GB2110934A - Fungicidal compositions - Google Patents

Abstract

Fungicidal compositions displaying "resistance breaking" effects and/or synergy, and having broader spectra of activity, comprise a fungicide (or co-fungitoxicant) which inhibits adenosine deaminase or blocks sterol biosynthesis in fungi and a further fungicide having a different mode of action.

Description

SPECIFICATION Fungicidal compositions This invention relates to compositions for combat ing plant fungi. More particularly the invention relates to mixtures of fungicidal substances contain ing a first fungicide which is either an inhibitor of adenosine deaminase or of sterol biosynthesis in fungi and at least one other anti-fungal substance having a different mode of anti-fungal effect.

itis known that plant fungi, especially races (strains, types) thereof, can develop resistance to, that is become insensitive to, anti-fungal chemicals thereby reducing the efficacy of a particular chemical. Indeed there are believed to be in existence certain plantfungal pathogens which are resistant to fungicides of the type which combat them, for example, by inhibiting their ability to biosynthesise certain steroids essential to their metabolism, for example ergosterol. These fungicides, more specifically either block the incorporation of acetate into ergosterol an essential metabolic pathway of the fungus, thereby disrupting the synthesis and function of cell membranes by the fungus.Plant pathogens of the latter type include, in particular, races etc., of powdery mildew diseases such as Erysiphe graminis which infect cereal plants, for example crops of barley and wheat, and mildews which infect non-cereal crops such as vines and apples, such latter diseases being, for example, Uncinula necator, Podosphaera leucotricha and Sphaerotheca fuliginea or other diseases such as Ventuda inacquatis on apples or Cercospora leaf spots on peanuts, banana and sugar beet It has now been found that certain mixtures of, or combinations of, fungicides are not only less prone than the individual components thereof to suffer from reduction in their efficacy due to resistant (insensitive) species of plant pathogens infecting crops uponwhich they are sprayed (or the seed- pre-treated with them), but in addition often display synergism, that is to say the combined antifungal effect of the mixture isgreaterthan that which would have been expected if the fungicidal components were acting separately. Such mixtures are ones in which a pyrimidine fungicide or a sterol biosynthesis inhibiting fungicide is combined with one or more fungicides having a different mode of action against the fungal pathogens being combated.

According to the present invention there is pro vided an anti-fungal composition comprising either, as a first ingredient, a co-fungitoxicant or a fungicide which inhibits adenosine deaminase or a fungicide having a sterol biosynthesis blocking mode of action in its anti-fungal effect, and at least one further fungicide having a different mode of action in combating fungi.

The fungicide which inhibits adenosine deaminase in fungi may be a pyrimidine fungicide and by "a pyrimidine fungicide" is intended single ring compounds such as ethirimol, dimethirimol and bupirimate. The term is not intended to embrace bicyclic and tricyclic compounds in which a central carbon atom bears a pyrimidine ring and one or more other aryl or heterocyclic rings.

The co-fungitoxicant need have no fungicidal activity in its own right; or have activity only against triazole resistant strains of a pathogen.

The fungicidal ethirimol is the subject of British Patent No. 1182584 and it has the chemical structure:

The fungicide dimethirimol is also the subject of British Patent No. 1182584 and it has the chemical structure:

The fungicide bupirimate is the subject of British Patent No. 1400710 and it has the chemical structure:

The foregoing fungicides are, as already stated, considered to have an anti-fungal effect by inhibition of the action of adenosine deaminase in the meta bolism of fungi.

In a further aspect, therefore, the invention provides an anti-fungal composition comprising a fungicide which is ethirimol, dimethirimol or bupirimate or an anti-fungal substance which is an inhibitor of the ability of the fungus to biosynthesise sterols and at least one further fungicide which has a different mode of action in combating fungi.Examples of fungicidal substances having the capacity to inhibit sterol biosynthesis and the classes to which the belong, are as follows: Table A CLASS AND TRADE NAMES OF FUNGICIDAL PRODUCTS COMMON NAME CONTAINING THE FUNGICIDE OF FUNGICIDE Imidazoles Imazalil Fungaflor, present in Mist-O-Matic Murbenine Plus, Mist-O-Matic Muridal Seed Treatment Prochloraz Sportak Fenaponil Piperazines Triforine Saprol, Triforine LST, present in Nimrod T Pyridines Buthiobate Parnon EL 241 Piperidines Fenpropidin Pyrimidines Fenarimol Rubigan Nuarimol Triminol, present in Mist-O-Matic Murox Seed Treatment Triarimol Triazoles Bitertanol Diclobutrazol Vigil, present in Vigil K, present in Vigil T Fluotrimazole Persulon Propiconazole Tilt 250 EC, in Tilt mbe 45WP Triadimefon Bayleton, Bayleton 5, in Bayleton, BM, Bayleton CF Triadimenol Baytan Etaconazole Vanguard, Sonax PP969 Morpholines Dodemorph BASF F238 Fenpropimorph Corbel, Mistral Tridemorph Calixin, Bardew, Beacon, Cosmic The chemical structures of the foregoing chemical substances are set out below:

IMlDAZOLES F' P CAZ- CH s CHZ -- = CH CH2CH2-CH2- CH3 2 2 ThClI cell tH2 kN k imazalil fenaponil PIPERAZINES 1oCH2CH2 CHO CHO Cl < CH2-CH2 CH3 CE3 NE NH NH C = 0 I I triforine e c = o CH-N N-CH Cl f N3 CC13 clg & 3 rochloraz W PYRIDINES - - CH2(CH3)3 oHj C4 9 - F - S - CBi-Q-ecCH3]3 t3CI b 6 buthiobate EL-241 PIPERIDINES CH -CS2-3-H2C(CH3)3 fenpropidin

PYR3 rU D3 Tras 6 cl wH) & l is' 11 SenarirJol nuarSxnol trSar;nol 'IRIAZO1ZS . cl R HoK-C CNCNONK (CH3)3 C'' -CS bitertanol propiconazole COL 64250 1 R=n*C3E? etaconazoe CGA 60251 Cl;= C H2CH{HoE^C(CE3373 64251 L i̲slobutrazol cy I - o --tRR-CHOH C (CR33 tK J O t C1 C1CBCC(CN3}3 -CH=C?3DH - (CH30 3 fluotrimazole tri2dimefon triai̲menol Dli t-C4N9-. Cli-CSII2- t t-C,N9 J50RPNOLlNoS < N /'CBl's 3 55)sS ( > 3)3ct3+C13tB274 3 3 aodemorph fespropilDoryb - txaorpb In afurtheraspect,therefore,the invention provides a fungicidal composition comprising, as active ingredients, a first fungicide which is eitherethirimol, dimethirimol or bupirimate or which is an inhibitor of the ability of a plant fungus to biosynthesise sterols and is a specificfungicidal substance from.the foregoing list of chemical compounds, and at least one further fungicidal substance having a mode of action in combating fungi which is different from that of the first fungicide. As far as suitable further fungicidal substances are concerned these may be any general, i.e. metabolic, inhibitor of plant fungal growth,for example a respiratory inhibitor.

Bytheterm"general metabolic inhibiting agent" (including respiratory inhibitors) are intended fungicidal and anti-fungal substances such as those listed below under chemical class headings with examples of specific fungicides listed and an indication of their believed mode of action.

Table B 1. Site specific inhibitors Acylalanies -furalaxyl, metalaxyl, ofurace, galben.

Mode of action -7 Antibiotics cycloheximide etc.

Mode of action -inhibits protein synthesis Benzimidazoles -benomyl, carbendazim, thiophanate methyl, thiabendazole, fuberidazole Mode of action -inhibition of mitosis Carboxamides -carboxin, oxycarboxi n, methfu roxam, fenfu ram, furmecyclox, benodanil, pyracarbolid Mode of action -interference with respiration by blocking succinate dehydrogenase Dicarboxamides -iprodione, procymidon, vinclozolin, M8164 (Serinal) Mode of action -interference with mitotic segregation Aromatic -2-phenylphenol, sodium -o-phenyl hydrocarbons phenate biphenyl, chloroneb, dichloran, quintozene, tecnazene.

Mode of action -interference with mitotic segregation Dinitrophenols -dinapacryl, dinocap Mode of action -uncouplers of oxidative phosphorylation Dimethyidithio- carbamates -thiram Mode of action -inhibitors of pyruvate dehydrogenation Guanidines -dodine, guazatine Mode of action -affect cell membrane permeability Organotin -fentin compounds Mode of action -inhibition of oxidative phosphorylation Organic -pyrazophos, edinfenphos, BP, phosphates and -isoprothiolane isoprothiolane Mode of action -inhibition of the conversion of phosphatidyl-ethanolamine to phosphatidyl-choline Acetamides -curzate Mode of action -unknown Aminobutane -2-aminobutane Mode of action -inhibition of pyruvic dehydrogenase Anthraquinones -dithianon Mode of action -inhibition of glycolysis Isoxazolones -drazoxalon Mode of action -uncoupler of respiration Nftroisophthalates -nitrothal-isopropyl Mode of action -unknown Organic phosphates -ditalimfos Mode of action -disrupts metabolism Quinoxalines -quinomethionate Mode of action -? Suiphamides -dichlofluanid, tolyfluanid Mode of action -? Thiocarbamates -prothiocarb, pro pa nocarb Mode of action -causes cell membrane disfunction A-Phenylcarbamate rivativas Such as those disclosed in European Patent Application No.81109561.1 (Publication No. 51871) having the general formula:

where X andY are alkyl, atkoxy or halogen and R is methol or ethyl.

Table C Thiadiazoles -etridazole Mode of action -interferes with respiration 2. Multisite inhibitors Dithiocarbamates -maneb, zineb, mancozeb, nabam, propineb etc.

Mode of ation -inhibitors of thiol groups Phthalimides -captafol, captan, folpet Mode of action -inhibitors of thiol groups Phthaionitriles -chlorothanlonil Mode of action -inhibitor of thiol groups Copper compounds -various Mode of action -? Mercury compounds -various Mode of action -? Sulphur Mode of action -7 Aluminium compounds -FOSETYLALUMINIUM Mode of action -? Anionic agents Sodium dodecylbenzene sulphonate Sodium dodecylsulphate Sodium C13/C15 alcohol ether sulphonate Sodium ceto stearyl phosphate ester Dioctyl sodium sulphosuccinate Sodium isopropyl naphthalene sulphonate Sodium methylene bis naphthalene sulphonate Cationic agents Cetyltrimethyl ammonium chloride Salts of long chain primary, secondary or tertiary amine Alkyl propylene gamines Lauryl pyridinium bromide Quaternised fatty amine ethoxylate Alkyidimethyt benzyl ammonium chloride 1- Kydroxyethyl- 2- alkyl imidazolina In a further aspect, therefore, the invention pro vides a fungicidal composition comprising, as active ingredients, a first fungicide which is either ethirimol, dimethirimol or bupirimate or which is an inhibitor oftheability of a plantfungusto biosynthe- sise sterols and is a specific fungicidal substance from the foregoing tist of chemical compounds, and at least one further fungicidal substance having a mode of action in combating fungi which is different from that of the first fungicide and which is a substance chosen from the specific fungicidal subst ances recited in the immediately preceding list The invention also provides a process for r.ating seed which comprises dressing seed with a com position according to the invention.

In another aspect seed may be dressed first with ethirimol, or with a fungicide which inhibits sterol biosynthesis in plant: fungi and then with a further fungicide as defined above. Batches of seed treated separately with a first fungicide and with a further fungicidal substance may be mixed wth untreated seed, e.g. tumbled therewith, so as to produce a batch of treated seed.

The invention further provides, in yet another aspect, a process for combating plant fungi which comprises applying to a plant, to seed of a plant, or to the locus of a plant or seed, an anti-fungal composition as defined in any of the preceding paragraphs.

In a still further aspect the invention provides a process of combating plant fungi which comprises alternately treating, e.g. spraying, crops with ethir imol, dimethirimol or bupirimate, or with a fungicide which inhibits sterol biosynthesis in plant fungi, and then with a furtherfungicidal substance as defined above.

The amounts offungicidal substance used in the invention compositions can readily be determined by simple experimentation, but in general, in view of the ability to counter resistant (insensitive) races etc., of fungi andlor the synergism displayed, it is not necessary to use the full rates of chemical normally applied.

EXAMPLE 1 A series of initial experiments were carried out to determine the efficacy of a range of co-fungitoxicants in controlling two isolates of E. graminisf.sp hordei in the absence of triadimefon with the following results (Table 1).

Sumisclex showed activity against one or both fungus isolates whereas Sanspor and Terrazole were inactive.

Sumisclex was further tested to determine in more detail its rate response against the two isolates of E graminis f.sp hordei (Table 2). Based on these data, suboptimal rates of this compound were chosen for a further interaction experiment involving triadimefon (Tables 3 and 4).

Against both isolates the addition of Sumisclex at 150 ppm to triadimefon at 0.1 ppm boosted the activity of triadimefon in the degree of disease control achieved. The margin of this increase in activity must be accounted for by a synergistic interaction between the two compounds.

Materials and Methods 1. Plant Sowing: Approximately 10 seeds/pot of Golden Promise spring barley were sown into John Innes compost number one in minipots.

1.1 Growth Conditions: Daytemperature 21 C, Relative Humidity 60%, Nighttemeprature 17"C, Rela t5ve Humidity 95%, 16 hours daylength. The plants werewatered by an automatic watering system.

2. Test Method forspraying the plants: Plants were sprayed at 6 days old; the chemicals under test were made up in 0.03% Tween 20; and the plants were sprayed to give an even coverage on both leaf surfaces, using a hand-held De Vilbiss spray gun at 15 psi (pounds per square inch).

After spraying, the plants were transferred to a second growth chamber for 24 hours to allow plants to dry.

2.1 Growth Conditions in this room were: Day temperature 24at, Relative Humidity 60%, Night temperature 17"C, Relative Humidity 95%, 16 hours daylength. The plants were watered by an automatic watering system.

3. Method for preparing the repli dishes: Plants were removed from the Growth Room and cut into 2 cm lengths from just below the tip of the prophyll.

Only uniform plants were chosen. Only one leaf piece was taken from each prophyll. The cut leaf pieces were then placed into a slit in the agar in the repli dish. (the dishes contained 45 ml of 10% Tap water agar), the top rate of chemical first proceeded by lower rate. For each chemical rate there were 5 replicate leaf pieces.

When changing from one rate of chemical to a lower rate the scissors and forceps were wiped with a swab soaked in Methanol to avoid contamination.

Particular attention was paid to ensure that the leaf pieces did not touch the lid nor overlap one another in the dish. The former would cause condensation to run down the leaf pieces and could wash off some spores, the latter would lead to uneven inoculation and hence misleading results.

4. Inoculation Method: Infected leaf pieces were cut from stock plants in propagating tubes and placed in petri dishes on moist foam squares 48 hours prior to inoculation. The infected leaf pieces were kept in a 19"C constant temperature room with a 16 hour day length.

Repli dishes were inoculated using a settling tower, the tower was placed over the opened repli dish and sporulating leaf pieces held in forceps were placed in the nose of the tower. An air line set at 3/4 lb per square inch pressure was used to blow the spores off the leaf pieces and into the settling tower.

The repli dishes remained inside the tower for 2 minutes after which the tower was removed and the lid replaced on the repli dish. The tower, forceps and air lines were swabbed with Methanol to decontaminate them.

Once all the repli dishes were inoculated they were placed in a 19"C constant temperature room with a 16 hour daylength where they remained until assessment 6 days later.

5. Assessment: Percentage sporulating disease was assessed on each leaf piece TABLE 7 Disease Control Erysiphe graminis f.sp hordei isolate Fungitoxicant Rate ppm 1 2 ai.

Sumisclex 500 99 100 (procymidone) 250 98 100 125 65 39 100 93 56 50 98 25 0 0 0 TABLE2 2 % Disease Control Erysiphe graminis f.sp hordei isolate Fungitoxicant Rate ppm 1 2 ai.

Sumisclex 250 99 87 (procymidone) 200 96 30 175 97 69 150 27 57 125 22 27 0 0 0 TABLE 3 Isolate 1% Disease Control Triadimefon Triadimefon Rage + ppm ai 150 ppm Sumisclex 0.25 - 0.1 59 (20) 0.05 30 0.025 43 0.01 Sumisclex 150 0 Untreated - 0 Actual 74% untreated disease level ( ) = Activity of triadimefon alone in same test dish at 0. ppm.

TABLE 4 Isolate 2 h Disease Control Triadimefon Triadimefon Rate + ppm ai 150 ppm Sumisclex 0.5 93(52) 0.25 0 0.1 -15 0.05 Sumisclex 150 -31 Untreated - 0 Actual Untreated 61 % Disease level ( ) = Activity of triadimefon in same test dish at 0.1 ppm.

Claims (9)

1. An anti-fungal composition comprising as a first ingredient either a co-fungitoxicant or a fungicide which inhibits adenosine deaminase or a fungicide having a sterol biosynthesis blocking mode of action in its anti-fungal effect, and at least one further fungicide having a different mode of action in combating fungi.

2. An anti4ungal composition according to claim 1 comprising a adenosine deaminase inhibitor which is a pyrimidine derivative having the structure:

or

3. An anti-fungal composition according to claim 1 comprising a fungicide having a sterol biosynthesis blocking mode of action and which is an imidazole, piperazine, pyridine, piperidine, pyrimidine, triazole or morpholine derivative as hereinbefore defined

4. An anti-fungal composition according to any of the preceding claims wherein the further fungicide is a site specific inhibitor or multisite inhibitor, as hereinbefore defined, or a generat, eg. metabolic, inhibitor of fungal growth.

5. An anti-fungal composition according to any of the preceding claims wherein the further fungicide comprises any of the specific fungicidal substances defined hereinbefore.

6. A process for treating seed which comprises dressing seed with a composition according to the invention.

7. A process for dressing seed wherein seed is dressed first with ethirimol, or with a fungicide which inhibits sterol biosynthesis in plant fungi, and then with a further fungicide as defined in any of the preceding claims.

8. A process for combating plant fungi which comprises applying to a plant, to seed of a plant, or to the locus of a plant or seed, an anti-fungal composition as defined in any of the proceeding claims.

9. Aprocessofcombating plant fungi which comprises alternately treating, eg. spraying, crops with ethirimol, dimethirimol or bupirimate, or with a fungicide which inhibits sterol- biosynthesis in plant fungi, and then with a further fungicidal substance as defined above.