Method to control septoriatritici resistant to c14-demethylase inhibitor fungicides

Abstract

Method to control Septoria tritici resistant to C14-demethylase inhibitor fungicides The present invention relates to a method for controlling Septoria tritici comprising at least one mutation in the CYP51 gene and being resistant to C14-demethylase (in sterol biosynthesis) inhibitor fungicides (DMI fungicides) on cereal plants, comprising applying to the plants, their seed or the soil a fungicidally effective amount of (I) methyl 2- [2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoate or (II) 2-[2-chloro-4-(4- chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic acid.

Description

[0001] Method to control Septoria tritici resistant to C14-demethylase inhibitor fungicides

[0002] Description

[0003] The present invention relates to a method for controlling Septoria tritici (synonym Zymoseptoria tritici) resistant to C14-demethylase (in sterol biosynthesis) inhibitor fungicides (also called DMI fungicides) on cereal plants, comprising applying to the plants, their seed or the soil a fungicidally effective amount of

[0004] (I) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propanoate or

[0005] (II) 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic acid

[0006] One task the farmer is faced with in relation to the use of pesticides is that the repeated and exclusive application of an individual pesticidal compound leads in many cases to a rapid selection of harmful fungi, which have developed acquired resistance against the active compound in question. Therefore, there is a need for pest control agents that help prevent or overcome such upcoming resistance.

[0007] The term “resistance” as used herein, refers to an acquired, heritable reduction in sensitivity of a fungus to a specific anti-fungal agent (or fungicide).

[0008] Septoria tritici is a species of filamentous fungus, an ascomycete in the family Myco-sphaerellaceae. It is a plant pathogen causing septoria leaf blotch, which is currently the most dominant cereal disease. Control of Septoria leaf blotch is becoming more and more difficult for farmers. Reason is the capability of the fungi to develop resistance to widely used powerful fungicidal agents.

[0009] For example, fungicides containing azole and strobilurine mixtures have been widely and successfully used in recent years for Septoria control

[0010] Strobilurins lost their activity due to the development of the G143A resistance which is meanwhile widespread in most cereal growing regions in Europe (Fraaije B. A., Brunett F. J., Clark W. S., Motteram J., Lucas J. A. (2005). Resistance development to Qol inhibitors in populations of Mycosphaerella graminicola in the UK. Modern fungicides and antifungal compounds II, eds Lyr H., Russell P. E., Dehne H-W. Gisi U. Kuck K-H, 14th International Rein- hardsbrunn Symposium, BCPC, Alton, UK, pp 63-71).

[0011] The activity of azole fungicides eroded due to a sensitivity shift of Septoria tritici. In particular, DMI (Demethlyation inhibitor) fungicides from the class of azoles lose their activity due to the development of resistance in different plant pathogenic fungi. The loss of activity is described in various publications such as

[0012] Cools H. J., Fraaije B.A. (2013). Update on mechanisms of azole resistance in Mycosphaerella graminicola and implications for future control. Pest Management Science 69: 150-155. - AHDB Fungicide performance update December 2017 (https: / / cereals.ahdb.org.uk / media / 1326769 / Fungicide- performance-data-2017-7-December-2017.pdf; page 24).

[0013] Huf A., Rehfus A., Lorenz K.-H., Bryson R., Voegele R.T. and Stammler G. (2018). Proposal for a new nomenclature for CYP51 haplotypes in Zymoseptoria tritici and analysis of their distribution in Europe. Plant Pathology DOI 10.1111 / ppa.12891.

[0014] DMI fungicides are acting by inhibiting the enzyme lanosterol 14a-demethylase encoded by the CYP51 gene resulting in amino acid alterations. The most important mechanisms leading to reduced DMI sensitivity are based on development of new mutations or on the accumulation of mutations in the CYP51 gene.

[0015] Surprisingly, we have found that the application (I) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4- triazol-1 -yl)propanoate or

[0016] (II) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic shows an unexpected fungicidal activity towards Septoria tritici being resistant against DMI fungicides, in particular, towards Septoria tritici comprising mutations in the CYP51 gene.

[0017] Thus, the present invention comprises a method for controlling Septoria tritici that is already resistant to DMI fungicides, in particular, Septoria tritici comprising mutations in the CYP51 gene, on cereals, said method comprising applying to the plants, their seed or the soil a fungicidal ly effective amount of (I) methyl 2-[2-chloro-4-(4- chlorophenoxy)phenyl]-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propanoate or (II) methyl 2-[2-chloro-4-(4- chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic

[0018] According to one embodiment compound (I) is applied

[0019] According to another embodiment, compound (II) is applied.

[0020] According to still another embodiment, a mixture of compound (I) and compound (II) is applied.

[0021] (I) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propanoate or

[0022] (II) 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propanoic acid both comprise chiral centers and are generally obtained in the form of racemates. The R- and S-enantiomers of compound (I) and compound (II) can be separated and isolated in pure form with methods known by the skilled person, e.g. by using chiral HPLC.

[0023] Therefore, in the method according to the present invention, compound (I) and compound (II), can be used in form of

[0024] - a racemic mixture of the of the (R)-enantiomer and the (S)-enantiomer;

[0025] - a mixture with any other proportions of the (R)-enantiomer and the (S)-enantiomer;

[0026] - pure (R)-enantiomer or

[0027] - pure (S)-enantiomer. According to one specific embodiment of the present invention, compound (I) is used as racemate.

[0028] According to one another specific embodiment, compound (I) is used as (R)-enantiomer with an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%. According to a particular embodiment, compound (I) is used as a pure (R)-enantiomer.

[0029] According to another specific embodiment, compound (I) is used as (S)-enantiomer with an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%. According to a particular embodiment, compound (I) is used as a pure (S)-enantiomer.

[0030] According one specific embodiment of the present invention, compound (II) is used as racemate.

[0031] According to one another specific embodiment, compound (II) is used as (R)-enantiomer with an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%. According to a particular embodiment, compound (II) is used as a pure (R)-enantiomer.

[0032] According to another specific embodiment, compound (II) is used as (S)-enantiomer with an enantiomeric excess (e.e.) of at least 40%, for example, at least 50%, 60%, 70% or 80%, preferably at least 90%, more preferably at least 95%, yet more preferably at least 98% and most preferably at least 99%. According to a particular embodiment, compound (II) is used as a pure (S)-enantiomer.

[0033] According to the present invention Septoria tritici resistant to DMI fungicides, in particular Septoria tritici comprising at least one mutation in the CYP51 gene, is controlled.

[0034] Preferably, the mutation occurs in the amino acid positions selected from 50, 107, 134, 136, 137, 178, 188, 208, 259, 284, 303, 311, 312, 379, 381, 410, 412, 459, 460, 461, 476, 490, 510, 513, 524; more preferably in the positions 50, 134, 136, 188, 379, 381 , 459, 460, 461, 513, 524, most preferably in the positions more preferably in the positions 50, 136, 381, 459, 460, 461 , 524.

[0035] The mutations are preferably selected from the alterations listed in Table 1 .

[0036] Table 1:

[0037] In this table, the alterations are to be understood as follows: for examples the alteration (M.1) L50S means that Leu- cin in position 50 is replaced by Serin.

[0038] According to one embodiment, Septoria tritici comprises at least one mutation in the CYP51 gene.

[0039] According one specific embodiment, the mutation is in the amino acid position 50, preferably the mutation is M.1.

[0040] According another specific embodiment, the mutation is in the amino acid position 107, preferably the mutation is M.2.

[0041] According another specific embodiment, the mutation is in the amino acid position 134, preferably the mutation is

[0042] M.3.

[0043] According another specific embodiment, the mutation is in the amino acid position 136, preferably the mutation is M.4 or M5.

[0044] According another specific embodiment, the mutation is in the amino acid position 137, preferably the mutation is M.6.

[0045] According another specific embodiment, the mutation is in the amino acid position 178, preferably the mutation is

[0046] M.7.

[0047] According another specific embodiment, the mutation is in the amino acid position 188, preferably the mutation is

[0048] M.8.

[0049] According another specific embodiment, the mutation is in the amino acid position 208, preferably the mutation is

[0050] M.9.

[0051] According another specific embodiment, the mutation is in the amino acid position 259, preferably the mutation is M.10.

[0052] According another specific embodiment, the mutation is in the amino acid position 284, preferably the mutation is M.11.

[0053] According another specific embodiment, the mutation is in the amino acid position 303, preferably the mutation is M.12.

[0054] According another specific embodiment, the mutation is in the amino acid position 311 , preferably the mutation is M.13.

[0055] According another specific embodiment, the mutation is in the amino acid position 312, preferably the mutation is

[0056] M.14.

[0057] According another specific embodiment, the mutation is in the amino acid position 379, preferably the mutation is M.15.

[0058] According another specific embodiment, the mutation is in the amino acid position 381 , preferably the mutation is M.16. According another specific embodiment, the mutation is in the amino acid position 410, preferably the mutation is M.17.

[0059] According another specific embodiment, the mutation is in the amino acid position 412, preferably the mutation is M.18.

[0060] According another specific embodiment, the mutation is in the amino acid position 459, preferably the mutation is M.19, M.20, M.21 or M.22.

[0061] According another specific embodiment, the mutation is in the amino acid position 460, preferably the mutation is M.23 or M.24.

[0062] According another specific embodiment, the mutation is in the amino acid position 461 , preferably the mutation is M.25, M.26, M.27, M.28, M.29 or M.30.

[0063] According another specific embodiment, the mutation is in the amino acid position 476, preferably the mutation is M.31.

[0064] According another specific embodiment, the mutation is in the amino acid position 490, preferably the mutation is M.32.

[0065] According another specific embodiment, the mutation is in the amino acid position 510, preferably the mutation is M.33.

[0066] According another specific embodiment, the mutation is in the amino acid position 513, preferably the mutation is M.34.

[0067] According another specific embodiment, the mutation is in the amino acid position 524, preferably the mutation is M.35.

[0068] According to another embodiment, Septaria tritici comprises at least two mutations in the CYP51 gene.

[0069] Preferably, the said two mutations occur in the positions selected from

[0070] 50+107, 50+134, 50+136, 50+137, 50+178, 50+188, 50+208, 50+259, 50+284, 50+303, 50+311 , 50+312, 50+379, 50+381, 50+410, 50+412, 50+459, 50+460, 50+461, 50+476, 50+490, 50+510, 50+513, 50+524,

[0071] 107+134, 107+136, 107+137, 107+178, 107+188, 107+208, 107+259, 107+284, 107+303, 107+311, 107+312, 107+379, 107+381 , 107+410, 107+412, 107+459, 107+460, 107-^461, 107+476, 107+490, 107+510, 107+513, 107+524,

[0072] 134+136, 134+137, 134+178, 134+188, 134+208, 134+259, 134+284, 134+303, 134+311 , 134+312, 134+379,

[0073] 134+381, 134+410, 134+412, 134+459, 134+460, 134+461, 134+476, 134+490, 134+510, 134+513, 134+524,

[0074] 136+137, 136+178, 136+188, 136+208, 136+259, 136+284, 136+303, 136+311, 136+312, 136+379, 136+381,

[0075] 136+410, 136+412, 136+459, 136+460, 136+461 , 136+476, 136+490, 136+510, 136+513, 136+524,

[0076] 137+178, 137+188, 137+208, 137+259, 137+284, 137+303, 137+311 , 137+312, 137+379, 137+381, 137+410,

[0077] 137+412, 137+459, 137+460, 137+461 , 137+476, 137+490, 137+510, 137+513, 137+524,

[0078] 178+188, 178+208, 178+259, 178+284, 178+303, 178+311, 178+312, 178+379, 178+381 , 178+410, 178+412,

[0079] 178+459, 178+460, 178+461, 178+476, 178+490, 178+510, 178+513, 178+524, 188+208, 188+259, 188+284, 188+303, 188+311 , 188+312, 188+379, 188+381, 188+410, 188+412, 188+459, 188+460, 188+461 , 188+476, 188+490, 188+510, 188+513, 188+524,

[0080] 208+259, 208+284, 208+303, 208+311 , 208+312, 208+379, 208+381 , 208+410, 208+412, 208+459, 208+460,

[0081] 208+461, 208+476, 208+490, 208+510, 208+513, 208+524,

[0082] 259+284, 259+303, 259+311, 259+312, 259+379, 259+381, 259+410, 259+412, 259+459, 259+460, 259+461,

[0083] 259+476, 259+490, 259+510, 259+513, 259+524,

[0084] 284+303, 284+311 , 284+312, 284+379, 284+381 , 284+410, 284412, 284+459, 284+460, 284+461, 284+476,

[0085] 284+490, 284+510, 284+513, 284+524,

[0086] 303+311, 303+312, 303+379, 303+381 , 303+410, 303+412, 303459, 303460, 303461 , 303476, 303490,

[0087] 303+510, 303+513, 303+524,

[0088] 311+312, 311+379, 311+381, 311410, 311412, 311+459, 311460, 311461, 311476, 311490, 311+510,

[0089] 311+513, 311+524,

[0090] 312+379, 312+381 , 312+410, 312412, 312459, 312+460, 312461 , 312476, 312490, 312+510, 312+513, 312+524,

[0091] 379+381, 379410, 379+412, 379459, 379460, 379+461, 379476, 379490, 379+510, 379+513, 379+524,

[0092] 381410, 381412, 381+459, 381460, 381461 , 381476, 381490, 381 +510, 381+513, 381 +524,

[0093] 410412, 410459, 410+460, 410461 , 410476, 410490, 410+510, 410+513, 410+524,

[0094] 412459, 412460, 412461, 412476, 412490, 412+510, 412+513, 412+524,

[0095] 459460, 459461 , 459+476, 459490, 459+510, 459+513, 459+524,

[0096] 460461, 460476, 460+490, 460+510, 460+513, 460+524,

[0097] 461476, 461490, 461 +510, 461+513, 461+524,

[0098] 476490, 476+510, 476+513, 476+524,

[0099] 490+510, 490+513, 490+524,

[0100] 510+513, 510+524,

[0101] 513+524.

[0102] The sign “+” is to be read as “and”, so that, for example, the mutations occuring in the positions 50+107 means that one mutation occurs in the position 50 and the second one in the position 107.

[0103] Specific combinations of the two mutations in CYP51 gene of Septoria tritici are given in Table A.

[0104] Table A

[0105] The combination A15 is particularly preferred.

[0106] According to a further embodiment, Septoria tritici comprises at least three mutations in the CYP51 gene.

[0107] Preferably, the said three mutations occur in the positions selected from 50+134+136, 50+134+188, 50+134+379, 50+134+381 , 50+134+459, 50+134+460, 50+134+461, 50+134+513, 50+134+524, 50+136+188, 50+136+379, 50+136+381, 50+136+459, 50+136+460, 50+136+461 , 50+136+513, 50+136+524, 50+188+379, 50+188+381 , 50+188+459,

[0108] 50+188+460, 50+188+461, 50+188+513, 50+188+524, 50+379+381 , 50+379+459, 50+379+460, 50+379+461, 50+379+513, 50+379+524, 50+381+459, 50+381+460, 50+381 +461, 50+381 +513, 50+381+524, 50+459+460, 50+459+461, 50+459+513, 50+459+524, 50+460+461 , 50+460+513, 50+460+524, 50+461 +513, 50+461 +524, 50+513+524, 134+136+188, 134+136+379, 134+136+381 , 134+136+459, 134+136+460,

[0109] 134+136+461 , 134+136+513, 134+136+524, 134+188+379, 134+188+381,

[0110] 134+188+459, 134+188+460, 134+188+461 , 134+188+513, 134+188+524,

[0111] 134+379+381 , 134+379+459, 134+379+460, 134+379+461 , 134+379+513,

[0112] 134+379+524, 134+381 +459, 134+381 +460, 134+381+461 , 134+381+513,

[0113] 134+381+524, 134+459+460, 134+459+461, 134+459+513, 134+459+524,

[0114] 134+460+461 , 134+460+513, 134+460+524, 134+461+513, 134+461+524

[0115] 134+513+524,

[0116] 136+188+379, 136+188+381, 136+188+459, 136+188+460, 136+188+461,

[0117] 136+188+513, 136+188+524, 136+379+381 , 136+379+459, 136+379+460,

[0118] 136+379+461 , 136+379+513, 136+379+524, 136+381+459, 136+381+460,

[0119] 136+381+461 , 136+381 +513, 136+381 +524, 136+459+460, 136+459+461,

[0120] 136+459+513, 136+459+524, 136 460+461 , 136+460+513, 136+460+524,

[0121] 136+461+513, 136+461 +524, 136+513+524,

[0122] 188+379+381 , 188+379+459, 188+379+460, 188+379+461 , 188+379+513,

[0123] 188+379+524, 188+381 +459, 188+381 +460, 188+381+461 , 188+381+513,

[0124] 188+381+524, 188+459+460, 188 459+461 , 188+459+513, 188+459+524,

[0125] 188+460+461 , 188+460+513, 1884460+524, 188+461+513, 188+461+524,

[0126] 188+513+524,

[0127] 379+381+459, 379+381 +460, 379+381 +461 , 379+381+513, 379+381+524,

[0128] 379+459+460, 379+459+461, 3794459+513, 379+459+524, 379+460+461,

[0129] 379+460+513, 379+460+524, 379+461 +513, 379+461+524, 379+513+524,

[0130] 381+459+460, 381+459+461, 381 +459+513, 381+459+524, 381+460+461,

[0131] 381+460+513, 381+460+524, 381 +461 +513, 381+461+524, 381 +513+524,

[0132] 459+460+461 , 459+460+513, 459+460+524, 459+461+513, 459+461+524,

[0133] 459+513+524,

[0134] 460+461+513, 460+461 +524, 460+513+524,

[0135] 461+513+524.

[0136] According to a further embodiment, Septoria tritici comprises at least four mutations in the CYP51 gene. Preferably, the said four mutations occur in the positions selected from

[0137] 50+134+136+188, 50+134+136+379, 50+134+136+381, 50+134+136+459,

[0138] 50+134+136+460, 50+134+136+461, 50+134+136+513, 50+134+136+524,

[0139] 50+134+188+379, 50+134+188+381, 50+134+188+459, 50+134+188+460,

[0140] 50+134+188+461 , 50+134+188+513, 50+134+188+524, 50+134+379+381 ,

[0141] 50+134+379+459, 50+134+379+460, 50+134+379+461, 50+134+379+513,

[0142] 50+134+379+524, 50+134+381+459, 50+134+381 +460, 50+134+381 +461 ,

[0143] 50+134+381+513, 50+134+381+524, 50+134+459+460, 50+134+459+461,

[0144] 50+134+459+513, 50+134+459+524, 50+134+460+461, 50+134+460+513,

[0145] 50+134+460+524, 50+134+461+513, 50+134+461 +524, 50+134+513+524,

[0146] 50+136+188+379, 50+136+188+381, 50+136+188+459, 50+136+188+460,

[0147] 50+136+188+461 , 50+136+188+513, 50+136+188+524, 50+136+379+381 ,

[0148] 50+136+379+459, 50+136+379+460, 50+136+379+461, 50+136+379+513,

[0149] 50+136+379+524, 50+136+381+459, 50+136+381 +460, 50+136+381 +461 ,

[0150] 50+136+381+513, 50+136+381+524, 50+136+459+460, 50+136+459+461 ,

[0151] 50+136+459+513, 50+136+459+524, 50+136+460+461, 50+136+460+513,

[0152] 50+136+460+524, 50+136+461+513, 50+136+461 +524, 50+136+513+524,

[0153] 50+188+379+381 , 50+188+379+459, 50+188+379+460, 50+188+379+461 ,

[0154] 50+188+379+513, 50+188+379+524, 50+188+381 +459, 50+188+381 +460,

[0155] 50+188+381+461 , 50+188+381+513, 50+188+381 +524, 50+188+459+460,

[0156] 50+188+459+461 , 50+188+459+513, 50+188+459+524, 50+188+460+461 ,

[0157] 50+188+460+513, 50+188+460+524, 50+188+461 +513, 50+188+461 +524,

[0158] 50+188+513+524, 50+379+381+459, 50+379+381 +460, 50+379+381 +461 ,

[0159] 50+379+381+513, 50+379+381+524, 50+379+459+460, 50+379+459+461 ,

[0160] 50+379+459+513, 50+379+459+524, 50+379+460+461, 50+379+460+513,

[0161] 50+379+460+524, 50+379+461+513, 50+379+461 +524, 50+379+513+524,

[0162] 50+381+459+460, 50+381 +459+461, 50+381 +459+513, 50+381+459+524,

[0163] 50+381+460+461 , 50+381 +460+513, 50+381 +460+524, 50+381+461 +513,

[0164] 50+381+461+524, 50+381 +513+524, 50+459+460+461, 50+459+460+513,

[0165] 50+459+460+524, 50+459+461+513, 50+459+461 +524, 50+459+513+524,

[0166] 50+460+461+513, 50+460+461+524, 50+460+513+524, 50+461+513+524,

[0167] 134+136+188+379, 134+136+188+381, 134+136+188+459, 134+136+188+460,

[0168] 134+136+188+461 , 134+136+188+513, 134+136+188+524, 134+136+379+381 ,

[0169] 134+136+379+459, 134+136+379+460, 134+136+379+461, 134+136+379+513,

[0170] 134+136+379+524, 134+136+381+459, 134+136+381 +460, 134+136+381 +461 ,

[0171] 134+136+381 +513, 134+136+381+524, 134+136+459+460, 134+136+459+461 ,

[0172] 134+136+459+513, 134+136+459+524, 134+136+460+461, 134+136+460+513, 134+136+460+524, 134+136+461+513, 134+136+461+524, 134+136+513+524,

[0173] 134+188+379+381, 134+188+379+459, 134+188+379+460, 134+188+379+461,

[0174] 134+188+379+513, 134+188+379+524, 134+188+381+459, 134+188+381+460,

[0175] 134+188+381+461, 134+188+381+513, 134+188+381+524, 134+188+459+460,

[0176] 134+188+459+461, 134+188+459+513, 134+188+459+524, 134+188+460+461,

[0177] 134+188+460+513, 134+188+460+524, 134+188+461+513, 134+188+461+524,

[0178] 134+188+513+524, 134+379+381+459, 134+379+381+460, 134+379+381+461,

[0179] 134+379+381+513, 134+379+381+524, 134+379+459+460, 134+379+459+461,

[0180] 134+379+459+513, 134+379+459+524, 134+379+460+461, 134+379+460+513,

[0181] 134+379+460+524, 134+379+461+513, 134+379+461+524, 134+379+513+524,

[0182] 134+381+459+460, 134+381+459+461, 134+381+459+513, 134+381+459+524,

[0183] 134+381+460+461, 134+381+460+513, 134+381+460+524, 134+381+461+513,

[0184] 134+381+461+524, 134+381+513+524, 134+459+460+461, 134+459+460+513,

[0185] 134+459+460+524, 134+459+461+513, 134+459+461+524, 134+459+513+524,

[0186] 134+460+461+513, 134+460+461+524, 134+460+513+524, 134+461+513+524,

[0187] 136+188+379+381, 136+188+379+459, 136+188+379+460, 136+188+379+461,

[0188] 136+188+379+513, 136+188+379+524, 136+188+381+459, 136+188+381+460,

[0189] 136+188+381+461, 136+188+381+513, 136+188+381+524, 136+188+459+460,

[0190] 136+188+459+461, 136+188+459+513, 136+188+459+524, 136+188+460+461,

[0191] 136+188+460+513, 136+188+460+524, 136+188+461+513, 136+188+461+524,

[0192] 136+188+513+524, 136+379+381+459, 136+379+381+460, 136+379+381+461,

[0193] 136+379+381+513, 136+379+381+524, 136+379+459+460, 136+379+459+461,

[0194] 136+379+459+513, 136+379+459+524, 136+379+460+461, 136+379+460+513,

[0195] 136+379+460+524, 136+379+461+513, 136+379+461+524, 136+379+513+524,

[0196] 136+381+459+460, 136+381+459+461, 136+381+459+513, 136+381+459+524,

[0197] 136+381+460+461, 136+381+460+513, 136+381+460+524, 136+381+461+513,

[0198] 136+381+461+524, 136+381+513+524, 136+459+460+461, 136+459+460+513,

[0199] 136+459+460+524, 136+459+461+513, 136+459+461+524, 136+459+513+524,

[0200] 136+460+461+513, 136+460+461+524, 136+460+513+524, 136+461+513+524,

[0201] 188+379+381+459, 188+379+381+460, 188+379+381+461, 188+379+381+513,

[0202] 188+379+381+524, 188+379+459+460, 188+379+459+461, 188+379+459+513,

[0203] 188+379+459+524, 188+379+460+461, 188+379+460+513, 188+379+460+524,

[0204] 188+379+461+513, 188+379+461+524, 188+379+513+524, 188+381+459+460,

[0205] 188+381+459+461, 188+381+459+513, 188+381+459+524, 188+381+460+461,

[0206] 188+381+460+513, 188+381+460+524, 188+381+461+513, 188+381+461+524,

[0207] 188+381+513+524, 188+459+460+461, 188+459+460+513, 188+459+460+524, 188+459+461 +513, 188+459+461+524, 188+459+513+524, 188+460+461 +513,

[0208] 188+460+461 +524, 188+460+513+524, 188+461 +513+524,

[0209] 379+381+459+460, 379+381 +459+461, 379+381 +459+513, 379+381+459+524,

[0210] 379+381+460+461 , 379+381 +460+513, 379+381 +460+524, 379+381+461 +513,

[0211] 379+381+461 +524, 379+381 +513+524, 379+459+460+461, 379+459+460+513,

[0212] 379+459+460+524, 379+459+461+513, 379+459+461 +524, 379+459+513+524,

[0213] 379+460+461 +513, 379+460+461+524, 379+460+513+524, 379+461+513+524,

[0214] 381+459+460+461 , 381+459+460+513, 381+459+460+524, 381+459+461 +513,

[0215] 381+459+461 +524, 381+459+513+524, 381+460+461 +513, 381+460+461 +524,

[0216] 381+460+513+524, 381+461 +513+524,

[0217] 459+460+461 +513, 459+460+461+524, 459+460+513+524, 459+461+513+524,

[0218] 460+461+513+524.

[0219] According to a further embodiment, Septoria tritici comprises at least five mutations in the CYP51 gene.

[0220] According to a further embodiment, Septoria tritici comprises at least six mutations in the CYP51 gene.

[0221] According to a further embodiment, Septoria tritici comprises at least seven mutations in the CYP51 gene.

[0222] According to a further embodiment, Septoria tritici comprises at least eight mutations in the CYP51 gene.

[0223] According to specific embodiments, Septoria tritici comprises at least the following mutation combinations:

[0224] . L50S (M 1) + 1381V (M 16) + Y461 H (M.26);

[0225] • L50S (M.1) +V136A (M.4) + Y461S (M.29);

[0226] • L50S (M.1) +V136A (M.4) + 1381V (M.16) + Y461S (M.29) + S524T (M.35);

[0227] • L50S (M.1) + D134G (M.3) + V136A (M.4) + 1381V (M.16) + Y461 H (M.26);

[0228] • L50S (M.1) + V136A (M.4) + 1381V (M.16) + Y461H (M.26);

[0229] • L50S (M.1) + S188N (M.8) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + N513K (M.34);

[0230] • L50S (M.1) + D134G (M.3) + V136A (M.4) + 1381V (M.16) + Y461 H (M.26) + S524T (M.35);

[0231] • L50S (M.1) + S188N (M.8) + A379G (M.15) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + N513K (M.34);

[0232] . L50S (M 1) + V136A (M.4) + S188N (M.8) + A379G (M.15) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) +

[0233] S524T (M.35);

[0234] . L50S (M 1) + V136C (M.5) + S188N (M.8) + A379G (M.15) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + S524T(M.35);

[0235] . V136A + S524T;

[0236] • V136A + 1381V + S524T;

[0237] • A379G + 1381V; . V136C + DEL459 + DEL460;

[0238] • A379G + 1381V + S524T + DEL459 + DEL460.

[0239] In one embodiment, the method comprises applying a fungicidally effective amount of compound (I) or compound (II) to the cereal plants.

[0240] In a further embodiment, the method comprises applying a fungicidally effective amount of compound (I) or compound (II) to the cereal seeds.

[0241] The term “cereal" as used herein comprises wheat and triticale.

[0242] Thus, in a preferred embodiment, the present invention relates to a method for controlling Septoria tritici that is resistant to DMI fungicides on wheat or triticale, comprising applying to the plants, their seed or the soil a fungicidally effective amount of compound (I) or compound (II).

[0243] In a further preferred embodiment, the method comprises applying to the wheat or triticale plants a fungicidally effective amount of compound (I) or compound (II).

[0244] In a further preferred embodiment, the method comprises applying to the wheat or triticale seeds a fungicidally effective amount of compound (I) or compound (II).

[0245] In a more preferred embodiment, the present invention relates to a method for controlling Septo a tritici that is resistant to DMI fungicides on wheat, comprising applying to the plants, their seed or the soil a fungicidally effective amount of compound (I) or compound (II).

[0246] In a further more preferred embodiment, the method comprises applying to the wheat plants a fungicidally effective amount of compound (I) or compound (II).

[0247] In a further more preferred embodiment, the method comprises applying to the wheat seeds a fungicidally effective amount of compound (I) or compound (II).

[0248] Application of the compound (I) or compound (II) to the plants, their seed or the soil in the method according to present invention may be carried out in spray application, in seed treatment, in drip and drench applications, in-furrow applications, on-seed application and overall soil incorporation, chemigation, i.e. by addition of the active ingredients to the irrigation water, and in hydroponic / mineral systems.

[0249] In the context of the present invention, fungicidal action against Septoria tritici means a significant reduction in primary infection by Septoria tritici, compared with the untreated plant, preferably a significant reduction (by a value of between 40-79% compared to an untreated control plant), compared with the untreated plant (100%); more preferably, the primary infection by Septaria tritici is entirely suppressed (by a value of between 80-100% compared to an untreated control plant). The control is for protection of plants which have not yet been infected.

[0250] In a preferred embodiment, the above reduction in primary infection by Septoria tritici, compared with the untreated plant is of at least 40%, more preferably at least 60%, even more preferably at least 70%.

[0251] In another preferred embodiment, the above reduction of at least 40%, more preferably at least 60%, even more preferably at least 70% is achieved by using at most 200 g a.i. 1 100kg seed, such as at most 150 g a.i. 1 100kg seed or such as at most 140 g a.i. / 100kg seed.

[0252] The term "plant propagation material" is to be understood to denote all the generative parts of the plant in particular seeds.

[0253] Plants and as well as the propagation material of said plants, which can be treated with fungicidally effective amount of compound (I) or compound (II) include all genetically modified plants or transgenic plants, e.g. crops which tolerate the action of herbicides or fungicides or insecticides owing to breeding, including genetic engineering methods, or plants which have modified characteristics in comparison with existing plants, which can be generated for example by traditional breeding methods and / or the generation of mutants, or by recombinant procedures.

[0254] For example, compounds (I) or (II) in a method according to the present invention can be applied (as seed treatment, spray treatment, in furrow or by any other means) also to plants which have been modified by breeding, mutagenesis or genetic engineering including but not limiting to agricultural biotech products on the market or in development (cf. http: / / www.bio.org / speeches / pubs / er / agri_products.asp). Genetically modified plants are plants, which genetic material has been so modified by the use of recombinant DNA techniques that under natural circumstances cannot readily be obtained by cross breeding, mutations or natural recombination. Typically, one or more genes have been integrated into the genetic material of a genetically modified plant in order to improve certain properties of the plant. Such genetic modifications also include but are not limited to targeted post-transitional modification of protein(s), oligo- or polypeptides e. g. by glycosylation or polymer additions such as prenylated, acetylated or farnesylated moie- ties or PEG moieties.

[0255] For use according to the present invention, compound (I) or compound (II) can be converted into the customary formulations, for example solutions, emulsions, suspensions, dusts, powders, pastes granules, pressings, capsules, and mixtures thereof. The use form depends on the particular intended purpose; in each case, it should ensure a fine and even distribution of the compound I or compound (II). The formulations are prepared in a known manner (cf. US 3,060,084, EP-A 707 445 (for liquid concentrates), Browning: "Agglomeration”, Chemical Engineering, Dec. 4, 1967, 147-48, Perry’s Chemical Engineer’s Handbook, 4th Ed., McGraw-Hill, New York, 1963, S. 8-57 und ff. WO 91 / 13546, US 4,172,714, US 4,144,050, US 3,920,442, US 5,180,587, US 5,232,701 , US 5,208,030, GB 2,095,558, US 3,299,566, Klingman: Weed Control as a Science (J. Wiley & Sons, New York, 1961), Hance et al.: Weed Control Handbook (8th Ed., Blackwell Scientific, Oxford, 1989) and Mollet, H. and Grubemann, A.: Formulation technology (Wiley VCH Verlag, Weinheim, 2001).

[0256] Examples for composition types (see also "Catalogue of pesticide formulation types and international coding system”, Technical Monograph No. 2, 6thEd. May 2008, CropLife International) are suspensions (e. g. SC, CD, FS), emulsifiable concentrates (e. g. EC), emulsions (e. g. EW, EC, ES, ME), capsules (e. g. CS, ZC), pastes, pastilles, wettable powders or dusts (e. g. WP, SP, WS, DP, DS), pressings (e. g. BR, TB, DT), granules (e. g. WG, SG, GR, FG, GG, MG), insecticidal articles (e. g. LN), as well as gel formulations for the treatment of plant propagation materials, such as seeds (e. g. GF).

[0257] The formulations may comprise auxiliaries which are customary in agrochemical formulations. The auxiliaries used depend on the particular application form and active substance, respectively.

[0258] Examples for suitable auxiliaries are solvents, solid carriers, dispersants or emulsifiers (such as further solubilizers, protective colloids, surfactants and adhesion agents), organic and inorganic thickeners, bactericides, anti-freezing agents, anti-foaming agents, if appropriate colorants and tackifiers or binders (e. g. for seed treatment formulations).

[0259] The formulations generally comprise between 0.01 and 95%, preferably between 0.1 and 90%, most preferably between 0.5 and 90%, by weight of active substances.

[0260] The active substance concentrations in the ready-to-use preparations can be varied within relatively wide ranges. In general, they are from 0 0001 to 10%, preferably from 0.001 to 1 % by weight of compound (I) or compound (II).

[0261] Compound (I) or compound (II) may be used together with other pesticides, such as herbicides, fungicides, insecticides or bactericides. These agents can be admixed with compound (I) or compound (II) in a weight ratio of 1 :100 to 100: 1, preferably 1 :10 to 10: 1 , if appropriate immediately prior to use (tank mix).

[0262] Compound (I) or compound (II) may also be used together with fertilizers such as ammonium nitrate, urea, potash, and superphosphate, phytotoxicants and plant growth regulators and safeners. These may be used sequentially or in combination with the above-described compositions, if appropriate also added only immediately prior to use (tank mix). For example, the plant(s) may be sprayed with a composition of this invention either before or after being treated with the fertilizers.

[0263] Compound (I) or compound (II) are applied by treating the fungi or the plants, plant propagation materials (preferably seeds), materials or soil to be protected from fungal attack with a pesticidal effective amount of compound (I) or compound (II). The application can be carried out both before and after the infection of the materials, plants or plant propagation materials (preferably seeds) by the pests. In general, " pesticidal effective amount" means the amount of compound (I) or compound (II) or of compositions comprising compound (I) or compound (II) needed to achieve an observable effect on growth, including the effects of necrosis, death, retardation, prevention, and removal, destruction, or otherwise diminishing the occurrence and activity of the target organism. The pesticidal effective amount can vary. A pesticidal effective amount will also vary according to the prevailing conditions such as desired pesticidal effect and duration, weather, target species, locus, mode of application, and the like.

[0264] In the method of combating harmful fungi depending on the desired effect, the application rates of compound (I) or compound (II) are from 0,1 g / ha to 10000 g / ha, preferably 2 g / ha to 2500 g / ha, more preferably from 5 to 1000 g / ha, most preferably from 10 to 750 g / ha, in particular from 20 to 700 g / ha.

[0265] In an alternative embodiment of the invention, the compound (I) or compound (II) are used for the protection of the seed and the seedlings' roots and shoots, preferably the seeds as set forth above.

[0266] The compositions comprising compound (I) or compound (II) can be applied to plant propagation materials, particularly seeds, diluted or undiluted. The compositions in question give, after two-to-tenfold dilution, active substance concentrations of from 0.01 to 60% by weight, prefer-ably from 0.1 to 40% by weight, in the ready-to-use preparations. Application can be carried out before or during sowing. Methods for applying agrochemical compounds and compositions thereof, respectively, on to plant propagation material, especially seeds, are known in the art, and include dressing, coating, pelleting, dusting and soaking application methods of the propagation material (and also in furrow treatment). In a preferred embodiment, the compounds or the compositions thereof, respectively, are applied on to the plant propagation material by a method such that germination is not induced, e. g. by seed dressing, pelleting, coating and dusting.

[0267] In the treatment of plant propagation material (preferably seed), the application rates of the inventive mixture are generally for the formulated product (which usually comprises frornlO to 750 g / l of the active(s)).

[0268] Greenhouse

[0269] Example 1 - Curative and protective control of Septoria spot blotch caused by Zymoseptoria tritici

[0270] The respective compound was dissolved in a mixture of acetone and the wetting agent / emulsifier Wettol, which is based on ethoxylated alkylphenoles, in a ratio (volume) solvent-emulsifier of 99 to 1 to give a total volume of 5 ml. Subsequently, water was added to total volume of 100 ml.

[0271] This stock solution was then diluted with the described solvent-emulsifier-water mixture to the concentration given in the table below. Leaves of potted wheat seedlings with 1-2 developed leaves were sprayed with the previously described spray solution. Plants are inoculated with spores of Zymoseptoria tritici either 4 days before (4 day curative application timing) or 7 days after (7 days protective application timing) the spray application, respectively. To ensure the success of the artificial inoculation, the plants were transferred to a moist chamber with a relative humidity of about 85% and 20°C. Following the incubation at ambient light for 24h, the plants were cultivated for 20 days in a greenhouse chamber at 20°C and a relative humidity of about 80%. The extent of fungal attack on the leaves was visually assessed as % diseased leaf area.

[0272] Two isolates representing CYP51 haplotypes E4 and H6 (Huf et al. 2018) were used in the experiment to inoculate the plants. The alterations of both haplotypes in the amino acid sequence of the CYP51 is described and shown to cause moderate (E4) to strong (H6) adaptation to prothioconazol in Huf et al. 2018.

[0273] Table 1 : Amino acid alterations of tested haplotypes of the CYP51 gene of Zymoseptoria tritici

[0274] Position of amino acid alterations

[0275] Haplotype L50 D134 V136 S188 A379 1381 Y459 G460 Y461 N513 S524

[0276] E4 S G A - - V - - H - -

[0277] H6 S - C N G V Del Del - - T

[0278] The disease ratings (or diseased leaf area) were converted into efficacies. An efficacy of 0 means that the infection level of the treated plants corresponds to that of the untreated control plants; an efficacy of 100 means that the treated plants were not infected.

[0279] Table 2: Efficacy of prothioconazol, mefentrifluconazol and compound (I) against Zymoseptoria tritici isolates adapted to DMIs

[0280] The results in table 2 show the efficacy of compound (I) in comparison to the important DMI benchmarks, prothio- conazol and mefentrifluconazol. Prothioconazol efficacy is significantly affected by the adaption of Zymoseptoria tritici haplotype E4 and shows only at the highest concentration of 63 ppm and only at the curative spray timing sufficient control, whereas mefentrifluconazol and compound (I) provide excellent control to this haplotype down to the lowest concentration of 1 ppm regardless of the spray timing (4 days curative or 7 days protective, respectively Prothioconazol does not control the currently most DMI adapted haplotype H6. This haplotype also causes moderate loss of efficacy for mefentrifluconazol at tested dose rates. Mefentrifluconazol shows still good to excellent control of the H6 haplotyp at 63 ppm in greenhouse conditions and poor to good control at 16ppm depending on the spray timing, but only no to poor control at 4 and 1 ppm. In contrast, compound (I) shows full and excellent control of the H6 haplotyp at 63 and 16 ppm, regardless of the spray timing and still a good control at the curative timing at 4 ppm. In conclusion, compound (I) is less affected by the adaption of the E4 haplotype of Zymoseptoria tritici against DMIs than prothioconazol similar to mefentrifluconazol and less affected by the H6 haplotype than both prothioconazol and mefentrifluconazol.

Claims

Claims1. A method for controlling Septoria tritici resistant to DM I fungicides in cereals, comprising applying to the plants, their seed or the soil a fungicidal ly effective amount of (I) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2- hydroxy-3-(1,2,4-triazol-1-yl)propanoate or (II) 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4- triazol- 1 -yl)propanoic acid, wherein the Septoria tritici comprises at least one mutation in the CYP51 gene.

2. A method according to claim 1 , wherein the mutation occurs in the amino acid positions selected from 50, 107, 134, 136, 137, 178, 188, 208, 259, 284, 303, 311, 312, 379, 381 , 410, 412, 459, 460, 461 , 476, 490, 510, 513 or 524.

3. A method according to claims 1 or 2, wherein the mutation occurs in the amino acid positions selected from 50, 134, 136, 188, 379, 381, 459, 460, 461, 513 or 524.

4. A method according to any one of claims 1 to 3, wherein the mutation is selected fromM.1 L50S, M.2 D107V, M.3 D134G, M.4 V136A, M.5 V136C,M.6 Y137F, M.7 N178S, M.8 S188N, M.9 S208T, M.10 S259F,M.11 N284H, M.12 H303Y, M.13 A311G, M.14 G312A, M.15 A379G,M.16 1381V, M.17 A410T, M.18 G412A, M.19 Y459C, M.20 Y459D,M.21 Y459S, M.22 Del459, M.23 G460D, M.24 Del460, M.25 Y461G,M.26 Y461H, M.27 Y461 L M 28 Y461 N, M.29 Y461S, M.30 Del461 ,M.31 G476S, M.32 V490L, M 33 G510C, M.34 N513K, M.35 S524T.5 A method according to to any one of claims 1 to 4, wherein the Septoria tritici comprises at least two mutations in the CYP51 gene.

6. A method according to any one of claims 1 to 5, wherein Septoria tritici comprises the mutations selected from the following combinations:. L50S (M.1) + 1381V (M.16) + Y461 H (M.26);. L50S (M.1) + V136A (M.4) + Y461S (M.29);. L50S (M.1) + V136A (M.4) + 1381V (M.16) + Y461S (M.29) + S524T (M.35);. L50S (M.1) + D134G (M.3) + V136A (M.4) + 1381V (M.16) + Y461 H (M.26);. L50S (M.1) + V136A (M.4) + 1381V (M.16) + Y461H (M.26);. L50S (M.1) + S188N (M.8) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + N513K (M.34);. L50S (M.1) + D134G (M.3) + V136A (M.4) + 1381V (M.16) + Y461H (M.26) + S524T (M.35);. L50S (M.1) + S188N (M.8) + A379G (M.15) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + N513K (M.34);. L50S (M.1) + V136A (M.4) + S188N (M.8) + A379G (M.15) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + S524T (M.35);. L50S (M.1) + V136C (M.5) + S188N (M.8) + A379G (M.15) + 1381V (M.16) + Del459 (M.22) + Del460 (M.24) + S524T (M.35);. V136A (M.4) + S524T (M.35);. V136A (M.4) + 1381V (M.16) + S524T (M.35);. A379G (M.15) + 1381V (M.16);. V136C (M.5) + DEL459 (M.22) + DEL460 (M.24);. A379G (M.15) + 1381V (M.16) + DEL459 (M.22) + DEL460 (M.24) + S524T (M.35).

7. A method according to any one of claims 1 to 6, wherein compound (I) or compound (II) is applied to the plants, soil or seed of plants.

8. A method according to any one of claims 1 to 7, wherein compound (I) or compound (II) is applied to the plants.

9. A method according to any one of claims 1 to 7, wherein compound (I) or compound (II) is applied to the soil.

10. A method according to any one of claims 1 to 7, wherein compound (I) or compound (II) is applied to the seed of plants.

11. A method according to any of claims 1 to 9, wherein compound (I) or compound (II) is applied to plants or soil in an amount from 5 g / h a to 2500 g / ha.

12. A method according to any one of claims 1 to 7 or 10, wherein compound (I) or compound (II) is applied to seeds in an amount from 0.01 g to 10 kg per 100 kg.

13. A method according to any of claims 1 to 12, wherein the cereal is wheat or triticale.

14. Use of (I) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1 ,2,4-triazol-1-yl)propanoate or (II) methyl 2-[2-chloro-4-(4-chlorophenoxy)phenyl]-2-hydroxy-3-(1,2,4-triazol-1-yl)propanoic to control Septoria tritici, that is resistant to DMI fungicides, in cereals, wherein Septoria tritici comprises at least one mutation in the CYP51 gene.

15. Use according to claim 14, wherein the cereal is wheat or triticale.

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