Novel glycosyl C-glycoside triazole derivative as well as preparation method and application thereof

Abstract

The invention belongs to the field of pesticides, and particularly relates to a novel glycosyl C-glycoside derivative as well as a preparation method and application thereof, and the structure of the novel glycosyl C-glycoside derivative is shown as a formula I or a formula II; the compound can be used as an insect chitin degrading enzyme, and has good target enzyme inhibition activity and insecticidal activity when being used for preventing diseases and insect pests caused by lepidoptera insects. # imgabs0 #

Description

Technical Field

[0001] The present invention belongs to the field of pesticides, and particularly relates to a novel class of glycosyl carbon glycoside derivatives, their preparation methods and applications. Background Art

[0002] Lepidopteran agricultural pests cause great harm to corn crops, seriously affecting the quality and yield of corn. Chitin, as a linear polysaccharide, is a major component of multiple tissues such as the insect cuticle, exoskeleton and peritrophic membrane, and shoulders the important responsibility of protecting insects from various external environmental stimuli and injuries. The growth and development of insects are accompanied by periodic molting, which is an indispensable physiological process for the normal growth and development of insects. Therefore, inhibiting the enzymes that degrade and metabolize the cuticle can lead to abnormal molting of insects and inhibit the growth and development of insects.

[0003] Chitin-degrading enzyme is a glycoside hydrolase that can hydrolyze and break the glycosidic bonds in chitin and chito-oligosaccharides. The chitinase OfChtII of the GH18 family and the β-N-acetylhexosaminidase OfHex1 of the GH20 family are key enzymes involved in insect molting and play important physiological roles in the growth and development process of insects. Chitinase can effectively convert long-chain chitin into short-chain chito-oligosaccharides. β-N-acetylhexosaminidase further hydrolyzes chito-oligosaccharides into monosaccharides, thus realizing the process of chitin degradation. It has been found that plants and mammals do not contain chitin, so chitin-degrading enzymes are a very promising class of green insecticide targets. Summary of the Invention

[0004] The present invention provides a novel glycosyl carbon glycoside compound containing N-acetylglucosamine, naphthalenesulfonyl chloride or NBD, or a pharmaceutically acceptable salt, solvate or hydrate thereof,

[0005] The structure is shown in Formula I or Formula II:

[0006]

[0007] Wherein X1 and X2 are independently selected from substituted or unsubstituted C1-C6 alkyl, amino, C3-C6 cycloalkyl, alkylamino; preferably alkyl;

[0008] Wherein X3 and X4 are independently selected from substituted or unsubstituted C1-C6 alkyl, amino, C3-C6 cycloalkyl, alkylamino; preferably amino;

[0009] R1 and R2 may or may not exist;

[0010] When R1 and R2 exist, R1 and R2 are independently selected from substituted or unsubstituted phenyl, benzyl, naphthyl, naphthalenesulfonyl, naphthalenesulfonamide, benzofurazan, nitrobenzofurazan NBD;

[0011] The substitution is mono-substitution or multi-substitution;

[0012] The substituents of the substitution are independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, N-N dimethyl, halogen-substituted C1-C6 alkyl, and C1-C6 alkyl-substituted amino at each position.

[0013] In some preferred embodiments, X1, X2, X3, and X4 are independently selected from substituted or unsubstituted -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -NH3, -CH2NH3, -CH2CH2NH3, -CH2CH2CH2NH3, -CH2CH2CH2CH2NH3,

[0014] In some preferred embodiments, X1 is methylene; X3 is imino; and / or

[0015] X2 is methylene; X4 is imino;

[0016]

[0017] In some preferred embodiments, the glycosyl carbonoside compound represented by Formula I is selected from any one of the following compounds:

[0018]

[0019] In some preferred embodiments, the glycosyl carbonoside compound represented by Formula II is any one of the following compounds:

[0020]

[0021] In a second aspect, the present invention also provides a method for preparing the glycosyl carbonoside compound described above, and its pharmaceutically acceptable salt, solvate or hydrate, comprising the following steps:

[0022] (1) Reacting the compound represented by Formula III with the compound represented by Formula IV in an ethanol solvent to obtain the compound represented by Formula V;

[0023] (2) Reacting the compound represented by Formula V with active manganese dioxide in chloroform to obtain the compound represented by Formula VI;

[0024] (3) Reacting the compound represented by Formula VII with the compound represented by Formula VIII in dichloromethane and triethylamine to obtain Formula IX;

[0025] (4) Reacting the compound represented by Formula VI with the compound represented by Formula IX or Formula X through a click reaction to obtain Formula X;

[0026] (5) The compounds of formula XI and / or formula II are deprotected under methanol ammonia conditions to obtain the target compounds shown in formula I and formula II;

[0027]

[0028] In some preferred embodiments, n is selected from integers between 0 and 10, including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10;

[0029] In some preferred embodiments, X1 in formula XI and / or formula XII is independently selected from substituted or unsubstituted C1-C6 alkyl, amino, C3-C6 cycloalkyl, alkylamino; preferably alkyl; more preferably methylene;

[0030] In some preferred embodiments, X2 in formula XI and / or formula XII is independently selected from substituted or unsubstituted C1-C6 alkyl, amino, C3-C6 cycloalkyl or alkylamino; preferably amino; more preferably imino;

[0031] In some preferred embodiments, the definition of R in formula VII and formula IX is the same as the definition of R1 and / or R2 in formula I and formula II;

[0032] R is independently selected from substituted or unsubstituted phenyl, benzyl, naphthyl, naphthalenesulfonyl, naphthalenesulfonamide, benzofurazanyl or nitrobenzofurazanyl NBD;

[0033] The substitution is mono-substitution or multi-substitution;

[0034] The substituents of the substitution are independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, N-N dimethyl, halogen-substituted C1-C6 alkyl or C1-C6 alkyl-substituted amino;

[0035] In some preferred embodiments, the definition of R in formula X is the same as the definition of R1 and / or R2 in formula I and formula II;

[0036] R is substituted or unsubstituted -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -NH3, -CH2NH3, -CH2CH2NH3, -CH2CH2CH2NH3, -CH2CH2CH2CH2NH3,

[0037] In some more preferred embodiments, the compound shown in formula (I) or formula (II) is prepared by a method comprising the following steps:

[0038] (1) React the compound shown in formula (III) with the compound shown in formula (IV) in an ethanol solvent to obtain the compound shown in formula (V);

[0039] (2) React the compound shown in formula (V) with activated manganese dioxide in chloroform to obtain the compound shown in formula (VI);

[0040] (3) React the compound shown in formula (VII) and the compound shown in formula (VIII) in dichloromethane and triethylamine to obtain formula (IX);

[0041] (4) React the compound shown in formula (VI) and the compound shown in formula (IX) through a click reaction to obtain formula (X);

[0042] (5) Deprotect formula (X) under methanol-ammonia conditions to obtain the target compounds shown in formula (I) and formula (II),

[0043]

[0044] In some preferred embodiments, n is selected from integers between 0 and 10, including 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10;

[0045] In some preferred embodiments, the definition of R in formula (VII) is the same as the definition of R1 and / or R2 in formula (I) and formula (II);

[0046] R is independently selected from substituted or unsubstituted phenyl, benzyl, naphthyl, naphthalenesulfonyl, naphthalenesulfonamide, benzofurazan, nitrobenzofurazan NBD;

[0047] The substitution is mono-substitution or multi-substitution;

[0048] The substituents of the substitution are independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, N-N dimethyl, halogen-substituted C1-C6 alkyl, C1-C6 alkyl-substituted amino.

[0049] In some preferred embodiments, the definition of R in formula (IX) is the same as the definition of R1 and / or R2 in formula (I) and formula (II);

[0050] R is independently selected from substituted or unsubstituted phenyl, benzyl, naphthyl, naphthalenesulfonyl, naphthalenesulfonamide, benzofurazan, nitrobenzofurazan NBD;

[0051] The substitution is mono-substitution or multi-substitution;

[0052] The substituents of the substitution are independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, N-N dimethyl, halogen-substituted C1-C6 alkyl, C1-C6 alkyl-substituted amino.

[0053] In some preferred embodiments, the definition of R in formula (Ⅹ) is the same as the definition of R1 and / or R2 in formula (I) and formula (II);

[0054] R is substituted or unsubstituted -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -NH3, -CH2NH3, -CH2CH2NH3, -CH2CH2CH2NH3, -CH2CH2CH2CH2NH3,

[0055] The compound represented by formula (Ⅹ) in the above method also belongs to the protection scope of the present invention.

[0056] In a second aspect, the present invention provides an application of a glycosyl carbon glycoside compound as described above, and a pharmaceutically acceptable salt, solvate or hydrate thereof in pesticides.

[0057] In a third aspect, the present invention provides an application of a glycosyl carbon glycoside compound as described above, and a pharmaceutically acceptable salt, solvate or hydrate thereof as an insect chitin degrading enzyme inhibitor.

[0058] In some preferred embodiments, for preventing and / or killing pests and diseases caused by Lepidoptera insects, preferably Plutellidae, more preferably Plutella; including Plutella xylostella.

[0059] In a fourth aspect, the present invention provides a pesticide, which contains a glycosyl carbon glycoside compound as described above, and a pharmaceutically acceptable salt, solvate or hydrate thereof.

[0060] In some preferred embodiments, the dosage form of the pesticide is selected from any one of the following: emulsifiable concentrate, wettable powder, suspension concentrate, powder, soluble powder, aqueous solution, water dispersible granule, smoke agent, granule, seed coating agent.

[0061] In some preferred embodiments, the dosage form of the pesticide is an emulsifiable concentrate, which is composed of the following substances in mass percentage: 1-10% of a glycosyl carbon glycoside compound as described in any one of claims 1-4, and a pharmaceutically acceptable salt, solvate or hydrate thereof, 5-15% of an emulsifier, 0.1-1% of a penetrant, and the balance being a solvent;

[0062] Preferably, the emulsifier is a surfactant; more preferably any one or a combination of at least two of the following: agricultural emulsion 0203B, 0208, GFC, OP-10, Tween-60;

[0063] Preferably, the solvent is selected from toluene and / or xylene.

[0064] The dosage form of the insecticide, which is a wettable powder and consists of the following substances in mass percentage: 15-50% of a glycosyl carbonoside compound described in any one of claims 1-4, and its pharmaceutically acceptable salt, solvate or hydrate, 10-20% of a surfactant and 30-75% of silica white;

[0065] Preferably, the surfactant includes a naphthol formaldehyde condensate, more preferably NNO.

[0066] The inventors of the present invention targeted the GH18 chitinase OfChtII and GH20 β-N-acetylhexosaminidase of the Asian corn borer (Ostrinia furnacalis), and used the designed glycosyl carbonoside thiodiazole compound B12 as a lead compound, aiming to improve the inhibition rate of OfChtII while retaining the enzyme activity of OfHex1, so as to enhance the insecticidal activity. The thiodiazole and benzene ring fragments of carbonoside B12 were retained, and multiple heterocycles or benzene rings were further introduced to extend the overall chain length of the compound to synthesize compounds C1-C8 and D1-D6. This series of compounds are compounds with good activity and selectivity, achieving good enzyme inhibition activity. Finally, through insecticidal activity tests, it was found that this series of compounds have good insecticidal activity against Plutella xylostella.

[0067] The beneficial effects of the present invention are at least as follows: The present invention targets insect chitin degrading enzymes and synthesizes novel glycosyl carbonoside compounds. The glycosyl carbonoside compounds described in the present invention or their pharmaceutically acceptable salts have good target enzyme inhibition activity and insecticidal activity, and the insecticidal activity of some compounds against Plutella xylostella is higher than that of the control agent diflubenzuron. The compounds described in the present invention have high pesticide research value. Description of the Drawings

[0068] Figure 1 1H NMR spectrum of compound CAUZA-C-01.

[0069] Figure 2 13C NMR spectrum of compound CAUZA-C-01. Detailed Embodiments

[0070] The present invention will be further described in detail below in conjunction with the specific embodiments. The provided embodiments are only for clarifying the present invention, rather than limiting the scope of the present invention. The following provided embodiments can be used as a guide for those of ordinary skill in the art to make further improvements, and do not limit the present invention in any way.

[0071] In the experimental methods of the following examples, unless otherwise specified, they are all conventional methods, carried out according to the techniques or conditions described in the literature in this field or according to the product instructions. The materials, reagents, etc. used in the following examples, unless otherwise specified, can be obtained from commercial sources.

[0072] Example 1: Preparation and structural identification of compound CAUZA-C-01.

[0073]

[0074] Add compound 1 (5 g, 21.2 mmol), glycosyl carbon glycoside (8.20 g, 21.2 mmol, 1.0 equivalent), and 100 mL of absolute ethanol to a 250 mL round-bottom flask. Stir at 80 °C for 8 hours. After the reaction is completed, concentrate the reaction mixture, and the concentrate is purified by column chromatography to obtain intermediate 3 (white solid, 9.20 g, yield 71.88%).

[0075] Structure confirmation data: 1 H NMR (500 MHz, Chloroform-d) δ 9.49 (d, J = 124.3 Hz, 1H, -NH-), 8.61 (s, 1H, -NH-), 7.80 - 7.60 (m, 2H, -PhH), 7.39 (t, J = 7.8 Hz, 1H, -PhH), 7.16 (d, J = 7.5 Hz, 1H, -PhH), 5.71 (d, J = 9.6 Hz, 1H, -NH-), 5.05 (dd, J = 7.3, 2.7 Hz, 2H, -CH2-), 4.37 (d, J = 3.7 Hz, 2H, -CH2-), 4.19 (qq, J = 7.7, 3.8, 2.7 Hz, 2H, H-3, H-5), 4.15 - 4.02 (m, 1H, H-1), 3.74 - 3.57 (m, 2H, H-2, H-4), 2.63 (d, J = 4.1 Hz, 1H, -CH2-), 2.57 (s, 1H, -CH2-), 2.15 - 1.89 (m, 15H, -CH3). 13 C NMR (125 MHz, CDCl3) δ 176.29, 171.67, 170.65, 170.20, 169.31, 149.11, 138.83, 135.99, 129.04, 125.38, 124.07, 123.82, 77.65, 75.92, 74.31, 68.34, 62.35, 54.58, 52.98, 39.98, 23.35, 20.75, 20.71, 20.62, 17.25.

[0076]

[0077] Compound 3 (8.0 g, 13.5 mmol) was added to a 100 mL round-bottom flask; activated manganese dioxide (11.77 g, 135 mmol, 10.0 equivalents), and 60 mL of chloroform. The mixture was stirred at room temperature for 5 hours. After the reaction was completed, the manganese dioxide was removed by filtration, and the filtrate was concentrated under reduced pressure. The crude product was purified by column chromatography to obtain intermediate 4 (yellow solid, 5.8 g, yield 72.77%).

[0078] Structure confirmation data: 1 H NMR (500 MHz, Chloroform-d) δ 7.42 (t, J = 7.7 Hz, 1H, -PhH), 7.25 - 7.15 (m, 3H, -PhH), 6.30 (d, J = 10.0 Hz, 1H, -NH-), 5.14 (t, J = 9.8 Hz, 1H, H-3), 5.00 (t, J = 9.7 Hz, 1H, H-5), 4.34 (s, 2H, -CH2-), 4.23 - 4.07 (m, 2H, -CH2-), 4.00 (dd, J = 12.2, 2.4 Hz, 1H, H-1), 3.55 (ddd, J = 10.1, 5.6, 2.4 Hz, 1H, H-2), 3.13 (ddd, J = 10.0, 7.8, 2.0 Hz, 1H, H-4), 2.68 (dd, J = 15.6, 2.0 Hz, 1H, -CH2-), 2.51 (dd, J = 15.6, 7.8 Hz, 1H, -CH2-), 2.00 (s, 3H, -CH3), 1.99 - 1.95 (m, 9H, -CH3), 1.88 (s, 3H, -CH3). 13 C NMR (125 MHz, CDCl3) δ 175.68, 171.22, 170.73, 170.57, 169.32, 148.57, 137.22, 130.02, 126.49, 120.48, 120.17, 109.87, 77.35, 76.66, 75.43, 73.74, 68.49, 62.29, 54.25, 53.25, 41.11, 28.17, 23.18, 20.65, 20.55.

[0079]

[0080] Compound 5 (5 g, 18.59 mmol), propargylamine (1.22 g, 22.31 mmol), and triethylamine (2.82 g, 27.89 mmol) were added to a 50 mL round-bottom flask, and 30 mL of dichloromethane was added. The reaction was carried out at room temperature for 5 h, concentrated, and purified by column chromatography to obtain intermediate 7 (green solid, 4.23 g, yield 83.4%).

[0081] Structure confirmation data:1 1H NMR (500 MHz, Chloroform-d) δ 8.56 (dt, J = 8.5, 1.2 Hz, 1H, -PhH), 8.39 - 8.16 (m, 2H, -PhH), 7.58 (dd, J = 8.7, 7.5 Hz, 1H, -PhH), 7.52 (dd, J = 8.5, 7.3 Hz, 1H, -PhH), 7.22 - 7.17 (m, 1H, -PhH), 4.89 (q, J = 5.6 Hz, 1H, -NH-), 3.77 (dd, J = 6.1, 2.5 Hz, 2H, -CH2-), 2.89 (s, 6H, -CH3), 1.91 (t, J = 2.6 Hz, 1H, ≡CH). 13 13C NMR (125 MHz, CDCl3) δ 152.10, 134.25, 130.86, 129.96, 129.91, 129.82, 128.62, 123.21, 118.58, 115.25, 77.82, 72.71, 45.43, 33.03.

[0082]

[0083] Compound 4 (0.47 g, 0.80 mmol), compound 7 (0.26 g, 0.96 mmol), copper(II) sulfate pentahydrate (50 mg, 0.25 eq.), sodium ascorbate (500 mg, 0.20 eq.) were added into a 50 mL round-bottom flask, and 20 mL of a mixed solution of tert-butanol and water (V 叔丁醇 / V 水 : 1 / 1) was added. The reaction was carried out at room temperature for 5 h, concentrated, and purified by column chromatography to obtain intermediate 8 (0.53 g of yellow solid, yield 77.14%).

[0084] Structure confirmation data: 11H NMR (500 MHz, Chloroform-d) δ 8.53 (dt, J = 8.5, 1.1 Hz, 1H, -PhH), 8.24 (d, J = 8.6 Hz, 1H, -PhH), 8.20 (dd, J = 7.3, 1.2 Hz, 1H, -PhH), 7.49 (tt, J = 8.7, 1.2 Hz, 2H, -PhH), 7.46 - 7.39 (m, 2H, -PhH), 7.20 (ddd, J = 8.0, 2.2, 1.0 Hz, 1H, -ArH), 7.16 (d, J = 7.5 Hz, 1H, -PhH), 7.11 (dd, J = 7.8, 1.5 Hz, 1H, -PhH), 7.03 (d, J = 2.0 Hz, 1H, -PhH), 6.64 (dd, J = 9.7, 4.3 Hz, 1H, -NH-), 6.38 (q, J = 6.5 Hz, 1H, -NH-), 5.48 - 5.37 (m, 2H, -CH2-), 5.08 (t, J = 9.8 Hz, 1H, H-4), 4.91 (t, J = 9.6 Hz, 1H, H-5), 4.24 - 4.14 (m, 2H, -CH2-), 4.10 (dt, J = 10.5, 5.2 Hz, 1H, H-2), 4.04 (t, J = 10.0 Hz, 1H, H-3), 3.97 (dd, J = 12.1, 2.2 Hz, 1H, H-1), 3.51 (td, J = 10.2, 2.0 Hz, 1H, -CH2-), 3.38 (ddd, J = 10.1, 6.0, 2.2 Hz, 1H, -CH2-), 2.88 (s, 6H, -CH3), 2.69 (ddd, J = 15.5, 10.2, 1.7 Hz, 1H, -CH2-), 2.42 (dd, J = 15.5, 2.0 Hz, 1H, -CH2-), 2.09 (d, J = 1.3 Hz, 3H, -CH3), 2.00 (d, J = 1.0 Hz, 3H, -CH3), 1.95 (d, J = 1.0 Hz, 3H, -CH3), 1.79 (d, J = 9.7 Hz, 6H, -CH3). 1313C NMR (125 MHz, CDCl3) δ 176.70, 171.37, 171.09, 170.82, 169.44, 152.06, 149.69, 144.82, 136.00, 134.61, 130.73, 130.33, 129.88, 129.49, 129.44, 128.52, 125.83, 123.16, 122.85, 121.99, 118.92, 118.64, 115.36, 108.83, 77.34, 76.00, 75.62, 74.11, 68.72, 62.37, 53.68, 53.18, 45.41, 40.99, 38.49, 27.66, 23.02, 20.87, 20.72, 20.60.

[0085]

[0086] The product obtained in (1) (0.53 g, 0.6 mmol) was added to a 50 mL round-bottom flask, along with 10 mL of methanol and 10 mL of saturated methanol ammonia solution. The reaction was carried out for 4 h, concentrated, and purified by column chromatography to obtain compound C1 (0.39 g of yellow solid, yield 86.67%).

[0087] Structure confirmation data 1 1H NMR (500 MHz, Methanol-d4) δ 8.50 - 8.42 (m, 1H, -PhH), 8.27 (d, J = 8.7 Hz, 1H, -PhH), 8.14 (dd, J = 7.3, 1.3 Hz, 1H, -PhH), 7.87 (s, 1H, -ArH), 7.52 - 7.43 (m, 3H, -PhH, -NH-), 7.39 (t, J = 7.8 Hz, 1H, -PhH), 7.21 - 7.13 (m, 2H, -PhH), 7.07 - 7.02 (m, 2H, -PhH), 5.39 (s, 2H, -CH2-), 4.14 (s, 2H, -CH2-), 3.73 (dd, J = 12.0, 2.5 Hz, 1H, H-3), 3.69 - 3.57 (m, 2H, H-4, H-1), 3.49 - 3.33 (m, 3H, H-5, -CH2-), 2.99 (s, 1H, H-2), 2.81 (s, 6H, -CH3), 2.46 (d, J = 6.4 Hz, 2H, -CH2-), 1.94 (s, 3H, -CH3), 1.78 (s, 3H, -CH3). 13¹³C NMR (125 MHz, MeOD) δ 177.38, 172.56, 151.78, 149.02, 144.76, 136.86, 135.36, 130.04, 129.64, 129.43, 129.04, 128.00, 125.91, 123.26, 123.06, 120.72, 119.62, 118.97, 115.12, 109.39, 80.28, 78.17, 75.72, 75.61, 70.43, 61.06, 55.35, 53.04, 44.57, 40.87, 37.66, 26.19, 21.82. HR-MS (ESI) m / z: calcd for C 34 H 41 N9O7S2 [M+H] + , 752.2649; found, 752.2651.

[0088] All other compounds in the series of CAUZL-C and CAUZL-D were prepared according to the above method. Their compound numbers, corresponding substituents, and physicochemical data are shown in Table 1, and the nuclear magnetic resonance hydrogen spectrum and mass spectrometry data for structural identification are shown in Table 2 and Figure 1 and Figure 2 .

[0089] Table 1 Compound numbers, substituents, and physicochemical data of some compounds in the CAUZL-C and CAUZL-D series

[0090]

[0091]

[0092] Table 2 Nuclear magnetic resonance hydrogen spectrum and mass spectrometry data of some compounds in the CAUZL-C and CAUZL-D series

[0093]

[0094]

[0095]

[0096] Example 2

[0097] In a 100 mL volumetric flask, add 0.110 g of compound CAUZA-C-01, 1.5 g of emulsifier, and 0.1 g of penetrant, and then make up the volume to a 10% emulsifiable concentrate with solvents such as toluene and xylene.

[0098] Example 3 Preparation of 10% Compound CAUZA-C-01 Emulsifiable Concentrate

[0099] Add 10 g of compound CAUZA-C-01, 15 g of Tween 80, and 1 g of fatty alcohol polyoxyethylene ether into a 100 mL volumetric flask, and then make up the volume with toluene to obtain an emulsifiable concentrate with a content of 10%.

[0100] Emulsifiable concentrates of other compounds with the general formulas CAUZA-C and CAUZA-D can all be prepared according to the above method.

[0101] Take 50 g of compound CAUZA-C-01, 20 g of surfactant, and 75 g of white carbon black, and obtain a wettable powder with a content of 50% after mixing and grinding.

[0102] Example 4. Preparation of a 50% wettable powder of compound CAUZA-C-01

[0103] Take 50 g of compound CAUZA-C-01, 20 g of sodium dodecylbenzenesulfonate, and 75 g of white carbon black, and obtain a wettable powder with a content of 50% after mixing and grinding.

[0104] Wettable powders of other compounds with the general formulas CAUZA-C and CAUZA-D can all be prepared according to the above method.

[0105] Example 5. Determination of the enzyme inhibitory activity of compounds with the general formulas CAUZA-C and CAUZA-D

[0106] Enzyme activity determination method: Use 4-Methylumbelliferyl N,N-diacetyl-β-D-chitobioside as the test substrate for OfChtⅡ; use pNP-β-GlcNAc as the test substrate for OfHex1. Mix the enzyme with the enzyme activity assay buffer (20 mM NaH2PO4, pH = 6.5) in a 96-well plate to a final volume of 54 μL, add 6 μL of 5 mM pNP-β-GlcNAc to start the reaction, incubate at 30 °C for 20 min, add 60 μL of 0.5 M sodium carbonate to terminate the reaction, and measure the absorbance at 450 nm.

[0107] Compound inhibitory activity determination method: Incubate the enzyme with inhibitors at different concentrations at room temperature for 10 min, and measure the enzyme activity at concentrations of 100 μM and 20 μM respectively by the above method. The inhibitory activities of some compounds against insect chitin degrading enzymes are shown in Table 3 below.

[0108] Example 6. Determination of the insecticidal activity of compounds with the general formula CAUZL-C

[0109] Determination method: The diamondback moth (Plutelaxylostela Linnaeus) to be tested was treated by the drop method, and the results were checked after 3 days respectively. The individuals that could not crawl normally were regarded as dead when gently touched, and the corrected mortality rate (%) was calculated. Compared with the control agent, the virulence of the agent was judged. The insecticidal activity data of some compounds are shown in Table 4.

[0110] The following test targets:

[0111] The diamondback moth (Plutelaxylostela Linnaeus) was purchased commercially and reared indoors with the corresponding feed. The rearing conditions were room temperature (27±1)°C, humidity 80%, light intensity 2000 lux, and light time 12 h per day. Under the indoor rearing conditions, the 3rd instar larvae with consistent instar, body weight and physiological conditions were used for the agent activity screening test. Diflubenzuron was purchased from Macklin reagent.

[0112] The inhibitory effects of the synthesized carbohydrate derivatives on two chitin-degrading enzymes, OfChtII and OfHex1, were investigated at different concentrations. As shown in Table 3, compounds C6, C7, C8 and D5 showed good inhibitory activity (more than 50%) against OfChtII at a concentration of 20 μM, while most of the other compounds showed moderate inhibitory effects on both OfChtII and OfHex1. Among them, the inhibition rate of compound C7 against OfChtII was 83.22%, and the inhibition rate against OfHex1 was 70.58%.

[0113] Table 3. Inhibition rates (%) of some compounds in CAUZA-C and CAUZA-D series

[0114]

[0115]

[0116] Table 4. Insecticidal activities (%) and pupation rates (%) of some compounds in CAUZL-C and CAUZA-D against diamondback moth

[0117]

[0118] At a concentration of 500 μg / mL, compounds C2, C5, C6, C7, C8, D1, D2 and D3 showed good insecticidal activities, and their insecticidal rates were all over 60% (Table 4). It is worth noting that the treatments of C2, C6 and C7 completely inhibited their pupation, reducing the pupation rate to 0%. When the concentration was reduced to 200 μg / mL, compound C7 still maintained a high efficacy, with a mortality rate of 75.48% and a pupation rate of 0%, which was better than the commercially available insecticide diflubenzuron and the lead compound B12.

Claims

1. A glycosyl carbon glycoside compound, and a pharmaceutically acceptable salt, solvate or hydrate thereof, The structure is shown in Formula I or Formula II: The X1 and X2 are independently selected from substituted or unsubstituted C1-C6 alkyl, amino, C3-C6 cycloalkyl or alkylamino; preferably alkyl; The X3 and X4 are independently selected from substituted or unsubstituted C1-C6 alkyl, amino, C3-C6 cycloalkyl or alkylamino; preferably amino; The R1 and R2 are present or absent; When the R1 and R2 are present, R1 and R2 are independently selected from substituted or unsubstituted phenyl, benzyl, naphthyl, naphthalenesulfonyl, naphthalenesulfonamide, benzofurazan or nitrobenzofurazan NBD; The substitution is mono-substitution or multi-substitution; The substituents of the substitution are independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, N-N dimethyl, halogen-substituted C1-C6 alkyl or C1-C6 alkyl-substituted amino at each position.

2. A glycosyl carbon - linked glycoside compound according to claim 1, and its pharmaceutically acceptable salts, solvates or hydrates, wherein, The X1, X2, X3 and X4 are independently selected from substituted or unsubstituted -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -NH3, -CH2NH3, -CH2CH2NH3, -CH2CH2CH2NH3, -CH2CH2CH2CH2NH3, 3. A glycosyl carbon glycoside compound according to claim 1, and a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein, The X1 is methylene; the X3 is imino; and / or The X2 is methylene; the X4 is imino; 4. A glycosyl carbon glycoside compound according to claim 1, and a pharmaceutically acceptable salt, solvate or hydrate thereof, wherein, The structural formula shown in Formula I is selected from any one of the following compounds: and / or The structural formula shown in Formula (II) is selected from any one of the following compounds:

5. A method for preparing a glycosyl carbon glycoside compound according to any one of claims 1 to 4, and a pharmaceutically acceptable salt, solvate or hydrate thereof, comprising the following steps: (1) Reacting the compound shown in Formula III with the compound shown in Formula IV in an ethanol solvent to obtain the compound shown in Formula V; (2) Reacting the compound shown in Formula V with activated manganese dioxide in chloroform to obtain the compound shown in Formula VI; (3) Reacting the compound shown in Formula VII with the compound shown in Formula VIII in dichloromethane and triethylamine to obtain Formula IX; (4) Reacting the compound shown in Formula VI with the compound shown in Formula IX or Formula X through a click reaction to obtain Formula X; (5) Deprotecting Formula XI and / or Formula II under methanol ammonia conditions to obtain the target compounds shown in Formula I and Formula II; Preferably, the definition of R in Formula VII and Formula IX is the same as the definition of R1 and / or R2 in Formula I and Formula II; The R is independently selected from substituted or unsubstituted phenyl, benzyl, naphthyl, naphthalenesulfonyl, naphthalenesulfonamide, benzofurazan or nitrobenzofurazan NBD; The substitution is mono-substitution or multi-substitution; The substituents of the substitution are independently selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 alkoxy, nitro, N-N dimethyl, halogen-substituted C1-C6 alkyl or C1-C6 alkyl-substituted amino at each position; Preferably, the definition of R in Formula X is the same as the definition of R1 and / or R2 in Formula I and Formula II; R is substituted or unsubstituted -CH3, -CH2CH3, -CH2CH2CH3, -CH2CH2CH2CH3, -NH3, -CH2NH3, -CH2CH2NH3, -CH2CH2CH2NH3, -CH2CH2CH2CH2NH3, 6. Use of a glycosyl carbon glycoside compound according to any one of claims 1 to 4, and a pharmaceutically acceptable salt, solvate or hydrate thereof in pesticides; preferably for preventing and / or killing pests caused by Lepidoptera insects, including Plutella xylostella.

7. Use of a glycosyl carbon glycoside compound according to any one of claims 1 to 4, and a pharmaceutically acceptable salt, solvate or hydrate thereof as an insect chitin degrading enzyme inhibitor; preferably, for preventing and / or killing pests caused by Lepidoptera insects, including Plutella xylostella.

8. An insecticide comprising a glycosyl carbon glycoside compound according to any one of claims 1 to 4, and a pharmaceutically acceptable salt, solvate or hydrate thereof; preferably, the dosage form of the insecticide is selected from any one of the following: emulsifiable concentrate, wettable powder, suspension concentrate, powder, soluble powder, aqueous solution, water dispersible granule, smoke agent, granule, seed coating agent.

9. An insecticide according to claim 8, wherein the dosage form is an emulsifiable concentrate and is composed of the following substances in mass percentage content: 1 to 10% of a glycosyl carbon glycoside compound according to any one of claims 1 to 4, and a pharmaceutically acceptable salt, solvate or hydrate thereof, 5 to 15% emulsifier, 0.1 to 1% penetrant, balance solvent; Preferably, the emulsifier is a surfactant; more preferably any one or a combination of at least two of the following: agricultural emulsion 0203B, 0208, GFC, OP-10, Tween-60; Preferably, the solvent is selected from toluene and / or xylene.

10. A pesticide according to claim 8, in the form of a wettable powder, and consisting of the following substances in the following mass percentages: 15 to 50% of a glycosyl carbon glycoside compound according to any one of claims 1 to 4, and a pharmaceutically acceptable salt, solvate or hydrate thereof, 10 to 20% surfactant and 30 to 75% silica white; Preferably, the surfactant includes naphthol formaldehyde condensate, more preferably NNO.

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