JPH07505781A - Antibacterially active compounds - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

[Detailed description of the invention] Antibacterially active compounds Industrial applications The present invention provides antibacterially active compounds and derivatives thereof, as well as the preparation of such compounds. and microorganisms. Further, the present invention may be used alone or in combination with Antimicrobial compositions containing these compounds in combination with biocides or growth regulators and for the use of the compounds or compositions of the invention for controlling fungi. Ru.

Background of the invention Various microorganisms produce secondary metabolites that exhibit biological activity, and these can lead to diseases. It has been known for many years that it can be useful as a biocide for controlling pests and It is publicly known.

Control of various diseases and pests in plants and animals of agricultural importance Although progress has been made in identifying and developing biological antimicrobials for Most insecticides in use are still difficult to degrade in practice and cannot be used over large areas. It is a synthetic compound with vector activity.

Over the past millennium, the impact of such pesticides on the environment and ecosystem surrounding farmland has increased. The interest felt in sound power increases, as a result of which its activity becomes more specific and spontaneous. There is no doubt that there is a need for biocides that are easily degradable in the natural environment.

Natural products have a different mode of action and are also biodegradable and safer for the environment May provide an alternative to synthetic antimicrobial agents.

It is therefore an object of the present invention to develop novel antimicrobially active compounds originating from natural sources. e.g. to identify microbial secondary metabolites or direct derivatives of such compounds. That is.

U.S. Patent No. 5.008.187 and Chaiet et al. (The Journal l of Antibiotics 42 1718-1721.1989) Fusarium (called MF 5000 (ATCCN o, 20883)) The following are antibacterial agents obtained by fermentation of microorganisms belonging to the genus Fusarium. A secondary metabolite of formula ib is described.

The present invention is closely related to the compounds described in U.S. Pat. No. 5,008,187, cited above. and their use in agriculture for controlling fungi.

Summary of the invention Briefly, the present invention provides the following formula I: (wherein +R' is hydrogen, straight-chain or branched alkyl having 1 to 6 carbon atoms, For example methyl, straight or branched hydroxyalkyl with 1 to 6 carbon atoms for example CH, OH, straight-chain or branched alkyl having 1 to 6 carbon atoms ether, or an optionally substituted aromatic ether; each R″ is uniquely hydrogen, straight-chain or branched alkyl having 1 to 6 carbon atoms, e.g. methyl straight-chain or branched hydroxyalkyl having 1 to 6 carbon atoms, e.g. CH, OH, straight-chain or branched alkyl ethers having 1 to 6 carbon atoms; or an optionally substituted aromatic ether; and each R2 is independently hydrogen , hydroxy, methoxy.

acetoxy, straight-chain or branched alkyl ethers having 1 to 6 carbon atoms; or an optionally substituted aromatic ether; and chiral centers a, b , c, d, e, f, and g can each independently have an R or S configuration. (provided that R1 is -CH, -OH and all Rf are -CH, and all R3 are -OH (except for the compound <21b); or and agriculturally acceptable salts thereof or esters thereof.

Formula ■ (In the formula, all R2 is -CH, all R3 are -OH, and R1 is The compound is CH, (formula Ia) or -CH, -0H (21b) , microorganisms belonging to the genus Fusarium, especially Fusarium pallid Fusarium pallidoroseum species, especially Fusarium Pallidroseum species, especially C Microorganisms belonging to a strain called L534-1 (IMI CC No. 351439) Obtained as a secondary metabolite from food.

The above compounds exhibit antibacterial activity and are used in agricultural and horticultural applications for the protection of plants against fungi. It can be used as an antibacterial compound.

According to a second aspect of the invention, the compounds of formula 1a and 1b are composed of Fusarium (Fu Microorganisms belonging to the genus sariuo+), especially Fusarium pallidroceum (Fus arium pallidoroseum) species, especially Fusarium pallidoroseum Fusarium pallidoroseum (IMI CCNo. 351439) is cultured, and then activated from the biological mass. Obtained by recovering the compound. These isolated compounds can then be chemically treated. to produce the above derivatives.

Another method of producing the compounds of the invention is by traditional chemical synthesis from appropriate starting materials. It is something.

In a third aspect of the invention, the invention provides a suitable excipient such as a diluent, carrier, etc. Antibacterial compositions containing the novel compounds of the present invention in combination with.

The invention further relates to the use of microorganisms producing the compounds of the invention as antimicrobial compositions. do.

Within the context of the present invention, the present invention further provides for the production of novel combination compositions. It is possible to combine the novel compounds with known biocides or plant growth regulators. intended.

Furthermore, the present invention in a fourth aspect contains the novel compounds of the present invention to the infected area. The present invention relates to a method for controlling plant diseases by applying compositions for controlling plant diseases.

In a fifth aspect, the invention provides a method for eradicating or controlling plant diseases, especially fungal attacks. The use of the novel compounds or compositions of the present invention for the control of

Finally, the present invention focuses on the microorganism Fusarium pallidroseum (Fusarium pall). Idoloseum) (IMI CC No. 351439) Regarding cultures.

Deposit of microorganisms In order to describe the invention in detail, the fungus Fusarium pallidroceum (Fusarium ium pallidoroseum) (IMI CC No. 351439 ) shares of International Microzica for patent proceedings as of the date below. Ruin Institute Culture Collection (International alMycological In5titutoCu1ture Co11 (IMI CC), Ferry Lane, Kew, Surly TW9 3AF, deposited in the UK. IMI CC, the international depositary authority under the Budapest Treaty shall perform the deposit in accordance with Rule 9 of the said Treaty.

Date of deposit: February 18, 1992 Depositor inquiry: CL534-I IMI CC designation: IMI CCNo, 3514391MT CCNo. 351439 is a detailed description of the Deuteromycetes invention As described above, in the first aspect of the present invention, the following formula Straight-chain or branched alkyl having 6 carbon atoms, e.g. methyl, 1 to 6 Straight-chain or branched hydroxyalkyl having carbon atoms, e.g. CH, OH, 1 Straight-chain or branched alkyl ethers having ~6 carbon atoms, or optionally is a substituted aromatic ether; each R2 is independently hydrogen, 1 to 6 carbon atoms; Straight-chain or branched alkyl atoms having 1 to 6 carbon atoms, e.g. methyl, straight-chain or branched hydroxyalkyl having, for example CH, OH, 1 to 6 carbons straight-chain or branched-chain alkyl ethers with elementary atoms or optionally substituted and each R2 is independently hydrogen, hydroxy, methoxy.

acetoxy, straight or branched alkyl ethers containing 1 to 6 carbon atoms; or an optionally substituted aromatic ether: and a chiral center a, b, c, d, e, f, and g can each independently have an R or S configuration. (However, R1 is -CH, -OH, and all R2 are -CH , and all R2 are 10H (except for compounds of formula Ib); and relates to their agriculturally acceptable salts or esters thereof.

Formula I (wherein all R1s are -CH, all R3s are -OH, and R1 is CH, (formula Ia) or -CH, -0H (2rb) , Fusarium (Fusarium) rl strain Fusarium pallidroseum (F usarium pallidoroseum) (IMI CC No.

351439).

According to a second aspect, the invention relates to a process for the preparation of the novel compounds of composition I.

Compounds of formula 1 can be added to Fusarium (Fusarii) on suitable nutrient media under the conditions described below. um) genus, especially Fusarium pallidroseum (Fusarium pallido) A strain of fungi belonging to the species Roseum) (IMI CC No. 351439) was used. aerobic cultivation and then recovery of the active ingredient from the biomass and/or fermentation medium. It can be prepared by

Natural metabolites are subsequently chemically or biologically conjugated to obtain their various derivatives. Can be modified by conversion. Derivatives improve certain properties of a metabolite, such as its performance in aqueous media. can be produced to improve its solubility, its hydrophobicity, hydrophilicity, stability, specificity, etc. .

Compounds of the invention can be produced by well-known chemical synthesis using available starting materials. It is also intended that

The compounds of the present invention are known to exhibit antibacterial activity; It is useful as an active ingredient in sexual compositions.

Therefore, the present invention encompasses antibacterial compositions containing a compound of formula (1) as an active ingredient. do. The present invention, alone or as an active ingredient in any antimicrobial composition, or any other biocidal active agent or plant growth regulator. The use of any of the compounds of the invention in combination is contemplated.

Antimicrobial compositions according to the invention having as their active ingredient an antimicrobially active compound according to the invention For agricultural and/or horticultural applications, the active ingredients may be combined with suitable inert and complementary materials. Formulated into agricultural compositions by mixing with soluble carriers or diluents. Compositions of commonly used types, such as wettable powders, emulsions, concentrated emulsions, granular formulations , obtain water-soluble powder, alginate, xanthan gum and/or aerosol . Solid carriers include bentonite, diatomaceous earth, apatite, gypsum, talc, and powder. Examples include ilophyllite, vermiculite, crushed grain, and clay. homogeneous and Surfactants may be added to produce stable formulations.

The diluent or carrier in the compositions of the invention is optionally associated with the surfactant. can be solid or liquid as described above, examples include e.g. dispersants. , emulsifiers or wetting agents.

Suitable surfactants include anionic compounds such as carboxylic acid salts, such as long chain lipids. Metal carboxylates of fatty acids; N-acyl sarcosinates; phosphoric acid and fatty alcohols Mono- or di-esters with ethoxylates or salts of such esters: Fatty alcohol sulfates, such as sodium F-decyl sulfate, sodium octadecyl sulfate Lium or sodium cetyl sulfate: ethoxylated fatty alcohol sulfate ; Ethoxylated alkylphenol sulfate: Lignosulfonate: Petroleum Sulfonates; alkylaryl sulfonates, e.g. alkyl-benzenesulfonates; phonate or lower alkylnaphthalene sulfonate, e.g. butyl-naphthalene sulfonate: salt of sulfonated naphthalene-formamide condensate; sulfonated Salts of phenol-formamide condensates; or more complex sulfonates, e.g. Sulfonation of amide sulfonates, e.g. oleic acid with N-methyltaurine condensation products, or dialkyl sulfosuccinates, e.g. dioctyl succinate Examples include salt sodium sulfonate. As a nonionic agent, fatty acid ether ster, fatty alcohol, fatty acid amide or fatty-alkyl- or alkyl Condensation product of nyl-substituted phenol and ethylene oxide, polyhydric alcohol ether fatty esters of esters, such as sorbitan fatty acid esters, Condensation products with ethylene oxide, such as polyoxyethylene sorbitan fatty acids Esters, block copolymers of ethylene oxide and propylene oxide, Cetyl glycol, e.g. 2, 4. 7. 9-tetraethyl-5-decyne -4,7-diol or ethoxylated acetylene glycol.

Examples of cationic surfactants include, for example, aliphatic mono- or polyamines, e.g. acetate, naphthinate or oleate; oxygen-containing amines e.g. acetate, naphthinate or oleate; Mine oxide or polyoxyethylene alkyl amine; carboxylic acid and is an amide-linked amine prepared by condensation with a polyamine; or a quaternary ammonium Examples include nium salts.

The compositions of the invention may be in any form known in the art for the formulation of pesticides, such as Liquids, dispersions, aqueous emulsions, spreading agents, seed finishing agents, dispersible powders, emulsions or granules It can take the form of Furthermore, the compositions of the invention are suitable for direct application. or need to be diluted with an appropriate amount of water or other diluent before application. It may be in a form suitable as a concentrate or primary composition.

Emulsions are dissolved in water-miscible solvents that are formed into emulsions using water in the presence of emulsifiers. It contains an active ingredient.

The dusting agent is mixed and ground directly with a solid powder diluent, e.g. kaolin. It contains an active ingredient.

Particulate solids contain active ingredients that can be associated with diluents similar to those that can be used in dispersants. However, the mixture is granulated by known methods. or granular solid is adsorbed onto pre-granular diluents, e.g. Fuller's earth, attapulgite or coarse limestone particles. The active ingredient is absorbed or adsorbed.

Wettable powders, granules or grits are usually prepared with suitable surfactants and inert powder diluents, e.g. The active ingredient is contained in a mixture with white clay.

Another suitable concentrate is the combination of the active ingredient with water or other liquids, wetting agents and suspending agents. It is a fluid suspension concentrate produced by grinding.

Fungi may be affected by circumstances such as the crop to be controlled, environmental conditions or other factors. Therefore, in addition to the above-mentioned antimicrobially active compounds of the invention, the compositions of the invention may contain other active ingredients. other biocides, e.g. antibacterial agents, insecticides, herbicides, insecticides, nematicides, etc. It may also contain pesticides, acaricides, or plant nutrients or fertilizers.

Examples of other antibacterial agents which may be combined with the active compounds of the invention include, in particular These include role biosynthesis inhibitors ("EBIs").

These are generally imidazole or triazole derivatives, such as Common names: prochloraz, triadimethin, propiconazole, diclobutrazo alcohol, triacyminol, flusilazole, flutriafol, microphytani quinconazole, imazalil, and diniconazole. can be lost. Examples of non-azole EBIs include Nuarimol, Fenarimol, Felimol, Examples include fenpropimorph, tridemorph and fenpropidine.

Other antibacterial agents that may be combined with the antibacterial formulations of the present invention include anilides, e.g. Luboxin, Mataraxyl, Fralaxyl, Ofras, Benaraxil, Mebroni benzimidazole, e.g. benomyl and carpendazine; carbamates e.g. maneb, mancoze and propamocarb: dicarpoximides, e.g. iprodione, vinclop Phosphorus and procymidone: Phosphorus derivatives, e.g. bilasifuose, dorcrophosme and other compounds such as dithiocal Bamate, bisdithiocarbamate, imidazole, triazole, fataloni Tolyl, polyhalogen alkylthio compounds, iminophtadine, guazatine, dichloride lorane, chlorothalonil, pirifexox, ethyrimol, cymoxanil and Anisidine is mentioned.

In its fourth aspect, the invention provides an effective amount of an antimicrobially active compound of the invention. A method for eradicating fungi on plants applied to the area to be treated.

In connection with this aspect, the compositions of the invention may be subjected to pre-emergence treatment for agricultural or horticultural use. Directly in the soil as a treatment or on plant leaves as a pre- and/or post-emergent treatment. or fruits. Depending on the crop and environment, seeds or fruits control fungi. Treatment may be postponed until the appearance of the desired plants.

The active preparations or compositions of the invention can also be used, for example, once fungi begin to appear on plants. is applied directly to plants by spraying or dusting as a protection measure before the emergence of fungi It is possible. In all such cases, the preferred method of application is foliar spraying. Ru. early in plant growth, as this is the time when plants can be most severely damaged. It is generally important to obtain good control of fungi at stage. considered necessary In some cases, spraying or application may be advantageous if it contains a pre-emergent or post-emergent herbicide. be.

The concentration of the active compounds of the invention as described herein in the compositions of the invention may vary depending on the type of plasticity. and can vary widely depending on the area of application.

The present invention in the compositions of the present invention when used alone or in combination with conventional antimicrobial agents. The concentration of antibacterially active compounds when applied to plants is preferably about 0. 001 to about 30% by weight, especially 0.001 to about 30% by weight. O is within the range of 1 to 3.0% by weight.

In the primary composition or concentrate, the amount of active compound can vary widely, e.g. may range from about 5 to about 95% by weight.

The concentration of antibacterially active ingredients in the mixed composition of the invention, when applied to plants, is Preferably within the range of 0.001 to 50% by weight, especially 0.01 to 10% by weight. . - In the following compositions, the amounts of other active ingredients can vary widely, e.g. It can be from 5 to 80% by weight of the composition.

Sometimes planting is done, for example by dipping the roots in a suitable liquid or solid composition. It is practical to treat plant roots before or during planting. Active product of the present invention When applying the agent directly to plants, the preferred application rate is 0.001 to 50 kg/hectare. per hectare, preferably 0.05 to 5 kg/ha.

In the method of the present invention, the activity of the present invention alone or in combination with conventional biocides The formulation may be applied to seeds or other habitats.

Therefore, the presence of active ingredients in the soil can attack the seeds before, during or after sowing. The formulation can be applied directly to the soil to control the growth of fungi that can cause damage.

The composition is compatible with about 1 g to about 50 kg of antimicrobially active compound per hectare. It can be applied in corresponding amounts.

For direct treatment of soil, active preparations alone or in mixtures with conventional biocides. solids by any method that can be intimately mixed with the soil, e.g. by spraying. By spreading granules of the form or by inserting them in the same furrow as the seeds. Application can be done by applying the active ingredient at the time of sowing. A suitable application rate is 0. 01-50 kg/ha, more preferably 0.05-5 kg/ha It is le.

Although the invention has been described in detail in connection with the control of fungi in plants, Antibacterially active compounds have been shown to eradicate or control fungi in mammals, including humans. and may also be used in wood preservation and/or impregnation compositions. It can also be used to preserve wood by adding compounds such as Furthermore, activation of the present invention Compounds are antibacterial agents and preservatives in paints – both of which inhibit growth in paints during storage. to prevent growth on painted surfaces such as plastered surfaces in homes. It is also useful as

Strain description Classification and morphology of fungi This fungus was described by Burgess, W. & Liddell C.M. (198 3), Laboratory manual for Fusari+nnr esearch:　Incorporation　a　key　anddesc Riptions of common 5 pieces found in Au5tralia, The University of 5ydney, 5ydney, (ISBN 0-909798-39-7), Booth, C.

(1971), The genus Fusarum, Co+++monw earth Mycological In5titutoB Kew 5urrey, England, and Booth, C, & B, C, 5utton, 1984.　Fusaruimpalidoros eum, the correct name for F, semitect um　Auct,　Trans.

Fusari using Br, Mycol, Soc, 83(4) Near 02-704 Fusarium pallidoroseum (Fusarium pallidoroseum) Cooke) 5acc, (syn, F, semitectum Berk, & Rav).

This fungus is of the Deuteromycetes class, Moniliare. It belongs to the order Moniliales.

Aerobic mycelium on potato sucrose agar It is hairy and gradually changes color from white to pink, hazel, and then pale yellowish brown. Conidia Children are divided into two types: primary and secondary. −Secondary conidia are slightly more than secondary ones. short. They grow cuneiform podocytes, are transparent, have septa of θ~5, 7.5–35 x2.5 to 4 μm. These subconidia are produced from each cell, with 6 conidia produced from each cell. Formed as holocytotic conidia from polyembryonic pseudococcal proliferating cells with separate spores up to will be accomplished.

Secondary conidia are formed from simple urine. These conidia are typical of heeled feet. cells (for further details see Booth and Sutton, 1 984).

Culture of bacterial strains The strain was cultured on potato dextrose agar (Difco) slant culture medium (1 2 ml/culture medium), autoclaved at 121°C for 40 min, It would then thereafter be called PD agar. After inoculation, keep it at 20-25°C can be incubated for 2 days or more.

Antibacterial agent manufacturing Slant cultures grown on PD agar for 7 days at room temperature consisting of mycelia and spores were ．． Mix with 10 ml of sterile water containing 1% Tween® 80. Combine yeast-extract sucrose (Yeast-E) using tap water. 500 ml containing 100 ml of xtract-Sucrose) medium Inoculated into an Erlenmeyer flask (2% yeast extract (Difco); 15% yeast extract (Difco); Sucrose; 10ppm ZnSO4-7Hz O; 5ppm CuSO s"5HtO and 0.3% agar (Dirco)). pH is 121 6.4 before autoclaving for 40 minutes at “C”. After inoculation, the The Sco was left at 26°C for 13 days.

The fungi can also be produced in surface culture according to well known procedures.

Fermentation also provides other sources of carbon and nitrogen that can be assimilated by microorganisms and generally at low levels. It can also be carried out in a medium containing Bell's inorganic salts. In addition, trace metals in the medium can be replenished, but when combined sources of carbon and nitrogen are used, they Usually present in complex sources.

compound extraction After adding 100 ml of methanol to each flask, the flasks were incubated at 18°C for 3 hours. Shake (200 rpm). Centrifuge at 20,000 rpm for 10 minutes. , the methanol supernatant containing antimicrobial agents was separated from the mycelium. It then contains mycelium. The pellet was discarded and the supernatant was analyzed for antibacterial activity.

The compounds of the present invention can be prepared using short chain alcohols, acetone, DMSO1 ethyl acetate, etc. The biomass can be extracted by any other conventional extraction method known in the art, such as and/or extracted from the growth medium. The concentrated extract is absorbed by the hydrophobic resin. It can be purified by attaching it. The resins used are non-ionic, especially cross-linked styrene/divinyl Nyl-benzene copolymer and halogenated styrene/divinyl-benzene It is a copolymer. A commonly used adsorption resin is XAD-8 (ROHM AN De Haas Inc.). A mixture of the two components is prepared by dissolving this resin in water. by increasing the concentration of alcohol/acetone, preferably methanol or ethanol. By elution, it can be obtained with a purity of 90% or more. Crude mixture of two components can be obtained by combining and concentrating these fractions. Optionally acidic The compound was further purified by conventional reverse phase chromatography using a mobile phase. , two purified compounds can be purified.

For convenience, the isolated compound (formula 1a) will be referred to hereinafter as BK219.

Characterization of isolated compounds Fermentation and extraction Slant cultures of the strains grown on PD agar were treated with yeast extract-sucro as described above. It was inoculated into a base medium, fermented and extracted.

Isolation/purification 1115 ml of supernatant was concentrated to 250 ml under reduced pressure. Amber concentrated extract Light (Amberlite) XAD-8 (c?-Mand Haas) 2 00 ml column and this was applied to a stepwise gradient of aqueous ethanol (0%, 30%, 50%, 70% and 100% each (200 all). Botrytis All samples were determined by disk diffusion assay using Botrytis cinenea. The activity of the fractions was monitored. Biological activity was determined by dissolution in 30-50% ethanol. The solvent was evaporated to give 780 mg of a yellow oil.

Further purification and separation of Compound 1a and Compound 1b was performed by reverse phase HPLC [Buch ( Biichi) column 26 x 230mm, LiChrop rep) (registered trademark) C10, 15-25 μm; 60% CH,,CN % formic acid buffered cHs starting and ending after 60 min with 1000% CH2,CN CN/H, O linear gradient, flow rate xoml/min, detection λ = 225 nm] 449 mg of compound Ib (Rt = 33 min) and 251 mg Compound 1a (Rt = 50 minutes) was obtained as a colorless glass.

Analytical HPLC method: Karam, Merck LichroSorb (Registered Trader) Standard) RP-184, 6mmx250mm Flow rate: 1.5 ml/min Eluent: 80% acetonitrile + 0.05% TFA dissolved in water detection, TJ V, 225 nm and 240 nm retention time = 5 minutes Compound 1a 2 minutes compound rb The novel compound BK219 of formula 1a is characterized by the following physicochemical properties: It is a colorless solid.

Molecular weight: 590 (negative FAB-MS) Molecular composition: Cs4HsaO* (mass Calculated value 589.3740 Actual value 589.3792) (Negative negative F A B -by MS) UV spectrum data: UVmax 216 rrn+ (3 2,000) 239 run (26,000) 281 nm (7,900 )[α]″,”=−23,6(c=0.4.MeOH)Activity shown by the Ib formula The compound is a colorless solid characterized by the following physicochemical properties:

Molecular weight: 606 (negative FAB-MS) Molecular composition: C5aHs40* (quality Calculated amount 605.36896 Actual value 605.3645) (Negative negative FAB -by MS) UV spectrum data: UVmax 216 nm (28, 000) 239 nm (24,000) 281 nm (6,500) [( Z]”,’=-21,2(c=0.3.MeOH)’H-NMR data is shown in Table 1, and the C-NMR data is shown in Table 2.

Spectra were obtained at ambient temperature on CD*OD. δ=3.3('H) and the signal at δ=49 ppm ("C) was used as an internal reference.

Table 1. 'HNMR data of compounds Ia and Ib 6 m J δ m J Ippml fHzl lppm1 1Hz11-H, 0,92 electric 70.941 7 2-H, 1,3m 1.3m 3-H, 1,3m 1.3m 4-H, 1,3' m 1.3 m 5-H, 13m 1.3m 6-8.1.4 m 1.3 m (H2) 6-H, 1,1 m 7-H1, 67m 1.04m 8-H, 0,94d 7 0.90 d 79-H, 2,11dd 14;7 2. OAB (H, J9-H, 1,97dd 14; 11 +1-H,1,72dl 1.68dl+2-H5,10ddl;9 5. +2 dd 9; 1+3-H3, 55m 3.46 d+ 9; 7; 714 - 3.41 dd II; 8 1.03 d 7 (H,) + 4-H, 3, 4 7dd II; 6 +5-H5,37d 9 5.37 bd 9+7-H,1,84d l 1. 111 d 118-H6, 32 d 16 6.28 d 1619-H5, 6 3dd 16;7 5.60 dd 16;720-H4,37dd 7;I 4.37 dd 7; 122-H, 1,21s 1.20 5 23-H, 1, 27s 1.26 5 25-H6,14s 6.13 5 29-H4,53d 94.53d 1030-H4,03dd 9.9 4 ．． 03 dd 10; 1031-H'3.65 m 3.65 m32-) (, 2,00dtld 13;5;2 2. Odd 11; 332-H, 1,61d dd 13; 12; 12 +, 6 d + IJII; ll33-8 3.65 m 3.65 mQ) 1 Table 2. "CNMR data of compounds ■ and ■" in methanol-d, 150M hz: 75Mhz in methanol, From the above spectrum data, the compound BK219 appears to have formula 1a.

All strains belonging to the genus Fusarium include varieties, recombinants and including mutants, obtained by natural selection or by ionizing or ultraviolet irradiation. or by the action of mutagens such as nitrosoguanidine, Whether or not caused by the action of a mutagen is included in the present invention. do.

Antibacterial activity A mixture (1:4) of compounds 1a and Ib was obtained from Oomycetes. es), Ascomycetes and Deuteromycetes In vitro inhibition of the growth of fungi belonging to the species Deuteromycetes It turns out that it does. It can have a particularly strong influence on: found: Oomycetes class: Pythium sp. , Type F.

Phytophthora 1nfest ans,) Class Ascomycetes: Benzilia Ina Venturta 1 naqualis Phom a betae) Phoma lingam (Phoma lingam) Ascochita Ascochyta pisi Sufflerotinia Sclerothiorum (S clerotinia sclerotiorum) Pyrenophora teres (P yrenophora teres) Saccharomyces cerevisiae (Sac caromyces cerevisiae) Deutelomycetes romycetes) class: Fusarium oxysporum (Fusarium o xysporum) Botrytis cinerea ) Rhizoctonia solant AG-3 (Rhizoctonia 5olant AG-3) Monilinia fructige na) Alternaria alterna ta) Aspergillus niger compound Identical mixtures of 1a and Ib are Eubacterial es) was found to have an in vitro inhibitory effect on the growth of bacteria belonging to the order. So This has a particularly strong impact on: Example Example I Fermentation and isolation/purification Yeast-Extract-3uc rose) medium (2% yeast extract (Dirco); 15% sucrose; 10ppm ZnSo, “7HtO; 5ppm CuSOs” 5HtO and 0.3% agar) in a 500ml triangular flask. A suspension of mycelium from strain CL 534-1 was inoculated into a flask. 2 flasks It was left at 6°C for 13 days.

Each flask was extracted with 100 ml of MeOH and shaken at 18 m″C for 3 h ( 20Orpm). The mixture is then centrifuged and the upper groove containing the metabolites is removed from the mycelium. Separated from.

Isolation and purification were performed as described in the “Characterization of isolated compounds” section. did.

Example■ Residual activity against Botrytis cinerea protective activity Host: Lycopersicon esculentum lentum) (Tomato, first variety var First in Field) using a handheld sprayer (Bink Bullows 900) The suspension was sprayed onto tomatoes (5 weeks old). Suspensions contain different concentrations of compound 1 a and Ib in combination or contained compound 1a alone. Keep plants warm and humid After drying for 24 hours at 1×10 spores/ml and 25% gray inoculated with a spore suspension containing juice. Inoculation is done using a grip-type atomizer (W Agner, Pico Be1). Then plant the polyethylene Incubate in a bag at 15-20°C with increased relative humidity of 95-100% ( 16 hours of light (10001 ux) and 8 hours of darkness).

Evaluation was performed after 6 days and the results are shown below: Compound 1a: 270 p pm 30% protection 90 ppm 20% protection 30911m 10% protection 10 l1l) Ell 10% protection Compound 1b: 270ppm 100% protection 9011p111 85% protection 30 ppm 75% protection 10 ppm 65% protection Example■ Preparation of methyl ether of Ib Add ether solution to a solution of Ib (24 mg) dissolved in 1 ml of dichloromethane. Extra amount of diazomethane dissolved in the solution was added at 0°C. After concentrating and drying in vacuum, The reaction mixture was purified by reverse phase chromatography to yield 16 mg (iD Ic). Ta.

Ic activity Compound 1c is derived from Ascomycetes and deuteroma In vitro inhibition of the growth of fungi belonging to the Deuteromycetes family. It turned out to be harmful. It has a particularly strong influence on: There was found: Ascomycetes: Satucharomyces cerevisi Ae (Saccharomyces cereviviae) deuteromycete Deuteromycetes Nipotrytis cinerea (Botryt is cineres) Rhizoctonia solani AG-3 (Rhizoctoni a 5olani AG-3) Aspergillus niger s niger) This compound is an Eubacteriale (Eubacteriale) It was also found that it exerts an in vitro inhibitory effect on the growth of bacteria belonging to s).

Eubacteriales: Bacillus subtilis (Bacillus 5ubtilis) Translation submission form of written amendment (Article 184-8 of the Patent Act) November 11, 1994

Claims (21)

[Claims] 1. Deuteromycetes, preferably Moni Moniliales genus, more preferably Fusarium rium), especially Fusarium pallidroseum (Fusarium pall) idoroseum) species, especially Fusarium pallidroseum (Fusariu Belongs to the strain M. pallidoroseu (IMI CC No. 351439). Antibacterial compounds that can be produced from strains that 2. Formula I: ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, R1 is hydrogen, 1 to 6 carbons straight-chain or branched alkyl atoms, e.g. methyl, having 1 to 6 carbon atoms; straight-chain or branched hydroxyalkyl, e.g. CH2OH, with 1 to 6 carbons Straight-chain or branched alkyl ethers with elementary atoms or optionally substituted each R2 is independently hydrogen, having 1 to 6 carbon atoms; straight-chain or branched alkyl, e.g. methyl, straight-chain with 1 to 6 carbon atoms or branched hydroxyalkyl, e.g. CH2OH, having 1 to 6 carbon atoms. linear or branched alkyl ethers, or optionally substituted aromatic ethers. and each R3 is independently hydrogen, hydroxy, methoxy, acetoxy , straight or branched alkyl ethers having 1 to 6 carbon atoms, or as desired aromatic ether substituted by; and chiral centers a, b, c, d, e, f, and g can each independently have the R configuration or the S configuration). antibacterial compound (provided that R1 is -CH2-OH and all R2 are -CH2 and all R2 are -OH (except for compounds of formula Ib); or Agronomically acceptable salts thereof or esters thereof. 3. Formula Ia: ▲There are mathematical formulas, chemical formulas, tables, etc.▼An antibacterial agent described in claim 2 having (Ia) antibiotic compounds, or their agriculturally acceptable salts or esters. 4. A compound according to claim 2 or 3 or a compound represented by formula Ib Deuteromycetes (deuteromycetes) on a relic nutrient medium under appropriate conditions. Deuteromycetes, preferably Moniliales es), more preferably Fusarium genus, especially Fusarium Fusarium pallidoroseum species, esp. Fusarium pallidoroseum m) Cultivate the seeds belonging to the (IMI CC No. 351439) strain and continue to grow the seeds. Formula Ia or the following formula Ib from iomas and fermentation medium: ▲ There are mathematical formulas, chemical formulas, tables, etc. The active compound represented by ▼(Ib) is isolated and, if desired, any of said compounds chemically modifying one of them to obtain a compound of formula I. 5. Symptomatic organisms are Fusarium pallidroseum (Fusarium palldoro) seum) (IMI CC No. 351439). is the method described in any of Section 4. 6. containing at least one compound according to one of claims 1, 2 or 3. An antibacterial composition consisting of 7. Claim 6 comprising a mixture of compound (Ia) and compound (Ib) The antibacterial composition described in Section. 8. At least one according to one of claims 1, 2 or 3 as active ingredient Contains seed compounds in combination with other biocides and/or plant growth regulators. An antibacterial composition consisting of. 9. Claims comprising a mixture of compounds of formula Ia and formula Ib as active ingredients The antibacterial composition according to item 8. 10. At least one active compound according to claim 1, 2 or 3 is inactivated. 1. A method of making an antimicrobially active composition comprising mixing with a sex carrier. 11. The at least one active compound further comprises one or more biolethal compounds. Claim 10 used in combination with compounds active in and/or plant growth regulators. Method described. 12. A method for eradicating fungi in infected or susceptible areas, the method of eradicating fungi in infected or susceptible areas, at least one compound of formula I according to claim 1 or 2. , or applying the composition according to any one of claims 6 to 9. A method comprising: 13. Claims that the above-mentioned single or plural compounds or compositions are applied to plants. The method according to paragraph 12. 14. 0.001 to 50 kg, preferably 0.05 to 5 kg of active ingredient of formula I 13. The method of claim 12, wherein the method is applied in a range of concentrations. 15. Claims for eradicating fungi on wood, in cosmetics, feed or food The method according to paragraph 12. 16. Ascomycetes, Oom ycetes) or Deuteromycetes Any one of claims 12 to 15 for controlling attack from fungi to which it belongs. The method described in section. 17. Potrytis genus, especially Potrytis cinerea (Botr) Claims for controlling attacks from fungi belonging to Ytis cinerea) The method according to paragraph 16. 18. Compounds according to one of claims 1, 2 or 3 for controlling fungi or the use of a composition according to any one of claims 6 to 9. 19. Ascomycetes, Oom ycetes) or Deuteromycetes 19. Use according to claim 18 for controlling attacks from fungi belonging to the group. 20. The genus Botrytis, especially Potrytis cinerea (Botrytis) Claims for controlling attack from fungi belonging to tis cinerea) The method according to paragraph 19. 21. Preparation of an antibacterially active compound according to any one of claims 1 to 3. Deuteromycetes useful for construction, preferably of the genus Moniliales, More preferably Fusarium genus, especially Fusarium pallid Fusarium pallidoroseum species, especially Fusarium pallidoroseum Fusarium pallidoroseum (IM ICC No. A substantially pure culture of a microorganism belonging to the strain 351439).