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WO1993012659A1 - Utilisation dans l'agriculture de certains composes et compositions; procedes de production desdits composes - Google Patents

Utilisation dans l'agriculture de certains composes et compositions; procedes de production desdits composes Download PDF

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Publication number
WO1993012659A1
WO1993012659A1 PCT/DK1992/000387 DK9200387W WO9312659A1 WO 1993012659 A1 WO1993012659 A1 WO 1993012659A1 DK 9200387 W DK9200387 W DK 9200387W WO 9312659 A1 WO9312659 A1 WO 9312659A1
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Prior art keywords
compound
compounds
derivatives
genus
methyl
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PCT/DK1992/000387
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English (en)
Inventor
Jens Breinholt
Ruby Ione Nielsen
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Novo Nordisk A/S
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Publication date
Application filed by Novo Nordisk A/S filed Critical Novo Nordisk A/S
Priority to EP93902094A priority Critical patent/EP0637916A1/fr
Priority to JP5511364A priority patent/JPH08504165A/ja
Publication of WO1993012659A1 publication Critical patent/WO1993012659A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • 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
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • 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
    • A01N63/00—Biocides, pest repellants or attractants, or plant growth regulators containing microorganisms, viruses, microbial fungi, animals or substances produced by, or obtained from, microorganisms, viruses, microbial fungi or animals, e.g. enzymes or fermentates
    • A01N63/30—Microbial fungi; Substances produced thereby or obtained therefrom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9728—Fungi, e.g. yeasts
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K11/00—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
    • C07K11/02—Depsipeptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof cyclic, e.g. valinomycins ; Derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14—Fungi; Culture media therefor
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/14—Fungi; Culture media therefor
    • C12N1/145—Fungal isolates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/524—Preservatives
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B27—WORKING OR PRESERVING WOOD OR SIMILAR MATERIAL; NAILING OR STAPLING MACHINES IN GENERAL
    • B27K—PROCESSES, APPARATUS OR SELECTION OF SUBSTANCES FOR IMPREGNATING, STAINING, DYEING, BLEACHING OF WOOD OR SIMILAR MATERIALS, OR TREATING OF WOOD OR SIMILAR MATERIALS WITH PERMEANT LIQUIDS, NOT OTHERWISE PROVIDED FOR; CHEMICAL OR PHYSICAL TREATMENT OF CORK, CANE, REED, STRAW OR SIMILAR MATERIALS
    • B27K3/00—Impregnating wood, e.g. impregnation pretreatment, for example puncturing; Wood impregnation aids not directly involved in the impregnation process
    • B27K3/34—Organic impregnating agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B27—WORKING OR PRESERVING WOOD OR SIMILAR MATERIAL; NAILING OR STAPLING MACHINES IN GENERAL
    • B27K—PROCESSES, APPARATUS OR SELECTION OF SUBSTANCES FOR IMPREGNATING, STAINING, DYEING, BLEACHING OF WOOD OR SIMILAR MATERIALS, OR TREATING OF WOOD OR SIMILAR MATERIALS WITH PERMEANT LIQUIDS, NOT OTHERWISE PROVIDED FOR; CHEMICAL OR PHYSICAL TREATMENT OF CORK, CANE, REED, STRAW OR SIMILAR MATERIALS
    • B27K3/00—Impregnating wood, e.g. impregnation pretreatment, for example puncturing; Wood impregnation aids not directly involved in the impregnation process
    • B27K3/34—Organic impregnating agents
    • B27K3/343—Heterocyclic compounds
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/645—Fungi ; Processes using fungi

Definitions

  • This invention relates to the use of certain compounds in agriculture or horticulture, compositions containing said compounds, and the use of such compositions for controlling fungi in valuable crops, and in the preservation of wood and timber, paints, cosmetics, foods and feeds, methods for producing the fungicidally active compounds, and microorganisms capable of producing said compounds.
  • C. lunata (Wakk.) Boed was found to produce at least two phytotoxins. They cause necrotic spots on plant leaves even when they are highly diluted. (F. Macri and A. Vianello, Physio- logical Plant Pathology 8:325-331, 1976).
  • the toxins are phytotoxins and are non host specific. Host specific toxins have been isolated from culture filtrates of C. pallescens Boedijn and from diseased host leaves attacked by this species (Olufolaji, Cryptogamie Mycol. 7(4):335-342, 1986). These toxic substances gave chlorotic spots to maize plants. They later became necrotic similar to in-vivo symptoms ofthe disease caused by C. pallescens.
  • Curvularin a macrocyclic metabolite, has been isolated from a Curvularia species (O. C. Musgrave, J. Chem Soc, 1956, 4301) and from C. lunata (Coombe et al, Aust. J. Chem. 21:783, 1968).
  • the compound has the composition C 16 H 20 O 5 (mole- cular weight 292.3) and has the formula 1 below:
  • curvularin nor the crude filtrates from Curvularia showed anti-bacterial activity (against Bacillus subtilis, Escerichia coli, and Staphylococcus aureus) or anti-fungal activity (spore germination test with Penicillium digitatum).
  • the invention consequently in its first aspect relates to the use of said compounds for combating or controlling plant diseases, especially fungal attack.
  • the invention relates to the use of said compounds as preservatives and/or additives to control fungi in foods and feeds, timber and wood, paints, growth media, cosmetics, etc.
  • compositions for use in the field of agriculture or horticulture comprising the above compounds in combination with suitable excipients, such as diluents, carriers, etc.
  • the invention in a fourth aspect relates to methods of combating plant diseases by application of compositions comprising the above compounds to infested areas.
  • the present invention in a still further aspect relates to the production of com- pounds having the general formula I defined below, by a) cultivation of a species belonging to the genus Curvularia, subsequent recovery of at least one active component of formula Ia from the biomass and the fermentation medium, and optionally modifying the active compound to obtain a desired compound of formula I.
  • the compound directly produced has as indicated the structure Ia
  • the invention relates to processes for the production of the com- pounds indicated above. These processes comprise use of specific microorganisms as well as chemical processes for full or semi synthetic production of said com- pounds.
  • the invention also relates to the use of microorganisms, especially of the genera Septoria and Curvularia, producing the aforementioned compounds as fungicidal compositions.
  • the invention relates to an isolated pure culture of the microorganism Curvularia sp.(IMl CC No. 346564).
  • IMI CC International Mycological Institute Collection
  • IMI CC No. 346564 belongs to the class Deuteromycetes, sub-class Hyphomyce- tidae and family Dematiaceae.
  • the fungus is a species of the genus Curvularia and was isolated from a leaf sample.
  • Fig. 1 shows the 400 MHz 1 H -NMR spectrum of the isolated compound BK 230 in CDCl 3 .
  • Fig. 2 shows a 100 MHz 13 C-NMR spectrum of the isolated compound BK 230 in CDCl 3 .
  • the present invention in its first aspect relates to the agricultural use of certain known compounds.
  • R1 and R2 are methyl and the other is hydrogen or methyl;
  • R3 is: cyclohexyl, cyclohexenyl, or phenyl substituted in the para position by a group -OR6, wherein -OR6 is hydroxy, alkoxy, alkenyloxy, acyloxy, geranyloxy, alkoxycar- bonyloxy, aralkoxycarbonylmethoxy, aralkoxy or aralkoxy substituted by a lower alkyl group or halogen;
  • R4 is hydrogen, carboxy alkoxycarbonyl, optionally mono- or plurisubstituted by aryl, alkenyloxycarbonyl, alkeninyloxycarbonyl, benzyloxycarbonyl, aryloxycar- bonyl, trimethylsilylethoxycarbonyl, formyl, alkylcarbonyl or aralkylcarbonyl; all three R5 groups are the same and are hydrogen or methyl;
  • X is oxygen or imino
  • Y is a direct bond or a group -CONHCH(CH 3 )-;
  • carbon atom bridging X and Y may be in the L- or D-configuration.
  • Formula I may alternatively be represented as formula I' cyclo[R5Gly-MeVal-A-B-Pec-MeVal-R5Val-D-R2Ile-RlIle] I' Wherein Me is methyl attached to the nitrogen atom in the carbamoyl group, R1,
  • R2, and R5 are defined as above, and are attached to the nitrogen atom in the carbamoyl group;
  • A is -N(R5)CH(CH 2 R3)CO- , wherein R3 and R5 are as defined above;
  • B is -X-CH(CH 3 )-Y- , wherein X and Y are as defined above;
  • Pec is L-pipecoloyl
  • D is -N(CH 3 )CH(CH 2 R4)CO- , wherein R4 is defined as above and the asyme- tric carbon atom has the S-configuration.
  • Alkoxy as such or as part of a substituent preferably is of 1 to 4 carbon atoms.
  • Alkenyloxy preferably is of 3 to 5 carbon atoms.
  • Acyloxy preferably is of 2 to 5 carbon atoms in the alkyl or alkylene portion thereof.
  • the aryl group preferably is phenyl. When it is substituted it preferably is monosubstituted, preferably in the para position. When it is plurisubstituted it preferably is disubstituted, preferably in the meta and para positions.
  • Aryl preferably is unsubstituted.
  • Halogen preferably is of atomic number of from 9 to 35, it preferably is chlorine or bromine.
  • Alkoxycarbonyl preferably is of 2 to 10 carbon atoms, expecially of 4 to 9 carbon atoms.
  • Alkenyloxycarbonyl preferably is of 4 to 10 carbon atoms, expecially of 4 to 6 carbon atoms.
  • a naturally-occurring amino acid is any amino acid found in nature, preferably an amino acid found in proteins unless indicated otherwise, especially an ⁇ -amino acid, and includes e.g. glycine, proline and serine.
  • Alkyl preferably is of 1 to 6 carbon atoms.
  • Lower alkyl preferably is of 1 to 4 carbon atoms, especially methyl.
  • Alkyl of 1 to 4 carbon atoms preferably is methyl, isopropyl or tert-butyl.
  • Alkenyl preferably is of 3 to 5 carbon atoms, it especially is allyl.
  • Hydroxy alkyl preferably is of 1 to 4 carbon atoms. It especial- ly is hydroxymethyl; however, when it is bound to a nitrogen atom it preferably is of 2 to 6 carbon atoms and the hydroxy group preferably is separated from the nitrogen atom by at least 2 carbon atoms.
  • Dialkylaminoalkyl preferably is of 1 to 4 carbon atoms in the alkyl parts and of 2 to 4 carbon atoms in the aminoalkyl part, it especially is 3-(dimethylamino)propyl.
  • Furylmethyl preferably is 2- fiirylmethyl.
  • Alkoxycarbonylalkyl preferably is of 1 to 4 carbon atoms in the alkoxy part and of 2 to 4 carbon atoms in the carbonylalkyl part.
  • Trialkylsilyl- oxyalkyl preferably is of 1 to 4 carbon atoms in the alkyl parts bound to the silicium atom and of 2 to 4 carbon atoms in the alkylene part.
  • Acyl as such or as part of a substituent preferably is alkylcarbonyl, preferably of altogether 2 to 4 carbon atoms.
  • Optionally substituted acyloxy methyl preferably is of 1 to 4 carbon atoms in the acyloxy part; if substituted is preferably is substi- tuted at the ⁇ carbon atom, preferably by carboxy or 2-carboxyphenyl.
  • Alkyl as part of a substituent such as dialkylaminomethyl preferably is of 1 to 4 carbon atoms, it especially is methyl.
  • Halogenomethyl preferably is chloromethyl.
  • EP 360 760 Although these compounds closely related or identical to the compounds indicated by this invention are disclosed in EP 360 760.
  • the compounds as described there would not be considered for agronomical use. This is due to the high toxicity (approximately 100 mg/kg p.o.) and low antifungal activity (dosage 25 to 300 mg/kg, daily dosage of 300 to 3000 mg) indicated, and as exemplified towards Candida on pages 47 to 49 of EP 360 760.
  • EP 360 760 only indicates pharmaceutical usage of these com- pounds. Consequently the surprising specificity and activity for the agronomical use of the same compounds indicated by the present invention can in no way be inferred from EP 360 760.
  • the compounds are to be used in agriculture as fun- gicidally active agents, and the invention therefore in its second aspect relates to fungicidally active compositions comprising said compounds of formula I in admixture with agronomically acceptable diluents and/or excipients.
  • a composition of the invention in addition to said fungicidally active compounds may also contain other active ingredients such as other biocides, such as fungicides, pesticides, herbicides, insecticides, nematicides, acaricides, or plant nutrients, plant growth regulators, or fertilizers.
  • EBIs ergosterol biosynthesis inhibitors
  • EBIs ergosterol biosynthesis inhibitors
  • These are generally imidazoie or triazole derivatives and examples include those known by the common names prochloraz, triadimefon, propiconazo- le, diclobutrazol, triadiminol, flusilazole, flutriafol, myclobutanil, penconazole, quinconazole, imazalil and diniconazole.
  • non azole EBIs include nuarimol, fenarimol, fenpropimorph, tridemorph and fenpropidine.
  • anilides e.g. carboxin, metalaxyl, fu ralaxyl, oftirace, benalaxyl, mepro- nil, flutolanil, pencycuron and oxadixyl
  • benzimidazoles e.g. be
  • pyrazophos tolclofos-methyl and fosetyl aluminum
  • miscellaneous com- pounds including dithiocarbamates, bisdithiocarbamates, imidazoles, triazoles, phathalonitriles, polyhalogenalkylthio compounds, iminoctadine, guazatine, dicloran, chlorothalonil, pyrifexox, ethirimol, cymoxanil, phenyl pyrroles, thiocyofenes, pyrimidines, and anilazine.
  • a fungicidal composition according to the invention having a fungicidally active compound of formula I as its active ingredient may for agronomical and/or horti- cultural applications be formulated by mixing the active principle with suitable inert and compatible carriers or diluents to obtain a composition of the type generally used in agricultural compositions such as a wettable powder, an emul- sifiable concentrate, a concentrated emulsion, a granular formulation, a water soluble powder, an alginate, a xanthan gum and/or an aerosol.
  • suitable inert and compatible carriers or diluents such as a wettable powder, an emul- sifiable concentrate, a concentrated emulsion, a granular formulation, a water soluble powder, an alginate, a xanthan gum and/or an aerosol.
  • solid carriers bentonite, diatomaceous earth, apatite, gypsum, talc, pyrophyllite, vermiculite, ground shells, and clay may be mentioned.
  • a surface active agent may also be added with the purpose of producing a homogeneous and stable formulation.
  • the diluent or carrier in the composition of the invention can as indicated be a solid or a liquid optionally in association with a surface-active agent, for example a dispersing agent, emulsifying agent or wetting agent.
  • Suitable surface-active agents include anionic compounds such as a carboxylate, for example a metal car- boxylate of a long chain fatty acid; an N-acylsarcosinate; mono- or di-esters of phosphoric acid with fatty alcohol ethoxylates or salts of such esters; fatty alcohol sulphates such as sodium dodecyl sulphate, sodium octadecyl sulphate or sodium cetyl sulphate; ethoxylated fatty alcohol sulphates; ethoxylated alkylphenol sul- phates; lignin sulphonates; petroleum sulphonates; alkyl aryl sulphonates such as alkyl-benzene sulphon
  • butyl- naphthalene sulphonate salts of sulphonated naphthalene-formaldehyde conden- sates; salts of sulphonated phenol-formaldehyde condensates; or more complex sulphonates such as the amide sulphonates, e.g. the sulphonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulphosuccinates, e.g. the sodium sulphonate of dioctyl succinate.
  • amide sulphonates e.g. the sulphonated condensation product of oleic acid and N-methyl taurine or the dialkyl sulphosuccinates, e.g. the sodium sulphonate of dioctyl succinate.
  • Non-ionic agents include condensation products of fatty acid esters, fatty alcohols, fatty acid amides or fatty-alky 1- of alkenyl-substituted phenols with ethylene oxide, fatty esters of polyhydric alcohol ethers, e.g. sorbitan fatty acid esters, condensation products of such esters with ethylene oxide, e.g. polyoxyethylene sorbitan fatty acid esters, block copolymers of ethylene oxide and propylene oxide, acetylenic glycols such as 2,4,7, 9-tetra- ethyl-5-decyn-4,7-diol, or ethoxylated acetylenic glycols.
  • a cationic surface-active agent examples include, for instance, an aliphatic mo- no-, di-, or polyamine as an acetate, naphthenate or oleate; an oxygen-containing amine such as an amine oxide or polyoxyethylene alkylamine; an amide-linked amine prepared by the condensation of a carboxylic acid with a di- or polyamine; or a quaternary ammonium salt.
  • compositions of the invention can take any form known in the art for the formulation of agrochemicals, for example, a solution, a dispersion, an aqueous emulsion, a dusting powder, a seed dressing, a dispersible powder, an emulsifi- able concentrate or granules. Moreover, it can be in a suitable form for direct ap- plication or as a concentrate or primary composition which requires dilution with a suitable quantity of water or other diluent before application.
  • An emulsifiable concentrate comprises the active ingredient dissolved in a water- immiscible solvent which is formed into an emulsion with water in the presence of an emulsifying agent.
  • a dusting powder comprises the active ingredient intimately mixed and ground with a solid pulverulent diluent, for example, kaolin.
  • a granular solid comprises the active ingredient associated with similar diluents to those which may be employed in dusting powders, but the mixture is granu- lated by known methods. Alternatively it comprises the active ingredient absorbed or adsorbed on a pre-granular diluent for example, Fuller's earth, attapulgite or limestone grit.
  • Wettable powders, granules or grains usually comprise the active ingredient in admixture with a suitable surfactant and an inert powder diluent such as china clay.
  • a suitable surfactant and an inert powder diluent such as china clay.
  • Another suitable concentrate is a flowable suspension concentrate which is formed by grinding the active ingredient with water or other liquid, a wetting agent and suspending agent.
  • the active compound according to the invention may be applied in concentrations ranging from about 0.001 ⁇ g/ml to 750 mg/ml, prefer- ably from 1 ⁇ g/ml to 10 mg/ml, for use in controlling fungi in plants.
  • the concentration of the active compounds of formula I in the compositions of the invention may vary within a wide range depending on the type of formulation and the field of application.
  • the invention relates to methods of combating fungi in plants, wherein an effective amount of a fungicidally active compound of formula I according to the invention is applied to a region to be treated.
  • compositions of the invention may for agrono- mical or horticultural uses be applied to a region to be treated either directly to the soil as a pre-emergence treatment to the seed surface as a seed dressing or to the foliage or fruits of the plants as a post-emergence treatment. Depending on the crop and circumstances the treatment may be postponed until seeds or fruits appear on the plants, wherein fungi are to be controlled.
  • the active preparation or the compositions of the invention can be applied directly to the plant by, for example, spraying or dusting either at the time when the fungus has begun to appear on the plant or before the appearance of fungus as a protective measure. In both such cases the preferred mode of application is by foliar spraying. It is generally important to obtain good control of fiingi in the early stages of plant growth as this is the time when the plant can be most severely damaged.
  • the spray or dust can conveniently contain a pre-or post- emergence herbicide, a mixture of other pesticides, plant growth regulators or fertilizers, if this is thought necessary.
  • a suitable rate of application is from 0.001 to 50 kg per hectare, preferably from 0.05 to 5 kg per hectare.
  • the active preparation of the invention alone or in combination with a conventional biocide can also be applied to seeds or habitat.
  • the preparation can be applied direcdy to the soil before, at or after drilling so that the presence of active ingredient in the soil can control the growth of fiingi which may attack seeds.
  • compositions may be applied in amounts corresponding to from about 1 g to about 100 kg fungicidally active compound per hectare.
  • the active preparation (alone or in admixture with the conventional biocide) can be applied in any manner which allows it to be intimately mixed with the soil such as by spraying, by broadcasting a solid form of granules, or by applying the active ingredient at the same time as drilling by inserting it in the same drill as the seeds.
  • a suitable application rate is within the range of from 0.01 to 50 kg per hectare, more preferably from 0.05 to 5 kg per hectare.
  • the concentration of the fungicidally active compounds in the compositions of the present invention when used alone or in combination with a conventional fungi- cide, as applied to plants is preferably within the range from about 0.001 to about 30 per cent by weight, especially 0.01 to 3.0 per cent by weight.
  • the amount of active compound can vary widely and can be, for example, in the range from about 5 to about 95 per cent by weight of the compo- sition.
  • the concentration of the other fungicidally active ingredient in the mixed com- position of the present invention, as applied to plants is preferably within the range of 0.001 to 50 per cent by weight, especially 0.01 to 10 per cent by weight.
  • the amount of other active ingredient can vary widely and can be, for example, from 5 to 80 per cent by weight of the composi- tion.
  • the present invention has been described in detail in connection with controlling fungi in plants, it is also anticipated that the fungicidally active com- pounds of the invention may be used for the preservation of wood by adding said compounds to wood preservation and/or impregnation compositions. Also, the active compounds according to the invention may be useful as a fungicide and preservant in paints - both to prevent growth in the paint during storage, and growth on the painted object such as the plastered surface of a house.
  • the fungicidally active compounds may due to their low toxicity be used for the preservation of cosmetics, foods and feeds, or other such items where the compounds may be added subsequent to any cooking process.
  • the fungicidally active compounds of the invention may be used as fungi- cidal additive to growth media for various microorganisms such as E. coli, and Pseudomonas aeroginosa.
  • the invention relates in a further aspect to the production of compounds of the general formula I as defined above, by a) cultivation on suitable nutrient media under suitable conditions of a species belonging to the genus Curvularia,
  • the compound of formula Ia was isolated as a metabolite from a novel species of the genus Curvularia, Curvularia sp. (IMI CC No. 346564) and is apparently identical to compound 1 of Example 1 in EP 360 760.
  • step c Guidance for producing other compounds of formula I using the compound of formula Ia as starting material (step c) can thus be found in EP 360760 whereto reference is made in its entirety.
  • the compound of formula Ia may be prepared by aerobic cultivation on suitable nutrient media under conditions hereinafter described with a strain of a fungus belonging to the genus Curvularia, especially the fungus Curvularia sp. (IMI CC 346564), and thereafter recovering the active component from the fermentation medium.
  • the natural metabolite may subsequently be modified chemically in order to obtain various derivatives thereof.
  • the derivatives may be produced in order to improve certain properties with the metabolite such as its solubility in aqueous media, its hydrophobicity, hydrophilicity, stability, specificity, etc.
  • Derivatives of the compound produced or related compounds and methods for producing such derivatives hereto are disclosed in detail in EP 360 760, which is hereby incorporated by reference in its entirety.
  • a specific type of derivatives from the compound of formula I are such com- pounds wherein the lactone ring has been opened.
  • strain IMI CC 346546 principally deals with the specific strain IMI CC 346546, it is well known in the art that the properties of microorganisms may be varied naturally and artificially. Thus all strains belonging to the genus Curvularia including variants, recombinants and mutants, whether obtained by natural selection, produced by the action of mutat- ing agents such as ionizing radiation or ultraviolet irradiation, or by the action of chemical mutagens such as nitrosoguanidine, are included in this invention.
  • a fungus is able to produce closely related metabolites (cf. compounds of formulae III and IV in our unpublished International Patent Ap- plication No. PCT/DK91/00273 (formulae 2 and 3 above), or see EP 360 760, where three related compounds were produced by the same fungus) of the same or similar activity, but with minor differences in chemical structure.
  • the present invention is therefore meant also to encompass the production of such closely related compounds produced by the same fungus and their use in agriculture or horticulture as fungicides.
  • Colonies grey, cottony, sometimes zonate.
  • Conidiophores Single to aggregated, simple, straight to flexuous, geniculate above.
  • Conidia acropleurogenous, 2-4 septate when mature, smooth, but becom- ing verrucose on the large central cell, mostly curved, concolourous or with central cell more pigmented than the other cells, mostly 20-39 ⁇ m long and 11- 14 ⁇ m thick in the broadest part.
  • IMI CC 346564 is 4 septate like C. verruciformis, but differs from it in the size of the conidia. The conidia of C. verruciformis are 16-26 ⁇ m x 8-12 ⁇ m in size.
  • IMI CC 346564 is a new species in the genus Curvularia. It belongs to the class Deuteromycetes, sub-class Hyphomycetidae and family Dematiaceae.
  • the fungus may be grown on agar slants containing the following ingredients in grams/litre: yeast extract 4.0
  • the substrate is autoclaved at 121 °C for 20 or 40 minutes and will, hereinafter, be referred to as YPG agar.
  • Slants contain 12ml YPG agar and after inoculation they are incubated at 20 - 25°C for 7 days or longer.
  • the fungicide was produced by surface cultivation on a semi-solid medium consisting of the following ingredients: 30 g wheat bran in a 500 ml Erlenmeyer flask, 45 ml liquid medium (yeast extract 0.4%, potassium dihydrogen phosphate 0.1 %, magnesium sulphate heptahydrate 0.05%, demineralised water). This was sterilized by autoclaving at 121 °C for 40 minutes. Each flask was inoculated with about 10 6 spores from a YPG agar slant previous- ly inoculated with IMI CC No. 346564.The flasks were incubated at 25°C for 7 - 14 days after which time the active compound was extracted with an organic solvent, e.g. ethanol, methanol, ethylacetate and acetone.
  • an organic solvent e.g. ethanol, methanol, ethylacetate and acetone.
  • the fungicide can also be produced in submerged cultures in media containing other sources of carbon and nitrogen assimilable by the micro-organism and generally low levels of inorganic salts.
  • the media may be supple- mented with trace metals, although if complex sources of carbon and nitrogen are used, they are usually present in the complex sources.
  • a substrate for shake flasks was prepared with the following ingredients per litre: 4.0 g yeast extract, 1.0 g potassium di-hydrogen phosphate, 0.1 g magnesium sulphate heptahydrate, 15 g glucose and 0.1 g PluronicTM L61 (BASF, Federal Republic of Germany) and demineralized water. Sterilization took place at 121°C for 20 minutes.
  • a 500 ml Erlenmeyer flask with 100 ml of substrate was inocu- lated with 10 6 spores from a YPG agar slant previously inoculated with Curvu- laria sp. IMI CC No.346564.
  • the flasks were shaken at 230 rpm at 25°C for 3-14 days whereafter the active ingredient was extracted with 100 ml ethanol, methanol, ethylacetate or acetone or any other suitable organic solvent as indicated above.
  • a substrate was prepared with the following ingredients per 500ml Erlenmeyer flask:
  • dilute salts ammonium hydrogen phosphate (66 mg), potassium dihydrogen phosphate (68 mg), dipotassium hydrogen phosphate (87 mg), calcium chloride.2 hydrate (7.4 mg), and magnesium chloride.6 hydrate (10 mg) made up to 1 litre with distilled water).
  • the substrate was sterilized at 121°C for 20 minutes.
  • Each flask was inoculated with about 10 6 spores from a YPG agar slant previously inoculated with IMI CC No. 346564.
  • the flasks were incubated at 25°C for 7 - 14 days after which time the active compound was extracted with 200 ml of an organic solvent, e.g.
  • the petri dishes were incubated at 20 - 25°C for 2 days.
  • the fungicide in the extract inhibited the growth of Botrytis and a rather diffuse zone appeared around the hole - the larger the zone the stronger the fungicide.
  • the extract under these conditions produced a zone of 30 - 42 mm. Under a stereo microscope, it could be seen that the fungus is present but normal growth had been inhibited. The mycelium appeared as large vesicles, suggesting a particular type of mode of action.
  • Genus Monilinia e.g. M. fructigena
  • Genus Erysiphe e.g. E. graminis
  • Genus Saccharomyces e.g. S.cerevisiae
  • Form-genus Aspergillus e.g. A. fumigatus
  • Penicillium e.g. P. digitatum
  • Genus Phoma e.g. P. lingam
  • Genus Ascochyta e.g. A. pisi
  • Total hydrolysis (6N HCl. 110°C, 24h - hydrolysis not complete) yields Lactic acid(1), Glycine(1), Valine(1), N-Methyl-Valine(2), N-Methyl-Isoleucine(2), Pipecolic acid(1), N-Methyl-Aspartic acid(1) and O-Methyl-Tyrosine, identified by GC/MS as n-butyl ester-triflouroacetyl derivatives.
  • Tomato plants (Lycopersicon esculentum cv. "First in Field", 3 weeks old) were each sprayed with 0.30 ml of a solution using a handhold "Aerograph 63" sprayer.
  • the solutions contained decreasing concentrations from 1000 ⁇ g/ml to 1 ⁇ g/ml of the purified active ingredient dissolved in 70 % (v/v) ethanol and a control containing no active ingredient.
  • the plants were dried for 24 hours before they were inoculated with a spore suspension containing 5x10 5 spores of B. cinerea per ml in 25 % (v/v) autoclaved grape fruit juice.
  • the inoculation was carried out with a hand held sprayer ("Wagener W 50" type 0237). To allow for optimal conditions for the fungus the plants were incubated at high humidity in the darkness at 19°C for five days and subsequently scored for the level of B. cinerea infection.
  • Hordeum vulgare Barley, var. Catrin Carlsberg Barley plants (1 week old) were sprayed to run off with a liquid suspension using a handhold sprayer (Bink Bullows 900).
  • the solution was a methanol extract (see above) containing about 100 ⁇ g/ml a.i.
  • the plants were kept 24 hours in a glass- house to dry before they were inoculated with conidia spores by shaking leaves from diseased plants over them (concentration around 100 spores/mm 2 ).
  • the infected plants were then incubated in a controlled environment room (16 hours light (6.000 lux) at 22-24°C and 8 hours dark) at 15-17°C.
  • BK230 gave approximately 90% and BK202 approximately 90% protection to Powdery mildew caused by Erysiphe graminis f.sp. hordei.
  • Triticum aestivum (Wheat, var. Anja Pajbjerg) Wheat plants (1 week old) were sprayed to run off with a liquid solution using a handhold sprayer (Bink Bullows 900). The solution was a methanol extract (see above) containing about 100 ⁇ g/ml a.i. The plants were kept 24 hours in a glass- house to dry before they were inoculated with a spore suspension containing 5x10 5 spores per ml. The inoculation was carried out with a handhold atomizer (Wagner, Pico Bel). The plants were then incubated at 20°C in a dark polythene bag for 24 hours. Thereafter the polythene bag was removed and the plants were placed in a controlled environment room (16 hours light (10.000 lux) and 8 hours dark) at 18-22°C. After 10-12 days the assessment was done:
  • BK230 gave approximately 90% protection to Leaf rust caused by Puccinia recondita f.sp. tritici.

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Abstract

Cette invention concerne l'utilisation de composés de formule (I). Dans cette formule R1 et R2 représentent méthyle ou hydrogène, R3 représente cyclohexyle, cyclohexényle ou phényle substitué en position para, R4 représente hydrogène, alkoxycarbonyle carboxy facultativement monosubstitué ou substitué plusieurs fois, tous les groupes R5 représentent hydrogène ou méthyle; X représente oxygène ou imino; et Y représente une liaison directe ou un groupe -CONHCH(CH3)-; l'atome de carbone reliant X et Y peut se trouver dans la configuration L- ou D-. Ces composés et leurs dérivés sont tout particulièrement utiles comme fongicides pour traiter des plantes horticoles ou agricoles. On peut produire ces composés en cultivant une souche du champignon Curvularia sp., ou Septoria sp., qu'on peut facultativement modifier chimiquement. On peut également utiliser ces composés pour réguler les moisissures pour conserver le bois, les peintures, les produits cosmétiques et les produits comestibles.
PCT/DK1992/000387 1991-12-20 1992-12-18 Utilisation dans l'agriculture de certains composes et compositions; procedes de production desdits composes WO1993012659A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP93902094A EP0637916A1 (fr) 1991-12-20 1992-12-18 Utilisation dans l'agriculture de certains composes et compositions; procedes de production desdits composes
JP5511364A JPH08504165A (ja) 1991-12-20 1992-12-18 特定の化合物の農業的使用、該化合物を含有する組成物および該化合物の製造方法

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DK9100405 1991-12-20
ATPCT/DK91/00405 1991-12-20

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WO1993012659A1 true WO1993012659A1 (fr) 1993-07-08

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EP (1) EP0637916A1 (fr)
JP (1) JPH08504165A (fr)
AU (1) AU3345093A (fr)
IL (1) IL104156A0 (fr)
TW (1) TW273501B (fr)
WO (1) WO1993012659A1 (fr)
ZA (1) ZA929909B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018128140A1 (fr) 2017-01-05 2018-07-12 国立研究開発法人産業技術総合研究所 Gène associé à la synthèse d'un composé peptidique cyclique, procédé de production d'un composé peptidique cyclique l'utilisant, et transformant comprenant le gène

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999031127A1 (fr) * 1997-12-18 1999-06-24 Ajinomoto Co., Inc. Cyclopeptolides
KR101323177B1 (ko) * 2013-01-17 2013-10-30 충남대학교산학협력단 식물 병원균 방제 효과를 가지는 바실러스 속 cnu-ba-2 균주 및 이의 용도

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0207653A1 (fr) * 1985-06-21 1987-01-07 The University Of Vermont And State Agricultural College Compositions herbicides comprenant des agents microbiens herbicides et des agents chimiques herbicides ou régulateurs de la croissance des plantes
EP0360760A2 (fr) * 1988-09-23 1990-03-28 Sandoz Ag Peptolides cycliques qui contiennent de l'acide pipecolique, leur préparation et compositions pharmaceutiques les contenant
WO1992005191A1 (fr) * 1990-09-17 1992-04-02 Novo Nordisk A/S Composes presentant une activite fongicide

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0207653A1 (fr) * 1985-06-21 1987-01-07 The University Of Vermont And State Agricultural College Compositions herbicides comprenant des agents microbiens herbicides et des agents chimiques herbicides ou régulateurs de la croissance des plantes
EP0360760A2 (fr) * 1988-09-23 1990-03-28 Sandoz Ag Peptolides cycliques qui contiennent de l'acide pipecolique, leur préparation et compositions pharmaceutiques les contenant
WO1992005191A1 (fr) * 1990-09-17 1992-04-02 Novo Nordisk A/S Composes presentant une activite fongicide

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018128140A1 (fr) 2017-01-05 2018-07-12 国立研究開発法人産業技術総合研究所 Gène associé à la synthèse d'un composé peptidique cyclique, procédé de production d'un composé peptidique cyclique l'utilisant, et transformant comprenant le gène
KR20190117511A (ko) * 2017-01-05 2019-10-16 고쿠리츠겐큐가이하츠호진 산교기쥬츠소고겐큐쇼 환형 펩티드 화합물 합성 관련 유전자, 이를 이용한 환형 펩티드 화합물의 제조방법 및 그것을 가지는 형질전환체
US11230726B2 (en) 2017-01-05 2022-01-25 National Institute Of Advanced Industrial Science And Technology Gene involved in synthesis of cyclic peptide compound, method for producing cyclic peptide compound using the same, and transformant comprising the same
KR102633026B1 (ko) * 2017-01-05 2024-02-01 고쿠리츠다이가쿠호진 도호쿠다이가쿠 환형 펩티드 화합물 합성 관련 유전자, 이를 이용한 환형 펩티드 화합물의 제조방법 및 그것을 가지는 형질전환체
US11946086B2 (en) 2017-01-05 2024-04-02 Tohoku University Gene involved in synthesis of cyclic peptide compound, method for producing cyclic peptide compound using the same, and transformant comprising the same

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IL104156A0 (en) 1993-05-13
TW273501B (fr) 1996-04-01
JPH08504165A (ja) 1996-05-07
ZA929909B (en) 1993-07-07
AU3345093A (en) 1993-07-28
EP0637916A1 (fr) 1995-02-15

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