WO2025093604A1

WO2025093604A1 - Fungicidal compositions

Info

Publication number: WO2025093604A1
Application number: PCT/EP2024/080692
Authority: WO
Inventors: Hanno Christian Wolf; Dimitrios PAPASOTIRIOU; Dianne IRWIN
Original assignee: Syngenta Crop Protection AG Switzerland
Current assignee: Syngenta Crop Protection AG Switzerland
Priority date: 2023-10-31
Filing date: 2024-10-30
Publication date: 2025-05-08
Anticipated expiration: 2026-04-30

Abstract

The present invention relates to a fungicidal composition comprising a component A comprising one or more streptothricins represented by formula (I) or stereoisomers thereof as defined in claim 1, and a component B comprising a compound represented by formula (II) or a stereoisomer thereof as defined in claim 1. The invention further relates to a method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on a plant, the locus thereof, or on propagation material thereof, the method comprising applying the composition to the plant, locus thereof, or propagation material thereof and a coated plant propagation material comprising the composition.

Description

FUNGICIDAL COMPOSITIONS

The present invention relates to new fungicidal compositions for the control of fungi. Methods of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on a plant or on propagation material thereof are also disclosed.

Background

Streptothricins (also known as nourseothricins, racemomycins, geomycins, and yazumycins) are antibiotics produced by various Streptomyces species and were first isolated from Streptomyces lavendulae (Waksman S.A. and Woodruff H.B., 1942, doi: 10.3181/00379727-49-13515).

Streptothricins comprise a variable beta-lysine peptide chain, which is used to identify the various streptothricins (e.g. A, B, C, D, E, F, and X). Streptothricins show antibacterial and antifungal activities and can be used to control bacterial and fungal diseases in the field of agriculture. Streptothricins inhibit protein synthesis by inducing miscoding.

Venturicidins (also known as aabomycins) are a group of antibiotics produced by various Streptomyces species. The first member, Venturicidin A, was first isolated from Streptomyces sp. in 1961 (Rhodes A. et al., 1961 , doi: doi: 10.1038/192952a0). Venturicidins have been shown to control phytopathogenic fungi (Shaaban K.A. et al., 2014, doi: 10.1038/ja.2013.113; Wang et al., 2022, doi: 10.3390/microorganisms10081612). Venturicidin A is reported to inhibit bacterial and mitochondrial ATP-synthase complexes.

However, streptothricins and venturicidins are not necessarily sufficiently effective by themselves and are at risk for the development of resistance. Hence, there remains a need for improved antifungal compositions for the control of phytopathogenic fungi.

Brief description of the invention

The present invention discloses an unexpected synergistic fungicidal effect of a composition comprising one or more streptothricins represented by formula (I) or stereoisomers thereof, and a compound represented by formula (II) or a stereoisomer thereof, in particular wherein the compound is Venturicidin A.

According to another aspect of the invention, there is provided a method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi, preferably phytopathogenic fungi, on a plant, locus thereof, or on plant propagation material thereof, the method comprising applying to the plant, locus thereof, or plant propagation material thereof, a composition as defined according to the invention. Preferably, the method comprises applying to the plant or locus thereof a composition according to the invention, more preferably to the plant. Preferably, the method comprises applying to the propagation material of the plant a composition according to the invention.

According to another aspect of the invention, there is provided a coated plant propagation material, wherein the coating comprises a composition according to the invention.

According to another aspect of the invention, there is provided the use of a composition comprising the components A and B as defined according to the invention as a fungicide, wherein the use is not for the treatment of the human or animal body by surgery or therapy . It has been found that a composition comprising component A comprising streptothricins represented by formula (I) or stereoisomers thereof, preferably wherein n is an integer selected from 1 to 4, and a component B comprising a compound represented by formula (II) or a stereoisomer thereof, a compound represented by formula (III) or a stereoisomer thereof, or a compound represented by formula (IV) or a stereoisomer thereof, preferably wherein the compound is Venturicidin A, surprisingly and substantially may enhance the effectiveness of the latter component against fungi, and vice versa. Additionally, the compositions of the invention may be effective against a wider spectrum of such fungi than can be combated with the individual active ingredients when used alone.

The benefits provided by certain fungicidal compositions according to the invention may also include, inter alia, advantageous levels of biological activity for protecting plants against diseases that are caused by fungi or superior properties for use as agrochemical active ingredients (for example, greater biological activity, an advantageous spectrum of activity, an increased safety profile, improved physico-chemical properties, or increased biodegradability).

Detailed description of the invention

The present invention relates to a fungicidal composition comprising:

(i) a component A, wherein the component A comprises one or more streptothricins represented by formula (I) or stereoisomers thereof:

(ii) a component B, wherein the component B comprises a compound represented by formula (II) or a stereoisomer thereof:

wherein R¹ is selected from CONH2 and H; wherein R², R⁴, R⁶, and R⁷ are each independently selected from CHs and H; wherein R³ is selected from OH and H; and wherein R⁵ is selected from CH2CH3 and CH3

The component A comprises one or more streptothricins represented by formula (I) or stereoisomers thereof:

Formula (I) as used herein may also be represented by formula (la):

Preferably, the component A comprises the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is an integer selected from 1 to 4, more preferably wherein n is 3 or 4.

Preferably, the component A comprises the streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 3 and 4; or wherein the component A comprises the streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 and 3. Preferably, the component A according to the invention comprises the streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 , 2, 3, and 4. Suitably, the component A according to the invention comprises the streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 , 2, 3, 4, 5, and 6.

Preferably, the component A comprises a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 3, and a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 4. Preferably, the component A comprises a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 1 , and a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 3. Preferably, the component A comprises a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 1 , a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 2, a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 3, and a streptothricin represented by formula (I) or a stereoisomer thereof, wherein n is 4.

Typically, streptothricin A is herein represented by formula (I), wherein n is 6, streptothricin B is herein represented by formula (I), wherein n is 5, streptothricin C is herein represented by formula (I), wherein n is 4, streptothricin D is herein represented by formula (I), wherein n is 3, streptothricin E is herein represented by formula (I), wherein n is 2, streptothricin F is herein represented by formula (I), wherein n is 1 , and streptothricin X is herein represented by formula (I), wherein n is 7. Preferably, the component A according to the invention comprises one or more streptothricins selected from the group consisting of: streptothricin A, streptothricin B, streptothricin C, streptothricin D, streptothricin E, streptothricin F, and streptothricin X, or stereoisomers thereof. Preferably, the component A according to the invention comprises streptothricin C, streptothricin D, streptothricin E and/or streptothricin F, or stereoisomers thereof, more preferably streptothricin C and/or streptothricin D, or stereoisomers thereof.

Suitably, the component A additionally comprises one or more streptothricins selected from the group consisting of: streptothricin A, streptothricin B, streptothricin C, streptothricin D, streptothricin E, streptothricin F, and streptothricin X, or stereoisomers thereof.

Suitably, the component A comprises two, three, four, or more streptothricins of formula (I) or stereoisomers thereof as defined above. Preferably, the component A comprises streptothricin C, D, E, or F, and one or more other streptothricins of formula (I) or stereoisomers thereof as defined above.

Streptothricins (also known as nourseothricins, racemomycins, geomycins, and yazumycins) are antibiotics produced by various Streptomyces species, but first isolated from Streptomyces lavendulae. Streptothricins comprise a variable beta-lysine peptide chain, which is used to identify the various streptothricins (e.g. A, B, C, D, E, F, and X). Streptothricins show antibacterial and antifungal activities and can be used to control bacterial and fungal diseases in the field of agriculture. Streptothricins inhibit protein synthesis by inducing miscoding.

Nourseothricin (also known as clonNAT) is a composition comprising streptothricins C, D, E, and F produced by fermentation of Streptomyces noursei. It is commercially available. Nourseothricin sulfate is registered under CAS 96736-11-7 and commercially available. Zhongshengmycin is a composition comprising streptothricins A, B, C, D, E, F, and X produced by fermentation of Streptomyces lavendulae var. hainanensis. Zhongshengmycin is registered under CAS 861228-39-9 and commercially available. Streptothricins, in particular streptothricin F, can also be chemically synthesized by procedures known in the art.

As used herein, the term “fermentation broth” refers to a composition obtained from a process of fermentation of a strain. In another embodiment according to the invention, the component A is a fermentation broth comprising two or more streptothricins of formula (I) or stereoisomers thereof as defined above. In an embodiment according to the invention, the component A is a fermentation broth comprising streptothricin C, D, E, or F, and one or more other streptothricins of formula (I) or stereoisomers thereof as defined above. In an embodiment according to the invention, the component A is a fermentation broth comprising streptothricins C and D or stereoisomers thereof, or streptothricins D and F or stereoisomers thereof. Preferably, the component A is a fermentation broth comprising streptothricins C, D, E, and F, or stereoisomers thereof.

The compounds and compositions of the components A and B are referred to herein and above by a so-called "ISO common name" or another "common name" being used in individual cases or a trademark name. The component A and B compounds and 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.

The fungicidal compositions according to the invention comprise a component B, wherein the component B comprises a compound represented by formula (II) or a stereoisomer thereof:

wherein R², R⁴, R⁶, and R⁷ are each independently selected from CHs and H; wherein R³ is selected from OH and H; and wherein R⁵ is selected from CH2CH3 and CH3

Suitably, the component B may comprise instead of or in addition to a compound represented by formula (II) or a stereoisomer thereof: a compound represented by formula (III) or a stereoisomer thereof:

wherein R¹ is selected from CONH2 and H; or a compound represented by formula (IV) or a stereoisomer thereof:

Preferably, the component B comprises the compound represented by formula (II) or a stereoisomer thereof, wherein R¹ is selected from CONH2 and H; R² is selected from CH3 and H; R³ is H; R⁴ is CH3; R⁵ is selected from CH2CH3 and CH3; R⁶ is H; and R⁷ is H. More preferably, R¹ is selected from CONH2 and H; R² is CH₃; R³ is H; R⁴ is CH₃; R⁵ is CH₃; R⁶ is H; and R⁷ is H.

Suitably, the component B comprises a compound selected from the group consisting of: Venturicidin A, Venturicidin B, Venturicidin C, Venturicidin D, Venturicidin E, Venturicidin F, Venturicidin G, Venturicidin H, Venturicidin I, Venturicidin J, X-14952B, 17-Hydroxyventuricidin A (YP- 02259L-C), Irumamycin (AM 3603), and 3'-O-Decarbamoylirumamycin(AM-3603A-3), or stereoisomers thereof. Suitably, the component B comprises a compound selected from the group consisting of: Venturicidin A, Venturicidin B, Venturicidin C, Venturicidin D, Venturicidin F, Venturicidin G, Venturicidin H, Venturicidin I, Venturicidin J, X-14952B, and 17-Hydroxyventuricidin A (YP-02259L- C), or stereoisomers thereof. Suitably, the component B comprises a compound selected from the group consisting of: Venturicidin A, Venturicidin D, and Venturicidin F, or stereoisomers thereof. Suitably, the component B comprises a compound selected from the group consisting of: Venturicidin A, Venturicidin B, Venturicidin G, Venturicidin H, Venturicidin I, and Venturicidin J, or stereoisomers thereof. Preferably, the component B comprises a compound selected from the group consisting of: Venturicidin A, Venturicidin B, Venturicidin C, and Venturicidin I. Preferably, the component B comprises a compound selected from the group consisting of: Venturicidin A, Venturicidin B, and Venturicidin C. More preferably, the component B comprises Venturicidin A and/or Venturicidin B. Even more preferably, the component B according to the invention comprises Venturicidin A.

Suitably, the compound of formula (II) is selected from a compound 1.001 to 1.010 listed in Table A below. The following lists provides definitions, including preferred definitions, for substituents R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ with reference to the compounds of formula (II) of the present invention.

For any one of these substituents, any of the definitions given below may be combined with any definition of any other substituent given below or elsewhere in this document.

Table A: This table discloses 10 compounds of formula (II), wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are as set forth in Table A below. “ID” indicates the (common) name of the structure is also known as.

Table A

Preferably, the compound of formula (II) is Venturicidin A or a stereoisomer thereof, typically represe

represented by formula (lib):

represented by formula (lie):

Suitably, the compound of formula (II) is Venturicidin I or a stereoisomer thereof, typically represented by formula (lid):

represented by formula (He):

Preferably, the compound of formula (III) is Irumamycin (AM 3603) or a stereoisomer thereof, typically represented by formula (Illa):

Preferably, the compound of formula (III) is 3'-0-Decarbamoylirumamycin (AM-3603A-3) or a stereoisomer thereof, typically represented by formula (lllb):

Preferably, the compound of formula (IV) is Venturicidin E or a stereoisomer thereof. Venturicidins (also known as aabomycins), herein represented by the compounds of formula (II), formula (III), formula (IV), and stereoisomers thereof, are a group of antibiotics and produced by various Streptomyces species. The first member, Venturicidin A, was first isolated from Streptomyces sp. in 1961. Venturicidins have been shown to control phytopathogenic fungi. Venturicidin A is reported to inhibit bacterial and mitochondrial ATP-synthase complexes. Venturicidins can be produced by fermentation of various Streptomyces species as reported in literature. Venturicidin A is registered under CAS 33538-71-5 and commercially available. Venturicidin B is registered under CAS 33538-72-6 and commercially available.

In another embodiment according to the invention, the component B is a fermentation broth comprising a compound of formula (II) or a stereoisomer thereof, as defined above, preferably wherein the compound is Venturicidin A.

In another embodiment according to the invention, the component B is a fermentation broth comprising two or more compounds of formula (II) or stereoisomers thereof as defined above. In an embodiment according to the invention, the component B is a fermentation broth comprising Venturicidin A and one or more other compounds of formula (II) or stereoisomers thereof as defined above, preferably wherein the one or more other compounds of formula (II) is Venturicidin B.

Preferably, the composition according to the invention comprises the component A of from 10% to 99.9% by weight, preferably of from 20% to 99.9% by weight, more preferably of from 40% to 99.9% by weight of streptothricin C or a stereoisomer thereof, and of from 0.1 % to 90% by weight, or of from 0.1 % to 80% by weight, or of from 0.1 % to 60% by weight of the one or more other streptothricins represented by formula (I) or stereoisomers thereof. Preferably, the composition according to the invention comprises the component A of at least 10% by weight, preferably of at least 20% by weight, more preferably of at least 30% or 40%, even more preferably of at least 50%, 60%, or 70% by weight of streptothricin C or a stereoisomer thereof.

Suitably, the composition according to the invention comprises the component A of from 10% to 99.9% by weight, or of from 20% to 99.9% by weight, or of from 40% to 99.9% by weight of streptothricin D or a stereoisomer thereof, and of from 0.1 % to 90% by weight, or of from 0.1 % to 80% by weight, or of from 0.1 % to 60% by weight of the one or more other streptothricins represented by formula (I) or stereoisomers thereof. Suitably, the composition according to the invention comprises the component A of at least 10% by weight, or of at least 20%, 30%, 40%, 50%, 60%, or 70% by weight, of streptothricin D or a stereoisomer thereof.

Preferably, the composition according to the invention comprises the component A of from 10% to 99.9% by weight, preferably of from 20% to 99% by weight, more preferably of from 60% to 95% by weight of the streptothricins C and D, and of from 0.1 % to 30% by weight, or of from 2% to 25% by weight, or of from 5% to 22% by weight of the streptothricins E and F.

Preferably, the composition according to the invention comprises the component A of from 10% to 99.9% by weight, preferably of from 20% to 99% by weight, more preferably of from 30% to 95% by weight of the one or more streptothricins C or D, and of from 0.1 % to 30% by weight, or of from 2% to 20% by weight, or of from 5% to 15% by weight of the one or more streptothricins E or F.

Suitably, the composition according to the invention has a weight ratio of the component A to the component B of from 60000:1 to 1 :1000, of from 30000:1 to 1 :1000, of from 20000:1 to 1 :1000, of from 10000:1 to 1 :1000, of from 5000:1 to 1 :1000, of from 1000:1 to 1 :1000, of from 1000:1 to 1 :400, of from 1000:1 to 1 :200, of from 1000:1 to 1 :100, of from 1000:1 to 1 :80, of from 1000:1 to 1 :40, of from 1000:1 to 1 :20, of from 1000:1 to 1 :10, of from 1000:1 to 1 :4, of from 400:1 to 1 :1000, of from 400:1 to 1 :400, of from 400:1 to 1 :200, of from 400:1 to 1 :100, of from 400:1 to 1 :80, of from 400:1 to 1 :40, of from 400:1 to 1 :20, of from 400:1 to 1 :10, of from 400:1 to 1 :4, of from 200:1 to 1 :1000, of from 200:1 to 1 :400, of from 200:1 to 1 :200, of from 200:1 to 1 :100, of from 200:1 to 1 :80, of from 200:1 to 1 :40, of from 200:1 to 1 :20, of from 200:1 to 1 :10, of from 200:1 to 1 :4, of from 100:1 to 1 :1000, of from 100:1 to 1 :400, of from 100:1 to 1 :200, of from 100:1 to 1 :100, of from 100:1 to 1 :80, of from 100:1 to 1 :40, of from 100:1 to 1 :20, of from 100:1 to 1 :10, of from 100:1 to 1 :4, of from 80:1 to 1 :1000, of from 80:1 to 1 :400, of from 80:1 to 1 :200, of from 80:1 to 1 :100, of from 80:1 to 1 :80, of from 80:1 to 1 :40, of from 80:1 to 1 :20, of from 80:1 to 1 :10, of from 80:1 to 1 :4, of from 40:1 to 1 :1000, of from 40:1 to 1 :400, of from 40:1 to 1 :200, of from 40:1 to 1 :100, of from 40:1 to 1 :80, of from 40:1 to 1 :40, of from 40:1 to 1 :20, of from 40:1 to 1 :10, of from 40:1 to 1 :4, of from 20:1 to 1 :1000, of from 20:1 to 1 :400, of from 20:1 to 1 :200, of from 20:1 to 1 :100, of from 20:1 to 1 :80, of from 20:1 to 1 :40, of from 20:1 to 1 :20, of from 20:1 to 1 :10, of from 20:1 to 1 :4, of from 10:1 to 1 :1000, of from 10:1 to 1 :400, of from 10:1 to 1 :200, of from 10:1 to 1 :100, of from 10:1 to 1 :80, of from 10:1 to 1 :40, of from 10:1 to 1 :20, of from 10:1 to 1 :10, of from 10:1 to 1 :4, of from 4:1 to 1 :4.

Preferably, the composition according to the invention has a weight ratio of the component A to the component B of from 60000:1 to 1 :1000, wherein the component A comprises streptothricins C and/or D and the component B comprises Venturicidin A. Suitably, the weight ratio is of from 10000:1 to 1 :1000, of from 1000:1 to 1 :1000, of from 200:1 to 1 :200, or of from 50:1 to 1 :50.

Preferably, the composition according to the invention has a weight ratio of the component A to the component B of from 1000:1 to 1 :1000, wherein the component A comprises streptothricins C and/or D and one or more other streptothricins of formula (I) or stereoisomers thereof. Suitably, the weight ratio is of from 200:1 to 1 :200 or of from 50:1 to 1 :50.

Suitably, the component A is a fermentation broth comprising one or more streptothricins represented by formula (I) or stereoisomers thereof as defined above. Suitably, the component B is a fermentation broth comprising a compound represented by formula (II) or stereoisomers thereof, as defined above. Suitably, the composition according to the invention is a fermentation broth.

Suitably, the component A is a fermentation broth comprising one or more streptothricins represented by formula (I) or stereoisomers thereof as defined above, and the component B comprises Venturicidin A. Preferably, the component A is a fermentation broth comprising streptothricins C and/or D, and the component B comprises Venturicidin A. Preferably, the component A is a fermentation broth comprising streptothricins C, D, E, and F, and the component B comprises Venturicidin A. Suitably, the component A is a fermentation broth comprising streptothricins C and D, and the component B comprises Venturicidin A, Venturicidin B, Venturicidin C, or Venturicidin I. Suitably, the component A is a fermentation broth comprising streptothricins C, D, E, and F, and the component B comprises Venturicidin A, Venturicidin B, Venturicidin C, or Venturicidin I. Suitably, the component A is a fermentation broth comprising streptothricins C and/or D, and the component B comprises Venturicidin A, wherein the weight ratio of the component A to the component B is of from 60000:1 to 1 :1000, of from 10000:1 to 1 :1000, of from 1000:1 to 1 :1000, of from 30000:1 to 1 :100, of from 5000:1 to 1 :100, of from 100:1 to 1 :100, of from 40:1 to 1 :40, or of from 4:1 to 1 :4.

Suitably, the component A is a fermentation broth comprising streptothricins C, D, E, and F, and the component B comprises Venturicidin A, wherein the weight ratio of the component A to the component B is of from 60000:1 to 1 :1000, of from 10000:1 to 1 :1000, of from 1000:1 to 1 :1000, of from 30000:1 to 1 :100, of from 5000:1 to 1 :100, of from 100:1 to 1 :100, of from 40:1 to 1 :40, or of from 4:1 to 1 :4.

The compounds of formula (I) or stereoisomers thereof can be prepared by methods known to the person skilled in the art. The compounds of formula (I) can be either purchased or prepared using synthetic or semi-synthetic chemistry or fermentation processes.

For example, the compounds of formula (I) or stereoisomers thereof, in particular wherein n is 1 , can be prepared by methods known in Kusumoto et al., 1982, “Total synthesis of antibiotic streptothricin F”, Tetrahedron Letters, doi: 10.1016/S0040-4039(00)87506-1 , and Dowgiallo et al., 2022, “The convergent total synthesis and antibacterial profile of the natural product streptothricin F”, Chemical Science, doi: 10.1039/D1 SC06445B.

For example, a fermentation broth or a composition comprising one or more compounds of formula (I) or stereoisomers thereof can be obtained from a process of fermentation of a strain of Streptomyces, generally by a strain of Streptomyces noursei or Streptomyces lavendulae. The fermentation broth may not require purification. Alternatively, one or more compounds of formula (I) can be isolated from the fermentation broth and purified, e.g. by chromatography using a sorbent (e.g., silica and reverse phase silica gels, optically active sorbents, resins) or one or more solvents (e.g., partitioning, counter current separation, mixture of polyphasic solvents) or other chemical means (e.g., crystallization, recrystallization, salt formation, and precipitation) to achieve the final degree of purity.

The compounds of formula (II), (III), (IV), or stereoisomers thereof, in particular Venturicidins A, B, C, D, E, F, G, H, I, and J, can be prepared by methods known to the person skilled in the art. The compounds of formula (II), (III), (IV), or stereoisomers thereof, in particular Venturicidins A, B, C, D, E, F, G, H, I, and J, can be either purchased or prepared using fermentation processes.

For example, a composition or a fermentation broth comprising one or more compounds of formula (II), (IV), or stereoisomers thereof, preferably Venturicidin A, can be obtained from a process of fermentation of a strain of Streptomyces, e.g. by a strain of Streptomyces sp. SN5452, Streptomyces sp. MST-117594, Streptomyces sp. NRRL S-4, Streptomyces sp. MA1078, Streptomyces aureofaciens (DUGGAR), Streptomyces sp. strain US80, Streptomyces sp. 135, or Streptomyces sp. TS-2-2. A composition or a fermentation broth comprising one or more compounds of formula (III), or stereoisomers thereof, can be obtained from a process of fermentation of a strain of Streptomyces subflavus subsp. irumaensis AM-3603 or Streptomyces sp. strain US80. The fermentation broth may not require purification. Alternatively, one or more compounds of formula (II), (III), (IV), or stereoisomers thereof, preferably formula (II), more preferably Venturicidin A and/or B, can be isolated from the fermentation broth and purified, e.g. by chromatography using a sorbent (e.g., silica and reverse phase silica gels, optically active sorbents, resins) or one or more solvents (e.g., partitioning, counter current separation, mixture of polyphasic solvents) or other chemical means (e.g., crystallization, recrystallization, salt formation, and precipitation) to achieve the final degree of purity.

The term “fungicide” as used herein means a compound that controls, modifies, or prevents the growth of fungi. The term “fungicidally effective amount” means the quantity of such a compound or combination of such compounds that is capable of producing an effect on the growth of fungi. Controlling or modifying effects include all deviation from natural development, such as killing, retardation and the like, and prevention includes barrier or other defensive formation in or on a plant to prevent fungal infection.

The term “plants” refers to all physical parts of a plant, including seeds, seedlings, saplings, roots, tubers, stems, stalks, foliage, and fruits.

The term "plant propagation material” denotes all generative parts of a plant, for example seeds or vegetative parts of plants such as cuttings and tubers. It includes seeds in the strict sense, as well as roots, fruits, tubers, bulbs, rhizomes, and parts of plants. Preferably, “plant propagation material” is understood to denote seeds. In a further aspect, the present invention also relates to plant propagation material coated with the compositions according to the invention.

The term “locus” as used herein means fields in or on which plants are growing, or where seeds of cultivated plants are sown, or where seed will be placed into the soil. It includes soil, seeds, and seedlings, as well as established vegetation.

Throughout this document the expression “composition” stands for the various mixtures or combinations of the components A and B (including the above-defined embodiments), for example in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.

The composition according to the invention is effective against harmful microorganisms, such as microorganisms, that cause phytopathogenic diseases, in particular against phytopathogenic fungi.

The composition of the invention may be used to control plant diseases caused by a broad spectrum of fungal plant pathogens in the Basidiomycete, Ascomycete, Oomycete, Deuteromycete, Blastocladiomycete, Chrytidiomycete, Glomeromycete and/or Mucoromycete classes. Hence, the method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi according to the invention may be particularly effective against phytopathogenic fungi selected from the Basidiomycete, Ascomycete, Oomycete, Deuteromycete, Blastocladiomycete, Chrytidiomycete, Glomeromycete and/or Mucoromycete classes.

The compositions and methods according to the invention are particularly effective against phytopathogenic fungi belonging to the following classes: Ascomycetes; Basidiomycetes; Fungi imperfecti (also known as Deuteromycetes); Oomycetes (e.g. Phytophthora, Peronospora, Pseudoperonospora, Albugo, Bremia, Pythium, Pseudosclerospora, Plasmopara), preferably Ascomycetes; Basidiomycetes; Fungi imperfecti.

Preferably, the compositions and methods according to the invention may be effective against phytopathogenic fungi selected from the group consisting of Alternaria, Ascochyta, Botrytis, Cercospora, Cochliobolus sativus, Colletotrichum, Colletotrichum lagenarium, Corynespora, Erysiphe, Erysiphe cichoracearum, Sphaerotheca fuliginea, Fusarium, Fusarium oxysporum, Gaumannomyces graminis, Guignardia, Helminthosporium, Hemileia vastatrix, Magnaporthe, Magnaporthe oryzae, Monilinia, Mycosphaerella, Mycosphaerella arachidis, Phakopsora, Phoma, Phomopsis, Puccinia, Pseudocercosporella, Pseudopezicula, Phragmidium mucronatum, Podosphaera, Pyrenophora, Pyrenophora teres, Pyricularia, Pyricularia oryzae, Ramularia, Ramularia collo-cygni, Rhizoctonia, Rhizoctonia solani, Rhynchosporium secalis, Sclerotinia, Septoria, Septoria tritici, Sphacelotheca reilliana, Tilletia, Urocystis occulta, Uncinula, Ustilago, Venturia, Monilia, and Penicillium.

The compositions and methods of the present invention may be particularly effective against phytopathogenic fungi selected from the group consisting of Alternaria, Botrytis, Cercospora, Colletotrichum, Corynespora, Fusarium, Glomerella, Guignardia, Magnaporthe, Mycosphaerella, Monilinia, Penicillium, Phakopsora, Phomopsis, Podosphaera, Pseudopezicula, Rhizoctonia, Septoria, Uncinula, Venturia, and Zymoseptoria, more preferably selected from the group consisting of: Alternaria, Botrytis, Fusarium, Glomerella, Mycosphaerella, and Zymoseptoria.

The compositions and methods of the present invention may be effective especially against phytopathogenic fungi selected from the group consisting of Alternaria solani, Alternaria alternata, Alternaria porri, Botrytis cinerea, Botrytis aim, Botrytis squamosa, Cercospora capsici, Colletotrichum lagenarium, Corynespora cassiicola, Fusarium culmorum, Fusarium oxysporum, Glomerella lagenarium, Guignardia bidwellii, Magnaporthe oryzae, Monilinia fructicola, Monilinia fructigena, Monilinia laxa, Penicillium digitatum, Penicillium italicum, Penicillium expansum, Phomopsis viticola, Podosphaera leucotricha, Podosphaera xanthii, Pseudopezicula tracheiphila, Rhizoctonia solani, Septoria tritici, Uncinula necator, Venturia inaequalis, and Zymoseptoria tritici, more preferably selected from the group consisting of: Alternaria solani, Alternaria alternata, Alternaria porri, Botrytis cinerea, Botrytis aim, Botrytis squamosa, Cercospora capsici, Colletotrichum lagenarium, Corynespora cassiicola, Fusarium culmorum, Fusarium oxysporum, Glomerella lagenarium, Guignardia bidwellii, Monilinia fructicola, Monilinia fructigena, Monilinia laxa, Mycosphaerella arachidis, Penicillium digitatum, Penicillium italicum, Penicillium expansum, Phomopsis viticola, Podosphaera leucotricha, Podosphaera xanthii, Pseudopezicula tracheiphila, Septoria tritici, Uncinula necator, Venturia inaequalis, and Zymoseptoria tritici, even more preferably selected from the group consisting of: Alternaria solani, Botrytis cinerea, Fusarium culmorum, Glomerella lagenarium, Mycosphaerella arachidis, and Zymoseptoria tritici.

According to the invention “useful plants” typically comprise the following perennial or annual plants: grains; fruits and tree nuts; vegetables; field crops; oil seed crops; forage crops; fiber crops; forest plants; horticulture crops; floriculture, greenhouse and nursery plants; propagative materials; culinary herbs and spices; and medicinal herbs. Preferably, the useful plants are selected from the group consisting of: fruits and tree nuts, vegetables, horticulture crops, and floriculture.

This list does not represent any limitation, however, preferably, the useful plant may be selected from the group consisting of: apples, almonds, cherries, raspberries, grapes, cucumbers, peanuts, tomatoes, strawberries, citrus, and bananas. Suitably, the useful plant may be selected from the group consisting of: grapevines, strawberries, apples, cherries, peaches, nectarines, blueberries, caneberries, tomatoes, potatoes, cucurbits, cucumbers, eggplants, lettuce, beans, brassicas, peas, oilseed rapes, soybeans, sugar beets, sunflowers, rice, peanuts, coffee, ornamental plants, and turfgrass.

Preferred is a method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi, preferably phytopathogenic fungi, according to the invention which comprises applying a composition according to the invention to useful plants.

The term "useful plants" is to be understood as including also useful plants that have been rendered tolerant to herbicides like bromoxynil or classes of herbicides (such as, for example, HPPD inhibitors, ALS inhibitors, for example primisulfuron, prosulfuron and trifloxysulfuron, EPSPS (5-enol- pyrovyl-shikimate-3-phosphate-synthase) inhibitors, GS (glutamine synthetase) inhibitors) as a result of conventional methods of breeding or genetic engineering. An example of a crop that has been rendered tolerant to imidazolinones, e.g. imazamox, by conventional methods of breeding (mutagenesis) is Clearfield® summer rape (Canola). Examples of crops that have been rendered tolerant to herbicides or classes of herbicides by genetic engineering methods include glyphosate- and glufosinate-resistant maize varieties commercially available under the trade names RoundupReady® , Herculex I® and LibertyLink®.

The term "useful plants" is to be understood as including also useful plants which have been so transformed by the use of recombinant DNA techniques that they are capable of synthesizing one or more selectively acting toxins, such as are known, for example, from toxin-producing bacteria. Examples of toxins which can be expressed include 6-endotoxins, vegetative insecticidal proteins (Vip), insecticidal proteins of bacteria colonizing nematodes, and toxins produced by scorpions, arachnids, wasps and fungi.

Some compositions according to the invention have a systemic action and can be used as foliar, soil and seed treatment fungicides.

With the compositions according to the invention it is possible to inhibit or destroy the phytopathogenic microorganisms which occur in plants or in parts of plants (fruit, blossoms, leaves, stems, tubers, roots) in different useful plants, while at the same time the parts of plants which grow later are also protected from attack by phytopathogenic microorganisms. Preferably, the microorganisms are fungi.

The compositions according to the invention can be applied to the phytopathogenic microorganisms, the useful plants, the locus thereof, the propagation material thereof, storage goods or technical materials threatened by microorganism attack. Preferably, the microorganisms are fungi. The compositions according to the invention may be applied before or after infection of the useful plants, the plant propagation material thereof, storage goods or technical materials by the microorganisms. Preferably, the microorganisms are fungi.

The amount of a composition according to the invention to be applied, will depend on various factors, such as the compounds employed; the subject of the treatment, such as, for example plants, soil or seeds; the type of treatment, such as, for example spraying, dusting or seed dressing; the purpose of the treatment, such as, for example prophylactic or therapeutic; the type of fungi to be controlled or the application time.

The compositions comprising component A in combination with the component B can be applied, for example, in a single “ready-mix” form, in a combined spray mixture composed from separate formulations of the single active ingredient components, such as a “tank-mix”, and in a combined use of the single active ingredients when applied in a sequential manner, i.e. one after the other with a reasonably short period, such as a few hours or days.

The compositions according to the invention are preventively and/or curatively valuable active ingredients in the field of pest control, even at low rates of application.

Suitably, according to the method of the invention, the component A is applied at a rate of from 10 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha of the component B. Suitably, the component A is applied at a rate of from 10 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha, 0.5 g a.i./ha to 1500 g a.i./ha, 0.5 g a.i./ha to 1000 g a.i./ha, 0.5 g a.i./ha to 500 g a.i./ha, 0.5 g a.i./ha to 250 g a.i./ha, 0.5 g a.i./ha to 100 g a.i./ha, 0.5 g a.i./ha to 50 g a.i./ha, 5 g a.i./ha to 2000 g a.i./ha, 5 g a.i./ha to 1500 g a.i./ha, 5 g a.i./ha to 1000 g a.i./ha, 5 g a.i./ha to 500 g a.i./ha, 5 g a.i./ha to 250 g a.i./ha, 5 g a.i./ha to 100 g a.i./ha, 5 g a.i./ha to 50 g a.i./ha, 10 g a.i./ha to 2000 g a.i./ha, 10 g a.i./ha to 1500 g a.i./ha, 10 g a.i./ha to 1000 g a.i./ha, 10 g a.i./ha to 500 g a.i./ha, 10 g a.i./ha to 250 g a.i./ha, 10 g a.i./ha to 100 g a.i./ha, 10 g a.i./ha to 50 g a.i./ha, 20 g a.i./ha to 2000 g a.i./ha, 20 g a.i./ha to 1500 g a.i./ha, 20 g a.i./ha to 1000 g a.i./ha, 20 g a.i./ha to 500 g a.i./ha, 20 g a.i./ha to 250 g a.i./ha, 20 g a.i./ha to 100 g a.i./ha, 20 g a.i./ha to 50 g a.i./ha, 50 g a.i./ha to 2000 g a.i./ha, 50 g a.i./ha to 1500 g a.i./ha, 50 g a.i./ha to 1000 g a.i./ha, 50 g a.i./ha to 500 g a.i./ha, 50 g a.i./ha to 250 g a.i./ha, or 50 g a.i./ha to 100 g a.i./ha of the component B.

Suitably, according to the method of the invention, the component A is applied at a rate of from 25 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha of the component B. Suitably, the component A is applied at a rate of from 25 g a.i./ha to 2000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha, 0.5 g a.i./ha to 1500 g a.i./ha, 0.5 g a.i./ha to 1000 g a.i./ha, 0.5 g a.i./ha to 500 g a.i./ha, 0.5 g a.i./ha to 250 g a.i./ha, 0.5 g a.i./ha to 100 g a.i./ha, 0.5 g a.i./ha to 50 g a.i./ha, 5 g a.i./ha to 2000 g a.i./ha, 5 g a.i./ha to 1500 g a.i./ha, 5 g a.i./ha to 1000 g a.i./ha, 5 g a.i./ha to 500 g a.i./ha, 5 g a.i./ha to 250 g a.i./ha, 5 g a.i./ha to 100 g a.i./ha, 5 g a.i./ha to 50 g a.i./ha, 10 g a.i./ha to 2000 g a.i./ha, 10 g a.i./ha to 1500 g a.i./ha, 10 g a.i./ha to 1000 g a.i./ha, 10 g a.i./ha to 500 g a.i./ha, 10 g a.i./ha to 250 g a.i./ha, 10 g a.i./ha to 100 g a.i./ha, 10 g a.i./ha to 50 g a.i./ha, 20 g a.i./ha to 2000 g a.i./ha, 20 g a.i./ha to 1500 g a.i./ha, 20 g a.i./ha to 1000 g a.i./ha, 20 g a.i./ha to 500 g a.i./ha, 20 g a.i./ha to 250 g a.i./ha, 20 g a.i./ha to 100 g a.i./ha, 20 g a.i./ha to 50 g a.i./ha, 50 g a.i./ha to 2000 g a.i./ha, 50 g a.i./ha to 1500 g a.i./ha, 50 g a.i./ha to 1000 g a.i./ha, 50 g a.i./ha to 500 g a.i./ha, 50 g a.i./ha to 250 g a.i./ha, or 50 g a.i./ha to 100 g a.i./ha of the component B.

In a preferred embodiment of the invention, the method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on a plant, preferably a useful plant, or on propagation material thereof, the method comprises applying to the plant, the locus thereof or propagation material thereof, a composition as defined according to the invention, wherein the component A is applied at a rate of from 10 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha or 10 g a.i/ha to 1500 g a.i./ha of the component B.

In a preferred embodiment of the invention, the method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on a plant, preferably a useful plant, or on propagation material thereof, the method comprises applying to the plant, the locus thereof or propagation material thereof, a composition as defined according to the invention, wherein the component A is applied at a rate of from 25 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha or 10 g a.i/ha to 1500 g a.i./ha of the component B.

The present invention also relates to a coated plant propagation material, wherein the coating of the plant propagation material comprises applying a composition according to the invention. The present invention further relates to a coated plant propagation material, wherein the coating comprises a composition according to the invention. Preferably, when the compositions according to the invention are used for treating seed, rates of from 0.001 to 50 g of a compound of the component A per kg of seed, preferably of from 0.01 to 10g per kg of seed, and of from 0.001 to 50 g of a compound of the component B, per kg of seed, preferably of from 0.01 to 10g per kg of seed, are generally sufficient.

Suitably, according to the method of the invention, the component A is applied at a rate of at least 0.001 ppm association with at least 0.001 ppm of the component B.

Suitably, according to the method of the invention, the component A is applied at a rate of at least 0.005 ppm association with at least 0.005 ppm or 0.01 ppm of the component B. Suitably, according to the method of the invention, the component A is applied at a rate of at least 0.01 ppm association with at least 0.005 ppm or 0.01 ppm of the component B. Suitably, according to the method of the invention, the component A is applied at a rate of at least 0.1 ppm association with at least 0.01 ppm or 0.1 ppm of the component B.

A preferred composition according to the invention comprises the component A comprising Nourseothricin (a composition comprising streptothricins C, D, E, and F) and the component B comprising Venturicidin A. Preferably, the weight ratio of Nourseothricin to Venturicidin A is of from 1 :4 to 4:1.

A preferred method according to the invention comprises a method of controlling or preventing phytopathogenic diseases or phytopathogenic fungi on a plant, the locus thereof, or on propagation material thereof, the method comprising applying to the plant, locus thereof, or propagation material thereof, a composition according to the invention, wherein the component A comprises Nourseothricin and the component B comprises Venturicidin A. Preferably, Nourseothricin is applied at a rate of from 0.0078 ppm to 0.5 ppm in association with 0.0039 ppm to 1 ppm of Venturicidin A. Preferably, the phytopathogenic fungi are selected from the group consisting of: Altemaria solani, Botrytis cinerea, Fusarium culmorum, Glomerella lagenarium, Mycosphaerella arachidis, and Zymoseptoria tritici. Preferably, Nourseothricin is applied at a rate of from 0.0156 ppm to 0.0625 ppm in association with 0.0078 ppm to 0.0625 ppm of Venturicidin A, wherein the phytopathogenic fungus is Altemaria solani. Preferably, Nourseothricin is applied at a rate of from 0.0156 ppm to 0.125 ppm in association with 0.0078 ppm to 0.0625 ppm of Venturicidin A, wherein the phytopathogenic fungus is Botrytis cinerea. Preferably, Nourseothricin is applied at a rate of from 0.0156 ppm to 0.125 ppm in association with about 0.0625 ppm of Venturicidin A, wherein the phytopathogenic fungus is Botrytis cinerea. Preferably, Nourseothricin is applied at a rate of from 0.0625 ppm to 0.25 ppm in association with 0.5 ppm to 1 ppm of Venturicidin A, wherein the phytopathogenic fungus is Fusarium culmorum.

Preferably, Nourseothricin is applied at a rate of about 0.25 ppm in association with 0.5 ppm to 1 ppm of Venturicidin A, wherein the phytopathogenic fungus is Fusarium culmorum. Preferably, Nourseothricin is applied at a rate of from 0.03 ppm to 0.5 ppm in association with 0.03 ppm to 0.125 ppm of Venturicidin A, wherein the phytopathogenic fungus is Glomerella lagenarium. Preferably, Nourseothricin is applied at a rate of from 0.03 ppm to 0.5 ppm in association with about 0.125 ppm of Venturicidin A, wherein the phytopathogenic fungus is Glomerella lagenarium. Preferably, Nourseothricin is applied at a rate of from 0.0078 ppm to 0.0156 ppm in association with 0.0039 ppm to 0.0313 ppm of Venturicidin A, wherein the phytopathogenic fungus is Mycosphaerella arachidis. Preferably, Nourseothricin is applied at a rate of from 0.01 ppm to 0.13 ppm in association with 0.0078 ppm to 0.0313 ppm of Venturicidin A, wherein the phytopathogenic fungus is Zymoseptoria tritici. Preferably, Nourseothricin is applied at a rate of from 0.01 ppm to 0.13 ppm in association with about 0.0313 ppm of Venturicidin A, wherein the phytopathogenic fungus is Zymoseptoria tritici.

Preferably, the composition according to the invention comprises an agriculturally acceptable carrier and/or formulation adjuvant, and optionally, a surfactant. The invention also provides fungicidal compositions comprising a combination of the components A and B as mentioned above in a synergistically effective amount, together with an agriculturally acceptable carrier and, optionally, a surfactant. In said compositions, the weight ratio of the component A to the component B is preferably from 1000:1 to 1 :1000, more preferably from 100:1 to 1 :100, even more preferably from 40:1 to 1 :40, still more preferably from about 4:1 to about 1 :4 as described hereinbefore.

The compositions of the invention may be employed in any conventional form, for example in the form of a twin pack, a powder for dry seed treatment (DS), an emulsion for seed treatment (ES), a flowable concentrate for seed treatment (FS), a solution for seed treatment (LS), a water dispersible powder for seed treatment (WS), a capsule suspension for seed treatment (CF), a gel for seed treatment (GF), an emulsion concentrate (EC), a suspension concentrate (SC), a suspo-emulsion (SE), a capsule suspension (CS), a water dispersible granule (WG), an emulsifiable granule (EG), an emulsion, water in oil (EG), an emulsion, oil in water (EW), a micro-emulsion (ME), an oil dispersion (OD), an oil miscible flowable (OF), an oil miscible liquid (OL), a soluble concentrate (SL), an ultra-low volume suspension (SU), an ultra-low volume liquid (UL), a technical concentrate (TK), a dispersible concentrate (DC), a wettable powder (WP) or any technically feasible formulation in combination with agriculturally acceptable adjuvants.

Such compositions may be produced in conventional manner, e.g. by mixing the active ingredients with appropriate formulation inerts (diluents, solvents, fillers and optionally other formulating ingredients). Also, conventional slow release formulations may be employed where long lasting efficacy is intended. Particularly, formulations to be applied in spraying forms, such as water dispersible concentrates (e.g. EC, SC, DC, OD, SE, EW, EO and the like), wettable powders and granules, may contain compounds that provide adjuvancy effects. In some embodiments, the compositions of the invention may be produced by mixing a fermentation broth comprising one or more streptothricins represented by formula (I) or stereoisomers thereof with the compound of component B.

A seed dressing formulation is applied in a manner known per se to the seeds employing the composition according to the invention and a diluent in suitable seed dressing formulation form, e.g. as an aqueous suspension or in a dry powder form having good adherence to the seeds. Such seed dressing formulations are known in the art. Seed dressing formulations may contain the single active ingredients or the combination of active ingredients in encapsulated form, e.g. as slow release capsules or microcapsules.

In general, the formulations include from 0.01 to 90% by weight of active agent, from 0 to 20% agriculturally acceptable surfactant and 10 to 99.99% solid or liquid formulation inerts and adjuvant(s), the active agent consisting of at least the compound of formula (I) together with the compound of formula (II), (III), or (IV), and other active agents, particularly microbiocides or conservatives or the like. Concentrated forms of compositions generally contain in between about 2 and 80%, preferably between about 5 and 70% by weight of active agent. Application forms of formulation may for example contain from 0.01 to 20% by weight, preferably from 0.01 to 5% by weight of active agent. Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ diluted formulations.

It has been found, surprisingly, that certain weight ratios of the component A to the component B are able to give rise to synergistic activity. Therefore, a further aspect of the invention are compositions, wherein the component A and the component B are present in the composition in amounts producing a synergistic effect. This synergistic activity is apparent from the fact that the fungicidal activity of the composition comprising the component A and the component B is greater than the sum of the fungicidal activities of the component A and the component B. This synergistic activity extends the range of action of the component A and the component B in two ways. Firstly, the rates of application of the component A and the component B are lowered whilst the action remains equally good, meaning that the active ingredient mixture still achieves a high degree of phytopathogen control even where the two individual components have become totally ineffective in such a low application rate range. Secondly, there is a substantial broadening of the spectrum of phytopathogens that can be controlled.

A synergistic effect exists whenever the action of an active ingredient combination is greater than the sum of the actions of the individual components. The action to be expected E for a given active ingredient combination obeys the so-called COLBY formula and can be calculated as follows (COLBY, S.R. "Calculating synergistic and antagonistic responses of herbicide combination", Weeds, Vol. 15, pages 20-22; 1967): ppm = milligrams of active ingredient (= a.i.) per liter of spray mixture,

X = % action by active ingredient (A) using p ppm of active ingredient,

Y = % action by active ingredient (B) using q ppm of active ingredient.

According to COLBY, the expected (additive) action of active ingredients (A)+(B) using p+q ppm of active ingredient is

If the action actually observed (O) is greater than the expected action (E), then the action of the combination is super-additive, i.e. there is a synergistic effect. In mathematical terms, synergism corresponds to a positive value for the difference of (O-E). In the case of purely complementary addition of activities (expected activity), said difference (O-E) is zero. A negative value of said difference (O-E) signals a loss of activity compared to the expected activity.

However, besides the actual synergistic action with respect to fungicidal activity, the compositions according to the invention can also have further surprising advantageous properties. Examples of such advantageous properties that may be mentioned are: more advantageous degradability; improved toxicological and/or ecotoxicological behaviour; or improved characteristics of the useful plants including: emergence, crop yields, more developed root system, tillering increase, increase in plant height, bigger leaf blade, less dead basal leaves, stronger tillers, greener leaf colour, less fertilizers needed, less seeds needed, more productive tillers, earlier flowering, early grain maturity, less plant verse (lodging), increased shoot growth, improved plant vigor, and early germination.

The composition according to the invention is preferably in a synergistically effective amount. Preferably, the component A and the component B of the composition according to the invention are each in an amount which results in in a synergistic effect, preferably a synergistic fungicidal effect. Preferably, the composition according to the invention has a weight ratio of the component A and the component B in a synergistically effective amount.

It was found that Venturicidin A advantageously provides more than an additive fungicidal effect when combined with one or more streptoth ricins represented by formula (I) as defined above, in particular wherein the streptothricins comprise streptothricins C, D, E, and F. Reference is made to the Examples below, where a synergistic antifungal effect of Nourseothricin and Venturicidin A is disclosed.

The Examples which follow serve to illustrate the invention and are not meant in any way to limit the invention.

Biological Examples The compositions according to the invention are tested for their biological (fungicidal) activity using one or more of the protocols as set out in Examples 1 to 6.

Nourseothricin is a composition comprising streptothricins C, D, E, and F. Nourseothricin sulfate was used in the Examples. As indicated previously, Nourseothricin and Nourseothricin sulfate are known and commercially available. As indicated previously, Venturicidin A is known and commercially available.

Methods and results of tests on the biological (fungicidal) activity outlined of the compositions according to the invention are shown below in Tables 1 to 6. These data show that synergistic fungicidal activity is observed for the combination of Nourseothricin and Venturicidin A against Botrytis cinerea, Altemaria solani, Glomerella lagenarium, Zymoseptoria tritici, Fusarium culmorum, and Mycosphaerella arachidis 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.

Example 1

Botrytis cinerea (Gray Mould):

Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (Vogel’s). After placing a (DMSO or DMSO/Tween 20) solution of the test compounds 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 and visually after 72 hrs.

Table 1 : Fungicidal activity of a composition of Nourseothricin and Venturicidin A against Botrytis cinerea as described above.

Example 2

Altemaria solani (Early Blight): Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB: potato dextrose broth). After placing a (DMSO or DMSO/Tween 20) solution of the test compounds 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 and visually after 48 hrs.

Table 2: Fungicidal activity of a composition of Nourseothricin and Venturicidin A against Alternaria solani as described above.

Example 3

Glomerella lagenarium (also known as Colletotrichum lagenarium) (Anthracnose of cucurbits): Conidia of the fungus, prepared from a freshly cultivated petri dish, were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO or DMSO/Tween 20) solution of the test compounds 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 and visually after 72 hrs.

Table 3: Fungicidal activity of a composition of Nourseothricin and Venturicidin A against Glomerella lagenarium as described above.

Example 4

Zymoseptoria tritici (Leaf Blotch):

Conidia of the fungus from cryogenic storage were directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO or DMSO/Tween 20) solution of the test compounds 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 and visually after 72 hrs.

Table 4: Fungicidal activity of a composition of Nourseothricin and Venturicidin A against Zymoseptoria tritici as described above.

Example 5

Fusarium culmorum (Head Blight):

Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO or DMSO/Tween 20) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically and visually after 3 days.

Table 5: Fungicidal activity of a composition of Nourseothricin and Venturicidin A against Fusarium culmorum as described above.

Example 6

Mycosphaerella arachidis (also known as Mycosphaerella arachidicola) (Early Leaf Spot of groundnut): Conidia of the fungus from cryogenic storage are directly mixed into nutrient broth (PDB potato dextrose broth). After placing a (DMSO or DMSO/Tween 20) solution of test compound into a microtiter plate (96-well format), the nutrient broth containing the fungal spores is added. The test plates are incubated at 24°C and the inhibition of growth is determined photometrically and visually after 4 days.

Table 6: Fungicidal activity of a composition of Nourseothricin and Venturicidin A against Mycosphaerella arachidis as described above.

Embodiments

Embodiment 1 . A fungicidal composition comprising:

wherein n is an integer selected from 1 to 7; and

wherein R¹ is selected from CONH2 and H; wherein R², R⁴, R⁶, and R⁷ are each independently selected from CHs and H; wherein R³ is selected from OH and H; and wherein R⁵ is selected from CH2CH3 and CH3.

Embodiment 2. The composition of embodiment 1 , wherein the component A comprises the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is an integer selected from 1 to 4, preferably wherein n is 3 or 4.

Embodiment 3. The composition of embodiment 1 or 2, wherein the component A comprises the streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 , 2, 3, and 4. Embodiment 4. The composition of any one of embodiments 1 to 3, wherein the component B comprises the compound represented by formula (II) or a stereoisomer thereof, wherein R¹ is selected from CONH2 and H; R² is selected from CH3 and H; R³ is H; R⁴ is CH3; R⁵ is selected from CH2CH3 and CH3; R⁶ is H; and R⁷ is H; preferably wherein R¹ is selected from CONH2 and H; R² is CH3; R³ is H; R⁴ is CH₃; R⁵ is CH₃; R⁶ is H; and R⁷ is H.

Embodiment 5. The composition of any one of embodiments 1 to 4, wherein the component B comprises Venturicidin A or a stereoisomer thereof, wherein Venturicidin A is represented by formula (Ha):

Embodiment 6. The composition of any one of embodiments 1 to 5, wherein the component A comprises of from 10% to 99.9% by weight, preferably of from 20% to 99% by weight of the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 3 and/or 4, and of from 0.1 % to 30% by weight, preferably of from 2% to 25% by weight of the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 and/or 2. Embodiment 7. The composition of any one of embodiments 1 to 6, wherein the weight ratio of the component A to the component B is of from 60000:1 to 1 :1000, preferably of from 1000:1 to 1 :1000, more preferably of from 100:1 to 1 :100, yet more preferably of from 40:1 to 1 :40, yet even more preferably of from about 4:1 to about 1 :4.

Embodiment 8. The composition of any one of embodiments 1 to 7, further comprising an agriculturally acceptable carrier and/or formulation adjuvant, and optionally, a surfactant. Embodiment 9. A method of controlling or preventing phytopathogenic fungi on a plant, locus thereof, or on propagation material thereof, the method comprising applying to the plant, locus thereof, or propagation material thereof, a composition according to any one of embodiments 1 to 8.

Embodiment 10. The method of embodiment 9, wherein the component A is applied at a rate of from 10 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha of the component B. Embodiment 11 . The method of embodiment 9 or 10, wherein the phytopathogenic fungi are selected from the group consisting of: Alternaria, Botrytis, Cercospora, Colletotrichum, Corynespora, Erysiphe, Fusarium, Glomerella, Guignardia, Helminthosporium, Hemileia, Magnaporthe, Monilinia, Mycosphaerella, Penicillium, Phakopsora, Phomopsis, Podosphaera, Pseudocercosporella, Pseudopezicula, Puccinia, Pyricularia, Rhizoctonia, Rhynchosporium, Septoria, Tilletia, Uncinula, Ustilago, Venturia, and Zymoseptoria, preferably wherein the phytopathogenic fungi are selected from the group consisting of: Alternaria, Botrytis, Fusarium, Glomerella, Mycosphaerella, and Zymoseptoria.

Embodiment 12. The method of any one of embodiments 9 to 11 , wherein the plant is a useful plant 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, preferably wherein the useful plant is selected from: fruits and tree nuts, vegetables, horticulture crops, and floriculture.

Embodiment 13. The method of any one of embodiments 9 to 12, wherein the plant is a useful plant selected from the group consisting of: grapevines, strawberries, apples, cherries, peaches, nectarines, blueberries, caneberries, tomatoes, potatoes, cucurbits, cucumbers, eggplants, lettuce, beans, brassicas, peas, oilseed rapes, soybeans, sugar beets, sunflowers, rice, peanuts, coffee, ornamental plants, and turfgrass, or wherein the plant is a useful plant selected from the group consisting of: apples, almonds, cherries, raspberries, grapes, cucumbers, peanuts, tomatoes, strawberries, citrus, and bananas.

Embodiment 14. A coated plant propagation material, wherein the coating comprises a composition according to any one of embodiments 1 to 8.

Embodiment 15. Use of the composition according to any one of embodiments 1 to 8 as a fungicide, wherein the use is not for the treatment of the human or animal body by surgery or therapy.

Claims

1 . A fungicidal composition comprising:

wherein R², R⁴, R⁶, and R⁷ are each independently selected from CHs and H; wherein R³ is selected from OH and H; and wherein R⁵ is selected from CH2CH3 and CH3.

2. The composition according to claim 1 , wherein the component A comprises the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is an integer selected from 1 to 4, preferably wherein n is 3 or 4.

3. The composition according to any one of claims 1 or 2, wherein the component A comprises the streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 , 2, 3, and 4.

4. The composition according to any one of claims 1 to 3, wherein the component B comprises the compound represented by formula (II) or a stereoisomer thereof, wherein R¹ is selected from CONH2 and H; R² is selected from CH3 and H; R³ is H; R⁴ is CH3; R⁵ is selected from CH2CH3 and CH₃; R⁶ is H; and R⁷ is H; preferably wherein R¹ is selected from CONH2 and H; R² is CH3; R³ is H; R⁴ is CH₃; R⁵ is CH₃; R⁶ is H; and R⁷ is H.

5. The composition according to any one of claims 1 to 4, wherein the component B comprises Venturicidin A or a stereoisomer thereof, wherein Venturicidin A is represented by formula (Ila):

6. The composition according to any one of claims 1 to 5, wherein the component A comprises of from 10% to 99.9% by weight, preferably of from 20% to 99% by weight of the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 3 and/or 4, and of from 0.1 % to 30% by weight, preferably of from 2% to 25% by weight of the one or more streptothricins represented by formula (I) or stereoisomers thereof, wherein n is 1 and/or 2.

7. The composition according to any one of claims 1 to 6, wherein the weight ratio of the component A to the component B is of from 60000:1 to 1 :1000, preferably of from 1000:1 to 1 :1000, more preferably of from 100:1 to 1 :100, yet more preferably of from 40:1 to 1 :40, yet even more preferably of from 4:1 to 1 :4.

8. The composition according to any one of claims 1 to 7, further comprising an agriculturally acceptable carrier and/or formulation adjuvant, and optionally, a surfactant.

9. A method of controlling or preventing phytopathogenic fungi on a plant, locus thereof, or on propagation material thereof, the method comprising applying to the plant, locus thereof, or propagation material thereof, a composition according to any one of claims 1 to 8.

10. The method according to claim 9, wherein the component A is applied at a rate of from 10 g a.i./ha to 3000 g a.i./ha in association with 0.5 g a.i./ha to 2000 g a.i./ha of the component B.

11 . The method according to claim 9 or 10, wherein the phytopathogenic fungi are selected from the group consisting of: Alternaria, Botrytis, Cercospora, Colletotrichum, Corynespora, Erysiphe, Fusarium, Glomerella, Guignardia, Helminthosporium, Hemileia, Magnaporthe, Monilinia, Mycosphaerella, Penicillium, Phakopsora, Phomopsis, Podosphaera, Pseudocercosporella, Pseudopezicula, Puccinia, Pyricularia, Rhizoctonia, Rhynchosporium, Septoria, Tilletia, Uncinula, Ustilago, Venturia, and Zymoseptoria, preferably wherein the phytopathogenic fungi are selected from the group consisting of: Alternaria, Botrytis, Fusarium, Glomerella, Mycosphaerella, and Zymoseptoria.

12. The method according to any one of claims 9 to 11 , wherein the plant is a useful plant selected from: grains, fruits and tree nuts, vegetables, field crops, oil seed crops, forage crops, forest plants, horticulture crops, floriculture, greenhouse and nursery plants, culinary herbs and spices, and medicinal herbs, preferably wherein the useful plant is selected from: fruits and tree nuts, vegetables, horticulture crops, and floriculture.

13. The method according to any one of claims 9 to 12, wherein the plant is a useful plant selected from the group consisting of: grapevines, strawberries, apples, cherries, peaches, nectarines, blueberries, caneberries, tomatoes, potatoes, cucurbits, cucumbers, eggplants, lettuce, beans, brassicas, peas, oilseed rapes, soybeans, sugar beets, sunflowers, rice, peanuts, coffee, ornamental plants, and turfgrass, or wherein the plant is a useful plant selected from the group consisting of: apples, almonds, cherries, raspberries, grapes, cucumbers, peanuts, tomatoes, strawberries, citrus, and bananas.

14. A coated plant propagation material, wherein the coating comprises a composition according to any one of claims 1 to 8.

15. Use of the composition according to any one of claims 1 to 8 as a fungicide, wherein the use is not for the treatment of the human or animal body by surgery or therapy.