FUNGICIDAL COMPOSITIONS

Abstract

A fungicidal composition comprising a mixture of components (A) and (B), wherein components (A) and (B) are as defined in claim 1, and use of the compositions in agriculture or horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

Claims

1. A fungicidal composition comprising a mixture of components (A) and (B) as active ingredients, wherein component (A) comprises a cyclic depsipeptide of formula (I-A1) or a stereoisomer thereof: ##STR00011## and component (B) is selected from the group consisting of quinofumelin, ipflufenoquin, N-[(1R)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide, N-[(1R)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8-fluoro-quinoline-3-carboxamide, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-7,8-difluoro-quinoline-3-carboxamide, 8-fluoro-N-[(1R)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide, 8-fluoro-N-[(1S)-1-[(3-fluorophenyl)methyl]-1,3-dimethyl-butyl]quinoline-3-carboxamide, N-[(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3-carboxamide, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline, 1-(6,7-dimethylpyrazolo[1,5-a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline, 4,4-difluoro-3,3-dimethyl-1-(6-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline, 4,4-difluoro-3,3-dimethyl-1-(7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline, 1-(6-chloro-7-methyl-pyrazolo[1,5-a]pyridin-3-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline, 1-(4,5-dimethylbenzimidazol-1-yl)-4,4-difluoro-3,3-dimethyl-isoquinoline, 6-chloro-4,4-difluoro-3,3-dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline, 4,4-difluoro-1-(5-fluoro-4-methyl-benzimidazol-1-yl)-3,3-dimethyl-isoquinoline, 3-(4,4-difluoro-3,3-dimethyl-1-isoquinolyl)-7,8-dihydro-6H-cyclopenta[e]benzimidazole, 1-(5,6-dimethyl-3-pyridyl)-4,4-difluoro-3,3-dimethyl-isoquinoline, 1-[6-(difluoromethyl)-5-methyl-3-pyridyl]-4,4-difluoro-3,3-dimethyl-isoquinoline, N-[2-(2-ethylpyrazol-3-yl)phenyl]-5,6-difluoro-3-methyl-quinoxalin-2-amine, 5,6-difluoro-N-[3-fluoro-2-(2-propylpyrazol-3-yl)phenyl]-3-methyl-quinoxalin-2-amine and 3-[[3-chloro-2-(2-ethylpyrazol-3-yl)phenyl]methyl]-7,8-difluoro-2-methyl-quinoline.

2. The composition according to claim 1, wherein the weight ratio of (A) to (B) is from 100:1 to 1:1000, preferably from 100:1 to 1:500, more preferably from 50:1 to 1:200, and even more preferably from 50:1 to 1:20.

3. The composition according to claim 1, wherein component (A) further comprises one or more other cyclic depsipeptides of formula (I-A) or stereoisomers thereof: ##STR00012## wherein R.sup.1 is methyl or ethyl; each of X.sup.1, X.sup.2 and X.sup.3 is hydrogen, or X.sup.1, X.sup.2 and X.sup.3 are hydrogen, fluorine or hydroxyl, with the proviso that only one of X.sup.1, X.sup.2 and X.sup.3 is fluorine or hydroxyl; X.sup.4 is CH, S or hydroxymethylene; A.sup.3 is an α-amino acid residue selected from the group consisting of N-methyl-L-phenylalanine (L-MePhe), L-phenylalanine (L-Phe), β-hydroxy-N-methyl-L-phenylalanine (L-β-OH-MePhe), ortho-fluoro-N-methyl-L-phenylalanine (L-o-F-MePhe), meta-fluoro-N-methyl-L-phenylalanine (L-m-F-MePhe), para-fluoro-N-methyl-L-phenylalanine (L-p-F-MePhe), meta-bromo-N-methyl-L-phenylalanine (L-m-Br-MePhe), para-bromo-N-methyl-L-phenylalanine (L-p-Br-MePhe), meta-iodo-N-methyl-L-phenylalanine (L-m-l-MePhe), para-iodo-N-methyl-L-phenylalanine (L-p-l-MePhe), 3-phenyl-N-methyl-L-phenylalanine, 4-phenyl-N-methyl-L-phenylalanine, 3-(4-fluorophenyl)-N-methyl-L-phenylalanine, 4-(4-fluorophenyl)-N-methyl-L-phenylalanine, 3-(4-pyridinyl)-N-methyl-L-phenylalanine, 4-(4-pyridinyl)-N-methyl-L-phenylalanine, 3-(1-pyridinyl)-N-methyl-L-phenylalanine, 4-(1-pyridinyl)-N-methyl-L-phenylalanine, 4-(2-chloro-4-pyridinyl)-N-methyl-L-phenylalanine, 3-(2-chloro-5-pyridinyl)-N-methyl-L-phenylalanine, 4-(2-chloro-5-pyridinyl)-N-methyl-L-phenylalanine, 3-[4-(piperazin-1-yl)phenyl]phenyl-N-methyl-L-phenylalanine, 4-[4-(piperazin-1-yl)phen-1-yl]phenyl-N-methyl-L-phenylalanine,3-[4-(4-methylpiperazin-1-yl)phenyl]phenyl-N-methyl-L-phenylalanine, 4-[4-(4-methylpiperazin-1-yl)phen-1-yl]phenyl-N-methyl-L-phenylalanine, β-oxo-N-methyl-L-phenylalanine (L-β-oxo-MePhe), β-acetoxy-N-methyl-L-phenylalanine (L-β-AcO-MePhe), N-methyl-L-tyrosine (L-MeTyr), O-methyl-N-methyl-L-tyrosine [L-MeTyr(Me)], N-methyl-L-alanine (L-MeAla), N-methyl-L-serine (L-MeSer), N-methyl-D-phenylalanine (D-MePhe), N-methyl-D-alanine (D-MeAla), N-methyl-D-valine (D-MeVal), N-methyl-D-serine (D-MeSer) and N-methyl-L-serine (L-MeSer) residues; A.sup.5 is an α-amino acid residue selected from the group consisting of L-allo-isoleucine (L-Alle), L-leucine (L-Leu), L-norleucine (L-Nle), L-norvaline (L-Nva) and L-valine (L-Val) residues; A.sup.6 is an α-amino acid residue selected from the group consisting of N-methyl-L-valine (L-MeVal), N-methyl-L-leucine (L-MeLeu), N-methyl-L-allo-isoleucine (L-MeAlle) and L-valine (L-Val) residues; A.sup.7 is an α-amino acid residue selected from the group consisting of L-leucine (L-Leu), L-allo-isoleucine (L-Alle) and L-norvaline (L-Nva) residues; and A.sup.8 is an α-amino acid residue selected from the group consisting of β-hydroxy-N-methyl-L-valine (L-β-OH-MeVal), γ-hydroxy-N-methyl-L-valine (L-γ-OH-MeVal), N-methyl-L-valine (L-MeVal), L-valine (L-Val), N-methyl-2,3-didehydro-L-valine (L-MeDH.sub.2,3Val), N-methyl-3,4-didehydro-L-valine (L-MeDH.sub.3,4Val), N-methyl-L-phenylalanine (L-MePhe), β-hydroxy-N-methyl-L-phenylalanine (L-β-OH-MePhe), N-methyl-L-threonine (L-MeThr), sarcosine (Sar) and N,β-dimethyl-L-aspartic acid (L-N,β-MeAsp) residues.

4. The composition according to claim 1, wherein component (A) further comprises at least one other cyclic depsipeptide of formula (I-A) or a stereoisomer thereof selected from the group consisting of Aureobasidin E and Aureobasidin G.

5. The composition according to claim 1, wherein component (A) comprises: from 10% to 99.9% by weight, preferably from 20% to 99.9% by weight, more preferably from 40% to 99.9% by weight of a cyclic depsipeptide of formula (I-A1) or a stereoisomer thereof, and from 0.1% to 90% by weight, preferably from 0.1% to 80% by weight, more preferably from 0.1% to 60% by weight of one or more other cyclic depsipeptides of formula (I-A) or stereoisomers thereof.

6. The composition according to claim 1, wherein component (A) further comprises one or more cyclic depsipeptides of formula (I-B) or stereoisomers thereof: ##STR00013## wherein R.sup.1 is methyl or ethyl; X.sup.4 is CH, S or hydroxymethylene; A.sup.5 is an α-amino acid residue selected from the group consisting of L-allo-isoleucine (L-Alle), L-leucine (L-Leu), L-norleucine (L-Nle) and L-valine (L-Val) residues; A.sup.6 is an α-amino acid residue selected from the group consisting of N-methyl-L-valine (L-MeVal), N-methyl-L-leucine (L-MeLeu), L-allo-isoleucine (L-Alle) and N-methyl-L-allo-isoleucine (L-MeAlle) residues; A.sup.7 is an α-amino acid residue selected from the group consisting of L-leucine (L-Leu), L-allo-isoleucine (L-Alle) and L-norvaline (L-Nva) residues; and A.sup.8 is an α-amino acid residue selected from the group consisting of β-hydroxy-N-methyl-L-valine (L-β-OH-MeVal), γ-hydroxy-N-methyl-L-valine (L-γ-OH-MeVal), N-methyl-L-valine (L-MeVal), N-methyl-2,3-didehydro-L-valine (L-MeDH.sub.2,3Val), N-methyl-3,4-didehydro-L-valine (L-MeDH.sub.3,4Val), N-methyl-L-phenylalanine (L-MePhe), β-hydroxy-N-methyl-L-phenylalanine (L-β-OH-MePhe), N-methyl-L-threonine (L-MeThr), sarcosine (Sar) and N,β-dimethyl-L-aspartic acid (L-N,β-MeAsp) residues.

7. The composition according to claim 1, further comprising an agriculturally acceptable carrier and/or formulation adjuvant, and optionally, a surfactant.

8. A method of controlling or preventing phytopathogenic diseases, especially phytopathogenic fungi, on useful plants or on propagation material thereof, which comprises applying to the useful plants, the locus thereof or propagation material thereof a composition as defined in claim 1.

9. The method according to claim 8, wherein the component (A) is applied at a rate of from 25 g a.i./ha to 500 g a.i./ha in association with 10 g a.i./ha to 500 g a.i./ha of component (B).

10. The method according to claim 8, wherein the phytophathogenic fungi are selected from the group consisting of Alternaria, Botrytis, Cercospora, Colletotrichum, Corynespora, Guignardia, Mycosphaerella, Monilinia, Penicillium, Phakopsora, Phomopsis, Podosphaera, Pseudopezicula, Septoria, Uncinula and Venturia.

11. The method according to claim 8, wherein the useful plant is selected from grains, fruits and tree nuts, vegetables, field crops, oil seed crops, forage crops, forest plants, horticulture crops, floriculture, greenhouse and nursery plants, propagative materials, culinary herbs and spices, and medicinal herbs.

12. The method according to claim 8, wherein the useful plant is selected from the group consisting of wheat, barley, rice, soybean, apples, almonds, cherries, raspberries, grapes, cucumbers, peanuts, tomatoes, strawberries, citrus and bananas.

13. The method according to claim 8, wherein the components (A) and (B) as defined in any one of claims 1 to 7 are applied in a sequential manner.

14. Use of a composition comprising component (A) and component (B) as defined in claim 1 as a fungicide.

Description

BIOLOGICAL EXAMPLES

[0228] The compositions according to the invention are tested for their biological (fungicidal) activity using application rates wherein the component (A) is applied at a rate of from 25 g a.i./ha to 500 g a.i./ha in association with 10 g a.i./ha to 500 g a.i./ha of component (B).

[0229] The compositions according to the invention are tested for their biological (fungicidal) activity as dimethylsulfoxide (DMSO) solutions using one or more of the following protocols (Examples 1-1 and 1-2). A standard description of the liquid culture tests is provided in Example 1.

[0230] Aureobasidin A and its synthesis are known from Takesako et al., The Journal of Antibiotics, 1991, 44, 919-924. Aureobasidin A is separated from the fermentation broth by extraction with ethyl acetate, followed by extraction of the ethyl acetate concentrate with a mixture of MeOH:H.sub.2O (80% by volume) and cyclohexane (20% by volume), and purified by silica gel column chromatography (silica-gel, elution with hexane:ethyl acetate) followed by reverse phase column chromatography (RP18, elution with acetonitrile:H.sub.2O). As already indicated, components (B) of the compositions are known and are commercially available and/or can be prepared using procedures known in the art and/or procedures reported in the literature.

Example 1: Liquid Culture Tests in Well Plates

[0231] Mycelia fragments or conidia suspensions of a fungus, prepared either freshly from liquid cultures of the fungus or from cryogenic storage, are directly mixed into nutrient broth. DMSO solutions of the test compound (max. 10 mg/mL) is diluted with 0.025% Tween20 by factor 50 and 10 μL of this solution is pipetted into a microtiter plate (96-well format). The nutrient broth containing the fungal spores/mycelia fragments is then added to give an end concentration of the tested compound. The test plates are incubated in the dark at 24° C. and 96% relative humidity (rh). The inhibition of fungal growth is determined photometrically and visually after 3-7 days, depending on the pathosystem, and percent antifungal activity relative to the untreated check is calculated.

Example 1-1: Botrytis cinerea (Gray Mould)

[0232] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of the test compositions into a microtiter plate (96-well format), the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically after 72 hours.

Example 1-2: Alternaria solani (Early Blight of Tomato/Potato)

[0233] Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a DMSO solution of the test compositions into a microtiter plate (96-well format) the nutrient broth containing the fungal spores was added. The test plates were incubated at 24° C. and the inhibition of growth was determined photometrically after 48 hours.

Results

[0234] Results from the tests outlined above are shown below in Tables 1 to 18. These data show that synergistic fungicidal activity is observed for the combination of Aureobasidin A and another active ingredient of component (B) against Botrytis cinerea and Alternaria solani at certain weight ratios. According to COLBY, in mathematical terms the synergism factor SF corresponds to O/E. In the agricultural practice an SF of 1.1 indicates significant improvement over the purely complementary addition of activities (expected activity), while an SF of <0.9 in the practical application routine signals a loss of activity compared to the expected activity.

TABLE-US-00003 TABLE 1 Fungicidal activity of a composition of Aureobasidin A and quinofumelint (B-1) agains Botrytis cinerea as described in Example 1-1 above. Aureo- Expected basidin Ratio (A) (B) (additive) Combined A com- inhibi- inhibi- activity inhibition (A) (B-1) pound tion tion (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0050 18 0.0100 27 0.0200 27 0.0003 27 0.0005 37 0.0010 52 0.0050 0.0003 20:1 40 45 0.0100 0.0005 20:1 54 63 0.0200 0.0010 20:1 65 74

TABLE-US-00004 TABLE 2 Fungicidal activity of a composition of Aureobasidin A and quinofumelin (B-1) against Alternaria solani as described in Example 1-2 above. Aureo- Expected basidin Ratio (A) (B) (additive) Combined A com- inhibi- inhibi- activity inhibition (A) (B-1) pound tion tion (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0200 32 0.0010 0 0.0200 0.0010 20:1 32 43

TABLE-US-00005 TABLE 3 Fungicidal activity of a composition of Aureobasidin A and N- [(1R)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3- carboxamide/N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro- quinoline-3-carboxamide (B-2) against Botrytis cinerea as described in Example 1-1 above. Aureo- Expected basidin Ratio (A) (B) (additive) Combined A com- inhibi- inhibi- activity inhibition (A) (B-2) pound tion tion (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0025 7 0.0050 1 0.0003  2 0.0006 35 0.0050 70 0.0025 0.0003 8:1  9 45 0.0025 0.0050 1:2 72 80 0.0050 0.0006 8:1 36 60

TABLE-US-00006 TABLE 4 Fungicidal activity of a composition of Aureobasidin A and N-[(1R)-1-benzyl-1,3-dimethyl- butyl]-8-fluoro-quinoline-3-carboxamide/N-[(1S)-1-benzyl-1,3-dimethyl-butyl]-8-fluoro-quinoline-3- carboxamide (B-2) against Alternaria solani as described in Example 1-2 above. Expected Combined Aureobasidin A Ratio (A) (B) (additive) inhibition (A) (B-2) compound inhibition inhibition activity (observed) (ppm) (ppm) (A):(B) (%) (%) (Colby) (%) (%) 0.0100 17 0.0200 17 0.0400 36 0.0025 0 0.0050 10 0.0100 52 0.0100 0.0100 1:1 61 69 0.0200 0.0025 8:1 17 49 0.0200 0.0050 4:1 25 51 0.0400 0.0050 8:1 42 60

TABLE-US-00007 TABLE 5 Fungicidal activity of a composition of Aureobasidin A and N-[(1R)-1-benzyl-3,3,3-trifluoro-1- methyl-propyl]-8-fluoro-quinoline-3-carboxamide/N-[(1S)-1-benzyl-3,3,3-trifluoro-1-methyl-propyl]-8- fluoro-quinoline-3-carboxamide (B-3) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-3) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0050 20 0.0100 22 0.0006 10 0.0012 32 0.0050 52 0.0050 0.0006 8:1 29 41 0.0100 0.0012 8:1 47 63 0.0100 0.0050 2:1 63 70

TABLE-US-00008 TABLE 6 Fungicidal activity of a composition of Aureobasidin A and N-[(1R)-1-benzyl-3-chloro-1- methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide/N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8- fluoro-quinoline-3-carboxamide (B-4) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-4) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0050 18 0.0100 18 0.0200 29 0.0006 33 0.0012 46 0.0025 60 0.0050 0.0006 8:1 45 53 0.0100 0.0012 8:1 56 73 0.0200 0.0025 8:1 72 82

TABLE-US-00009 TABLE 7 Fungicidal activity of a composition of Aureobasidin A and N-[(1R)-1-benzyl-3-chloro-1- methyl-but-3-enyl]-8-fluoro-quinoline-3-carboxamide/N-[(1S)-1-benzyl-3-chloro-1-methyl-but-3-enyl]-8- fluoro-quinoline-3-carboxamide (B-4) against Alternaria solani as described in Example 1-2 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-4) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0050 5 0.0050 32 0.0050 0.0050 1:1 36 41

TABLE-US-00010 TABLE 8 Fungicidal activity of a composition of Aureobasidin A and 1-(6,7-dimethylpyrazolo[1,5- a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline (B-5) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-5) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0003 9 0.0006 0 0.0012 9 0.0025 0 0.0050 29 0.0100 28 0.0200 29 0.0006 17 0.0012 40 0.0025 57 0.0050 75 0.0003 0.0006 1:2 24 40 0.0006 0.0012 1:2 40 53 0.0012 0.0025 1:2 61 72 0.0025 0.0012 2:1 40 46 0.0025 0.0025 1:1 57 68 0.0025 0.0050 1:2 75 84 0.0050 0.0006 8:1 41 48 0.0100 0.0012 8:1 56 67 0.0200 0.0025 8:1 69 77

TABLE-US-00011 TABLE 9 Fungicidal activity of a composition of Aureobasidin A and 1-(6,7-dimethylpyrazolo[1,5- a]pyridin-3-yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline (B-5) against Alternaria solani as described in Example 1-2 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-5) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0012 0 0.0025 11 0.0100 14 0.0200 14 0.0012 30 0.0025 56 0.0012 0.0025 1:2 56 70 0.0025 0.0025 1:1 61 69 0.0100 0.0012 8:1 39 50 0.0200 0.0025 8:1 62 78

TABLE-US-00012 TABLE 10 Fungicidal activity of a composition of Aureobasidin A and 1-(6,7-dimethylpyrazolo[1,5- a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline (B-6) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-6) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0001 0 0.0002 0 0.0003 0 0.0006 9 0.0012 0 0.0025 12 0.0050 12 0.0006 25 0.0012 34 0.0025 68 0.0050 84 0.0001 0.0006 1:8 25 70 0.0002 0.0006 1:4 25 49 0.0002 0.0012 1:8 34 85 0.0003 0.0012 1:4 34 66 0.0003 0.0025 1:8 68 92 0.0006 0.0006 1:1 32 40 0.0006 0.0012 1:2 40 48 0.0006 0.0025 1:4 71 80 0.0006 0.0050 1:8 86 97 0.0012 0.0006 2:1 25 47 0.0012 0.0012 1:1 34 63 0.0025 0.0012 2:1 42 62 0.0025 0.0025 1:1 72 86 0.0050 0.0025 2:1 72 80

TABLE-US-00013 TABLE 11 Fungicidal activity of a composition of Aureobasidin A and 1-(6,7-dimethylpyrazolo[1,5- a]pyridin-3-yl)-4,4,6-trifluoro-3,3-dimethyl-isoquinoline (B-6) against Alternaria solani as described in Example 1-2 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-6) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0001 9 0.0002 0 0.0003 8 0.0006 11 0.0025 20 0.0006 22 0.0012 39 0.0025 59 0.0001 0.0006 1:8 29 64 0.0002 0.0006 1:4 22 42 0.0002 0.0012 1:8 39 82 0.0003 0.0012 1:4 44 64 0.0003 0.0025 1:8 63 88 0.0006 0.0025 1:4 64 83 0.0025 0.0012 2:1 51 59

TABLE-US-00014 TABLE 12 Fungicidal activity of a composition of Aureobasidin A and 4,4-difluoro-3,3-dimethyl-1-(7- methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline (B-7) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-7) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0001 0 0.0002 5 0.0003 1 0.0006 6 0.0025 0 0.0006 18 0.0012 40 0.0001 0.0006 1:8 18 47 0.0002 0.0012 1:8 42 58 0.0003 0.0012 1:4 40 47 0.0006 0.0012 1:2 43 52 0.0025 0.0012 2:1 40 53

TABLE-US-00015 TABLE 13 Fungicidal activity of a composition of Aureobasidin A and 4,4-difluoro-3,3-dimethyl-1- (7-methylpyrazolo[1,5-a]pyridin-3-yl)isoquinoline (B-7) against Alternaria solani as described in Example 1-2 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-7) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0025 0 0.0100 63 0.0025 0.0100 1:4 63 73

TABLE-US-00016 TABLE 14 Fungicidal activity of a composition of Aureobasidin A and 1-(4,5-dimethylbenzimidazol-1- yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline (B-8) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-8) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0025 3 0.0050 13 0.0100 19 0.0003 22 0.0006 40 0.0012 50 0.0025 0.0003 8:1 24 44 0.0025 0.0006 4:1 42 50 0.0050 0.0006 8:1 48 63 0.0100 0.0012 8:1 59 71

TABLE-US-00017 TABLE 15 Fungicidal activity of a composition of Aureobasidin A and 1-(4,5-dimethylbenzimidazol-1- yl)-4,4,5-trifluoro-3,3-dimethyl-isoquinoline (B-8) against Alternaria solani as described in Example 1-2 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-8) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0006 0 0.0050 3 0.0100 27 0.0012 38 0.0006 0.0012 1:2 38 49 0.0050 0.0012 4:1 40 51 0.0100 0.0012 8:1 55 61

TABLE-US-00018 TABLE 16 Fungicidal activity of a composition of Aureobasidin A and 1-(4,5-dimethylbenzimidazol-1- yl)-4,4-difluoro-3,3-dimethyl-isoquinoline (B-9) against Botrytis cinerea as described in Example 1-1 above. Expected (additive) Combined Aureobasidin A Ratio (A) (B) activity inhibition (A) (B-9) compound inhibition inhibition (Colby) (observed) (ppm) (ppm) (A):(B) (%) (%) (%) (%) 0.0006 9 0.0025 9 0.0050 9 0.0100 27 0.0003 9 0.0006 28 0.0012 45 0.0006 0.0006 1:1 34 41 0.0025 0.0003 8:1 17 42 0.0025 0.0006 4:1 34 48 0.0050 0.0006 8:1 34 60 0.0050 0.0012 4:1 50 56 0.0100 0.0012 8:1 60 68

TABLE-US-00019 TABLE 17 Fungicidal activity of a composition of Aureobasidin A and 1-(4,5-dimethylbenzimidazol-1- yl)-4,4-difluoro-3,3-dimethyl-isoquinoline (B-9) against Alternaria solani as described in Example 1-2 above. Expected Combined Aureobasidin A Ratio (A) (B) (additive) inhibition (A) (B-9) compound inhibition inhibition activity (observed) (ppm) (ppm) (A):(B) (%) (%) (Colby) (%) (%) 0.0100 14 0.0012 24 0.0100 0.0012 8:1 35 42

TABLE-US-00020 TABLE 18 Fungicidal activity of a composition of Aureobasidin A and 6-chloro-4,4-difluoro-3,3- dimethyl-1-(4-methylbenzimidazol-1-yl)isoquinoline (B-10) against Botrytis cinerea as described in Example 1-1 above. Expected Combined Aureobasidin A Ratio (A) (B) (additive) inhibition (A) (B-10) compound inhibition inhibition activity (observed) (ppm) (ppm) (A):(B) (%) (%) (Colby) (%) (%) 0.0050 17 0.0100 17 0.0200 32 0.0006 21 0.0012 39 0.0025 49 0.0050 0.0006 1:1 34 50 0.0100 0.0012 1:1 49 59 0.0200 0.0025 1:1 66 73