd，J＝8.5，6.2Hz，1H)，4.58(d，J＝6.5Hz，1H)，3.73(s，3H)，3.24(dt，J＝9.3，7.8Hz，1H)，3.00-2.88(m，1H)，2.66(td，J＝8.2，2.0Hz，1H)，2.15-2.05(m，1H). 13 C NMR(100MHz，CDCl 3 )δ195.0，168.2，153.4，152.8，136.8，132.9，129.6，126.7，121.9，110.6，96.4，72.2，51.5，47.3，39.2，36.0.HRMS(ESI)calcd for C 18 H 22 NO 6 S[M+NH 4 ] + 380.1162，found 380.1157.
TABLE 1 structural List of Compounds I-a
Example 4: synthesis of I-b-1 to 6
Target compound I-b-1: a50 mL round bottom flask was charged with 10mL absolute ethanol, 2 (1 mmol) and organic amine (2 mmol), refluxed, and monitored by TLC. And after the reaction is finished, performing rotary evaporation and desolventizing, adding dichloromethane and water, extracting the organic phase for three times by using dichloromethane, combining the organic phases, washing the organic phases by using saturated saline solution, drying the organic phases by using anhydrous sodium sulfate, performing desolventizing to obtain a crude product, and directly entering the next reaction without purification. The crude product from the previous step was dissolved in tetrahydrofuran, glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) were added under ice-bath, warmed to room temperature for reaction, and monitored by TLC. When the reaction is complete, rotary evaporation is carried out for desolventizing, silica gel column chromatography (petroleum ether: ethyl acetate = 2: 1) is carried out to obtain the target product I-b-1 colorless oily substance with the yield of 53%. 1 H NMR(400MHz，CDCl 3 )δ8.06-8.00(m，1H)，7.74(s，1H)，7.59-7.45(m，2H)，7.04(d，J＝8.5Hz，1H)，6.74(ddd，J＝7.3，5.1，0.9Hz，1H)，6.29-6.13(m，1H)，4.84(d，J＝8.7Hz，1H)，3.71(s，3H)，3.36-3.16(m，1H)，3.11-2.94(m，2H)，2.23(ddt，J＝18.3，9.5，2.2Hz，1H)，2.01(s，1H). 13 C NMR(100MHz，CDCl 3 )δ167.8，156.1，152.8，146.7，139.0，138.7，138.5，116.0，110.2，107.2，96.4，51.4，47.2，40.1，36.4.HRMS(ESI)calcd for C 16 H 18 N 3 O 4 [M+H] + 316.1292，found 316.1296.
The target compounds I-b-2 to 6 can be synthesized by referring to I-b-1.
Target compound I-b-2: silica gel column chromatography (petroleum ether: ethyl acetate = 3: 1) to obtain the target product I-b-2 as white powder, meltingPoint 160-162 ℃ and yield 65%. 1 H NMR(400MHz，CDCl 3 )δ8.26(s，1H)，7.62(d，J＝1.4Hz，1H)，7.43-7.21(m，2H)，7.14-6.89(m，2H)，6.41(dt，J＝11.5，3.8Hz，2H)，4.81(dd，J＝8.9，4.3Hz，1H)，3.75(s，3H)，3.55(s，3H)，3.32-3.22(m，1H)，3.17-3.02(m，2H)，2.29(ddt，J＝12.0，9.8，4.9Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ167.9，167.2，153.0，151.5，141.5，140.9，139.4，126.6，123.8，122.3，122.2，110.1，109.6，96.6，51.4，47.2，40.4，36.6，31.0.HRMS(ESI)calcd for C 19 H 20 N 3 O 4 S[M+H] + 386.1169，found 386.1173.
Target compound I-b-3: silica gel column chromatography (petroleum ether: ethyl acetate = 7: 1) gave the desired product I-b-3 as a pale red oil in a yield of 68%. 1 H NMR(400MHz，CDCl 3 )δ8.01(s，1H)，7.55(d，J＝1.4Hz，1H)，7.42-7.28(m，5H)，6.36-6.26(m，1H)，5.29(d，J＝5.9Hz，1H)，5.15-5.05(m，2H)，4.71(dd，J＝8.8，5.6Hz，1H)，3.72(s，3H)，3.45-3.33(m，1H)，3.04(ddd，J＝18.2，8.5，3.4Hz，1H)，2.91-2.73(m，1H)，2.19(ddt，J＝18.3，9.7，2.2Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ167.7，152.9，147.7，141.6，136.6，135.9，128.6，128.5，128.4，110.0，96.2，76.7，51.3，47.0，40.0，36.7.HRMS(ESI)calcd for C 18 H 20 NO 5 [M+H] + 330.1336，found 330.1334.
Target compound I-b-4: silica gel column chromatography (dichloromethane: methanol = 80: 1) gave the desired product I-b-4 as a pale yellow oil in 78% yield. 1 H NMR(400MHz，CDCl 3 )δ10.25(d，J＝19.8Hz，1H)，7.84(d，J＝18.0Hz，1H)，7.49(d，J＝4.3Hz，1H)，6.63-6.42(m，1H)，5.84-5.27(m，1H)，5.26-4.61(m，1H)，4.02-3.57(m，5H)，3.31-2.85(m，3H)，2.56-2.12(m，1H). 13 C NMR(100MHz，CDCl 3 )δ167.9，165.0，152.9，147.9，145.0，138.6，115.1，110.3，95.6，51.5，46.3，40.1，35.9，24.9.HRMS(ESI)calcd for C 14 H 16 N 3 O 5 [M+H] + 306.1084，found 306.1081.
Target compound I-b-5: silica gel column chromatography (dichloromethane: methanol = 80: 1) gave the desired product I-b-5 as red crystals, mp 144-146 ℃ in 60% yield. 1 H NMR(400MHz，CDCl 3 )δ7.80(s，1H)，7.55(s，1H)，6.58-6.25(m，2H)，4.75(d，J＝8.8Hz，1H)，4.21(s，2H)，3.71(s，3H)，3.48(d，J＝4.5Hz，1H)，3.20(q，J＝8.7Hz，1H)，3.09-2.88(m，2H)，2.21(ddt，J＝18.3，9.8，2.2Hz，1H)，1.40-1.16(m，3H). 13 C NMR(100MHz，CDCl 3 )δ167.9，155.6，153.0，142.8，140.9，138.8，109.8，96.6，62.2，51.4，47.0，40.3，36.5，14.5.HRMS(ESI)calcd for C 14 H 19 N 2 O 6 [M+H] + 311.1238，found 311.1240.
Target compound I-b-6: silica gel column chromatography (petroleum ether: ethyl acetate = 2: 3) gave the desired product I-b-6 as a colorless oil in 62% yield. 1 H NMR(400MHz，CDCl 3 )δ11.22(s，1H)，8.34(s，1H)，7.77-7.59(m，2H)，7.43(s，1H)，7.32(q，J＝9.4，8.5Hz，1H)，7.25-7.14(m，2H)，6.40(s，1H)，4.69(d，J＝8.8Hz，1H)，3.68(s，3H)，3.38(d，J＝4.8Hz，1H)，3.12(q，J＝8.7Hz，1H)，3.04-2.84(m，1H)，2.77-2.50(m，1H)，2.13(dd，J＝18.2，9.6Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ167.9，165.2，152.9，146.9，142.7，139.0，132.3，132.1，128.5，127.6，109.8，96.6，51.3，46.8，40.4，36.3.HRMS(ESI)calcd for C 18 H 19 N 2 O 5 [M+H] + 343.1288，found 343.1292.
Example 5: synthesis of I-b-7
Target compound I-b-7: dissolve 3 in tetrahydrofuran, add glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) under ice bath, warm to room temperature for reaction, and monitor the reaction by TLC. And after the reaction is complete, performing rotary evaporation and desolventizing, and performing column chromatography to obtain a target product I-b-7. Pale yellow oil, yield 87%. 1 H NMR(400MHz，CDCl 3 )δ9.52(s，1H)，7.96(d，J＝3.5Hz，1H)，7.51(d，J＝3.1Hz，1H)，6.30(d，J＝3.4Hz，1H)，4.75(d，J＝8.7Hz，1H)，3.69(s，3H)，3.44-3.32(m，1H)，3.26-3.11(m，1H)，3.00(ddt，J＝17.7，8.2，3.6Hz，1H)，2.92-2.67(m，1H)，2.17(dt，J＝17.0，6.4Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ168.0，152.8，148.1，140.8，136.0，110.0，96.1，51.5，47.0，39.9，36.3.HRMS(ESI)calcd for C 11 H 14 NO 5 [M+H] + 240.0866，found 240.0864.
Example 6: synthesis of I-b-8
Target compound I-b-8: in a 50mL round bottom flask was added 10mL dichloromethane, substrate 3 (1 mmol), triethylamine (3 mmol) and m-chlorophenyl isocyanate (1.5 mmol), reacted at room temperature and monitored by TLC. And after the reaction is finished, adding water to quench the reaction, extracting the organic phase for three times by using dichloromethane, combining the organic phases, washing the organic phases by using saturated saline solution, drying the organic phases by using anhydrous sodium sulfate, performing desolventization to obtain a crude product, and directly entering the next reaction without purification. The crude product from the previous step was dissolved in tetrahydrofuran, glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) were added under ice bath, warmed to room temperature for reaction, and the reaction was monitored by TLC. When the reaction is complete, rotary evaporation is carried out for desolventizing, and column chromatography is carried out to obtain the target product I-b-8, yellow crystals are obtained, the yield is 54 percent, and the melting point is 88-90 ℃. 1 H NMR(400MHz，CDCl 3 )δ8.29(s，1H)，8.01(s，1H)，7.56(s，1H)，7.50(s，1H)，7.30(dd，J＝8.1，2.1Hz，1H)，7.24-7.14(m，1H)，7.08-6.98(m，1H)，6.60-6.40(m，2H)，4.82(t，J＝7.9Hz，1H)，3.74(s，3H)，3.30-3.21(m，1H)，3.13-2.90(m，2H)，2.20(ddt，J＝18.6，9.6，2.0Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ167.9，153.3，152.7，151.4，146.9，138.3，136.1，134.6，130.1，124.3，119.8，117.9，109.7，96.4，51.5，45.5，40.2，36.9.HRMS(ESI)calcd for C 18 H 18 ClN 2 O 6 [M+H] + 393.0848，found 393.0843.
Example 7: synthesis of I-b-9
Target compound I-b-9: in a 50mL round-bottom flask, 10mL of methylene chloride was added, and 3 (1 mmol) was added) Triethylamine (3 mmol), 4-dimethylaminopyridine (0.2 mmol) and methylcarbamoyl chloride (1.5 mmol), refluxing the reaction, and monitoring the reaction by TLC. And after the reaction is finished, adding water to quench the reaction, extracting the organic phase for three times by using dichloromethane, combining the organic phases, washing the organic phases by using saturated saline solution, drying the organic phases by using anhydrous sodium sulfate, performing desolventization to obtain a crude product, and directly entering the next reaction without purification. The crude product from the previous step was dissolved in tetrahydrofuran, glacial acetic acid (1 equiv) and tetrabutylammonium fluoride (1 mmol/mL THF solution, 1 equiv) were added under ice-bath, warmed to room temperature for reaction, and monitored by TLC. And after the reaction is complete, performing rotary evaporation and desolventizing, and performing column chromatography to obtain a target product I-b-9 which is colorless oily matter with the yield of 75%. 1 H NMR(400MHz，CDCl 3 )δ8.05(s，1H)，7.47(s，1H)，6.63(q，J＝4.7Hz，1H)，6.54-6.45(m，1H)，4.75(d，J＝8.7Hz，1H)，3.65(s，3H)，3.17(q，J＝8.6Hz，1H)，3.07-2.89(m，2H)，2.74(d，J＝4.7Hz，3H)，2.16(dd，J＝18.7，9.7Hz，1H). 13 C NMR(100MHz，CDCl 3 )δ167.8，156.7，153.3，150.3，145.6，136.5，109.5，96.4，51.3，45.3，39.9，36.8，27.50.HRMS(ESI)calcd for C 13 H 17 N 2 O 6 [M+H] + 297.1081，found 297.1082.
TABLE 2 structural List of Compounds I-b
Example 8: determination of tetranychus cinnabarinus-killing adult mite activity
When the dwarf beans for experiments grow to two true leaves, plants with regular growth, 4-5 square centimeters of leaf area and about 10 centimeters of plant height are selected for inoculation, and the quantity of insects of each plant is controlled to be about 60-100. And after inoculating the insects for 24 hours, treating the insects with medicaments with corresponding concentrations. The medicament treatment adopts a plant dipping method, and the dipping time is 5 seconds. After the plants are taken out of the liquid medicine, the plants are shaken slightly to throw off the redundant liquid medicine, and then the plants are moved into a water culture tank and placed at room temperature. The results were examined under binoculars 24 hours after treatment. (average value of three parallel experiments)
Mortality (%) = (dead insect number/total insect number) × 100%
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ] × 100%
Table 3 shows insecticidal activity of the compounds against adult tetranychus cinnabarinus
As can be seen from the table 3, the series of compounds show certain tetranychus cinnabarinus-killing activity, the tetranychus cinnabarinus-killing activity of the compounds I-a-1, I-a-12 and I-b-3 is over 50% at the concentration of 200mg/L, and the genipin acylhydrazone I-b-5 is even up to 80% at the concentration of 200mg/L, so that the series of compounds can effectively control the insect pests of various crops.
Example 9: plutella xylostella larva Activity test
The leaf dipping method proposed by the International Resistance Action Committee (IRAC) was adopted. After the required concentration of the medicament is prepared, the cabbage leaves are soaked by straight-head ophthalmic tweezers for 2 to 3 seconds, and residual liquid is thrown away. 1 tablet at a time, 3 tablets per sample. And the samples are sequentially placed on the processing paper according to the sample marking sequence. After the liquid medicine is dried, the liquid medicine is put into a straight pipe with the length of 10cm and provided with a mark, 2-year-old plutella xylostella larvae are inoculated, and the pipe orifice is covered by gauze. The experimental treatments were placed in a standard treatment chamber and the results checked after 96 hours. Each compound was repeated 3 times. The control was prepared by adding the emulsifier and solvent to distilled water and stirring the mixture uniformly.
Mortality (%) = (dead insect number/total insect number) × 100%
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ] × 100%
Table 4 shows insecticidal activity of the compounds against plutella xylostella
Example 10: diamondback moth larva LC 50 Testing
The leaf dipping method proposed by the International Resistance Action Committee (IRAC) was adopted. After the preparation of the required concentration (400 mg/L, 200mg/L, 100mg/L, 50mg/L, 25 mg/L), the leaves of the cabbage were soaked with straight-head ophthalmic forceps for 2-3 seconds, and the remaining solution was discarded. 1 tablet at a time, 3 tablets per sample. And the samples are sequentially placed on the processing paper according to the sample marking sequence. After the liquid medicine is dried, the liquid medicine is put into a straight pipe with the mark length of 10cm, 2-instar plutella xylostella larvae are inoculated, and the pipe orifice is covered by gauze. The experimental treatments were placed in a standard treatment chamber and the results checked after 96 hours. Each compound was repeated 3 times. The control was prepared by adding the emulsifier and solvent to distilled water and stirring the mixture uniformly.
Mortality (%) = (dead insect number/total insect number) × 100%
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ] × 100%
From the measurement results, the toxicity regression equation y = a + bx was obtained by using the logarithmic value of the drug concentration as x and the corrected mortality as a few value as y, and the lethal mid-concentration (LC) was obtained 50 ) And carrying out reliability check.
Table 5 shows LC of compounds against plutella xylostella 50 Activity of
| Compound (I) | y＝a+bx | Coefficient of correlation (r) | LC 50 (mg/L) | 95% confidence interval (mg/L) |
| Rotenone | y＝-0.4981+3.5484x | 0.9514 | 35.4 | 22.2-56.4 |
| I-a-12 | y＝-4.5304+5.9312x | 0.9250 | 40.4 | 23.5-69.7 |
The insecticidal activity of the series of target compounds on diamond back moths is shown in table 4. A series of compounds relative to commercial pesticide, YUTENGKetones also perform better. The compounds I-a-1 to 3, I-a-6, I-a-8, I-a-10 and I-a-12 have 100 percent of mortality rate to diamondback moth at the concentration of 600mg/L, and still have more than 50 percent of mortality rate when the concentration is reduced to 200 mg/L. Wherein the p-toluate genipin derivative I-a-12 shows the optimal insecticidal activity and LC for plutella xylostella 50 40.4mg/L (95% confidence interval 23.5-69.7mg/L; table 5), close to commercial pesticide rotenone activity (LC) 50 Value 35.4mg/L with 95% confidence interval 22.2-56.4 mg/L), and therefore has the potential to serve as a lead for genipin-derived diamondback moth killing.
Example 11: test of Compounds on the Activity of armyworm
The experimental method of the armyworm comprises the following steps: the leaf dipping method proposed by the International Resistance Action Committee (IRAC) was adopted. After the required concentration (600 mg/L) of the preparation is prepared, the leaves with the diameter of about 5-6cm are soaked in the liquid medicine for 5-6 seconds, taken out, put on absorbent paper to be dried, put in a specified culture dish, inoculated with 10 larvae of 3 years old, put in an insect-raising room at 27 +/-1 ℃ and observed for 3-4 days, and then the result is checked.
Mortality (%) = (dead insect number/total insect number) × 100%
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ] × 100%
Example 12: compound activity test on corn borer
The experimental method of the corn borer comprises the following steps: the leaf dipping method proposed by the International Resistance Action Committee (IRAC) was adopted. After the required concentration (600 mg/L) of the preparation is prepared, the leaves with the diameter of about 5-6cm are soaked in the liquid medicine for 5-6 seconds, taken out, put on absorbent paper to be dried, put in a specified culture dish, inoculated with 10 larvae of 3 years old, put in an insect-raising room at 27 +/-1 ℃ and observed for 3-4 days, and then the result is checked.
Mortality (%) = (dead insect number/total insect number) × 100%
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ] × 100%
Example 13: activity test of Compounds against Cotton bollworm
The experimental method of the cotton bollworm comprises the following steps: the feed mixing method is a method in which 3mL of the solution is transferred from the prepared solution and added to about 27g of the freshly prepared feed to obtain a desired concentration of ten times the dilution. Uniformly mixing the medicines, uniformly pouring the medicines into a clean 24-hole plate, cooling, inoculating the 24-head 3-year-old cotton bollworms, and observing the inspection result after 3-4 days.
Mortality (%) = (dead insect number/total insect number) × 100%
Corrected mortality (%) = [ (treatment mortality-control mortality)/(1-control mortality) ] × 100%
Table 6 shows the results of the insecticidal activity test of the compounds against armyworm, ostrinia nubilalis and cotton bollworm
We also tested a series of genipin derivatives for insecticidal activity against armyworm, bollworm and corn borer, as shown in table 6. Most of the compounds have general insecticidal activity on the three lepidoptera pests, but the insecticidal activity exceeds that of a parent compound genipin. The 2-fluorobenzoic acid ester genipin I-a-5 and the nitrile acetyl hydrazone genipin I-b-4 have good activity, and the lethality to armyworms reaches 100% at the concentration of 600 mg/L. The activity of the compounds I-a-5 and I-b-4 on the cotton bollworm and the corn borer is higher than that of the commercial pesticide rotenone at 600mg/L, and respectively reaches 70 percent (the cotton bollworm), 60 percent (the corn borer), 65 percent (the cotton bollworm) and 75 percent (the corn borer).
Example 14: the bactericidal activity was measured by the following procedure
In-vitro plate method (Disc paper method) is adopted to determine the bactericidal activity of the target compound on fourteen thalli of cucumber wilt, peanut brown spots, apple ring rot, tomato early blight, wheat scab, rice bakanae, rape sclerotium, phytophthora capsici, wheat sharp rot, corn microspots, watermelon anthracnose, potato late blight, rice sharp rot and cucumber gray mold; the test agent is diluted to a certain multiple under the aseptic condition by adopting a thallus growth rate test method (mycelium growth rate test), then 1mL (500 mu g/mL) of liquid medicine is respectively sucked and injected into a culture dish, 9mL of culture medium is respectively added, after shaking uniformly, a drug-containing plate of 50 mu g/mL is prepared, and a plate added with 1mL of sterilized water is used as a blank control. The plate was cut along the outer edge of the hyphae with a punch of 4mm diameter and transferred to a drug-containing plate, and each treatment was repeated three times. The culture dish is placed in a constant temperature incubator at the temperature of (24 +/-1) DEG C for culturing for 72h, the expansion diameter of each treated bacterium plate is investigated, the average value is calculated, and the relative bacteriostasis rate is calculated by comparing with a blank control. Relative inhibition (%) = (control group disc expansion average diameter-treatment group disc expansion average diameter)/control group disc expansion average diameter. The results are shown in Table 7.
Table 7 shows the results of the bactericidal activity test of the compounds
The in vitro bacteriostatic activity of the target compound against 14 common plant pathogenic bacteria at a concentration of 50mg/L is shown in Table 7. In general, the series of genipin derivatives have bacteriostatic activity. The inhibitory activity of the compounds I-a-6, I-a-9, I-a-14 and I-b-3 on the peanut brown spot germ exceeds that of the commercial broad-spectrum bactericide carbendazim. The bacteriostatic activity of the phenyl carbamate I-a-14 on phytophthora capsici pathogenic bacteria reaches 63%. Compared with other compounds, the oxime benzyl ether I-b-3 has more outstanding bacteriostatic activity, and the inhibition rate of the oxime benzyl ether I-b-3 on peanut brown spots, rape sclerotium, wheat rhizoctonia rot, rice rhizoctonia rot and cucumber botrytis cinerea pathogenic bacteria is over 50 percent. Fully indicates that the series of compounds can be further optimized as a new lead bacteriostatic medicament.
Claims (10)
1. Genipin derivatives I containing ester, oxime and hydrazone fragments, specifically genipin ester I-a, genipin oxime and genipin hydrazone I-b,
the compounds are characterized in that the general formulas I-a and I-b are compounds with structures shown in tables 1 and 2:
TABLE 1
TABLE 2
2. The method for preparing genipin derivatives I-a-1-13 containing ester fragment according to claim 1, characterized in that it comprises the following steps:
wherein RCOCl is the general formula of acyl chloride compounds with 13 different substituents shown in the structures I-a-1-13.
3. The method for preparing genipin derivatives I-a-14-15 containing ester fragment according to claim 1, comprising the steps of:
wherein RNCO is a general formula of 2 isocyanate compounds with different substituent groups shown in the structure I-a-14-15.
4. The method for preparing genipin derivatives I-a-16-19 containing ester fragment according to claim 1, characterized in that it comprises the following steps:
wherein RNCS is a general formula of isothiocyanate compounds with 2 different substituents shown in structures I-a-17-18.
5. The method for preparing genipin derivative I-b-1, I-b-2, I-b-4-I-b-6 containing hydrazone fragment and genipin derivative I-b-3 containing oxime ether fragment according to claim 1, comprising the steps of:
wherein RNH2 is a general formula of organic amine compounds with 6 different substituents shown in structures I-b-1-6.
6. The method for preparing genipin derivative I-b-7 containing oxime fragment as claimed in claim 1, characterized in that it comprises the steps of:
7. the method for preparing genipin derivative I-b-8 containing oxime fragment as claimed in claim 1, characterized in that it comprises the steps of:
8. the method for preparing genipin derivative I-b-9 containing oxime fragment as claimed in claim 1, characterized in that it comprises the steps of:
9. the use of the genipin derivative I containing ester, oxime and hydrazone fragments as claimed in claim 1, characterized in that the compound I-a-1 to I-a-3, I-a-6 to I-a-14, I-a-16, I-b-1, I-b-3, I-b-5, I-b-8 has killing activity against Tetranychus cinnabarinus adult mites, the compound I-a-1 to I-a-14, I-a-16 to I-a-19, I-b-1, I-b-2, I-b-4, I-b-6, I-b-7 has killing activity against Plutella xylostella, the compounds I-a-3 to I-a-5, I-a-7, I-a-8, I-a-10 to I-a-12, I-a-14, I-a-18, I-b-2 to I-b-4, I-b-6, I-b-7, I-b-9 have killing activity on armyworms, the compounds I-a-3 to I-a-5, I-a-7, I-a-8, I-a-10, I-a-13, I-a-14, I-a-18, I-b-2 to I-b-4, I-b-6, I-b-7, i-b-9 has killing activity to corn borer, compounds I-a-1, I-a-3-I-a-5, I-a-7, I-a-8, I-a-11, I-a-13, I-a-14, I-a-18, I-a-19, I-b-3, I-b-4, I-b-6, I-b-7, I-b-9 have killing activity to cotton bollworm.
10. The use of genipin derivative I containing ester, oxime and hydrazone fragments as claimed in claim 1 for the control of plant pathogens, characterized in that said plant pathogens are cucumber wilt, peanut brown spot, apple ring rot, tomato early blight, wheat scab, rice bakanae, rape sclerotium, phytophthora capsici, wheat sheath blight, corn small spot, watermelon anthrax, potato late blight, rice sheath blight, cucumber gray mold.
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