CN108276473A - A kind of insect kassinin kinin analog and its application in control of insect - Google Patents
A kind of insect kassinin kinin analog and its application in control of insect Download PDFInfo
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- CN108276473A CN108276473A CN201810225612.9A CN201810225612A CN108276473A CN 108276473 A CN108276473 A CN 108276473A CN 201810225612 A CN201810225612 A CN 201810225612A CN 108276473 A CN108276473 A CN 108276473A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N37/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids
- A01N37/44—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom having three bonds to hetero atoms with at the most two bonds to halogen, e.g. carboxylic acids containing at least one carboxylic group or a thio analogue, or a derivative thereof, and a nitrogen atom attached to the same carbon skeleton by a single or double bond, this nitrogen atom not being a member of a derivative or of a thio analogue of a carboxylic group, e.g. amino-carboxylic acids
- A01N37/46—N-acyl derivatives
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N47/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid
- A01N47/40—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides
- A01N47/42—Biocides, pest repellants or attractants, or plant growth regulators containing organic compounds containing a carbon atom not being member of a ring and having no bond to a carbon or hydrogen atom, e.g. derivatives of carbonic acid the carbon atom having a double or triple bond to nitrogen, e.g. cyanates, cyanamides containing —N=CX2 groups, e.g. isothiourea
- A01N47/44—Guanidine; Derivatives thereof
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Abstract
The invention discloses a kind of insect kassinin kinin analog and its applications in control of insect.The structural formula of the insect kassinin kinin analog is as shown in formula I, and in formula I, Raa is H or comes from natural amino acid or non-natural amino acid.The present invention uses the strategy and method of peptidomimetics, passes through the turning point Phe of the activity conformation VI type β-bends to active kassinin kinin analog2Substitution modification is carried out, i.e., in Phe2Side chain aromatic rings replaces, piperidine ring similar with benzene ring structure, saturation hexatomic ring, hydrophobic grouping, hydrophilic radical are introduced simultaneously carries out the Novel insect kassinin kinin analog that a kind of structure novel has been invented in substitution modification, the insecticidal activity of noval chemical compound is clearly, especially there is good preventive effect to aphid, can be applied in the prevention of agricultural pests such as aphid.
Description
Technical field
The invention belongs to injurious insect control technical field, more particularly to a kind of insect kassinin kinin analog and its in control of insect
Application.
Background technology
Insect kassinin kinin (Insect kinins) is a kind of active peptide being prevalent in invertebrate body, is had more
Kind physiological function.American scientist Holman in 1984 et al. for the first time from the cockroach brain extract of Madeira it is isolated 5 tool
Have and promote the active octapeptide of hindgut contraction, then there are 3 octapeptides to be extracted to obtain again.Due to being detached out of Madeira cockroach body
It arrives, this 8 peptides are named as Leueokinin I-VIII respectively.People have also isolated such peptide in cricket and locust body,
Then again using various biological and pharmacological method in succession in different insects, such as bollworm, culex, yellow-fever mosquito, American cockroach
Deng separating and extracting new insect kassinin kinin in vivo, Nieto etc. also isolates 6 kinds of families from shellfish white shrimp and swashs
Peptide, using immunological method it has also been found that there is also the same clans of family in the organisms such as spider, snail and pseudocoelomata ascaris suum
Kassinin kinin.Cox in 1997 etc. clones the receptor sequence of encoding nerve peptide in lymnaea stagnalis central nervous system for the first time
GRLl04, to lay a good foundation for the further investigation insect kassinin kinin mechanism of action.
Insect kassinin kinin is with conservative pentapeptide H-Phe1-Xaa2-Yaa3-Trp4-Gly5-NH2For C-terminal, wherein Xaa can be with
It is Tyr, His, Ser, Phe or Asn；Yaa can be Ser, Pro or Ala, which is to maintain the smallest pieces needed for bioactivity
Section, referred to as core pentapeptide.Oneself has isolated more than 40 kinds of different insect kassinin kinin from 17 kinds of animals at present.Insect kassinin kinin is a kind of
Highly conserved high activity small molecule neuroactive substance has and promotes the contraction of insect hindgut, Malpighian tube twisting, crude urine secretion,
Hemolymph amount and water salt balance are adjusted, Malpighian tube membrane potential is made to depolarize, inhibits the digested enzyme r e lease of insect bodies, larval weight
The multiple functions such as growth can be used as a kind of potential drug regulation and control insect physiological activity.However, natural insect kassinin kinin be easy to by
Protease is degraded, and must carry out structure of modification and structure activity study to it, to develop more potential false peptide and have anti-
The insect kassinin kinin analogies of enzymolysis ability.
In recent years, as people are to the growing interest of environmental ecology and food security, the new agriculture for the purpose of ecological close friend
Medicine is developed into inexorable trend.In view of the polypeptide compound that insect kassinin kinin is made of multiple amino acid, there is environmental-friendly peace
Full feature, therefore people attempt, based on insect kassinin kinin core pentapeptide, to develop novel agent for controlling noxious insect pests.Domestic and foreign scholars are first
It introduces the non-natural amino acid with steric effect in the molecule afterwards, structural modification and transformation has been carried out to it, had
Good resistance to enzymolysis activity has the insect kassinin kinin analog of preferable bioactivity concurrently.But the bioactivity of these kassinin kinin analogs is still
It is very not prominent, and molecular weight is larger, being directly applied to as pesticide molecule still has certain limitation in agricultural production.Cause
This, the novel simple high activity kassinin kinin analog of development structure seems very necessary.
Invention content
The present invention in view of the deficiencies of the prior art, to the turning point of the activity conformation VI type β-bends of active kassinin kinin analog
Phe2Substitution modification has been carried out, Phe is passed through2Side chain aromatic rings replaces, while introducing piperidine ring similar with benzene ring structure, saturation
Hexatomic ring, hydrophobic grouping, hydrophilic radical expansion modify simultaneously carries out biological activity test, provide a kind of insect kassinin kinin analog and
Its application in control of insect, such compound have good insecticidal activity.
One kind insect kassinin kinin analog provided by the invention, structural formula as shown in formula I,
In formula I, Raa is H or comes from natural amino acid or non-natural amino acid.
β-Ala come from Beta-alanine；
Trp comes from tryptophan；
Gly comes from glycine.
In above-mentioned insect kassinin kinin analog, the natural amino acid can be alanine, glycine, serine, asparagus fern ammonia
Acid, threonine, asparagine, glutamine, cysteine, leucine, glutamic acid, lysine, arginine, histidine, figured silk fabrics ammonia
Acid, isoleucine or proline.The non-natural amino acid can be monosubstituted or polysubstituted substitution phenylalanine, phenylglycine,
2- amino-4-phenyls butyric acid, pyrazoleahtnine, Cyclohexylalanine, cyclohexyl glycine, 2-amino-butyric acid, 2,3- diamino
Propionic acid, ornithine, citrulling or hydroxyproline etc..
Preferably, in formula I, the natural amino acid can be alanine, glycine, serine, aspartic acid, threonine,
Asparagine, glutamine, cysteine, leucine, glutamic acid, lysine, arginine, histidine, valine, isoleucine
Or proline.The non-natural amino acid can be 2- chlorophenylalanines, 3- chlorophenylalanines, 4- chlorophenylalanines, 4- bromobenzenes third
Propylhomoserin, 4- hydroxy phenylalanines, 4- amino phenylalanines, 4- formamido groups phenylalanine, 4- methoxyphenylalanines, 4- methyl
Phenylalanine, 4- nitrophenylalanines, 4- trifluoromethyl-phenylalanines, 1- naphthylalanines, phenylglycine, 2- amino -4- benzene
Base butyric acid, 4- pyrazoleahtnines, Cyclohexylalanine, cyclohexyl glycine, 2-amino-butyric acid, 2,3- diaminopropionic acids, bird ammonia
Acid, citrulling or hydroxyproline etc..
It is particularly preferred that in formula I, the natural amino acid can be alanine, glycine, serine, aspartic acid, Soviet Union's ammonia
Acid, asparagine, glutamine, leucine, glutamic acid, lysine, arginine, histidine, valine, isoleucine, dried meat ammonia
Acid.The non-natural amino acid can be 2- chlorophenylalanines, 3- chlorophenylalanines, 4- chlorophenylalanines, 4- hydroxy phenylalanines,
4- methoxyphenylalanines, 4- methylphenylalanines, 4- nitrophenylalanines, 4- trifluoromethyl-phenylalanines, the third ammonia of 1- naphthalenes
Acid, phenylglycine, 2- amino-4-phenyls butyric acid, 4- pyrazoleahtnines, Cyclohexylalanine, cyclohexyl glycine, 2- amino fourths
Acid, 2,3- diaminopropionic acids, ornithine, citrulling or hydroxyproline etc..
(ginseng is prepared according to the Solid-phase synthesis peptides method in document in compound shown in formula I provided by the present invention
Examine document：Chan WG,White PD.Fmoc solid phase peptide synthesis A Practical
Approach,Oxford UnIersity Press,2000；pp.9-74.).
Invention further provides application of the above-mentioned insect kassinin kinin analog in control of insect.The pest can be
Aphid.
A kind of drug (such as insecticide), active constituent is insect kassinin kinin analog described in any one of the above embodiments, also at this
In the protection domain of invention.
The compounds of this invention uses leaf dipping method (leaf-dipping methods) (bibliography to the insecticidal activity assay of aphid：
Busvine,J.R.,Recommended methods for measurement of pest resistance to
pesticides.1980.)；It is raw survey the result shows that：The compound of the present invention has obviously cytotoxicity, tool to aphid
There is the value as the further application and development of aphid controlling agent.
Beneficial effects of the present invention：The present invention uses the strategy and method of peptidomimetics, by active kassinin kinin analog
Activity conformation VI type β-bends turning point Phe2Substitution modification is carried out, i.e., in Phe2Side chain aromatic rings replace, while introduce with
The similar piperidine ring of benzene ring structure, saturation hexatomic ring, hydrophobic grouping, hydrophilic radical carry out substitution modification, and to have invented a class formation new
The Novel insect kassinin kinin analog of grain husk, the insecticidal activity of noval chemical compound clearly, especially have good preventive effect to aphid, can
With in the prevention applied to agricultural pests such as aphid.
Specific implementation mode
Experimental method used in following embodiments is conventional method unless otherwise specified.
The materials, reagents and the like used in the following examples is commercially available unless otherwise specified.
The preparation of compound shown in embodiment 1, I-A-1 (Raa comes from 2- chlorophenylalanines)
Compound shown in I-A-1 is prepared using Solid-phase synthesis peptides method, is as follows：
After checking Peptide synthesizer air-tightness, takes Rink Amide-Am resins (0.3mmol) to be placed in 5mL DCM and activate
2h, after then washing 5 times with DMF, the DMF solution reaction 20min that 20% piperidines of 5mL is added is protected with removing Fmoc on resin
Group；5mL is prepared containing Fmoc-Gly-OH (1.2mmol), HBTU (1.2mmol), HOBt (1.2mmol), DIEA (1.2mmol)
DMF solution, react 2h at room temperature with resin after activating 5min and obtain Fmoc-Gly with Rink Amide-Am
resin.Continue to remove Fmoc groups, is sequentially ingressed into Fmoc-Trp (Boc)-OH, Fmoc- β-Ala-OH, Fmoc- in the same way
L-2-Cl-Phe-OH and cinnamic acid.Finally utilize trifluoroacetic acid：Phenol：Thioanisole：Water=90:5:2.5:2.5 mixing is molten
Liquid obtains object with resin reaction 4h.TFA is removed in filtering, nitrogen blowing, and suitable frost ether precipitation, centrifugation removal upper layer is added
Clear liquid obtains crude product after obtained solid freeze-drying.Crude product is after the separation of half preparative high-performance liquid chromatographics of reverse phase C18
Sterling is obtained, chromatographic condition is：Mobile phase is the aqueous solution (TFA for containing 0.1%) of 50% acetonitrile, and flow velocity is 10mL/min, detection
Wavelength is 215nM, and HPLC retention times are in 14min or so.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 2, I-A-2 (Raa comes from 3- chlorophenylalanines)
Compound shown in I-A-2 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-3-Cl-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 3, I-A-3 (Raa comes from 4- chlorophenylalanines)
Compound shown in I-A-3 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-4-Cl-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 4, I-A-4 (Raa comes from 4- hydroxy phenylalanines)
Compound shown in I-A-4 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-4-OH-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 5, I-A-5 (Raa comes from 4- methoxyphenylalanines)
Compound shown in I-A-5 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-4-OCH3-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 6, I-A-6 (Raa comes from 4- methylphenylalanines)
Compound shown in I-A-6 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-4-CH3-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 7, I-A-7 (Raa comes from 4- nitrophenylalanines)
Compound shown in I-A-7 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-4-NO2-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 8, I-A-8 (Raa comes from 4- trifluoromethyl-phenylalanines)
Compound shown in I-A-8 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-L-4-CF3-Phe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 9, I-A-9 (Raa comes from 1- naphthylalanines)
Compound shown in I-A-9 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
For Fmoc-Ala (1-Naphthyl)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 10, I-A-10 (Raa comes from phenylglycine)
Compound shown in I-A-10 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
It is changed to Fmoc-Phg-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 11, I-A-11 (Raa comes from 2- amino-4-phenyls butyric acid)
Compound shown in I-A-11 is prepared according to step same as Example 1, only replaces Fmoc-L-2-Cl-Phe-OH
It is changed to Fmoc-HomoPhe-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 12, I-B-1 (Raa is hydrogen)
Compound shown in I-B-1 is prepared using Solid-phase synthesis peptides method, is as follows：
After checking Peptide synthesizer air-tightness, takes Rink Amide-Am resins (0.3mmol) to be placed in 5mL DCM and activate
2h, after then washing 5 times with DMF, the DMF solution reaction 20min that 20% piperidines of 5mL is added is protected with removing Fmoc on resin
Group；5mL is prepared containing Fmoc-Gly-OH (1.2mmol), HBTU (1.2mmol), HOBt (1.2mmol), DIEA (1.2mmol)
DMF solution, react 2h at room temperature with resin after activating 5min and obtain Fmoc-Gly with Rink Amide-Am
resin.Continue to remove Fmoc groups, is sequentially ingressed into Fmoc-Trp (Boc)-OH, Fmoc- β-Ala-OH and Chinese cassia tree in the same way
Acid.After accessing amino acid each time, need whether complete to react using the detection of Kaiser ' s reagents, if it is indicated that the aobvious blue of agent,
It then feeds intake again until reaction completely；If indicator is non-discolouring, illustrate that the reaction was complete.Finally utilize trifluoroacetic acid：Phenol：Benzene first
Thioether：Water=90:5:2.5:2.5 mixed solution obtains object with resin reaction 4h.TFA is removed in filtering, nitrogen blowing, is added suitable
The frost ether of amount precipitates, and centrifugation removal supernatant liquor obtains crude product after obtained solid freeze-drying.Crude product is by anti-
Sterling is obtained after the separation of half preparative high-performance liquid chromatographics of phase C18, chromatographic condition is：Mobile phase is that the aqueous solution of 40% acetonitrile (contains
0.1% TFA), flow velocity is 10mL/min, and Detection wavelength 215nM, HPLC retention time is in 15min or so.Structural Identification number
According to being shown in Table 1, verified, structure is correct.
The preparation of compound shown in embodiment 13, I-B-2 (Raa comes from 4- pyrazoleahtnines)
Compound shown in I-B-2 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-Ala (4-pyridyl)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 14, I-B-3 (Raa comes from Cyclohexylalanine)
Compound shown in I-B-3 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-L-Cha-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 15, I-B-4 (Raa comes from cyclohexyl glycine)
Compound shown in I-B-4 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-L-Chg-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 16, I-B-5 (Raa comes from alanine)
Compound shown in I-B-5 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-L-Ala-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 17, I-B-6 (Raa comes from 2-amino-butyric acid)
Compound shown in I-B-6 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-L-Abu-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 18, I-B-7 (Raa comes from leucine)
Compound shown in I-B-7 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-L-Leu-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 19, I-B-8 (Raa comes from glycine)
Compound shown in I-B-8 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-Gly-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 20, I-B-9 (Raa comes from serine)
Compound shown in I-B-9 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-Ser-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 21, I-B-10 (Raa comes from aspartic acid)
Compound shown in I-B-10 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-Asp (Otbu)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 22, I-B-11 (Raa comes from threonine)
Compound shown in I-B-11 is prepared according to the step identical as embodiment 12, only after accessing Fmoc- β-Ala-OH,
It accesses before cinnamic acid, accesses Fmoc-Thr (tbu)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 23, I-C-1 (Raa comes from glutamic acid)
Compound shown in I-C-1 is prepared using Solid-phase synthesis peptides method, is as follows：
After checking Peptide synthesizer air-tightness, takes Rink Amide-Am resins (0.3mmol) to be placed in 5mL DCM and activate
2h, after then washing 5 times with DMF, the DMF solution reaction 20min that 20% piperidines of 5mL is added is protected with removing Fmoc on resin
Group；5mL is prepared containing Fmoc-Gly-OH (1.2mmol), HBTU (1.2mmol), HOBt (1.2mmol), DIEA (1.2mmol)
DMF solution, react 2h at room temperature with resin after activating 5min and obtain Fmoc-Gly with Rink Amide-Am
resin.Continue to remove Fmoc groups, is sequentially ingressed into Fmoc-Trp-OH, Fmoc- β-Ala-OH, Fmoc-Glu- in the same way
OH and cinnamic acid.After accessing amino acid each time, need whether complete to react using the detection of Kaiser ' s reagents, if it is indicated that agent
Aobvious blue is then fed intake again until reaction completely；If indicator is non-discolouring, illustrate that the reaction was complete.Finally utilize trifluoroacetic acid：Benzene
Methyl sulfide：Water=90:5:5 mixed solution obtains object with resin reaction 4h.Filtering, nitrogen blowing are removed TFA, are added suitable
Ether precipitation is freezed, centrifugation removal supernatant liquor obtains crude product after obtained solid freeze-drying.Crude product passes through reverse phase
Sterling is obtained after the separation of half preparative high-performance liquid chromatographics of C18, chromatographic condition is：Mobile phase is that the aqueous solution of 30% acetonitrile (contains 0.1%
TFA), flow velocity is 10mL/min, and Detection wavelength 215nM, HPLC retention time is in 12min or so.Structural Identification data are shown in
Table 1, verified, structure is correct.
The preparation of compound shown in embodiment 24, I-C-2 (Raa comes from asparagine)
Compound shown in I-C-2 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Asn(trt)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 25, I-C-3 (Raa comes from glutamine)
Compound shown in I-C-3 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Gln-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 26, I-C-4 (Raa comes from 2,3- diaminopropionic acids)
Compound shown in I-C-4 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Dap(Boc)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 27, I-C-5 (Raa comes from ornithine)
Compound shown in I-C-5 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Orn(Boc)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 28, I-C-6 (Raa comes from lysine)
Compound shown in I-C-6 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Lys(Boc)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 29, I-C-7 (Raa comes from arginine)
Compound shown in I-C-7 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Arg(Mtr)-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 30, I-C-8 (Raa comes from citrulling)
Compound shown in I-C-8 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Cit-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 31, I-C-9 (Raa comes from histidine)
Compound shown in I-C-9 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-His-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 32, I-C-10 (Raa comes from hydroxyproline)
Compound shown in I-C-10 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Hyp-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 33, I-C-11 (Raa comes from valine)
Compound shown in I-C-11 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Val-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 34, I-C-12 (Raa comes from isoleucine)
Compound shown in I-C-12 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Ile-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
The preparation of compound shown in embodiment 35, I-C-13 (Raa comes from proline)
Compound shown in I-C-13 is prepared according to the step identical as embodiment 23, only replaces with Fmoc-Glu-OH
Fmoc-Pro-OH.Structural Identification data are shown in Table 1, and verified, structure is correct.
Structure, high resolution mass spectrum, the purity data of compound shown in table 1, formula I
Embodiment 37, the compounds of this invention are to the bioactivity of aphid
The compounds of this invention uses leaf dipping method (leaf-dipping method) to the insecticidal activity assay of aphid, measures
Bioactivity of the compound to soybean aphid (Aphis glycines).Sample uses the aqueous solution containing 0.05% triton x-100 to match
The solution of various concentration gradient is made.By indoor culture not in contact with the soybean leaves of excessively any medicament and insect, with diameter 15mm
Card punch get the blade of suitable size, immerse respectively in liquid dilute, after 15s taking-up dry, be put into raw drafting board.
Blade back is face-up, and 1% agar moisturizing is added in bottom, and soybean aphid 20 ± 3 is accessed per hole.It is placed in growth cabinet, temperature
(25 ± 1) DEG C check the death toll of aphid after 48h.Dead criterion is：Polypide is touched, to only have 1 foot dynamic or completely not
Dynamic person is considered as death.It is compareed with pymetrozine, blank control is done with the aqueous solution containing 0.05% triton x-100.Experiment repeats 3
It is secondary, it is averaged.Primary dcreening operation concentration is set as 200mg/L.Corrected mortality is calculated, formula is as follows：Corrected mortality (%)=
(the sample death rate-blank control death rate)/(1- blank controls death rate) * 100%.
It kills aphid active testing and the results are shown in Table 2.
Insecticidal activity of the compound to soybean aphid shown in 2 formula I of table
Remarks：Nt indicates the IC without testing compound50Value.
2 biological activity test of table the result shows that, the compound of the present invention to aphid all have kill activity, plurality ofization
It closes object and 85% is higher than to the killing rate of soybean aphid.Compound I-A-8, I-A-9, I-A-11, I-B-3, I-B-4, I-B-11, I-C-
13 activity are more prominent, are higher than comparison medicament pymetrozine to soybean aphid killing rate (more than 95%).Especially it is worth noting that：
The LC of compound I-A-8, I-A-9, I-B-3, I-B-4 to soybean aphid50Value is further demonstrated that far below commercialization medicament pymetrozine
These compounds kill aphid superior activity, have the value further developed as aphid controlling agent.
Claims (8)
1. compound shown in formula I,
In formula I, Raa is H or comes from natural amino acid or non-natural amino acid.
2. insect kassinin kinin analog according to claim 1, it is characterised in that：The natural amino acid is alanine, sweet
Propylhomoserin, serine, aspartic acid, threonine, asparagine, glutamine, cysteine, leucine, glutamic acid, lysine,
Arginine, histidine, valine, isoleucine or proline；The non-natural amino acid is monosubstituted or polysubstituted substituted benzene
Alanine, phenylglycine, 2- amino-4-phenyls butyric acid, pyrazoleahtnine, Cyclohexylalanine, cyclohexyl glycine, 2- amino
Butyric acid, 2,3- diaminopropionic acids, ornithine, citrulling or hydroxyproline.
3. insect kassinin kinin analog according to claim 1, it is characterised in that：The natural amino acid is alanine, sweet
Propylhomoserin, serine, aspartic acid, threonine, asparagine, glutamine, cysteine, leucine, glutamic acid, lysine,
Arginine, histidine, valine, isoleucine or proline；The non-natural amino acid is 2- chlorophenylalanines, 3- chlorobenzenes third
Propylhomoserin, 4- chlorophenylalanines, 4- bromophenyl alanines, 4- hydroxy phenylalanines, 4- amino phenylalanines, 4- formamido group phenylpropyl alcohol ammonia
Acid, 4- methoxyphenylalanines, 4- methylphenylalanines, 4- nitrophenylalanines, 4- trifluoromethyl-phenylalanines, 1- naphthalenes third
Propylhomoserin, phenylglycine, 2- amino-4-phenyls butyric acid, 4- pyrazoleahtnines, Cyclohexylalanine, cyclohexyl glycine, 2- amino
Butyric acid, 2,3- diaminopropionic acids, ornithine, citrulling or hydroxyproline.
4. insect kassinin kinin analog according to claim 1, it is characterised in that：The natural amino acid is alanine, sweet
Propylhomoserin, serine, aspartic acid, threonine, asparagine, glutamine, leucine, glutamic acid, lysine, arginine, group
Propylhomoserin, valine, isoleucine or proline；The non-natural amino acid is 2- chlorophenylalanines, 3- chlorophenylalanines, 4- chlorine
Phenylalanine, 4- hydroxy phenylalanines, 4- methoxyphenylalanines, 4- methylphenylalanines, 4- nitrophenylalanines, 4- trifluoros
Methylphenylalanine, 1- naphthylalanines, phenylglycine, 2- amino-4-phenyls butyric acid, 4- pyrazoleahtnines, the third ammonia of cyclohexyl
Acid, cyclohexyl glycine, 2-amino-butyric acid, 2,3- diaminopropionic acids, ornithine, citrulling or hydroxyproline.
5. according to the compound described in claim 1-4, it is characterised in that：The compound is prepared using polypeptide solid-state reaction method
It obtains.
6. application of the compound described in any one of claim 1-4 in control of insect.
7. application according to claim 6, it is characterised in that：The pest is aphid.
8. a kind of drug, it is characterised in that：Its active constituent is the compound described in any one of claim 1-4.
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