WO2002059104A1

WO2002059104A1 - Rustmicin derivatives

Info

Publication number: WO2002059104A1
Application number: PCT/EP2002/000617
Authority: WO
Inventors: Andreas Gypser; Ingo Rose; Eberhard Ammermann; Siegfried Strathmann; Gisela Lorenz; Reinhard Stierl; John-Bryan Speakman
Original assignee: Basf Aktiengesellschaft
Priority date: 2001-01-24
Filing date: 2002-01-23
Publication date: 2002-08-01

Abstract

The invention relates to rustmicin derivatives of formula (I) wherein the radicals have the following designations: R1 represents hydrogen or -C(=O)R5; R2 represents -CH¿2?-OR?6, -CH¿2-SR6 or =CH¿2; R?3 represents OCH¿3?, CH3 or NHOR?7; R4¿ represents OH, =0 or =NOR8; R5 represents hydrogen, C¿1?-C6 alkyl or optionally substituted phenyl; R?6¿ represents hydrogen or the group -C(=0)R5; R7 represents hydrogen, C¿1?-C6 alkyl, or phenyl-C1-C6-alkyl, said phenyl radical being able to be unsubstituted or substituted; and R?8¿ represents hydrogen, C¿1?-C6 alkyl, or phenyl-C1-C6-alkyl, said phenyl radical being able to be unsubstituted or substituted. The invention also relates to agrochemical or pharmaceutical compositions containing a fungicidally active quantity of a compound of formula (I).

Description

Rustmicin-Deπvate

description

The present invention relates to new rustmicin derivatives, as well as agrochemical and pharmaceutical compositions with fungicidal activity, which contain these rustmicin derivatives.

From the state of the art, the polyketides include the compounds galbonolide A (rustmicin) and galbonolide B are known (J. Antibiotics 1985, 38: 1807 and J. Antibiotics 1985, 39: 1760).

Fig. 1:

Galbonolide A Galbonolide B Galbonolide C Rustmicin Neorustmicin A

The compounds show fungicidal activity against various pathogens in the human field (Candida species, Fusarium, Rhodotorula) and agricultural areas, here in particular Botrytis cinerea and Puccinia graminis. JP 60-6197 (Meji Seika) describes the fermentation of rustmicin and galbonolide B from Micromomospora chalcea and their use against rust fungi (Puccinia graminis) on wheat. DE 3632168 (Ciba Geigy) describes the fermentation of rustmicin and galbonolide B from Streptomyces galbus and its use as a fungicide against gray mold (Botrytis cinerea). DE 3632168 also describes the compounds derivatized on the two hydroxyl groups as esters, ethers or salts.

Other derivatives, the so-called neorustmicins, exist in the environment of the compounds mentioned above. Neorustmicin A is described in Annais of the Y Academy of Sciences 1988, 544: 128 with the structure shown in Fig. 1. In J. Antibiotics 1985, 38: 1810 the structure for Neorustmicin A was however postulated by Galbonolide B. In the present application the nomenclature used in CAS is used (see Fig. 1).

The structures of the Neorustmicine B, C and D are given in Fig. 2.

Fig. 2:

Neorustmicin B Neorustmicin C Neorustmicin D

GB 2324300 (Merck & Co. Inc.) describes two further derivatives obtained from rustmicin or neorustmicin A by bio-transformation (see Fig. 3) and their preparation (see also J. Antibiotics 1998, 51: 837) ,

Fig. 3:

US Pat. No. 5,948,770 (Merck, S&D) describes further derivatives which differ structurally in particular from longer alkyl or alkoxy radicals. In addition, the macrocycle can also be closed by a lactam instead of an acton ring (Fig. 4). Fig.

In two further publications it is described that rustmicin and the derivatives derived therefrom develop their biological action by inhibiting the enzyme inositol phosphorylceramide synthase (J. Antibiotics 1998, 51: 837; J. Biol. Chem. 1998, 273: 14942).

It is also known from the literature (Annais of the NY Acade y of Sciences 1988, 544: 128) that rustmicin and its derivatives are not chemically stable (see Fig. 5).

Fig. 5

2-epi-Rustmicin

Under the influence of aqueous acids, the enol ether functionality is split into the ketone. Cyclization to furan takes place under anhydrous conditions. Bases like pyridine provide Epimerization of the C2 atom, conditions such as potassium carbonate / methanol cleave the macrolactone ring and lead to the formation of an α-valerolactone within two minutes, which no longer exhibits any fungicidal activity. J. Biol. Chem. 1998, 273: 14942 states that the half-life of rustmicin in a neutral solution is 80 min. The highest stability can be found at pH 5.5. In view of the low stability of these macrolides, their use as active ingredients in the agrochemical or pharmaceutical industry is not suitable for the production of agrochemical compositions or of medicaments.

The problem on which the present invention is based was to provide new macrolides which have increased stability in comparison with the known, not sufficiently stable macrolides.

This problem was solved by the new rustmicin derivatives. Surprisingly, by means of suitable chemical modification, it was possible to significantly increase the stability of the rustmicin derivatives according to the invention, without this being associated with a loss of the fungicidal action. Compared to the known (unstable) rustmicin derivatives, the compounds according to the invention even show an improvement in the fungicidal activity. The improvement is based on the one hand on a broader effect against various pathogenic fungi, and on the other hand also in an increased effectiveness (lower application rates).

The present invention accordingly relates to rustmicin derivatives of the formula I.

where the residues have the following meanings: R ^{1 is} hydrogen or -C (= 0) R ⁵ ; R ² -CH ₂ -OR ⁶ , CH ₂ -SR ⁶ or = CH ₂ ; R ³ -OCH ₃ , -CH ₃ or -NHOR ⁷ ; R ⁴ OH, = 0 or = NOR ⁸ ; R ^{5 is} hydrogen, -CC ₆ alkyl or optionally substituted

Phenyl; R ^{5 is} hydrogen or the group -C (= 0) R ⁵ ; R ^{7 is} hydrogen, Ci-C _δ alkyl; Phenyl-Ci-C _δ- alkyl, the

Phenyl radical may be unsubstituted or substituted; R ^{8 is} hydrogen, Ci-C _ß alkyl; Phenyl-Ci-C _δ- alkyl, the

Phenyl radical may be unsubstituted or substituted;

and their agriculturally and / or pharmaceutically acceptable salts or tautomers,

with the exception of those compounds in which, in the event that R ^{1 is} hydrogen, R ^{2 is} the group = CH and R ^{4 is} the group = 0, R ^{3 is} not C ₁ -C ₆ -alkyl or Cχ-C ₆ -alkoxy.

The aforementioned dislaimer excludes the compounds galbonolide A and galbonolide B described in the prior art (see FIG. 1) and the compounds described in US Pat. No. 5,948,770 (see FIG.).

In the definition of the substituents R ¹ - R ⁸ , the terms given stand as a collective term for a group of compounds.

The radicals each have the meanings given below, alone or in combination with one another.

In particular:

Halogen for fluorine, chlorine or bromine;

Ci-Cg-alkyl for a straight-chain or branched alkyl radical with 1-6 C atoms, such as e.g. Methyl, ethyl, n-propyl, 1-methyl-ethyl, n-butyl, 1-methylpropyl, 2-methylpropyl or 1, 1-dimethylethyl, especially for ethyl;

- Phenyl for a phenyl radical which is unsubstituted or can be substituted one or more times. The substituents are arbitrary and can be ortho, eta or para; such as halogen atoms, Ci-Cg-alkyl, halogen-Ci-C _δ- alkyl, Cι-C ₅ alkoxy, Cx-Ce-haloalkoxy, Cι-C ₆ alkylthio, Ci-Cg-alkylsulfonyl, Ci-Cg-haloalkylsulfonyl as mentioned above; Cχ-C ₆ haloalkyl for a Ci-Cg-alkyl radical as mentioned above, which is partially or completely substituted by fluorine, chlorine, bromine and / or iodine, such as trichloromethyl, trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2nd -Bromethyl, 2,2-difluoroethyl, 2, 2, 2-trifluoroethyl, 2, 2, 2-trichloroethyl, 2-fluoropropyl, 3-fluoropropyl, 2-chloropropyl or 3-chloropropyl, in particular for 2-fluoroethyl or 2 chloroethyl;

Ci-C _δ alkoxy for a straight-chain or branched Ci-Cg alkoxy radical, such as methoxy, ethoxy, n-propoxy,

1-methylethoxy, n-butoxy, 1-methylpropoxy, 2-methylpropoxy or 1, 1-dirnethylethoxy, especially for methoxy or ethoxy;

- Halogen-Cχ-C ₆ -alkoxy for a Ci-Cg alkoxy radical as mentioned above, which is substituted one or more times by fluorine, chlorine or bromine, for example trifluoromethoxy;

C ₁ -C ₆ alkylthio for a sulfur atom which is substituted by a C ₁ -C ₆ -alkyl radical as mentioned above;

Ci-C _ß- alkylsulfonyl for a sulfonyl group which is substituted by a C] _- C ₆ -alkyl radical as mentioned above;

- Halogen-Ci-C _δ- alkylsulfonyl for a C] _- Cg-alkylsulfonyl radical as mentioned above, which is mono- or polysubstituted by fluorine, chlorine or bromine.

The compounds of the formula I can also be present in the form of their agriculturally and / or pharmaceutically acceptable salts, the type of salt generally not being important. In general, the salts of those cations or the acid addition salts of those acids whose cations or anions do not adversely affect the fungicidal activity of the compounds I are suitable.

As agriculturally useful cations there are in particular ions of the alkali metals, preferably lithium, sodium and potassium, of the alkaline earth metals, preferably calcium and magnesium, and of the transition metals, preferably manganese, copper, zinc and iron, and ammonium, where one to four hydrogen atoms pass through if desired -C-C ₄ alkyl, hydroxy-Cχ-C ₄ -alkyl, C ₁ -C ₄ -AI- koxy-Cι-C ₄ -alkyl, hydroxy-Cι-C ₄ -alkoxy-Cι-C ₄ alkyl, phenyl or may be replaced by benzyl, preferably ammonium, dimethylammonium, diisopropylammonium, tetramethylammonium, tetrabutylammonium, 2- (2-hydroxy-eth-l-oxy) eth-l-yl-ammonium, di (2-hydroxy-eth -l-yl) ammonium, trimethylbenzylammonium, furthermore, phosph honiumionen, sulfonium ions, preferably tri _(C]. -C ₄ alkyl) sulfonic Fonium and Sulfoxoniu ions, preferably tri _(Cι-C4 alkyl) sulfoxides oxonium, into consideration.

Anions of acid addition salts which can be used in agriculture are primarily chloride, bro id, fluoride, hydrogen sulfate, sulfate, dihydrogen phosphate, hydrogen phosphate, nitrate, hydrogen carbonate, carbonate, hexafluorosilicate, hexafluorophosphate, benzoate and the anions of C 1 -C ₄ -alkanoic acids, preferably Formate, acetate, propionate and butyrate.

Possible pharmaceutically usable cations are, in particular, ions of the alkali metals, preferably sodium and potassium, and of the alkaline earth metals, preferably calcium and magnesium.

Pharmaceutically usable anions of usable acid addition salts are, for example, hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate or bisulfate, phosphate or hydrogen phosphate, acetate, lactate, citrate or hydrogen citrate, tastrat or bi-tartar, succinate, maleate, fumarate, gluconate, Saccharate, benzoate, methyl sulfonate, ethyl sulfonate, benzenesulfonate, p-toluenesulfonate and pamoates (e.g. 1, 1 '-methylene-bis- (2-hydroxy-3-naphthoate).

The compounds I according to the invention can also exist in their corresponding tautomeric forms, which are also encompassed by the general formula I and are the subject of the present invention. In the event that, for example, R ³ denotes the group -NHOR ⁷ , compounds I can also exist in the following form:

For the purposes of the present invention, the following compounds I and definitions of the radicals R ¹ -R ⁸ are preferably used alone or in combination with one another or in connection with the general conditions described in the claims Writing of the present invention meanings of the various radicals or their preferred meanings mentioned in question:

1. Compounds I, where the radicals have the following meanings: R ² -CH ₂ -OR ⁶ ; R ³ = N0R ⁷ ; R ⁴ = 0 (see formula IA).

2. Compounds I, where the radicals have the following meanings: R ² = CH ₂ ; R ³ = NOR ⁷ ; R ⁴ = N0R ⁸ (see formula IB).

3. Compounds I, where the radicals have the following meanings: R ² -CH ₂ - OR ⁶ ; R ³ OCH ₃ or CH ₃ ; R ⁴ = N0R ⁸ (see formula IC).

4. Compounds I, where the radicals have the following meanings: R ² = CH ₂ ; R ³ = NOR ⁷ ; R ⁴ OH (see formula ID).

5. Compounds I, where the radicals have the following meanings: R ² -CH ₂ -OR ⁶ ; R ³ 0CH ₃ or CH ₃ ; R ⁴ OH (see formula IE).

6. Compounds I, where the radicals have the following meanings: R ² -CH ₂ - OR ⁶ ; R ³ OCH ₃ or CH ₃ ; R ⁴ = 0 (see formula IF).

7. Compounds I, where the radicals have the following meanings: R ² = CH ₂ ; R ³ = N0R ⁷ ; R ⁴ = 0 (see formula IG).

8. Compounds I, where the radicals have the following meanings: R ² = CH ₂ ; R ³ 0CH ₃ or CH ₃ ; R ⁴ OH (see formula IH).

9. Compounds I, where the radicals have the following meanings: R ² = CH ₂ ; R ³ 0CH ₃ or CH ₃ ; R ⁴ = N0R ⁸ (see formula IJ).

For the purposes of the present invention, the following compounds are preferred as fungicidal active ingredients IA - IE:

ID IE

For the purposes of the present invention, the following compounds of the formula IF-IJ are particularly preferred:

IF IG

IJ

The compounds of the formula IA 1 are extraordinarily preferred (corresponds to formula IA with R ⁷ = CH ₃ )

10 I A 1

in particular the compounds I A 1.1 to I A 1.289 (Table 1):

Table 1

15

The compounds of the formula I A 2 are likewise preferred,

I A 2

in particular the compounds IA 2.1 to IA 2.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} C ₂ H ₅ .

The compounds of the formula I A 3 are likewise preferred,

I A 3

in particular the compounds IA 3.1 to IA 3.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} nC ₃ H.

The compounds of the formula IA 4 are likewise preferred,

IA 4 in particular the compounds IA 4.1 to IA 4.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} iC ₃ H.

The compounds of the formula I A 5 are likewise preferred,

I A 5

in particular the compounds IA 5.1 to IA 5.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} nC ₄ Hg.

The compounds of the formula IA 6 are likewise preferred,

IA 6 in particular the compounds IA 6.1 to IA 6.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 stands} for iC ₄ Hg.

The compounds of the formula I A 7 are likewise preferred,

I A 7

in particular the compounds IA 7.1 to IA 7.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} SC ₄ H ₉ .

The compounds of the formula I A 8 are likewise preferred,

IA in particular the compounds IA 8.1 to IA 8.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} tC ₄ H ₉ .

The compounds of the formula I A 9 are likewise preferred,

IA 9 in particular the compounds IA 9.1 to IA 9.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} nC ₅ Hn.

The compounds of the formula I A 10 are likewise preferred,

I A 10

in particular the compounds IA 10.1 to IA 10.289, which differ from the compounds IA 1.1 to IA 1.289 (Table 1) in that R ^{7 is} nC ₆ Hι ₃ .

The compounds of the formula IB 1 are extremely preferred (corresponds to formula IB with R ⁷ = CH ₃ )

I B 1

in particular the compounds I B 1.1 to I B 1.289 (Table 2):

Table 2

The compounds of the formula I B 2 are likewise preferred,

I B 2

in particular the compounds IB 2.1 to IB 2.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ^{7 is} CHs.

The compounds of the formula I B 3 are likewise preferred,

I B 3

in particular the compounds IB 3.1 to IB 3.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ^{7 is} nC ₃ H ₇ .

Likewise preferred are the compounds of formula IB 4,

I B 4

in particular the compounds IB 4.1 to IB 4.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ⁷ stands for iCH.

The compounds of the formula I B 5 are likewise preferred,

I B 5

in particular, the compounds of IB 5.1 to 5,289 IB, the IB to 1,289 (Table 2) thereby separate from the compounds IB 1.1 under ^¬ that R ⁷ nC ₄ H ₉ stands.

The compounds of the formula I B 6 are likewise preferred,

IB 6 in particular the compounds IB 6.1 to IB 6.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ^{7 is} iC ₄ Hg.

The compounds of the formula I B 7 are likewise preferred,

I B 7

in particular the compounds IB 7.1 to IB 7.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ^{7 stands} for sCH ₉ .

The compounds of the formula I B 8 are likewise preferred,

I B

in particular the compounds IB 8.1 to IB 8.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ^{7 is} tC ₄ H ₉ .

The compounds of the formula IB 9 are likewise preferred,

I B 9

in particular the compounds IB 9.1 to IB 9.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ⁷ stands for nCsHn.

The compounds of the formula I B 10 are likewise preferred,

I B 10

in particular the compounds IB 10.1 to IB 10.289, which differ from the compounds IB 1.1 to IB 1.289 (Table 2) in that R ^{7 is} nCgH] _ ₃ .

The compounds of the formula IC 1 are extraordinarily preferred (corresponds to formula IC with R ⁸ = CH ₃ )

IC 1 in particular the compounds IC 1.1 to IC 1.289 (Table 3):

Table 3

Likewise preferred are the compounds of formula IC 2

I C 2

in particular the compounds IC 2.1 to IC 2.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} C ₂ H ₅ .

Likewise preferred are the compounds of formula I C 3,

I C 3

in particular the compounds IC 3.1 to IC 3.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} nC ₃ H ₇ .

Likewise preferred are the compounds of formula I C 4,

IC 4 in particular the compounds IC 4.1 to IC 4.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} iC ₃ H.

Likewise preferred are the compounds of formula I C 5,

I C 5

in particular the compounds IC 5.1 to IC 5.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} nC ₄ H ₉ .

Likewise preferred are the compounds of formula I C 6,

I C 6

in particular the compounds IC 6.1 to IC 6.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} iC ₄ H ₉ .

Likewise preferred are the compounds of formula IC 7

I C 7

in particular the compounds IC 7.1 to IC 7.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} ΞC ₄ H ₉ .

Likewise preferred are the compounds of formula I C 8,

I C 8

in particular the compounds IC 8.1 to IC 8.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 stands} for tC ₄ Hg.

The compounds of the formula I are also preferred,

IC 9 in particular the compounds IC 9.1 to IC 9.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ⁸ stands for nCsHn.

Likewise preferred are the compounds of the formula I C 10,

I C 10

in particular the compounds IC 10.1 to IC 10.289, which differ from the compounds IC 1.1 to IC 1.289 (Table 3) in that R ^{8 is} nCHι ₃ .

The compounds of the formula ID are extraordinarily preferred (corresponds to formula I, where the radicals R ² , R ³ and R ^{4 have the} following meanings: R ² = CH ₂ , R ³ = NOR ₇ , R ⁴ OH)

I D

in particular the compounds I D 1 to I D 170 (Table 4):

Table 4

The compounds of the formula I G are likewise preferred

I G

in particular the compounds IG 1 to IG 170, which differ from the compounds ID 1 to ID 170 (Table 4) in that R ^{4 stands} for = 0.

The compounds of the formula IE are particularly preferred (corresponds to formula I, where the radicals R ² , R ³ and R ^{4 have the} following meanings: R ² -CH ₂ -OR ⁶ , R ³ OCH ₃ or CH ₃ , R ⁴ OH)

I E

in particular the compounds I E 1 to I E 289 (Table 5;

Table 5

Likewise preferred are the compounds of formula I F,

I F

in particular the compounds IF 1 to IF 289, which differ from the compounds ID 1 to ID 289 (Table 5) in that R ^{4 is} = 0.

The compounds of the formula IH are extraordinarily preferred (corresponds to formula I, where the radicals R ² , R ³ and R ^{4 have the} following meanings: R ² = CH ₂ , R ³ OCH ₃ or CH ₃ , R ⁴ OH)

I H

in particular the compounds IH 1 to IH 17 (Table 6): Table 6

The compounds of the formula IJ are extraordinarily preferred (corresponds to formula I, where the radicals R ² , R ³ and R ^{4 have the} following meanings: R ² = CH ₂ , R ³ 0CH ₃ or CH ₃ , R ⁴ = NOR ⁸ )

I J

in particular the compounds I J 1 to I J 170 (Table 7)

The synthesis of the compounds according to the invention is carried out analogously to the synthesis described from rustmicin or galbonolide B, which is described in J. Antibiotics 1998, 51: 829. or Ann. N. Y: Acad. Be. 1988, 544: 128, described fermentation processes are accessible. The synthesis strategy was designed in such a way that the methods used for the derivatization of the individual parts of the molecule can also be used for the synthesis of more highly derivatized compounds.

The simply derivatized rustmicin analogues are accessible via the following reaction sequences:

A multi-stage reaction sequence is carried out for the substances of type VII: after protecting the two alcoholic hydroxyl groups as triethylsilyl ether (TES) (J. Chem. Soc. Chem. Commun. 1979, 156), the exoeyclic double bond is selectively hydroborated and then oxidized to alcohol ( J. Am Chem. Soc. 1988, 110, 1963). The resulting hydroxyl group can then by standard methods to the corresponding ester or sulfonic säureester be converted (Protective Groups in Organic synthesis sis, 2 ed ^nd., Iley & Sons Inc., NY, 1991), for example by reaction with an acid chloride such as R ⁶ C0C1 or a sulfonic acid chloride such as R ⁶ S0 ₂ C1 under the influence of base (for example DIPEA = diisopropylethyla in = Hünig base). The TES groups are split off with, for example, 2% HF in aprotic solvent such as B. Acetonitrile leads in the final step to the derivatives of type VII (Tetrahedron Lett. 1985, 26, 5239).

OCH ₃ or CH ₃

VII

Sequence A

Type VIII derivatives are obtained after acid-catalyzed cleavage of the enol ether function to give the ketone (previously described in Annais of the NY Academy of Sciences 1988, 544: 128) and subsequent reaction of the keto function with hydroxylamines to give oxime ether VIII (analogously to Heterocycles 1990, 31: 2121-2124 ) (Sequence B).

Sequence B

The reaction of rustmicin or galbonolide B with at least three equivalents of lithium (tris (sec. Butyl)) borohydride leads to the derivatives of type IX (Tetrahedron Lett. 1987, 28:35) (sequence C).

The keto function already present in rustmicin or galbonolide B can also be converted into the oxime ether by reaction with hydroxylamine hydrochloride and subsequent alkylation: sequence D leads to the derivatives of type X.

Sequence D

Starting from these simply derivatized rustmicins, the doubly modified representatives II to VI are synthesized in the following way:

Starting from structures of type VII, the oxime ether derivatives II are synthesized using sequence B.

Sequence B

VII

Starting from X, the same reaction pathway leads to the compounds of type III. Sequence B

III

Sequence D converts the compounds VII into the final stages IV.

VII IV

Type V compounds are obtained by converting the enol ether function to IX using sequence B.

IX V

Finally, the triply derivatized representatives Ia and Ib can be synthesized from the compounds of types II to V, II being expediently used as the starting product. Use of sequence C leads to la, use of sequence D results in Ib.

lb

In all the above described compounds I to X, the primary hydroxyl group can be selectively at the end by standard methods to the corresponding ester or sulfonic acid ester are transferred {Protective Groups in Organic Synthesis, 2 ^nd ed., Wiley S Sons Inc., NY, 1991).

The compounds according to the invention are distinguished by better stability in comparison with the rustmicin derivatives known from the prior art. A useful stability criterion is the investigation of the half-life under standard conditions (aqueous solution at pH 7). This half-life is an indication of the general stability of the rustmicin derivatives, although higher stability of the rustmicin derivatives can be achieved under changed conditions (e.g. shifting the pH optimum). For example, while rustmicin has a half-life of 80 minutes under standard conditions, the compounds according to the invention are distinguished by an increased half-life of at least 100 minutes.

The compounds I are distinguished by an outstanding action against a broad spectrum of phytopathogenic fungi, in particular from the class of the Ascomycetes, Deuteromycetes,

Phycomycetes and Basidiomycetes, from. Some of them are systemic effective and can therefore also be used as leaf and soil fungicides.

Usually the plants are sprayed or dusted with the active ingredients or the seeds of the plants are treated with the active ingredients.

The formulations (fungicidal agents) are prepared in a known manner, for example by extending the active ingredient with solvents and / or carriers, if desired using emulsifiers and dispersants, where in the case of water ^' other diluents are also used as auxiliary solvents can. The following are essentially considered as auxiliaries: solvents such as aromatics (e.g. xylene), chlorinated aromatics (e.g. chlorobenzenes), paraffins (e.g. petroleum fractions), alcohols (e.g. methanol, butanol), ketones (e.g. cyclohexanone), amines (e.g. ethanolamine) , Dirnethylformamide) and water; Carriers such as natural rock powder (eg kaolins, clays, talc, chalk) and synthetic rock powder (eg highly disperse silica, silicates); Emulsifiers such as nonionic and anionic emulsifiers (eg polyoxyethylene fatty alcohol ethers, alkyl sulfonates and aryl sulfonates) and dispersants such as lignin sulfite waste liquors and methyl cellulose.

The alkali, alkaline earth, ammonium salts of aromatic sulfonic acids, e.g. Lignin, phenol, naphthalene and dibutylnaphthalenesulfonic acid, as well as of fatty acids, alkyl and alkylarylsulfonates, alkyl, lauryl ether and fatty alcohol sulfates, and salts of sulfated hexa-, hepta- and octadecanols, as well as fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ether, ethoxylated iso-octyl, octyl or nonylphenol, alkylphenol, tributylphenyl polyglycol ether, alkyl aryl polyether alcohols, iso-tridecyl alcohol, ethoxylated fatty alcohol alcohol Castor oil, polyoxyethylene alkyl ether or polyoxypropylene, lauryl alcohol polyglycol ether acetate, sorbitol ester, lignin sulfite waste liquor or methyl cellulose.

Powders, materials for broadcasting and dusts can be prepared by mixing or grinding the active substances together with a solid carrier. Granules, for example coating granules, impregnating granules and homogeneous granules, can be prepared by binding the active ingredients to solid carriers. Solid carriers are mineral soils such as silica gel, silicas, silica gels, silicates, talc, kaolin, limestone, lime, chalk, bolus, loess, clay, dolomite, diatomaceous earth, calcium and magnesium sulfate, magnesium oxide, ground plastics, fertilizers, such as Ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas and vegetable products, such as grain flour, tree bark, wood and nutshell flour, cellulose powder or other solid carriers.

Examples of such preparations are:

I. a solution of 90 parts by weight of a compound I according to the invention and 10 parts by weight of N-methyl-2-pyrrolidone, which is suitable for use in the form of tiny drops;

II. A mixture of 10 parts by weight of a compound I according to the invention, 70 parts by weight of xylene, 10 parts by weight of the adduct of 8 to 10 moles of ethylene oxide and 1 mole of oleic acid-N-monoethanolamide, 5 parts by weight of calcium - Salt of dodecylbenzenesulfonic acid, 5 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil; A dispersion is obtained by finely distributing the solution in water.

III. an aqueous dispersion of 10 parts by weight of a compound I according to the invention, 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts by weight of the adduct of 40 mol of ethylene oxide and 1 mol of castor oil;

IV. An aqueous dispersion of 10 parts by weight of a compound I according to the invention, 25 parts by weight of cyclohexanol, 55 parts by weight of a mineral oil fraction with a boiling point of 210 to 280 ° C. and 10 parts by weight of the adduct of 40 mol Ethylene oxide in 1 mol castor oil;

V. a mixture found in a hammer mill

80 parts by weight, preferably a solid compound I according to the invention, 3 parts by weight of the sodium salt of di-iso-butylnaphthalene-2-sulfonic acid, 10 parts by weight of the sodium salt of a lignosulfonic acid from a sulfite waste liquor and 7 parts by weight powdered silica gel; by finely distributing the mixture in water a spray liquor;

VI. an intimate mixture of 3 parts by weight of a compound I according to the invention and 97 parts by weight of finely divided kaolin; this dust contains 3% by weight of active ingredient;

VII. An intimate mixture of 30 parts by weight of a compound I according to the invention, 62 parts by weight of powdered silica gel and 8 parts by weight of paraffin oil which is based on the

Surface of this silica gel has been sprayed; This preparation gives the active ingredient good adhesion;

VIII. A stable aqueous dispersion of 40 parts by weight of a compound I according to the invention, 10 parts by weight of the sodium salt of a phenolsulfonic acid-urea-formaldehyde condensate, 2 parts by weight of silica gel and 48 parts by weight of water can be further diluted;

IX- a stable oily dispersion of 20 parts by weight of a compound I according to the invention, 2 parts by weight of the calcium salt of dodecylbenzenesulfonic acid, 8 parts by weight of fatty alcohol polyglycol ether, 20 parts by weight of the sodium salt of a phenolsulfonic acid-urea-formaldehyde con- densates and 50 parts by weight of a paraffinic mineral oil.

The compounds I are of particular importance for combating a large number of fungi on various crop plants, such as wheat, rye, barley, oats, rice, corn, lawn, cotton,

Soy, coffee, sugar cane, wine, fruit and ornamental plants and vegetables such as cucumber, beans and squash, as well as on the seeds of these plants.

The compounds are used by treating the fungi or the seeds, plants, materials' to be protected from fungal attack or the soil with a fungicidally active amount of the active compounds. It is used before or after the infection of the materials, plants or seeds by the fungi.

The new compounds are particularly suitable for combating the following plant diseases: Erysiphe graminis (powdery mildew) in cereals, Erysiphe cichoracearum and Sphaerotheca fuliginea on pumpkin plants, Podosphaera leucotricha on apples, Uncinula necator on vines, Puccinia cotton and ceronia species and Rhonia species Lawn, Ustilago species on cereals and sugar cane, Venturia inaequalis (scab) on apples, Helminthosporium Species on cereals, Septoria nodorum on wheat, Botrytis cinerea (gray mold) on strawberries, vines, ornamental plants and vegetables, Cercospora arachidicola on peanuts, Pseudocercosporella herpotrichoides on wheat, barley, Pyricularia oryzae on rice, Phytophthora infestans on potatoes and tomatoes and tomatoes, Verticillium species on various plants, Plasmopara viticola on vines, Alternaria species on vegetables and fruits.

The fungicidal compositions generally contain between 0.1 and 95, preferably between 0.5 and 90% by weight of active ingredient.

Depending on the type of effect desired, the application rates are between 0.025 and 2, preferably 0.1 to 1 kg of active ingredient per ha.

In the case of seed treatment, amounts of active compound of 0.001 to 50, preferably 0.01 to 10 g per kg of seed are generally required.

The agents according to the invention can also be present in the use form as fungicides together with other active ingredients, e.g. with herbicides, insecticides, growth regulators, fungicides or even with fertilizers.

When mixed with fungicides, the fungicidal spectrum of activity is enlarged in many cases.

The following list of fungicides with which the compounds according to the invention can be used together is intended to explain, but not to limit, the possible combinations:

Sulfur, dithiocarbamates and their derivatives, such as ferridimethyldithiocarbamate, zinc dimethyldithiocarbamate, zinc ethylenebisdithiocarbamate, manganese ethylene bisdithiocarbamate, manganese-zinc-ethylenediamine-bis-dithiocarbamate, tetramethylthiaminodi- nitro-ethylenedi- disulfide (ethylenedi- naphthyl- disulfide), dithiocarbamate), ammonia complex of zinc (N, N'-propylene-bis-dithiocarbamate), zinc (N, N'-propylene-bis-dithiocarbamate), N, N'-polypropylene-bis- (thiocarbamoyl ) disulfide;

Nitroderivate, such as dinitro- (1-methylheptyl) phenylerotonate, 2-sec-butyl-4, 6-dinitrophenyl-3, 3-dimethylacrylate, 2-sec-butyl-4, 6-dinitrophenyl-iso-propyl carbonate, 5- Nitro-iso-phthalic acid di-iso-propyl ester;

heterocyclic substances such as 2-heptadecyl-2-imidazoline acetate, 2,4-dichloro-6- (o-chloroanilino) -s-triazine, 0, 0-diethyl-phthalimidophosphonothioate, 5-amino-l- [bis - (dimethyl- amino) -phosphinyl] -3-phenyl-l, 2, 4-triazole, 2, 3-dicyano-l, 4-di-thioanthraquinone, 2-thio-l, 3-dithiolo [, 5-b] quinoxaline, 1 - (Butyl-carbamoyl) -2-benzimidazole-carbamic acid methyl ester, 2-methoxycarbonylamino-benzimidazole, 2- (furyl- (2)) -benzimidazole, 2- (thiazolyl- (4)) -benzimidazole, N- (1, 1, 2, 2-tetrachloroethylthio) tetrahydrophthalimide, N-trichloromethylthio-tetrahydrophthalimide, N-trichloromethylthio-phthalimide, N-dichlorofluoromethyl-thio-N ', N' -dimethyl-N-phenylsulfuric acid diamide, 5-eththoxide - 3-tri-chloromethyl-1, 2, 3-thiadiazole, 2-rhodanmethylthiobenzthiazole, 1, 4-dichloro-2, 5-dimethoxybenzene, 4- (2-chlorophenylhydrazono) -3-methyl-5-isoxazolone, pyridine -2-thione-l-oxide, 8-hydroxyquinoline or its copper salt, 2, 3-dihydro-5-carboxanilido-6-methyl-l, 4-oxathiin, 2, 3-dihydro-5-carboxanilido -6-methyl-l, 4-oxathiin-4, 4-dioxide, 2-methyl-5, 6-di-hydro-4H-pyran-3-carboxylic acid anilide, 2-methyl-furan-3-carboxylic acid anilide , 2, 5-dimethyl-furan-3-car bonic acid anilide, 2,4,5-trimethyl-furan-3-carboxylic acid anilide, 2, 5-dimethyl-furan-3-carboxylic acid-cyclohexylamide, N-cyclohexyl-N-methoxy-2, 5-dimethyl-furanane 3-carboxamide, 2-methyl-benzoic acid anilide, 2-iodo-benzoic acid anilide, N-formyl-N-morpholine-2, 2, 2-trichloroethyl acetal, piperazin-1, 4-diylbis- (1- ( 2,2,2-tri chloroethyl) -formamide, 1- (3, -dichloranilino) -l-formylamino-2,2,2-trichloroethane, 2,6-dimethyl-N-tridecyl-morpholine or its salts, 2, 6-dimethyl-N-cyclododecyl-morpholine or its salts, N- [3- (p-tert-butylphenyl) -2-methylpropyl] -cis-2, 6-dimethylmorpholine, N- [3- (p-tert-butylphenyl) -2-methylpropyl] piperidine, 1- [2- (2,4-dichlorophenyl) -4-ethyl-1,3-dioxolane-2- yl-ethyl] -lH-l, 2,4-triazole 1- [2- (2,4-dichlorophenyl) -4-n-propyl-l, 3-dioxolan-2-yl-ethyl] -lH-l, 2,4-triazole, N- (n-propyl) -N- (2,4,6-trichlorophenoxyethyl) -N'-imidazol-yl-urea, 1- (4-chlorophenoxy) -3, 3rd -dimethyl-l- (1H-1,2,4-triazol-l-yl) -2- butanone, (2-chlorophenyl) - (4-chlorophenyl) -5-pyrimidine-methanol, 5-butyl-2-dimethylamino-4-hydroxy-6-methyl-pyrimidine, bis- (p-chlorophenyl) - 3-pyridinomethanol, 1,2-bis (3-ethoxycarbonyl-2-thioureido) benzene, 1,2-bis (3-methoxycarbonyl-2-thioureido) benzene, [2- (4-chloro phenyl) ethyl] - (1, 1-dimethylethyl) -1H-1,2,4-triazole-1-ethanol, 1- [3- (2-chlorophenyl) -1- (4-f luorphenyl) oxirane-2- yl-methyl] -1H-1, 2, 4-triazole, and

various fungicides, such as dodecylguanidine acetate,

3- [3- (3,5-Dimethyl-2-oxycyclohexyl) -2-hydroxyethyl] glutarimide, hexachlorobenzene, DL-methyl-N- (2,6-dimethylphenyl) -N-furoyl (2) - alaninate, DL-N- (2,6-dimethylphenyl) -N- (2'-methoxyacetyl) -alanine ethyl ester, N- (2,6-dimethylphenyl) -N-chloroacetyl-D, L-2 -aminobutyrolactone, DL-N- (2, 6-dimethylphenyl) -N- (phenylacetyl) -alanine methyl ester, 5-methyl-5-vinyl-3- (3, 5-dichlorophenyl) -2, 4-dioxo -l, 3-oxazolidine, 3- [(3, 5-dichloro- phenyl) -5-methyl-5-methoxymethyl-l, 3-oxazolidin-2, 4-dione,

3- (3, 5-dichlorophenyl) -1-iso-propylcarbamoylhydantoin,

N- (3, 5-dichlorophenyl) -1, 2-dimethylcyclopropane-l, 2-dicarboxylic acid imide, 2-cyano- [N- (ethylaminocarbonyl) -2-methoximino] acetamide,

1- [2- (2, -Dichlorophenyl) pentyl] -1H-1,2,4-triazole, 2,4-difluoro-a- (1H-1,2,4-triazolyl-l-methyl) -benzhydrylalkohol,

N- (3-chloro-2, 6-dinitro-4-trifluoromethyl-phenyl) -5-trifluoromethyl-3-chloro-2-aminopyridine, 1- ((bis- (4-fluorophenyl) ethylsilyl) ethyl) -1H-1,2,4-triazole,

Strobilurins such as methyl-E-methoximino- [a- (o-tolyloxy) -o-tolyl] acetate, methyl-E-2- {2- [6- (2-cyanophenoxy) pyridimin-4-yloxy] phenyl} -3-methoxyacrylate, methyl-E-methoximino- [a- (2,5-dimethyl-loxy) -o-tolyl] cetamide,

Anilino-pyrimidines such as N- (4, 6-dimethylpyrimidin-2-yl) aniline, N- [4-methyl-6- (1-propynyl) pyrimidin-2-yl] aniline, N- (4-methyl-6- cyclopropyl-pyrimidin-2-yl) aniline,

Phenylpyrroles such as 4- (2,2-difluoro-1,3-benzodioxol-4-yl) pyrrole-3-carbonitrile,

Cinnamic acid such as 3- (4-chlorophenyl) -3- (3, 4-dimethoxyphenyl) acrylic morpholide.

The compounds of the present invention offer new therapeutic potential for the treatment of hypertension, pulmonary high pressure, myocardial infarction, angina pectoris, arrhythmia, acute / chronic kidney failure, chronic heart failure, renal failure, cerebral vasospasm, cerebral ischemia, subarachnoid hemorrhage, migraine, asthma Atherosclerosis, endotoxic shock, endotoxin-induced organ failure, intravascular coagulation, restenosis after angioplasty and by-pass surgery, benign prostate hyperplasia, cirrhosis of the liver, erectile dysfunction, ischemic and intoxication-caused

Kidney failure or hypertension, metastasis and growth of mesenchymal tumors, contrast agent-induced kidney failure, pancreatitis, especially acute pancreatitis, gastrointestinal ulcers.

The compounds according to the invention can be administered orally or parenterally (subcutaneously, intavenously, intramuscularly, intraperotonally) in the usual way. It can also be applied with vapors or sprays through the nasopharynx. The dosage depends on the age, condition and weight of the patient and on the type of application. As a rule, the daily dose of active substance is between approximately 0.5 and 50 mg / kg body weight when administered orally and between approximately 0.1 and 10 mg / kg body weight when administered parenterally.

The new compounds can be used in the customary pharmaceutical application forms, solid or liquid, e.g. as tablets, film-coated tablets, capsules, powders, granules, coated tablets, suppositories, solutions, ointments, creams or sprays. These are manufactured in the usual way. The active ingredients can be processed with the usual pharmaceutical auxiliaries such as tablet binders, fillers, preservatives, tablet disintegrants, flow regulators, plasticizers, wetting agents, dispersants, emulsifiers, solvents, retardants, antioxidants and / or propellants (see H. Sucker et al.: Pharmaceutical Technology, Thieme Verlag, Stuttgart, 1991). The administration forms obtained in this way normally contain the active ingredient in an amount of 0.1 to 90% by weight.

The invention is explained in more detail using the following exemplary embodiments:

example 1

Rustmicin

1 equivalent of rustmicin is dissolved in methanol and 10 vol% & dil. Aqueous hydrochloric acid is added. The mixture is left to stir at room temperature for 24 h. For working up, it is first diluted with water and then extracted with ethyl acetate. The combined organic phases are washed with sodium hydrogen carbonate and water. After evaporation of the solvent, the ketone is obtained as a crude product, which is used in the next step without further purification.

VIII

One equivalent of the ketone is dissolved in methanol and three equivalents of hydroxylamine hydrochloride are added. Allow to stir overnight. For working up, it is first diluted with water and then extracted with ethyl acetate. The combined organic phases are washed with sodium hydrogen carbonate and water. After evaporation of the solvent, the ketone is obtained as a crude product, which is used in the next step without further purification. The oxime is dissolved in DMF and potassium carbonate is added as the base. The mixture is heated to 60 ° C. and then a solution of free equivalents of n-butyl chloride in DMF is added dropwise. The mixture is stirred at this temperature for 24 h. For working up, it is first diluted with water and then extracted with ethyl acetate. The combined organic phases are washed with dilute hydrochloric acid, with sodium hydrogen carbonate and water. After evaporation of the solvent, VIII is obtained as a crude product, which is purified by chromatography.

Example 2

One equivalent of rustmicin is dissolved in methanol and three equivalents of hydroxylamine hydrochloride are added. Allow to stir overnight. For working up, it is first diluted with water and then extracted with ethyl acetate. The combined organic phases are washed with sodium hydrogen carbonate and water. After evaporation of the solvent, the ketone is obtained as a crude product, which can be passed into the next one without further purification Stage is used. The oxi is dissolved in DMF and potassium carbonate is added as the base. The mixture is heated to 60 ° C. and then a solution of three equivalents of n-propyl chloride in DMF is added dropwise. The mixture is stirred at this temperature for 24 h. For working up, it is first diluted with water and then extracted with ethyl acetate. The combined organic phases are washed with dil. Hydrochloric acid, sodium hydrogen carbonate and water.

After evaporation of the solvent, X is obtained as a crude product, which is purified by chromatography.

The reaction can also be carried out analogously with Galbonolide B.

Example 3

X III

One equivalent of X is dissolved in methanol and three equivalents of hydroxylamine hydrochloride are added. Allow to stir overnight.

For working up, it is first diluted with water and then extracted several times with ethyl acetate. The combined organic phases are washed with sodium hydrogen carbonate and water. After evaporation of the solvent, the oxime is obtained as a crude product, which is used in the next step without further purification.

The oxime is dissolved in DMF and potassium carbonate is added as the base. The mixture is heated to 60 ° C. and then a solution of three equivalents of n-butyl chloride in DMF is added dropwise. The mixture is stirred at this temperature for 24 h. For working up, it is first diluted with water and then extracted with ethyl acetate. The combined organic phases are washed with dil. Hydrochloric acid, sodium hydrogen carbonate and water. After evaporation of the solvent, III is obtained as a crude product, which is purified by chromatography.

Claims

claims

1. Rustmicin derivatives of the formula I

where the residues have the following meanings:

R ^{1 is} hydrogen or -C (= 0) R ⁵ ;

R ² -CH ₂ -OR ⁵ , -CH ₂ -SR ⁵ or = CH ₂ ; R ³ 0CH ₃ , CH ₃ or NHOR ⁷ ;

R ⁴ OH, = 0 or = N0R ⁸ ;

R ^{5 is} hydrogen, Cχ-C ₆ alkyl, unsubstituted or substituted phenyl;

R ^{6 is} hydrogen or the group -C (= 0) R ⁵ ; R7 is hydrogen, -CC ₆ alkyl; Phenyl -CC ₆ alkyl, where the phenyl radical may be unsubstituted or substituted;

R ^{8 is} hydrogen, Ci-Cg-alkyl; Phenyl-Ci-Cg-alkyl, where the phenyl radical can be unsubstituted or substituted;

as well as their agriculturally and / or pharmaceutically usable salts and tautomers,

with the exception of those compounds in which, in the event that R ^{1 is} hydrogen, R ^{2 is} the group = CH ₂ and R ^{4 is} the group = 0, R ^{3 is} not C ₁ -C ₆ -alkyl or Ci-Ce-alkoxy.

Rustmicin derivatives according to claim 1, wherein the radicals have the following meanings:

R ² -CH ₂ -0R ⁶ ; R3 NHOR ⁷ ; R ⁴ = 0.

3. rustmicin derivatives according to claim 1, wherein the radicals have the following meanings: R ² = CH ₂ ; R ³ NHOR ⁷ ; R ⁴ = NOR ⁸ .

4. Rustmicin derivatives according to claim 1, wherein the radicals have the following meanings:

R ² -CH ₂ -OR ⁶ ; R ³ OCH ₃ or CH ₃ ; 0 R ⁴ = NOR ⁸ .

5. rustmicin derivatives according to claim 1, wherein the radicals have the following meanings:

5 R ² ₌ CH ₂ ; R ³ NHOR ⁷ ; R ⁴ OH.

6. rustmicin derivatives according to claim 1, wherein the radicals have the following 0 meanings:

R ² -CH ₂ -OR ⁶ ;

R ³ OCH ₃ or CH ₃ ;

R ⁴ OH. 5

7. rustmicin derivatives according to claim 1, wherein the radicals have the following meanings:

R ² -CH ₂ -OR ⁶ ; 0 R ³ OCH ₃ or CH ₃ ;

R ⁴ = 0.

8. rustmicin derivatives according to claim 1, wherein the radicals have the following meanings: 5

R ² = CH ₂ ; R ³ NHOR ⁷ ; R ⁴ = 0.

® 9. rustmicin derivatives according to claim 1, wherein the radicals have the following meanings:

R ² = CH ₂ ;

R ³ 0CH ₃ or CH ₃ ; ⁵ R ⁴ OH.

10. rustmicin derivatives according to claim 1, wherein the radicals have the following meanings:

R ² = CH ₂ ; R ³ 0CH ₃ or CH ₃ ; R ⁴ = N0R ⁸ .

11. Agrochemical composition containing as active ingredient at least one compound according to claim 1.

12. A method for controlling harmful fungi in plants, characterized in that the harmful fungi, their habitat or the plants, areas, materials or spaces to be kept free of them with a fungicidally effective amount of a compound of the formula I according to claims 1 to 10 or one Composition treated according to claim 11.

13. Pharmaceutical compositions containing as active ingredients at least one compound of formula I according to claims 1 to 10.

14. Pharmaceutical composition containing a compound of formula I according to claims 1 to 10 for the manufacture of medicaments with antifungal activity.

15. Use of compounds of formula I according to claims 1 to 10 as a fungicide or a composition according to claim 11 as an agrochemical composition with a fungicidal action.