CN110759905A - 9S-acyloxy cinchonine derivative, preparation method and application thereof, and botanical pesticide - Google Patents

Abstract

The invention belongs to the technical field of heterocyclic compounds, in particular to a 9S-acyloxycinchonine derivative, a preparation method and application thereof, and a botanical insecticide. 9S-acyloxycinchonine derivatives of the present invention, its structural formula is:

Wherein, R is selected from any one of alkyl, phenylalkylene, naphthylene, phenyl, and substituted phenyl; the number of carbon atoms in the alkyl is 1 to 5; the phenylene The number of carbon atoms in the alkylene group is 1 to 4; the substituents in the substituted phenyl group are halogen, nitro, alkoxy, and alkyl with 1 to 4 carbon atoms. One or more of the alkoxy groups, the number of carbon atoms in the alkoxy group is 1-3. The 9S-acyloxycinchonine derivatives of the present invention have good insecticidal activity, and the insecticidal effect of most of the derivatives has exceeded the commercial plant-derived insecticide toosendanin, and has good application prospects, It provides a new direction for the development of botanical pesticides.

Description

A kind of 9S-acyloxycinchonine derivatives and preparation method and application thereof, plant source Insecticide

technical field

The invention belongs to the technical field of heterocyclic compounds, in particular to a 9S-acyloxycinchonine derivative, a preparation method and application thereof, and a botanical insecticide.

Background technique

Studies have shown that the roots and stems of C.calisaya are toxic to melon moth (Diaphaniahyalinata L.) and diamondback moth (Plutellaxylostella L.); (Tineapellionella L.) has repellent effect; the stem bark of C. pubescens can also repel moths (Xu Hanhong, Insecticidal Plants and Botanical Insecticides, China Agricultural Press, Beijing: 2000, 49-50 ). Therefore, the cinchona tree should have active ingredients that can kill or repel insects. Studies have shown that the quinine in the cinchona tree has certain insecticidal activity ("Research Progress on Quinine Compounds", Che Zhiping, Chemical Bulletin , 2018, 81(9):792-796).

Cinchonine is one of the secondary metabolites of cinchona tree, its molecular formula is C ₁₉ H ₂₂ N ₂ O, and its structural formula is

At present, the research on cinchonine mainly focuses on the fields of asymmetric synthesis and chiral catalysis, and there is no report on the research on the insecticidal aspects of cinchonine and its derivatives.

SUMMARY OF THE INVENTION

The object of the present invention is to provide a 9S-acyloxycinchonine derivative, which has insecticidal activity.

Another object of the present invention is to provide a method for preparing the above-mentioned 9S-acyloxycinchonine derivatives.

The present invention also aims to provide a kind of cinchonine and the application of the above-mentioned 9S-acyloxycinchonine derivatives in preventing and controlling lepidopteran pests.

The present invention also aims to provide a botanical insecticide with better insecticidal activity.

For achieving the above object, the technical scheme adopted by the 9S-acyloxycinchonine derivatives of the present invention is:

A 9S-acyloxycinchonine derivative, its structural formula is:

Wherein, R is selected from any one of alkyl, phenylalkylene, naphthylene, phenyl, and substituted phenyl; the number of carbon atoms in the alkyl is 1 to 5; the phenylene The number of carbon atoms in the alkylene group is 1 to 4; the substituents in the substituted phenyl group are halogen, nitro, alkoxy, and alkyl with 1 to 4 carbon atoms. One or more of the alkoxy groups, the number of carbon atoms in the alkoxy group is 1-3.

Wherein the alkyl group is a chain alkyl group, preferably a straight chain alkyl group without branching.

Preferably, R is selected from any one of methyl, pentyl, benzylidene, naphthylmethylene, phenyl, and substituted phenyl; the substituent in the substituted phenyl is chlorine, bromine, nitro , one or more of methoxy, methyl and butyl.

Preferably, R is selected from methyl, n-pentyl, naphthylene, benzylidene, 3-methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butyl Any of phenyl, 4-chlorophenyl, 4-bromophenyl, 3-nitrophenyl, and 4-nitrophenyl. Among them, 3-methylphenyl, 4-methylphenyl, 4-methoxyphenyl, 4-tert-butylphenyl, 4-chlorophenyl, 4-bromophenyl, 3-nitrophenyl, 4-Nitrophenyl all belong to substituted phenyl, in the above-mentioned substituted phenyl, the benzene ring is used as the parent ring, and the numbering of the carbon atoms in the benzene ring is based on the C connected to the acyloxy group as the 1-position, and the remaining carbon atoms are based on the existing There are technical numbering principles for numbering. For example, in 3-methylphenyl, the methyl group is located in the meta position of the acyloxy group.

In the present invention, an ester group is introduced into the C9 position of cinchonine to form a series of 9S-acyloxycinchonine derivatives. Such derivatives have certain insecticidal activity, and the insecticidal effect of most of the derivatives has exceeded the commercialized ones. The botanical insecticide toosendanin has good application prospects and provides a new direction for the development of botanical pesticides.

A preparation method of above-mentioned 9S-acyloxycinchonine derivatives, comprising the following steps: under the action of N,N'-dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) , Cinchonine and carboxylic acid carry out esterification reaction in solvent; The molecular formula of described carboxylic acid is RCOOH, and R is selected from any one in alkyl, phenylalkylene, naphthylene, phenyl, substituted phenyl; The number of carbon atoms in the alkyl group is 1-5; the number of carbon atoms in the alkylene group in the phenylalkylene and naphthylene alkylene is 1-4; the substituent in the substituted phenyl group is One or more of halogens, nitro groups, alkoxy groups, and alkyl groups with 1 to 4 carbon atoms, and the number of carbon atoms in the alkoxy group is 1 to 3.

The invention uses the plant secondary metabolite cinchonine as the leading compound, and adopts the Steglich esterification reaction system to prepare 9S-acyloxycinchonine derivatives. The preparation method of the invention has mild reaction conditions, little influence on the configuration of cinchonine, simple operation, and is suitable for large-scale production.

The solvent used in the preparation process can dissolve the raw material and not react with the raw material. Preferably, the solvent used is dichloromethane.

The yield of the product is improved by optimizing the amount of each raw material. Preferably, during the reaction, (1-1.3) mol of carboxylic acid is used for each mole of cinchonine. Preferably, during the reaction, (1-1.3) mol of N,N'-dicyclohexylcarbodiimide and (0.1-0.3) mol of 4-dimethylaminopyridine are used for each mol of cinchonine.

The preparation method of the 9S-acyloxycinchonine derivatives of the present invention further comprises: after the reaction is completed, solid-liquid separation is performed to obtain a liquid phase; then the liquid phase is diluted, washed and dried; and after drying, concentration and separation are performed. The solvent used for dilution is dichloromethane. The washing was successively washed with hydrochloric acid, saturated sodium bicarbonate solution and saturated brine. Drying is drying with anhydrous sodium sulfate. Concentrate under reduced pressure. The separation was carried out by column chromatography.

Application of cinchonine or the above-mentioned 9S-acyloxycinchonine derivatives in controlling insect pests. Preferably, the pest control is the pest control caused by Lepidopteran pests.

Both cinchonine and the 9S-acyloxycinchonine derivatives of the present invention have insecticidal activity, so they can be used for insect pests, especially those caused by lepidopteran pests.

Further preferably, the Lepidoptera pests are armyworm pests.

Further preferably, cinchonine or the 9S-acyloxycinchonine derivatives of the present invention can control armyworm pests by inducing abnormal growth of armyworms.

When the cinchonine and the 9S-acyloxycinchonine derivatives of the present invention are used to prevent and control armyworm pests, they cause death by deforming armyworms and reduce the survival rate of armyworms, thereby realizing the control of armyworm pests.

The technical scheme of the botanical insecticide of the present invention is:

A botanical insecticide, comprising active ingredients including at least one of the above-mentioned 9S-acyloxycinchonine derivatives and cinchonine.

Both cinchonine and the 9S-acyloxycinchonine derivatives of the present invention have good insecticidal effects, so the botanical insecticides using them as active ingredients have good insecticidal activities.

Description of drawings

Fig. 1 is the hydrogen spectrogram of compound 3a in the embodiment 1 of the present invention;

Fig. 2 is the hydrogen spectrogram of compound 3b in the embodiment 2 of the present invention;

Fig. 3 is the hydrogen spectrogram of compound 3c in the embodiment of the present invention 3;

4 is a representative photograph of abnormal larvae in armyworms during the insecticidal activity test in Example 27 of the present invention;

5 is a representative photo of abnormal pupa in the armyworm during the insecticidal activity test in the embodiment of the present invention 27;

6 is a representative photograph of abnormal moths among armyworms in the insecticidal activity test in Example 27 of the present invention.

Detailed ways

The present invention will be further described below with reference to specific embodiments and accompanying drawings.

1. Examples of 9S-acyloxycinchonine derivatives

Table 1 shows the specific compounds and their physical properties in the examples of each 9S-acyloxycinchonine derivative.

Compounds and their physical properties in each example of Table 1

Two, the embodiment of the preparation method of 9S-acyloxy cinchonine derivatives

The general reaction formula involved in the preparation process of the following examples is:

In the general reaction formula, 1 is the reaction raw material cinchonine; 2a-2m are a series of carboxylic acids used, respectively 2a,..., 2m; 3a-3m are the prepared compounds 3a,..., 3m; r.t. represents room temperature .

Example 14

This embodiment is the preparation method of compound 3a in embodiment 1, and specifically comprises the following steps:

(1) Weigh 0.5 mmol of cinchonine (1), 0.6 mmol of glacial acetic acid (2a), 0.6 mmol of DCC and 0.1 mmol of DMAP, respectively, and place them in a 50 mL flask and mix well, then add 10 mL of calcium hydride-dried Dichloromethane, after mixing uniformly, react at room temperature, adopt TLC tracking detection during the reaction process, and the reaction ends after the reaction of the raw materials is complete;

(2) then remove urea by filtration to obtain a filtrate; the filtrate is diluted with 40 mL of dichloromethane, and then the dilution is sequentially used with 0.1 mol/L hydrochloric acid (25 mL), saturated sodium bicarbonate solution (25 mL) and saturated Each washing of brine (25mL) is successively followed by drying with anhydrous sodium sulfate; the dried diluent is carried out under reduced pressure distillation to remove the solvent to obtain a solid, and then the solid is separated by silica gel column chromatography (the eluent is that the volume ratio is 1: 1 of a mixture of ethyl acetate and petroleum ether) to obtain compound 3a (21% yield).

The reactions involved in the preparation process of the present embodiment are:

The obtained compound 3a was subjected to a 400MHz hydrogen nuclear magnetic resonance spectrum test. The solvent used in the test was CDCl ₃ , and TMS was the internal standard. The test results are shown in Figure 1. The specific chemical shift δ of each peak is: 8.88(d, J=4.8Hz, 1H), 8.21 (d, J=8.4Hz, 1H), 8.13 (d, J=8.4Hz, 1H), 7.69-7.73 (m, 1H), 7.57-7.61 (m, 1H), 7.39 (d, J=4.4Hz, 1H), 6.57 (d, J=7.2Hz, 1H), 5.98-6.07 (m, 1H), 5.07-5.13 (m, 2H), 3.30 (q, J=8.4Hz , 1H), 2.91(d, J=8.8Hz, 2H), 2.66-2.81(m, 2H), 2.29(q, J=8.4Hz, 1H), 2.12(s, 3H), 1.81-1.87(m, 2H), 1.50-1.56 (m, 3H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3a are: Calcd for C ₂₁ H ₂₅ N ₂ O ₂ ([M+H] ⁺ ), 337.1911; found, 337.1913.

Example 15

The present embodiment is the preparation method of compound 3b, and the specific reference is made to the preparation process of Example 14. The difference is only that: glacial acetic acid (2a) is replaced with n-hexanoic acid (2b), and the involved reactions are:

The yield of compound 3b prepared by the preparation method of this example was 39%. The obtained compound 3b was subjected to a 400MHz hydrogen nuclear magnetic resonance spectrum test. The solvent used in the test was CDCl ₃ , and TMS was the internal standard. The test results are shown in Figure 2. The specific chemical shift δ of each peak is: 8.88 (d , J=4.4Hz, 1H), 8.22 (dd, J=8.8Hz, 1.2Hz, 1H), 8.13 (dd, J=8.4Hz, 1.2Hz, 1H), 7.69-7.73 (m, 1H), 7.57- 7.61 (m, 1H), 7.38 (d, J=4.4Hz, 1H), 6.56 (d, J=7.2Hz, 1H), 5.98-6.07 (m, 1H), 5.07-5.13 (m, 2H), 3.33 (q, J=8.4Hz, 1H), 2.85-2.95(m, 2H), 2.65-2.80(m, 2H), 2.32-2.41(m, 2H), 2.22-2.29(m, 1H), 1.80-1.85 (m, 2H), 1.51-1.58 (m, 3H), 1.19-1.29 (m, 4H), 0.89-0.98 (m, 2H), 0.86 (t, J=7.2Hz, 3H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3b are: Calcd for C ₂₅ H ₃₃ N ₂ O ₂ ([M+H] ⁺ ), 393.2537; found, 393.2539.

Example 16

The present embodiment is the preparation method of compound 3c, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced by benzoic acid (2c), and the reactions involved are:

The yield of compound 3c prepared by the preparation method of this example was 54%. The obtained compound 3c was subjected to a 400MHz hydrogen nuclear magnetic resonance spectrum test. The solvent used in the test was CDCl ₃ , and TMS was the internal standard. The test results are shown in Figure 3. The specific chemical shift δ of each peak is: 8.87(d , J=4.4Hz, 1H), 8.32 (dd, J=8.4Hz, 1.2Hz, 1H), 8.08-8.14 (m, 3H), 7.70-7.74 (m, 1H), 7.57-7.65 (m, 2H) , 7.44-7.48(m, 3H), 6.80(d, J=7.2Hz, 1H), 5.98-6.07(m, 1H), 5.06-5.13(m, 2H), 3.48(q, J=8.4Hz, 1H) ), 2.90-3.03(m, 2H), 2.68-2.85(m, 2H), 2.25-2.32(m, 1H), 1.94-2.01(m, 1H), 1.85-1.87(m, 1H), 1.56-1.69 (m, 3H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3c are: Calcd for C ₂₆ H ₂₇ N ₂ O ₂ ([M+H] ⁺ ), 399.2067; found, 399.2071.

Example 17

The present embodiment is the preparation method of compound 3d, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with m-toluic acid (2d), and the reactions involved are:

The yield of compound 3d prepared by the preparation method of this example was 46%. The prepared compound 3d was subjected to a 400MHz hydrogen nuclear magnetic resonance spectrum test, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.87 (d, J=4.8Hz, 1H), 8.31 ( dd, J=8.4Hz, 1.2Hz, 1H), 8.14 (dd, J=8.4Hz, 1.2Hz, 1H), 7.88-7.90 (m, 2H), 7.70-7.74 (m, 1H), 7.61-7.65 ( m, 1H), 7.47 (d, J=4.4Hz, 1H), 7.32-7.41 (m, 2H), 6.81 (d, J=6.8Hz, 1H), 6.00-6.09 (m, 1H), 5.06-5.14 (m, 2H), 3.46 (q, J=8.4Hz, 1H), 2.90-3.04 (m, 2H), 2.80-2.87 (m, 1H), 2.69-2.77 (m, 1H), 2.41 (s, 3H) ), 2.25-2.32 (m, 1H), 1.96-2.03 (m, 1H), 1.84-1.88 (m, 1H), 1.54-1.66 (m, 3H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3d are: Calcd for C ₂₇ H ₂₉ N ₂ O ₂ ([M+H] ⁺ ), 413.2224; found, 413.2228.

Example 18

The present embodiment is the preparation method of compound 3e, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with p-toluic acid (2e), and the reactions involved are:

The yield of compound 3e prepared by the preparation method of this example was 39%. The prepared compound 3e was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.86 (d, J=4.8Hz, 1H), 8.31 ( dd, J=8.4Hz, 1.2Hz, 1H), 8.13 (dd, J=8.4Hz, 1.2Hz, 1H), 7.96-7.99 (m, 2H), 7.69-7.73 (m, 1H), 7.60-7.64 ( m, 1H), 7.46 (d, J=4.4Hz, 1H), 7.24-7.27 (m, 2H), 6.78 (d, J=7.2Hz, 1H), 5.99-6.07 (m, 1H), 5.06-5.13 (m, 2H), 3.46 (q, J=8.4Hz, 1H), 2.89-3.03 (m, 2H), 2.68-2.85 (m, 2H), 2.41 (s, 3H, ), 2.24-2.31 (m, 1H), 1.94-2.00 (m, 1H), 1.85 (s, 1H), 1.54-1.67 (m, 3H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3e are: Calcd for C ₂₇ H ₂₉ N ₂ O ₂ ([M+H] ⁺ ), 413.2224; found, 413.2226.

Example 19

The present embodiment is the preparation method of compound 3f, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with p-methoxybenzoic acid (2f), and the reactions involved are:

The yield of compound 3f prepared by the preparation method of this example was 53%. The prepared compound 3f was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.87 (d, J=4.4Hz, 1H), 8.34 ( dd, J=8.4Hz, 1.2Hz, 1H), 8.14 (dd, J=8.4Hz, 1.2Hz, 1H), 8.03-8.07 (m, 2H), 7.70-7.74 (m, 1H), 7.60-7.64 ( m, 1H), 7.46 (d, J=4.4Hz, 1H), 6.92-6.95 (m, 2H), 6.83 (d, J=6.8Hz, 1H), 5.99-6.07 (m, 1H), 5.06-5.15 (m, 2H), 3.86 (s, 3H), 3.47 (q, J=8.4Hz, 1H), 2.94-3.06 (m, 2H), 2.83-2.90 (m, 1H), 2.71-2.79 (m, 1H) ), 2.27-2.34 (m, 1H), 1.98-2.02 (m, 1H), 1.86-1.89 (m, 1H), 1.56-1.65 (m, 3H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3e are: Calcd for C ₂₇ H ₂₉ N ₂ O ₃ ([M+H] ⁺ ), 429.2173; found, 429.2178.

Example 20

The present embodiment is the preparation method of compound 3g, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with p-tert-butylbenzoic acid (2g), and the reactions involved are:

The yield of compound 3g prepared by the preparation method of this example was 50%. The prepared compound 3g was subjected to 400MHz hydrogen nuclear magnetic resonance spectrum test, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.86 (d, J=4.4Hz, 1H), 8.32 ( dd, J=8.4Hz, 1.2Hz, 1H), 8.13 (dd, J=8.4Hz, 1.2Hz, 1H), 8.01-8.04 (m, 2H), 7.69-7.74 (m, 1H), 7.60-7.64 ( m, 1H), 7.45-7.49 (m, 3H), 6.79 (d, J=7.2Hz, 1H), 5.99-6.08 (m, 1H), 5.06-5.14 (m, 2H), 3.47 (q, J= 8.4Hz, 1H), 2.91-3.04(m, 2H), 2.69-2.85(m, 2H), 2.32(q, J=8.4Hz, 1H), 1.94-2.00(m, 1H), 1.86(s, 1H) ), 1.56-1.66 (m, 3H), 1.34 (s, 9H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3g are: Calcd for C ₃₀ H ₃₅ N ₂ O ₂ ([M+H] ⁺ ), 455.2693; found, 455.2695.

Example 21

The present embodiment is the preparation method of compound 3h, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with p-chlorobenzoic acid (2h), and the involved reactions are:

The yield of compound 3h prepared by the preparation method of this example was 22%. The prepared compound 3h was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.88 (d, J=4.4Hz, 1H), 8.29 ( dd, J=8.4Hz, 1.2Hz, 1H), 8.14 (dd, J=8.4Hz, 1.2Hz, 1H), 8.03 (t, J=2.4Hz, 1H), 8.01 (t, J=2.4Hz, 1H) ), 7.70-7.75(m, 1H), 7.60-7.65(m, 1H), 7.42-7.45(m, 3H), 6.78(d, J=7.6Hz, 1H), 5.97-6.05(m, 1H), 5.06-5.14(m, 2H), 3.47(q, J=8.4Hz, 1H), 2.89-3.00(m, 2H), 2.68-2.79(m, 2H), 2.25-2.32(m, 1H), 1.85- 1.96 (m, 2H), 1.55-1.68 (m, 3H).

The results of high resolution chromatography (HRMS, ESI) of compound 3h are: Calcd for C ₂₆ H ₂₆ ClN ₂ O ₂ ([M+H] ⁺ ), 433.1677; found, 433.1678.

Example 22

The present embodiment is the preparation method of compound 3i, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with p-bromobenzoic acid (2i), and the reaction involved is:

The yield of compound 3i prepared by the preparation method of this example was 36%. The prepared compound 3h was subjected to 400MHz hydrogen nuclear magnetic resonance spectrum test, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.88 (d, J=4.8Hz, 1H), 8.29 ( dd, J=8.8Hz, 1.2Hz, 1H), 8.14 (dd, J=8.4Hz, 1.6Hz, 1H), 7.92-7.95 (m, 2H), 7.70-7.74 (m, 1H), 7.58-7.64 ( m, 3H), 7.44 (d, J=4.4Hz, 1H), 6.77 (d, J=7.6Hz, 1H), 5.96-6.05 (m, 1H), 5.06-5.14 (m, 2H), 3.47 (q , J=8.4Hz, 1H), 2.89-2.99(m, 2H), 2.68-2.84(m, 2H), 2.25-2.32(m, 1H), 1.85-1.96(m, 2H), 1.54-1.68(m , 3H).

The results of high resolution chromatography (HRMS, ESI) of compound 3i are: Calcd for C ₂₆ H ₂₆ BrN ₂ O ₂ ([M+H] ⁺ ), 477.1172; found, 477.1177.

Example 23

The present embodiment is the preparation method of compound 3j, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with m-nitrobenzoic acid (2j), and the reactions involved are:

The yield of compound 3j prepared by the preparation method of this example was 48%. The prepared compound 3j was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.92 (t, J=2.0Hz, 1H), 8.90 ( d, J=4.4Hz, 1H), 8.43-8.46 (m, 1H), 8.36-8.39 (m, 1H), 8.31 (dd, J=8.4Hz, 1.2Hz, 1H), 8.15 (dd, J=8.4 Hz, 1.6Hz, 1H), 7.72-7.76 (m, 1H), 7.63-7.69 (m, 2H), 7.48 (d, J=4.8Hz, 1H), 6.83 (d, J=7.6Hz, 1H), 6.00-6.09 (m, 1H), 5.07-5.16 (m, 2H), 3.54 (q, J=8.4Hz, 1H), 2.96 (dd, J=8.8Hz, 1.2Hz, 2H), 2.80-2.86 (m , 1H), 2.69-2.76 (m, 1H), 2.26-2.34 (m, 1H), 1.88-1.98 (m, 2H), 1.68-1.73 (m, 1H), 1.56-1.64 (m, 2H).

The high-resolution chromatography (HRMS, ESI) test results of compound 3j are: Calcd for C ₂₆ H ₂₆ N ₃ O ₄ ([M+H] ⁺ ), 444.1918; found, 444.1919.

Example 24

The present embodiment is the preparation method of compound 3k, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with p-nitrobenzoic acid (2k), and the reactions involved are:

The yield of compound 3k prepared by the preparation method of this example was 32%. The prepared compound 3k was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.90 (d, J=4.8Hz, 1H), 8.23- 8.32(m, 5H), 8.15(dd, J=8.4Hz, 1.2Hz, 1H), 7.72-7.76(m, 1H), 7.62-7.66(m, 1H), 7.46(d, J=4.4Hz, 1H) ), 6.81(d, J=7.6Hz, 1H), 5.96-6.05(m, 1H), 5.07-5.16(m, 2H), 3.52(q, J=8.4Hz, 1H), 2.95(d, J= 8.8Hz, 2H), 2.68-2.85(m, 2H), 2.26-2.34(m, 1H), 1.87-1.93(m, 2H), 1.65-1.72(m, 1H), 1.56-1.62(m, 2H) .

The high-resolution chromatography (HRMS, ESI) test results of compound 3k are: Calcd for C ₂₆ H ₂₆ N ₃ O ₄ ([M+H] ⁺ ), 444.1918; found, 444.1923.

Example 25

The present embodiment is the preparation method of compound 31, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with naphthalene acetic acid (21), and the reactions involved are:

The yield of compound 31 prepared by the preparation method of this example was 32%. The prepared compound 31 was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.59 (d, J=4.8Hz, 1H), 8.07 ( dd, J=8.4Hz, 1.2Hz, 1H), 8.02 (dd, J=8.4Hz, 1.2Hz, 1H), 7.89 (dd, J=8.4Hz, 1.2Hz, 1H), 7.81-7.83 (m, 2H) ), 7.63-7.67(m, 1H), 7.36-7.49(m, 5H), 6.88(d, J=4.4Hz, 1H), 6.50(d, J=7.2Hz, 1H), 5.82-5.91(m, 1H), 5.02-5.10(m, 2H), 4.12(s, 2H), 3.16(q, J=8.4Hz, 1H), 2.80-2.83(m, 2H), 2.58-2.68(m, 2H), 2.15 -2.66 (m, 1H), 1.66-1.70 (m, 1H), 1.54-1.61 (m, 1H), 1.41-1.46 (m, 2H), 1.18-1.25 (m, 1H).

The high-resolution chromatography (HRMS, ESI) test results of compound 31 are: Calcd for C ₃₁ H ₃₁ N ₂ O ₂ ([M+H] ⁺ ), 463.2380; found, 463.2387.

Example 26

The present embodiment is the preparation method of compound 3m, with specific reference to the preparation process of Example 14, the difference is only that: glacial acetic acid (2a) is replaced with phenylacetic acid (2m), and the reactions involved are:

The yield of compound 3m prepared by the preparation method of this example was 38%. The prepared compound 3m was tested by 400MHz hydrogen nuclear magnetic resonance spectrum, the solvent used in the test was CDCl ₃ , TMS was the internal standard, and the specific chemical shift δ was: 8.81 (d, J=4.4Hz, 1H), 8.11- 8.17(m, 2H), 7.69-7.73(m, 1H), 7.55-7.59(m, 1H), 7.23-7.25(m, 2H), 7.22(d, J=4.4Hz, 1H), 6.97-7.01( m, 1H), 6.83-6.86 (m, 2H), 6.66 (d, J=7.6Hz, 1H), 5.98-6.07 (m, 1H), 5.07-5.12 (m, 2H), 4.68 (d, J= 2.4Hz, 2H), 3.34 (q, J=8.4Hz, 1H), 2.89 (d, J=8.4Hz, 2H), 2.64-2.79 (m, 2H), 2.22-2.28 (m, 1H), 1.77- 1.80 (m, 2H), 1.47-1.55 (m, 3H).

The results of high resolution chromatography (HRMS, ESI) of compound 3m are: Calcd for C ₂₇ H ₂₉ N ₂ O ₂ ([M+H] ⁺ ), 413.2224; found, 413.2222.

3. Examples of botanical insecticides

Example 27

The botanical insecticide in this example is a mixed solution with a concentration of 1 mg/mL prepared from Compound 3a in Example 1 and acetone.

In other embodiments of the botanical insecticide, the active ingredient in the existing botanical insecticide, such as toosendanin, can also be replaced by cinchonine or 3j or 3j in the 9S-acyloxycinchonine derivatives of the present invention. 3m. Cinchonine and/or 9S-acyloxycinchonine derivatives of the present invention can also be used as active ingredients, compounded with other existing active ingredients, and processed into compounded insecticides according to existing processing methods. agent.

4. Test case

The compounds 3a to 3m and cinchonin in Examples 1 to 13 were respectively tested for their activity against lepidopteran insect armyworm by adding a small leaf disc. The test insects were the first third instar armyworm, and the commercial plant-derived insecticide Toosendanin was used as the positive control group. The specific test process is as follows:

1) Compounds 3a～3m, Cinchonin and Toosendanin are respectively prepared into acetone solutions with a concentration of 1 mg/mL to obtain the medicinal liquid of 3a～3m, the medicinal liquid of Cinchoning and the medicinal solution of Toosendanin; the fresh corn leaves are cut into 1cm ×1cm small-leaf plate, then immersed in 3a-3m liquid medicine, Xinkening liquid, toosendanin liquid (positive control) and pure acetone liquid (blank control) for 3s, and dried naturally for later use.

2) Feed the test worms on the dried leaflets respectively. After the test worms have eaten the leaflets, add the dried leaflets in time, and feed the normal leaves (ie, the leaflets without the liquid medicine) after feeding for 48 hours. Until eclosion; three replicates were set for each medicinal solution, and 10 robust, uniform-sized pre-third-instar armyworms were selected for each replicate and reared in a petri dish with a diameter of 9 cm. The rearing conditions were as follows: temperature 25±2°C, relative humidity 65-80%, light time 12h, dark time 12h, light and dark were carried out at intervals in turn.

3) During the feeding period, record the mortality rate (%) of the test worms in different periods, and calculate according to the following formula: Corrected mortality rate (%)=(death rate of treatment group-death rate of control group)*100/(1-control group death rate), where the death rate of the control group was the death rate of the blank control group. The calculation results are shown in Table 2.

Table 2 Insecticidal activity results

The test results showed that the insecticidal effect of Cinchonin on armyworms was remarkable, and the insecticidal effect had surpassed the commercial plant-derived insecticide toosendanin. The insecticidal effects of 3c, 3d, 3g, 3h and 3j-m in the 9S-acyloxycinchonine derivatives (compounds 3a to 3m) of the present invention on armyworms are also more than those of toosendanin, especially compounds 3j and 3j-m. 3m; the insecticidal effect of compound 3a is the same as that of toosendanin, and the insecticidal effect of compounds 3b, 3e, and 3f is still better than that of toosendanin in a short time (10 days); day), the insecticidal effect is the same as that of senimin.

During the test, the abnormal worms in the larval stage, the pupal stage and the moth stage were selected and photographed, as shown in Figures 4 to 6 (CK in the figure is the normal test worm in the blank control group). As can be seen from FIGS. 4 to 6 , cinchonine and the cinchonine derivatives of the present invention can cause abnormal growth of armyworms and death.

The test results of insecticidal activity show that cinchonine and the 9S-acyloxycinchonine derivatives of the present invention have good insecticidal activity, especially against lepidopteran insect armyworm, so they can be used to control insect pests.

Claims (10)

1. a 9S-acyloxy cinchonine derivative, is characterized in that, the structural formula of this 9S-acyloxycinchonine derivative is: Wherein, R is selected from any one of alkyl, phenylalkylene, naphthylene, phenyl, and substituted phenyl; the number of carbon atoms in the alkyl is 1 to 5; the phenylene The number of carbon atoms in the alkylene group is 1 to 4; the substituents in the substituted phenyl group are halogen, nitro, alkoxy, and alkyl with 1 to 4 carbon atoms. One or more of the alkoxy groups, the number of carbon atoms in the alkoxy group is 1-3. 2. 9S-acyloxycinchonine derivatives according to claim 1, is characterized in that, R is selected from among methyl, amyl, benzylidene, naphthylmethylene, phenyl, substituted phenyl Any; the substituent in the substituted phenyl group is one or more of chlorine, bromine, nitro, methoxy, methyl, and butyl. 3. 9S-acyloxy cinchonine derivatives according to claim 1 or 2, wherein R is selected from methyl, n-pentyl, 3-methylphenyl, 4-methylphenyl, 4 -Methoxyphenyl, 4-tert-butylphenyl, 4-chlorophenyl, 4-bromophenyl, 3-nitrophenyl, 4-nitrophenyl, naphthylmethylene, benzylidene any of the . 4. The preparation method of 9S-acyloxycinchonine derivatives according to any one of claims 1 to 3, characterized in that, comprising the following steps: in N,N'-dicyclohexylcarbodiimide and 4 -Under the action of dimethylaminopyridine, cinchonine and carboxylic acid are esterified in a solvent; the molecular formula of the carboxylic acid is RCOOH, and R is selected from alkyl, phenylalkylene, naphthylene, phenyl, Any of the substituted phenyl groups; the number of carbon atoms in the alkyl group is 1-5; the number of carbon atoms in the alkylene group in the phenylalkylene and naphthylene alkylene groups is 1-4; The substituents in the substituted phenyl group are one or more of halogen, nitro, alkoxy, and alkyl groups with 1 to 4 carbon atoms, and the number of carbon atoms in the alkoxy group is 1 ~3. 5 . The method for preparing 9S-acyloxycinchonine derivatives according to claim 4 , wherein, during the reaction, (1-1.3) mol of carboxylic acid is used for each mole of cinchonine. 6 . 6 . The application of cinchonine or the 9S-acyloxycinchonine derivative according to any one of claims 1 to 3 in controlling insect pests. 7 . 7 . The application according to claim 6 , wherein the pest control is the control of Lepidopteran pests. 8 . 8 . The application according to claim 7 , wherein the Lepidopteran pests are armyworm pests. 9 . 9 . The application according to claim 8 , wherein the cinchonine or 9S-acyloxycinchonine derivatives realize the control of armyworm pests by inducing abnormal growth of armyworms. 10 . 10. A botanical insecticide, characterized in that it comprises an active ingredient comprising at least one of the 9S-acyloxycinchonine derivatives and cinchonine according to any one of claims 1 to 3. A sort of.

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