CN108129476A - A kind of heterocycle lactam derivatives and its purposes for crop pathogens fungicide - Google Patents
A kind of heterocycle lactam derivatives and its purposes for crop pathogens fungicide Download PDFInfo
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- CN108129476A CN108129476A CN201711204716.3A CN201711204716A CN108129476A CN 108129476 A CN108129476 A CN 108129476A CN 201711204716 A CN201711204716 A CN 201711204716A CN 108129476 A CN108129476 A CN 108129476A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07—ORGANIC CHEMISTRY
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- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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Abstract
The invention discloses a kind of heterocycle lactam derivatives, it has the structure shown in formula (I), and the invention also discloses the purposes that the compound is used as crop pathogens fungicide.Result of the test shows：Formula (I) compound represented is under 100ppm, preferable bactericidal activity is respectively provided with to fusarium graminearum, rice blast fungus, rape nuclear disk germ, tea tree Alternaria alternate, tea tree anthrax bacteria, tea tree phomopsis disease bacterium, and activity is apparently higher than heterocycle lactams alcohol intermediate, therefore has great application prospect in terms of pathogen of crop integrated control.
Description
Technical field
The invention belongs to chemical pesticide fields, and in particular to a kind of new type heterocycle lactam derivative with bactericidal activity
Object and its control and application in crop pathogens.
Background technology
In view of Environmental security and resistance problem during Pesticide use, initiative and the innovation of pesticide become direct relation
To Agriculture Production, national economy is healthy and stable, the sustainable important subject of Environmental security.It is well known that natural production
Object has that type is various, active unique, characteristics such as Environmental compatibility is good, but there are complicated, no for most natural products
It is easily-synthesized, is unstable, is volatile, the drawbacks such as difficult separation, just because of the good speciality of natural products, having attracted numerous domestic surgeries
Grind a large amount of scientific researches of personnel and scientific research institutions.Make a general survey of the road of pesticides discovery, based on natural products for guide, by and to its
The method that novel agrochemical kind is developed in structure progress modification of leading structure and optimization, synthesis remains as a kind of effective approach.
By carrying out structure optimization to having the natural products of good biological activity, on the one hand can more fast and efficiently find out
Active preferably natural products analog, on the other hand can effectively develop performance it is more excellent and with Environmental security sustainable development
The more identical new varieties of pesticides of exhibition demand.
It is deep by section when heterocyclic compound is because it has " efficiently, low toxicity, safety " the features such as in modern synthesis field
Grind the concern of worker.Wherein, nitrogen-containing heterocycle compound is as highly important branch a kind of in heterocyclic compound, due to its tool
Have similar to alkaloid (such as purine, pyrimidine) chemical constitution in organism so that it has the high, environment to target specificity
The characteristics such as compatibility is good, therefore, MOLECULE DESIGN, synthesis and bioactivity research in relation to nitrogen-containing heterocycle compound have become newly
One of mainstream hot spot of pesticides discovery.
Heterocycle lactams is a kind of important nitogen-contained heterocycle derivant, universally present in terrestrial organism and marine organisms
In.According to lot of documents, the heterocycle lactam analog compound of natural activity has desinsection, antibacterial, weeding, antiviral, cell
The multiple biological activities such as genetoxic, had at present largely the natural products molecule containing the structure fragment by separation identify, such as
Shown in Scheme 1：By Tenuazonic acid isolated in antitumor Alternaia tenuis zymotic fluids, by right
The cell micronucleus and mitogenic assay of Root Tip Cells of Vicia Faba show：The compound has certain something lost to plant cell in higher concentrations
Pass toxicity；Reutericyclin is isolated from industrial yeast lactic acid bacteria Lactobacillus reuteri, research
Show that it has good inhibitory activity effect to gram-positive bacteria；It is isolated from Penicillium Penicillium sp
Ravenic acid, then be to staphylococcus aureus have apparent inhibitory activity；Harzianic acid are from the big profit of Australia
The Trichoderma harzianum bacterial strains isolated in sub- hardwood bark find that such compound has antifungal activity such as：
Pythium spp, sclerotinite, rhizoctonia etc., and have promotion Effects on Plant Growth under 1ppm low concentrations.
For the present invention specifically using structure diversity to be oriented to, the antibiotic progress guide to natural source with lactam structure is excellent
Change, a series of new type heterocycle lactams ester derivative that design has synthesized structure novels, polyfunctional group replaces, and to being closed
Preliminary screening active ingredients are carried out into compound, it was found that amount of activated good heterocycle lactams ester derivative.
Invention content
The purpose of the present invention is to provide a kind of new heterocycle lactam derivatives, and the compound is to various crop pathogen
It is inhibited, it can be used as fungicide.
Heterocycle lactam derivatives provided by the invention, shown in structure such as formula (I)：
Wherein：
R1For hydrogen, alkyl, alkoxy, 2- fluorine, 4- fluorine, 2- chlorine, 4- chlorine, 2,4- dichloros, 3,4- dichloros, 2- bromines, 4- bromines, 3,
One kind in 4- dibromos, nitro, trifluoromethyl, trifluoromethoxy, nitro, amino or cyano；
R2For hydrogen, phenyl, C1-3One kind in alkyl substituting aromatic base, aryl substituted with halogen or halogen substituted arylmethyl；
R3For C1-6One kind in alkyl, phenyl, substituted aryl, arylmethyl, alkylthio group or arylthio；
R4For C1-6Alkyl-acyl, C1-6Alkoxy-acyl group, C1-6One kind in alkyl sulphonyl；
Or R2With R3The nitrogen and carbon connected together with them forms five yuan of saturation or hexa-member heterocycle.
The representation compound for wherein meeting above-mentioned general formula I is with one of lower structure：
The preparation method of the compound includes the following steps：
(1) preparation of intermediate M-4, using substituted amino acid M-1 as starting material, obtaining structural formula through esterification is
M-2 intermediates；Then intermediate M-3 is made through acylation reaction under alkaline condition with substituted phenyllacetyl chloride again in intermediate M-2；
Last intermediate M-3 occurs jeterocyclic chemistry and obtains intermediate heterocycle lactams alcohol M-4 under alkaline condition, and specific reaction equation is as follows：
(2) preparation of heterocycle lactam derivatives I, intermediate M-4 synthesize to obtain through acylation reaction under alkaline condition
Final product I, reaction equation are as follows：
The alkali is：One in sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, triethylamine, pyridine, potassium tert-butoxide
Kind；
Reaction dissolvent is：In acetonitrile, acetone, ethyl alcohol, methanol, tetrahydrofuran, benzene, toluene, N,N-dimethylformamide
It is a kind of；
Reaction time is 2-24h, and reaction temperature is 0-100 DEG C；
After reaction, through being conventionally treated heterocycle lactam derivatives.
Result of the test shows：Compound with general structure I expressions is under 100ppm, to fusarium graminearum, rice
Pyricularia oryzae, rape nuclear disk germ, tea tree Alternaria alternate, tea tree anthrax bacteria, tea tree phomopsis disease bacterium are respectively provided with preferably
Inhibitory activity, and activity is apparently higher than hydridization lactams alcohol intermediate.Wherein, chemical compounds I -12, I -25 pair of various disease fungus
Show higher inhibitory activity.
It is a series of with bactericidal activity that for guide structure synthesis is designed the present invention is based on natural source lactam antibiotics
The polysubstituted lactam derivatives of new type heterocycle, synthesize that such compound preparation manipulation process is simple and easy to do, and raw material is easy to get, and production is set
Standby requirement is simple, has great application prospect in terms of the integrated control to the various plants disease fungus of crops.
Specific embodiment
The present invention constructs the miscellaneous of a kind of structure novel by the synthesis of system and sterilization bioactivity primary dcreening operation test system
Cyclic lactam derivative, test show that such compound has preferable bactericidal activity compared with corresponding lactam intermediate, can be wide
It is applied to the prevention of a variety of fungal diseases of plant generally.Come to preparation method of the invention and its answer with reference to specific example
With being described in further details, but the present invention is not limited in following embodiment.
The preparation of 1 compound of embodiment
One kind in the structural formula particular compound as listed in Table 1 of the part of compounds of the present invention：
1 part representative compound structure list of table and physicochemical property
(1) preparation of intermediate M-2, by taking hexatomic ring 2-piperidinecarboxylic acid as an example, reaction equation is as follows：
2-piperidinecarboxylic acid (134mmol) is added in 250ml round-bottomed flasks, methanol about 50ml stirring and dissolvings are added in, by body
System is placed at 0 DEG C in ice bath, and thionyl chloride (200mmol) is slowly added dropwise using constant pressure funnel, and drop finishes, be heated to 80 DEG C it is cold
Solidifying back flow reaction 12h, TLC track to that the reaction was complete.Treat that reaction is finished, concentration is treated that solid will be precipitated, filtered, and with a small amount of methanol
It rinses, collects filter cake, oven drying obtains the hydrochloride of white solid 2-piperidinecarboxylic acid methyl esters, is directly used in and reacts in next step.
(2) preparation of intermediate M-3, by taking phenyllacetyl chloride as an example, reaction equation is as follows：
The hydrochloride (0.02mol) of 2-piperidinecarboxylic acid methyl esters is added in 100ml round-bottomed flasks, measures about 20ml dichloromethanes
System is placed under ice bath (0 DEG C) by alkane stirring and dissolving, and triethylamine (0.05mol) is added dropwise, and drop is finished, dripped using constant pressure funnel
Adding the dichloromethane solution (0.024mol) of phenyllacetyl chloride, ice bath stirring 0.5h removes ice bath, is warmed to room temperature and is stirred to react 12h,
TLC tracks to that the reaction was complete.Treat that reaction is finished, into system plus water, dichloromethane each (30ml × 2) extract, and merge organic phase, have
Machine is mutually respectively through 5%NaCO3Solution (30ml × 2) is washed, is washed, and anhydrous sodium sulfate drying filters, brown color liquid is concentrated under reduced pressure to obtain
Body 1- (2- phenylacetyl groups) piperidines -2- carboxylate methyl esters are directly used in and react in next step.
(3) preparation of intermediate M-4, reaction equation are as follows：
1- (2- phenylacetyl groups) piperidines -2- carboxylate methyl esters (17.5mmol) are added in 100ml round-bottomed flasks, are added in
THF30ml stirring and dissolvings are weighed in potassium tert-butoxide (30.0mmol) addition system, and 70 DEG C of condensing reflux reactions are heated in oil bath
12h, TLC track to that the reaction was complete.Treat that reaction is finished, into reaction solution plus a small amount of water stirs 10min, 10% dilute hydrochloric acid tune pH to 2
~3, then extracted with ethyl acetate (3 × 30ml), merge organic phase, organic phase is washed to neutrality, and anhydrous sodium sulfate drying is dense
Contracting filters, obtains intermediate M-4 white solids, is directly used in and reacts in next step.
(4) preparation of heterocycle lactam derivatives, by taking isobutyryl chloride as an example, reaction equation is as follows：
In 50ml round-bottomed flasks add in lactams alcohols intermediate M-4 (0.87mmol), measure 20ml dichloromethane in
Stirring and dissolving in system adds in triethylamine (1.31mmol), and isobutyryl chloride (1.05mmol), ice bath are added dropwise under ice bath (0 DEG C)
Stir 0.5h, remove ice bath, be warmed to room temperature and be stirred to react 12h, TLC tracks to that the reaction was complete, treats that reaction is finished, into system plus water,
Dichloromethane (30ml × 3) extract, merge organic phase, organic phase respectively through saturated salt solution, be washed to neutrality, anhydrous sodium sulfate
Dry, final product is concentrated under reduced pressure to obtain in filtering.
With reference to above-mentioned basic synthetic method, and the structure feature of combining target compound selects different conventional chemical industry former
Material, can prepare other compounds in implementation table 1, the physicochemical property of representative compound is as follows：
Compound I-1 5-oxo-6-phenyl-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl
isobutyrate:Faint yellow semisolid,1H NMR(600MHz,CDCl3):δ=7.72 (d, J=6Hz, 2H), 7.39 (t, J1=
6Hz,J2=12Hz, 2H), 7.32 (t, J1=12Hz, J2=6Hz, 1H), 4.67 (q, J=6Hz, 1H), 3.66-3.61 (m,
1H),3.35-3.31(m,1H),2.80-2.76(m,1H),2.33-2.28(m,1H),2.25-2.17(m,2H),1.55-1.48
(m,1H),1.28-1.25(m,6H).MS(ESI)m/z 308.3(M+Na)+,calcd.for C17H19O3M/z=285.1.
Compound I-2 5-oxo-6-phenyl-2,3,5,7a-tetrahydro-1H-pyrrolizin-7-yl 2,2-
dimethylbutanoate:Orange semisolid,1H NMR(600MHz,CDCl3):δ=7.71 (d, J=6Hz, 2H), 7.38 (t,
J1=J2=12Hz, 2H), 7.31 (t, J1=J2=6Hz, 1H), 4.68 (q, J=6Hz, 1H), 3.66-3.61 (m, 1H),
3.35-3.31(m,1H),2.34-2.28(m,1H),2.25-2.17(m,2H),1.67(q,J1=12Hz, J2=6Hz, 2H),
1.55-1.48 (m, 1H), 1.26 (s, 6H), 0.88 (t, J=6Hz, 3H) .MS (ESI) m/z 336.3 (M+Na)+,
calcd.for C19H23NO3M/z=313.2.
Compound I-7 6- (4-fluorophenyl) -5-oxo-2,3,5,7a-tetrahydro-1H-pyrrolizin-
7-yl isobutyrate:Faint yellow semisolid,1H NMR(600MHz,CDCl3):δ=7.73 (dd, 2H), 7.08 (t, J1=
6Hz,J2=12Hz, 2H), 4.67 (q, J=6Hz, 1H), 3.65-3.60 (m, 1H), 3.35-3.31 (m, 1H), 2.81-2.74
(m, 1H), 2.32-2.28 (m, 1H), 2.26-2.17 (m, 2H), 1.54-1.47 (m, 1H), 1.28 (q, J=6Hz, 6H) .MS
(ESI)m/z 326.3(M+Na)+,calcd.for C17H18FNO3M/z=303.1.
Compound I-9 6- (4-methoxyphenyl) -5-oxo-2,3,5,7a-tetrahydro-1H-
pyrrolizin-7-yl isobutyrate:Faint yellow semisolid,1H NMR (600MHz, CDCl3):δ=7.71 (d, J=
6Hz, 2H), 6.92 (d, J=12Hz, 2H), 4.64 (q, J=6Hz, 1H), 3.82 (s, 3H), 3.65-3.60 (m, 1H), 3.33
(t,J1=12Hz, J2=6Hz, 1H), 2.81-2.76 (m, 1H), 2.32-2.28 (m, 1H), 2.24-2.16 (m, 2H), 1.53-
1.46 (m, 1H), 1.28 (q, J=6Hz, 6H) .MS (ESI) m/z 338.3 (M+Na)+,calcd.for C18H21NO4M/z=
315.1.
Compound I-11 3-oxo-2-phenyl-3,5,6,7,8,8a-hexahydroindolizin-1-yl
isobutyrate:Brown color semisolid,1H NMR(600MHz,CDCl3):δ=7.73 (m, 2H), 7.38 (t, J1=J2=
6Hz,2H),7.31(t,J1=J2=6Hz, 1H), 4.42 (q, J=6Hz, 1H), 4.35 (q, J=6Hz, 1H), 2.88-2.83
(m,1H),2.80-2.75(m,1H),2.07-2.04(m,1H),1.98-1.95(m,1H),1.98-1.95(m,1H),1.83-
1.76(m,1H),1.57-1.50(m,1H),1.43-1.35(m,1H),1.27(t,J1=J2=6Hz, 6H) .MS (ESI) m/z
322.3(M+Na)+,calcd.for C18H21NO3M/z=299.2.
Compound I-12 3-oxo-2-phenyl-3,5,6,7,8,8a-hexahydroindolizin-1-yl 2,2-
dimethylbutanoate:Brown color semisolid,1H NMR(600MHz,CDCl3):δ=7.71 (d, J=12Hz, 2H), 7.37
(t,J1=12Hz, J2=6Hz, 2H), 7.30 (t, J1=J2=6Hz, 1H), 4.43 (q, J=6Hz, 1H), 2.88-2.83 (m,
1H),2.80-2.75(m,1H),2.07-2.04(m,1H),1.98-1.95(m,1H),1.79-1.76(m,1H),1.72-1.63
(m, 2H), 1.63-1.56 (m, 2H), 1.55-1.50 (m, 1H), 1.26 (d, J=6Hz, 6H), 0.87 (t, J=6Hz, 3H) .MS
(ESI)m/z 350.3(M+Na)+,calcd.for C20H25NO3M/z=327.2.
Compound I-21 2-benzyl-5-oxo-4-phenyl-2,5-dihydro-1H-pyrrol-3-yl
isobutyrate:White powder,1H NMR(400MHz,CDCl3):δ=7.66 (d, J=8Hz, 2H), 7.41-7.27 (m,
6H), 7.23 (d, J=8Hz, 2H), 5.89 (s, 1H), 4.86-4.84 (m, 1H), 3.10 (dd, 1H), 2.77-2.67 (m, 2H),
1.27 (d, J=8Hz, 6H) .MS (ESI) m/z 358.2 (M+Na)+,calcd.for C21H21NO3M/z=335.2.
Compound I-22 2-benzyl-5-oxo-4-phenyl-2,5-dihydro-1H-pyrrol-3-yl 2,2-
dimethylbutanoate:White solid,1H NMR(400MHz,CDCl3):δ=7.64 (d, J=8Hz, 2H), 7.40-7.27
(m, 6H), 7.25 (d, J=4Hz, 2H), 6.00 (s, 1H), 4.85-4.82 (m, 1H), 3.13 (dd, 1H), 2.64 (q, J=
8Hz, 1H), 1.74-1.68 (m, 2H), 1.28 (d, J=4Hz, 6H), 0.90 (t, J1=8Hz, J2=4Hz, 3H) .MS (ESI) m/
z 386.3(M+Na)+,calcd.for C23H25NO3M/z=363.2.
Compound I-23 2-benzyl-5-oxo-4-phenyl-2,5-dihydro-1H-pyrrol-3-yl ethyl
carbonate:Pale yellow powder,1H NMR(600MHz,CDCl3):δ=7.71 (d, J=12Hz, 2H), 7.41 (t, J1=
6Hz,J2=12Hz, 2H), 7.34 (q, J=6Hz, 3H), 7.28 (d, J=12Hz, 1H), 7.24 (s, 2H), 6.00 (m, 1H),
4.85-4.82 (m, 1H), 4.28-4.23 (m, 2H), 3.20 (dd, 1H), 2.75 (q, J=12Hz, 1H), 1.33 (t, J1=J2=
12Hz,3H).MS(ESI)m/z 360.3(M+Na)+,calcd.for C20H19NO4M/z=337.1.
Compound I-28 2-benzyl-4- (4-fluorophenyl) -5-oxo-2,5-dihydro-1H-pyrrol-3-
yl ethyl carbonate:Pale yellow powder,1H NMR(600MHz,CDCl3):δ=7.75 (q, J=6Hz, 2H), 7.34
(t,J1=J2=6Hz, 2H), 7.30-7.27 (m, 1H), 7.26-7.24 (m, 2H), 7.12-7.07 (m, 2H), 6.03 (s, 1H),
4.87-4.83 (m, 1H), 4.27 (q, J=12Hz, 2H), 3.19 (dd, 1H), 2.74 (q, J=12Hz, 1H), 1.35 (t, J1=
J2=12Hz, 3H) .MS (ESI) m/z 378.3 (M+Na)+,calcd.for C20H18FNO4m/z=355.1.
Compound I-29 2-benzyl-4- (4-fluorophenyl) -5-oxo-2,5-dihydro-1H-pyrrol-3-
yl meth anesulfonate:White solid,1H NMR(600MHz,CDCl3):δ=7.76 (m, 2H), 7.36-7.33 (m,
2H),7.31-7.27(m,2H),7.26-7.24(m,1H),7.15-7.11(m,2H),6.00(s,1H),4.75-4.72(m,
1H), 3.42 (q, J=6Hz, 1H), 3.00 (s, 3H), 2.75 (q, J=12Hz, 1H) .MS (ESI) m/z 384.3 (M+Na)+,
calcd.for C18H16FNO4S m/z=361.1.
Compound I-33 5-oxo-2,4-diphenyl-2,5-dihydro-1H-pyrrol-3-yl isobutyrate:
Pale yellow powder,1H NMR(400MHz,CDCl3):δ=7.79 (d, J=12Hz, 2H), 7.44-7.35 (m, 8H), 6.24 (s,
1H), 5.74 (d, 1H), 2.60-2.53 (m, 1H), 1.06 (d, J=8Hz, 3H), 0.97 (d, J=8Hz, 3H) .MS (ESI) m/z
344.3(M+Na)+calcd.for C20H19NO3M/z=321.1.
Compound I-34 5-oxo-2,4-diphenyl-2,5-dihydro-1H-pyrrol-3-yl 2,2-
dimethylbutanoate:Pale yellow powder,1H NMR(400MHz,CDCl3):δ=7.78 (d, J=8Hz, 2H), 7.42-
7.28 (m, 8H), 6.09 (s, 1H), 5.75 (d, J=4Hz, 1H), 1.51-1.38 (m, 2H), 1.03 (s, 3H), 0.96 (s,
3H), 0.63-0.59 (t, J=8Hz, 3H) .MS (ESI) m/z 372.5 (M+Na)+,calcd.for C22H23NO3M/z=
349.2.
Compound I-41 2-methyl-5-oxo-1,4-diphenyl-2,5-dihydro-1H-pyrrol-3-yl
isobutyrate:Orange/yellow solid,1H NMR(600MHz,CDCl3):δ=7.76 (d, J=6Hz, 2H), 7.54 (d, J=
6Hz,2H),7.42(t,J1=12Hz, J2=6Hz, 4H), 7.35 (t, J1=12Hz, J2=6Hz, 1H), 7.20 (t, J1=J2=
6Hz, 1H), 5.23 (q, J=6Hz, 1H), 2.86-2.79 (m, 1H), 1.34 (d, J=6Hz, 3H), 1.26 (s, 6H) .MS
(ESI)m/z 358.4(M+Na)+,calcd.for C21H21NO3M/z=335.2.
Compound I-42 2-methyl-5-oxo-1,4-diphenyl-2,5-dihydro-1H-pyrrol-3-yl 2,
2-dimethylbutanoate:Orange/yellow solid,1H NMR(600MHz,CDCl3):δ=7.74 (d, J=6Hz, 2H), 7.54
(d, J=6Hz, 2H), 7.42 (q, J1=6Hz, J2=12Hz, 4H), 7.34 (t, J1=J2=6Hz, 1H), 7.20 (t, J1=J2
=6Hz, 1H), 5.24 (q, J=6Hz, 1H), 1.76-1.66 (m, 2H), 1.34 (d, J=6Hz, 3H), 1.29 (d, J=12Hz,
6H),0.89(t,J1=J2=6Hz, 3H) .MS (ESI) m/z 386.4 (M+Na)+,calcd.for C23H25NO3M/z=
363.2.
2 compound of embodiment tests the bactericidal activity of Different Kinds of Pathogens fungi
Heterocycle lactam derivatives provided by the invention may be used as preparing fusarium graminearum, rhizoctonia cerealis, water
Rice Pyricularia oryzae, Botrytis cinerea germ, rape nuclear disk germ, Strawberry anthracnose bacterium, Rhizoctonia solani Kuhn, botrytis cinerea pers,
Peanut Cercospora bacteria, Botryosphaeria berengeriana f. sp, P. capsici, dry rot of potato bacterium, withered germ of water-melon, corn southern leaf blight
Bacterium, watermelon anthrax bacteria, cucumber fusarium axysporum, phytophthora infestans, matrimony vine anthrax bacteria, tea tree phomopsis disease bacterium, tea tree
Alternaria alternate, tea tree anthrax bacteria, Stem of Tea point germ, tea tree intend the sterilization of the chief crops pathogens such as disk stey germ
Agent.
For this purpose, the applicant uses Plating, sterilization bioactivity of the different derivatives to plant pathogenic fungi is measured, is had
Body situation is as follows：
(1) test object
Fusarium graminearum (Gibberella zeae), rice blast fungus (Magnapothe grisea), rape core
Disk germ (Sclerotinia sclerotiorum), tea tree Alternaria alternate (Altermaria alternata), tea tree charcoal
Subcutaneous ulcer germ (Colletotrichum fructicola sinensis Miyake), tea tree phomopsis disease bacterium (Phomopsis
adianticola)。
(2) medicament is prepared
The target compound of certain mass, intermediate M-4-1, M-4-2, M-4-3, M- are weighed with assay balance (0.01mg)
4-4, M-4-5, M-4-6 add acetone solution to be configured to 1 × 104Homogeneous phase solution, it is now with the current.
The structural formula of intermediate M-4 class compounds is as follows：
(3) test method
The liquid prepared above is added in into a certain amount of PDA, the band medicine PDA culture medium tablet of a concentration of 100ppm is made,
To add in the PDA of acetone as blank control.The germ fungus block (preparing fungus block with the card punch of Φ=0.50cm) activated more than taking,
It is inoculated in above-mentioned PDA plate, the blank of each strain and corresponding strain is repeated twice, and preservative film sealing is placed on 28+1 DEG C of training
It supports and is cultivated in case.After Pathogen culture length to 2/3rds of about culture dish, colony diameter is measured with crossing method, is calculated every
Kind compound is under the concentration to the bacteriostasis rate of the bacterium.
(4) test statistics
Average production diameter of each compound under 100ppm concentration is counted, and calculates its growth inhibition to various bacterium
Rate.
The plant source fungi that only listing the present invention above can prevent is not particularly limited, representative plant source disease
Example includes but not limited to：Downy mildew, leaf mold, gray mold, phytophthora root rot, head blight, rice blast, false smut, scab, red star
It is disease, leaf spot, brown spot, epidemic disease, glume blight, damping-off, leaf blight, banded sclerotial blight, net blotch, black spot, spot defoliation, red
Maize ear rot, rot disease, root rot, brown rot, bakanae disease, ring spot, anthracnose, sclerotiniose, powdery mildew, rust, epidemic disease, Huang wither
Disease, helminthosporium maydis, full rot, branch-rot, Pestalotiopsis funrea etc..
Claims (4)
1. a kind of heterocycle lactam derivatives, it is characterised in that there is the structure shown in formula (I)：
Wherein：
R1For hydrogen, alkyl, alkoxy, 2- fluorine, 4- fluorine, 2- chlorine, 4- chlorine, 2,4- dichloros, 3,4- dichloros, 2- bromines, 4- bromines, 3,4- bis-
One kind in bromine, nitro, trifluoromethyl, trifluoromethoxy, nitro, amino or cyano；
R2For hydrogen, phenyl, C1-3One kind in alkyl substituting aromatic base, aryl substituted with halogen or halogen substituted arylmethyl；
R3For C1-6One kind in alkyl, phenyl, substituted aryl, arylmethyl, alkylthio group or arylthio；
R4For C1-6Alkyl-acyl, C1-6Alkoxy-acyl group, C1-6One kind in alkyl sulphonyl；
Or R2With R3The nitrogen and carbon connected together with them forms five yuan of saturation or hexa-member heterocycle.
2. heterocycle lactam derivatives as described in claim 1, it is characterised in that：
R1For hydrogen, 2- methyl, 4- fluorine, 4- methoxyl groups or 2,4- dichloros；
R2For hydrogen, phenyl, contraposition C1-3 alkyl-substituted phenyls or contraposition halogen substituted phenyl；
R3For C1-4Alkyl, phenyl, benzyl, phenethyl or methylmercaptan ethyl alkyl；
R4For C1-5Alkyl-acyl, C1-2Alkoxy-acyl group or mesyl；
Or R2With R3The nitrogen and carbon connected together with them forms five yuan of saturation or hexa-member heterocycle.
3. heterocycle lactam derivatives according to claim 1 or 2 are used for the purposes of crop pathogens fungicide.
4. purposes according to claim 3, it is characterised in that：The crop pathogens are fusarium graminearum, wheat line
Blight bacterium, rice blast fungus, Botrytis cinerea germ, rape nuclear disk germ, Strawberry anthracnose bacterium, Rhizoctonia solani Kuhn, cucumber
Ash arrhizus bacteria, peanut Cercospora bacteria, Botryosphaeria berengeriana f. sp, P. capsici, dry rot of potato bacterium, withered germ of water-melon,
Southern corn leaf blight, watermelon anthrax bacteria, cucumber fusarium axysporum, phytophthora infestans, matrimony vine anthrax bacteria, tea tree intend stem point
Germ, tea tree Alternaria alternate, tea tree anthrax bacteria, Stem of Tea point germ, tea tree intend disk stey germ.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3714156A (en) * | 1970-06-22 | 1973-01-30 | Univ California | Lactam process |
| US4220646A (en) * | 1974-11-07 | 1980-09-02 | Rhone-Poulenc Industries | Heterocyclic compounds |
| US4985063A (en) * | 1988-08-20 | 1991-01-15 | Bayer Aktiengesellschaft | 3-aryl-pyrrolidine-2,4-diones |
| US5350861A (en) * | 1991-01-26 | 1994-09-27 | Bayer Aktiengesellschaft | Substituted 3-aryl-pyrrolidine-2,4-diones |
| WO2013083975A2 (en) * | 2011-12-05 | 2013-06-13 | University Of Leicester | Novel pyrrole derivatives |
-
2017
- 2017-11-27 CN CN201711204716.3A patent/CN108129476A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3714156A (en) * | 1970-06-22 | 1973-01-30 | Univ California | Lactam process |
| US4220646A (en) * | 1974-11-07 | 1980-09-02 | Rhone-Poulenc Industries | Heterocyclic compounds |
| US4985063A (en) * | 1988-08-20 | 1991-01-15 | Bayer Aktiengesellschaft | 3-aryl-pyrrolidine-2,4-diones |
| US5350861A (en) * | 1991-01-26 | 1994-09-27 | Bayer Aktiengesellschaft | Substituted 3-aryl-pyrrolidine-2,4-diones |
| WO2013083975A2 (en) * | 2011-12-05 | 2013-06-13 | University Of Leicester | Novel pyrrole derivatives |
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Application publication date: 20180608 |