阅读说明：本技术 一类新型昆虫激肽类似物及其在蚜虫防治中的应用 (Novel insect kinin analogs and application thereof in aphid control ) 是由 杨新玲 周源琳 张怡萌 赵英儒 徐伟龙 冯浩原 于 2021-09-28 设计创作，主要内容包括：本发明提供一类新型昆虫激肽类似物及其在蚜虫防治中的应用。其结构式如式A所示。本发明采用模拟肽学的策略和方法,发明了一类新型的昆虫激肽类似物,对活性激肽类似物的活性构象VI型β转角的转折点Phe～(2)进行取代修饰,即在关键性位点Phe～(2)侧链芳香环取代,同时引入酯基、醚键、脂肪环以及脂肪链等进行取代修饰,经固相多肽方法制备获得式A化合物。新化合物的杀蚜虫活性非常明显,优于对照商品化药剂吡蚜酮,尤其对多种蚜虫具有很好的防效,可以应用于农业蚜虫的防治中。(The invention provides a novel insect kinin analogue and application thereof in aphid control. The structural formula is shown as formula A. The invention adopts the strategy and method of mimic peptide science, invents a novel insect kinin analog, and aims at the transition point Phe of the active conformation VI type beta corner of the active kinin analog 2 By substitution, i.e. Phe at the critical position 2 The side chain aromatic ring is substituted, ester group, ether bond, aliphatic ring, aliphatic chain and the like are simultaneously introduced for substitution modification, and the compound of the formula A is prepared by a solid phase polypeptide method. The novel compound has very obvious aphid killing activity, is superior to that of a contrast commercial pesticide pymetrozine, particularly has good control effect on various aphids, and can be applied toPreventing and treating agricultural aphids.)

1. A compound of formula A:

wherein, Raa is natural amino acid or unnatural amino acid.

2. The compound of claim 1, wherein: the natural amino acid or the unnatural amino acid is selected from the group consisting of: 5-cyclohexyl glutamate, tert-leucine, allylglycine, 2-amino-5-phenylpentanoic acid, aminocyclopropanecarboxylic acid, 3- (2-furyl) -L-alanine, 1-amino-1-cyclohexanecarboxylic acid, cyclobutylalanine, methionine, 2-amino-5-methylhexanoic acid, 1-aminocyclobutanecarboxylic acid, 3- (2-thienyl) -L-alanine, 1-allyl glutamate, 1-benzyl aspartate, methyl glutamate, 4-cyclohexyl aspartate, O-acetyl-L-threonine, 5-benzyl glutamate, O-benzyl-L-serine, O-tert-butyl-L-threonine, alpha-hydroxy-methyl-amino-1-quinolinecarbonate, alpha-hydroxy-methyl-quinolinecarbonate, alpha-hydroxy-quinolinecarbonate, alpha-5-quinolinecarbonate, alpha-amino-5-phenylpentanoic acid, alpha-amino-carboxylic acid, alpha-2- (2-furanyl) -L-alanine, 1-cyclohexylamino-1-cyclohexanecarboxylic acid, 1-amino-1-cyclohexylcarboxylic acid, O-acetyl-threonine, alpha-quinolinecarbonic acid, alpha-quinolinic acid, a, S-acetamidomethyl-L-cysteine, glutamic acid-1-benzyl ester, L-aspartic acid-1-allyl ester, O-tert-butyl-L-serine, O-benzyl-L-threonine.

3. The compound of claim 1 or 2, wherein: the natural amino acid or the unnatural amino acid is selected from the group consisting of glutamic acid-5-cyclohexyl ester, tert-leucine, allylglycine, aminocyclopropanecarboxylic acid, cyclobutylalanine, 2-amino-5-methylhexanoic acid, 1-aminocyclobutanecarboxylic acid, 3- (2-thienyl) -L-alanine, 1-allyl glutamate, 1-benzyl aspartate, methyl glutamate, 4-cyclohexyl aspartate, O-acetyl-L-threonine, 5-benzyl glutamate, O-benzyl-L-serine, O-tert-butyl-L-threonine, S-acetamidomethyl-L-cysteine, 1-allyl L-aspartate, N-acetyl-L-threonine, N-acetyl-L-alanine, N-acetyl-L-cysteine, N-acetyl-L-alanine, N-acetyl-L-alanine, N-acetyl-L-glutamate, N-L-ester, and L-ester, O-benzyl-L-threonine.

4. A compound according to any one of claims 1-3, characterized in that: the compound shown in the formula A is prepared according to a polypeptide solid phase synthesis method.

5. Use of a compound according to any one of claims 1 to 3 for pest control.

6. Use according to claim 5, characterized in that: the pests are aphids.

7. Use according to claim 6, characterized in that: the aphids are at least one of soybean aphids, pea aphids and green peach aphids.

8. A medicament, the active ingredient of which is a compound according to any one of claims 1 to 3.

9. The medicament of claim 8, wherein: the drug is an aphicide.

Technical Field

The invention relates to a novel insect kinin analogue and application thereof in aphid control, belonging to the field of agriculture.

Background

Aphids are one of the main agricultural pests, cause serious damage to plants, and bring huge economic loss to agricultural production. Aphids cause damage to plants mainly by sucking plant juices, and at the same time, aphids spread various plant viruses, and the damage of the spread viruses is far more than that of the aphids. Therefore, control of aphids is extremely important in agriculture. At present, a chemical pesticide control method is mainly adopted, the dosage of the aphid is continuously increased due to the drug resistance of the aphid to the traditional chemical aphicide, and the toxicity of some chemical aphicides to non-target organisms such as bees causes great risks to the environmental safety and ecological safety of the traditional chemical aphicide. Therefore, on the premise of being eco-friendly, the development of a high-efficiency aphid control agent with a novel action mechanism and a novel structure is very important.

Insect Kinins (IKs) are small molecule active peptides with abundant physiological functions, periodically synthesized, secreted and transmitted by specific nerve cells in Insect brain through nerves or body fluid. IKs has a plurality of physiological functions of regulating the release of digestive enzymes, balancing water and salt, contracting muscles, participating in the trachea clearance and inflation before exuviation of fruit flies, participating in the regulation and control of the body temperature of insects, regulating the movement in the early period of exuviation by feeding and the like, thereby being capable of regulating the growth and development of the insects. Due to this series of important physiological functions possessed by insect kinins, they are considered as a potential class of pest control agents. The insect kinins have the characteristics of high activity, simple structure, easy modification by a chemical method, environmental friendliness and the like, and therefore, the insect kinins can be widely considered as a lead of a pest control agent. As indicated above, insect kinins contain many advantages: (1) the activity is high; (2) the environment is friendly, the amino acid is easy to degrade, the pollution is not caused, and the safety is good (3) and the amino acid is nontoxic to human and livestock; (4) simple structure, and easy chemical modification. Insect kinins are conserved pentapeptide H-Phe¹-Xaa²-Yaa³-Trp⁴-Gly⁵-NH₂Is C-terminal, wherein Xaa can be Tyr, His, Ser, Phe, or Asn; yaa can be Ser, Pro or Ala, and the pentapeptide is the smallest fragment required to maintain biological activity, called the core pentapeptide. Over 40 different insect kinins have been isolated from 17 animals. However, because of the poor stability of natural insect kinins, structural modifications and alterations of natural insect kinins using peptidomimetic means and methods are needed to overcome the drawbacks while maintaining excellent biological activity in order to find new pest control agents of practical use.

In recent years, development of novel pest control agents has been attempted using an insect kinin core pentapeptide as a lead. Scholars at home and abroad introduce unnatural amino acid with steric hindrance effect into molecules in sequence, and structural modification and reformation are carried out on the unnatural amino acid to obtain the insect kinin analog with good enzymolysis resistance activity and good biological activity. Some insect kinin analogues have been disclosed in the following documents: such as Nachman, R.J., et al, Diuretic activity of C-terminal group identities of the insects in acetic medicaments. peptides (Tarrytown, N.Y.)1995,16, 809-13; nachman, R.J., et al, Aib-relating analogues of the insulation kinase and refractory family resistance to an insulation angiotensin-converting enzyme and reactive microorganisms 1997,18, 53-57; c-terminal aldehyde insulation in organic aldehydes enhancement of weight gain and indeces design mortalities in Helicoverpa zea larvaes 2003,24,1615-21, et al; nachman, r.j. et al, Stereochemistry of infection in tetrazolium analytes and of metabolic activity in crickets.acta biochem. pol.2004,51, 121-; active induced kinase analog with 4-aminopyrazole, alpha novel cis-peptide bond, type VI beta-turn mole biopolymer 2004,75, 412-; zubrzak, P, et al, beta-Amino acid analogs of an antibiotic neuroactivity and resistance to peptide hydrolytics. biopolymers 2007,88, 76-82; nachman, r.j. et al, aware of novel peptide management agents based on immune inducing in neuro-activity assays, an.n.n.y.acad.sci.2009, 1163, 251-261; smagghe, G, et al, antibiotic activity and high reliability in the pea apple, apple, apple, apple, apple, etc.; a review of novel classes of antisteeds and aphacitides, Pestycydy 2011, 23-34; nachman, r.j. et al Active diagnostic peptide inducing protein analogs that protein residues β -turn mimetic 4-aminopropylamino and lack native peptide substrates 2012,34, 262-peptides 265 (New York, NY, United States); zhang C.L. et al Design, synthesis and aphasic activity of N-terminal modified infection in animals. peptides (N.Y., NY, U.S.)2015,68, 233-; zhang C, et al Synthesis, aphasic activity and transformation of novel antibodies as potential antibodies in pest Management Science 2020,76(10) 3432-; yang X, Li X, Zhang Z, et al, glasses of insulation in assays and the same applications CN108276473A [ P ]; yang X, Zhang C.L, Ling.Y. and the like, Novel insects in animals and peptides CN105061556A [ P ] the above documents obtain corresponding analogues by modifying natural insect kinins with unnatural amino acids or carboxylic acids with larger steric hindrance, can improve the enzymolysis resistance of the insects and simultaneously have certain biological activity. However, the biological activity of the kinin analogues is not very outstanding, and the application of the kinin analogues as pesticide molecules in agricultural production still has certain limitations.

Disclosure of Invention

The invention aims at the turning point of the beta turn of the active conformation VI of the active kinin analogue, namely the critical site Phe²Substituted and modified, and uses linear, cyclic, esterified, steric hindrance and orientation-limited natural amino acid or non-natural amino acid and other groups to make Phe²Substitution modification is carried out, a novel insect kinin analog is invented, and biological activity tests show that the compound not only has good activity of killing soybean aphids, but also has certain activity on pea aphids and green peach aphids.

The invention provides a novel insect kinin analogue, the structural general formula of which is formula A:

wherein, Raa is natural amino acid or unnatural amino acid, and the natural amino acid or the unnatural amino acid can be selected from: 5-cyclohexyl glutamate, tert-leucine, allylglycine, 2-amino-5-phenylpentanoic acid, aminocyclopropanecarboxylic acid, 3- (2-furyl) -L-alanine, 1-amino-1-cyclohexanecarboxylic acid, cyclobutylalanine, methionine, 2-amino-5-methylhexanoic acid, 1-aminocyclobutanecarboxylic acid, 3- (2-thienyl) -L-alanine, 1-allyl glutamate, 1-benzyl aspartate, methyl glutamate, 4-cyclohexyl aspartate, O-acetyl-L-threonine, 5-benzyl glutamate, O-benzyl-L-serine, O-tert-butyl-L-threonine, alpha-hydroxy-methyl-amino-1-quinolinecarbonate, alpha-hydroxy-methyl-quinolinecarbonate, alpha-hydroxy-quinolinecarbonate, alpha-5-quinolinecarbonate, alpha-amino-5-phenylpentanoic acid, alpha-amino-carboxylic acid, alpha-2- (2-furanyl) -L-alanine, 1-cyclohexylamino-1-cyclohexanecarboxylic acid, 1-amino-1-cyclohexylcarboxylic acid, O-acetyl-threonine, alpha-quinolinecarbonic acid, alpha-quinolinic acid, a, S-acetamidomethyl-L-cysteine, glutamic acid-1-benzyl ester, L-aspartic acid-1-allyl ester, O-tert-butyl-L-serine, O-benzyl-L-threonine.

Specifically, the natural amino acid or unnatural amino acid may preferably be selected from the group consisting of 5-cyclohexyl glutamate, tert-leucine, allylglycine, aminocyclopropanecarboxylic acid, cyclobutylalanine, 2-amino-5-methylhexanoic acid, 1-aminocyclobutanecarboxylic acid, 3- (2-thienyl) -L-alanine, 1-allyl glutamate, 1-benzyl aspartate, methyl glutamate, 4-cyclohexyl aspartate, O-acetyl-L-threonine, 5-benzyl glutamate, O-benzyl-L-serine, O-tert-butyl-L-threonine, S-acetamidomethyl-L-cysteine, 1-allyl L-aspartate, L-alanine, O-benzyl-L-threonine.

The compounds represented by the formula A provided by the invention are all prepared according to a polypeptide solid phase synthesis method (reference document: Chan WG, White PD. Fmoc solid phase peptide synthesis A Practical Approach, Oxford Ulersality Press, 2000; pp.9-74.).

The invention further provides application of the compound shown in the formula A in pest control.

The pest may be aphids.

The aphid may be at least one of soybean aphid (Aphis glycines Matsmura), pea aphid (acrythospon pisum) and green peach aphid (Myzus persicae (Sulzer)).

The invention also provides a medicament (such as an aphicide) of which the active ingredient is the compound shown in the formula A, and belongs to the protection scope of the invention.

The insecticidal activity of the compounds of the invention against aphids was determined by the leaf-spreading method (ref: Busvine, J.R., Recommended methods for measuring delivery to pests.1980.). The bioassay results show that: the compound has very obvious poisoning activity on soybean aphids and also has better activity on pea aphids and green peach aphids. The activity of part of compounds is superior to that of a commercial medicament pymetrozine, and the compounds have further application and development values as aphid control agents.

The invention has the beneficial effects that: the invention adopts the strategy and method of mimic peptide science, invents a novel insect kinin analog, and aims at the transition point Phe of the active conformation VI type beta corner of the active kinin analog²By substitution, i.e. Phe at the critical position²The side chain is substituted by aromatic ring, and ester group, ether bond, aliphatic ring, aliphatic chain and the like are introduced for substitution modification, so that the novel compound has very obvious aphid killing activity, is superior to commercial medicament pymetrozine, especially has good control effect on various aphids, and can be applied to prevention and control of agricultural aphids.

Detailed Description

The experimental procedures used in the following examples are all conventional procedures unless otherwise specified.

Materials, reagents and the like used in the following examples are commercially available unless otherwise specified.

EXAMPLE 1 preparation of the Compound represented by AI-1 (Raa from glutamic acid-5-cyclohexyl)

After checking the air tightness of the polypeptide synthesizer, taking Rink Amide-Am resin (0.3mmol) and placing the Rink Amide-Am resin in 5mL DCM for activating for 2h, then washing the Rink Amide-Am resin for 5 times by DMF, and adding 5mL of 20% piperidine DMF solution for reacting for 20min to remove Fmoc protective groups on the resin; 5mL of a solution containing Fmoc-Gly-OH (1.2mmol), HBTU (1.2mmol) and HOBt (1) was prepared.2mmol) and DIEA (1.2mmol) in DMF, activating for 5min, and reacting with resin at room temperature for 2h to obtain Fmoc-Gly with Rink Amide-Am resin. And continuously removing the Fmoc group, and sequentially accessing Fmoc-Trp (Boc) -OH, Fmoc-beta-Ala-OH, Fmoc-glutamic acid-5-cyclohexyl and cinnamic acid by the same method. Finally, trifluoroacetic acid is utilized: phenol: thioanisole: and (3) reacting the mixed solution of water and resin for 4 hours to obtain the target product, wherein the mixed solution is 90:5:2.5: 2.5. Filtering, removing TFA, adding a proper amount of frozen ether for precipitation, centrifuging to remove supernatant, and freeze-drying the obtained solid to obtain a crude product. The crude product is subjected to phase inversion C₁₈The semi-preparative high performance liquid chromatography is used for separating to obtain a pure product, and the chromatographic conditions are as follows: the mobile phase was 50% acetonitrile in water (containing 0.1% TFA), the flow rate was 10mL/min, the detection wavelength was 215nm, and the HPLC retention time was around 12 min. The structural identification data are shown in table 1, and the structure is confirmed to be correct by high-resolution mass spectrometry.

Other target compounds are prepared according to the method.

Example 2 preparation of the Compound AI-2 (Raa from Tertiary leucine)

The compound represented by AI-2 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-tert-leucine. The structure identification data are shown in table 1, and the structure is correct after verification.

Preparation of the Compound shown in example 3 and AI-3 (Raa from L-allylglycine)

The compound represented by AI-3 was prepared by following the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-L-allylglycine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 4 preparation of the Compound represented by AI-4 (Raa from L-2-amino-5-phenylpentanoic acid)

The compound represented by AI-4 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-L-2-amino-5-phenylpentanoic acid. The structure identification data are shown in table 1, and the structure is correct after verification.

Preparation of the Compound shown in example 5, AI-5 (Raa from aminocyclopropanecarboxylic acid)

The compound represented by AI-5 was prepared according to the same procedure as in example 1, except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-aminocyclopropanecarboxylic acid. The structure identification data are shown in table 1, and the structure is correct after verification.

Example 6 preparation of the Compound represented by AI-6 (Raa from 3- (2-furyl) -L-alanine)

The compound represented by AI-6 was prepared according to the same procedure as in example 1, except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-3- (2-furyl) -L-alanine. The structure identification data are shown in table 1, and the structure is correct after verification.

Preparation of the Compound shown in example 7 and AI-7 (Raa from 1-amino-1-Cyclohexylcarboxylic acid)

The compound represented by AI-7 was prepared according to the same procedure as in example 1, except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-1-amino-1-cyclohexanecarboxylic acid. The structure identification data are shown in table 1, and the structure is correct after verification.

Preparation of the Compound shown in example 8 and AI-8 (Raa from Cyclobutylalanine)

The compound represented by AI-8 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-cyclobutylalanine. The structure identification data are shown in table 1, and the structure is correct after verification.

Preparation of the Compound shown in example 9 and AI-9 (Raa derived from methionine)

The compound represented by AI-9 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-methionine. The structure identification data are shown in table 1, and the structure is correct after verification.

Example 10 preparation of the Compound represented by AI-10 (Raa from 2-amino-5-methylhexanoic acid)

The compound represented by AI-10 was prepared according to the same procedure as in example 1, except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-2-amino-5-methylhexanoic acid. The structure identification data are shown in table 1, and the structure is correct after verification.

Preparation of the Compound shown in example 11 and AI-11 (Raa from 1-aminocyclobutanecarboxylic acid)

The compound represented by AI-11 was prepared according to the same procedure as in example 1, except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-1-aminocyclobutanecarboxylic acid. The structure identification data are shown in table 1, and the structure is correct after verification.

Example 12 preparation of the Compound shown in AI-12 (Raa from 3- (2-thienyl) -L-alanine)

The compound represented by AI-12 was prepared according to the same procedure as in example 1, except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-3- (2-thienyl) -L-alanine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 13 preparation of the compound shown in AII-1 (Raa derived from 1-allyl glutamate)

The compound shown in AII-1 was prepared by following the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-glutamic acid 1-allyl ester. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 14 preparation of the Compound shown in AII-2 (Raa derived from aspartic acid-1-benzyl ester)

The compound of AII-2 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-aspartic acid-1-benzyl ester. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 15 preparation of the Compound shown in AII-3 (Raa from glutamic acid methyl ester)

The compound represented by AII-3 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-glutamic acid methyl ester. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 16 preparation of the Compound shown in AII-4 (Raa from aspartic acid-4-cyclohexyl)

The compound of AII-4 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl was replaced with Fmoc-aspartic acid-4-cyclohexyl. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 17 preparation of the Compound shown in AII-5 (Raa from O-acetyl-L-threonine)

The compound represented by AII-5 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-O-acetyl-L-threonine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 18 preparation of the Compound shown in AII-6 (Raa derived from glutamic acid-5-benzyl ester)

The compound represented by AII-6 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-glutamic acid-5-benzyl ester. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 19 preparation of the Compound shown in AII-7 (Raa from O-benzyl-L-serine)

The compound as shown in AII-7 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-O-benzyl-L-serine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 20 preparation of the Compound shown in AII-8 (Raa from O-t-butyl-L-threonine)

The compound represented by AII-8 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-O-t-butyl-L-threonine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 21 preparation of the Compound shown in AII-9 (Raa from S-acetamidomethyl-L-cysteine)

The compound of AII-9 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-S-acetamidomethyl-L-cysteine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 22 preparation of the Compound shown in AII-10 (Raa derived from glutamic acid-1-benzyl ester)

The compound represented by AII-10 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-glutamic acid-1-benzyl ester. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 23 preparation of the Compound shown in AII-11 (Raa derived from L-aspartic acid-1-allyl ester)

The compound shown in AII-11 was prepared by following the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-L-aspartic acid-1-allyl ester. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 24 preparation of the Compound shown in AII-12 (Raa from O-t-butyl-L-serine)

The compound represented by AII-12 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-O-t-butyl-L-serine. The structure identification data are shown in table 1, and the structure is correct after verification.

EXAMPLE 25 preparation of the Compound shown in AII-13 (Raa from O-benzyl-L-threonine)

The compound represented by AII-13 was prepared according to the same procedure as in example 1 except that Fmoc-glutamic acid-5-cyclohexyl ester was replaced with Fmoc-O-benzyl-L-threonine. The structure identification data are shown in table 1, and the structure is correct after verification.

The structure, high resolution mass spectral data and purity of the compound of formula A are shown in Table 1

TABLE 1

Example 27 biological Activity of Compounds of the invention against Aphis glycines (Aphis Glycines Matsmura)

The insecticidal activity of the compound of the invention on aphids is determined by a liquid immersion method (leaf-spreading method). The target compound was prepared as a 200mg/L assay. And then adding 1mL of LDMSO into a weighing bottle by using a 1-5mL pipette, adding 9mL of aqueous solution containing 0.1% triton X-100, fully and uniformly mixing to obtain 200mg/L of determination solution, then gradually diluting by using aqueous solution containing 0.1% triton X-100, and fully and uniformly mixing to obtain the required concentration. And (3) cultivating soybean aphids and soybean leaves which are not contacted with any medicament indoors, punching the leaves with proper sizes by using a puncher with the diameter of 15mm, respectively soaking the leaves into the diluted liquid medicine for 15 seconds, taking out and airing the leaves. Then, the leaves are put into a bioassay plate, 1.5% of agar is added to the bottom of the bioassay plate for moisturizing, 20 +/-3 soybean aphids are inoculated into each hole, and the steps are repeated for 3 times. The results were checked after 48 hours. The death judgment criteria were: the worms were palpated and unable to crawl normally were considered dead. Corrected mortality was calculated as follows:

corrected mortality (%) — (sample mortality-placebo mortality)/(1-placebo mortality) × 100%.

Aphid-killing virulence LC₅₀Values were calculated using statistical analysis software SPSS.

The test results of soybean aphid killing activity are shown in Table 2

TABLE 2 insecticidal Activity of Compounds of formula A against Aphis glycines (Aphis glycines Matsmura)

The results of biological activity tests in table 2 show that the compounds of the present invention all have killing activity against soybean aphids, wherein the lethality of 8 compounds against soybean aphids is higher than 80%. All compounds were further subjected to lethal medium concentration (LC)₅₀) The compounds AI-1, AII-2, AII-3, AII-4 and AII-7 have been found to be LC against soybean aphid₅₀The value is far lower than that of a commercial medicament pymetrozine, and further shows that the compounds have excellent aphidicidal activity and have further development value as aphid control agents.

Example 28 biological Activity of partial Compounds of the invention against Piper pisum (Acyrthosporin pisum) and Myzus persicae (Sulzer)

The leaf-clipping method described in example 2 was also used for the determination of the insecticidal activity against the pea aphid and the green peach aphid, the results of which are shown in tables 3 and 4, respectively.

TABLE 3 insecticidal Activity of some Compounds of formula A on Piper pisum (Acyrthosporin pisum)

The activity measurement shows that the insect kinin compound also has good activity on pea aphids, wherein the compounds AI-1 and AI-8 have LC on pea aphids₅₀Are all lower than pymetrozine, and show that the pea aphid killing activity of the pymetrozine is better than that of the commercial medicament pymetrozine.

TABLE 4 insecticidal Activity of part of Compounds of formula A against Myzus persicae (Sulzer)

The insecticidal activity test on the myzus persicae shows that the compounds have certain activity on the myzus persicae, wherein the LC of the compounds AI-1, AII-2 and AII-3₅₀Are all lower than pymetrozine, and show that the insecticidal activity of the pymetrozine is better than that of the commercial medicament pymetrozine.

The above results show that the compound of the present invention has killing activity against soybean aphid, pea aphid and green peach aphid. Especially via LC₅₀Activity tests show that the aphid killing activity of AI-1 on the three aphids is superior to that of a commercial pesticide pymetrozine, has a certain broad spectrum and has application and development values as an aphid control agent.