DD157663A1 - MEANS FOR CHEMOTHERAPY OF CULTURAL PLANT VIRUSES - Google Patents

Abstract

The invention relates to agents for chemotherapy of cropviruses. The aim of the invention is to improve the chemotherapeutic measures against plant viruses. The object is to be found in finding chemical agents that allow due to their chemical constitution in conjunction with adjuvants and Traegerstoffen an antiphytoviral therapy against hard-to-catch plant viruses and prevent resistance to the virus. The object is achieved by the use of Preparations containing substituted oxazoles of the general formula. Corresponding Spritzbruehen prevent or slow down the virus multiplication, u.a. Even the heavily bekamempfbaren Tabakmosaikvirus.Virusbedingte depression of the Pflanzenertraege be avoided or restricted and thus stabilizes the Pflanzenertraege. Alternating application of different preparations prevents resistance formation.

Description

Title of the invention

Means of chemotherapy of

The invention relates to compositions for the chemotherapy of viruses of .Culture plants, which are used with the addition of conventional excipients and carriers used and the yields of virus-infected "or ' The latter is urgently needed in the economy, as viral diseases cause large yield losses in a large number of crops, which can be caused by considerable quantitative as well as qualitative reductions of the crop, for example the European potato is affected by 29 virus species ( K.Schmelzer and P. Wolf, host plants-the viruses and viroses, liova Acta Leopoldina, 3§, -1971 ₅ Supplementum 2, 262 p.) Of these, for example, the leaf roll virus of the potato and the potato disease virus of the potato cause severe In addition, the starch content of the crop is in some cases considerably reduced, and in the case of beet, for example sugar beet, viral diseases, especially virulent turnip yellowing, cause losses on a yearly basis caused both the beet mass and the. Sugar content concern: * feed gums, z «, B. Alfalfa j, lupine, horse bean and also. Grain legumes, such as pea or phase oil bean, are infested in the GDR and in many other countries by numerous viruses, which lead to sensitive losses in these protein-rich crops, which are particularly suitable for closing the protein gap. "

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Significant damage is caused by the presence of viruses in vegetables, eg in tomatoes, in the cultivation of citrus and culinary plants, in the production of fruit and ornamental plants in ' _β Β * in t'abak. In view of the numerous virions that are found in a variety of host plants, it is imperative to have highly effective chemical preparations available. enable control of plant viruses. By such a chemotherapy of crops' viroses, ie by "the use of substances - which to a certain extent retard or inhibit virus multiplication or disease development in crop plants" (M. Klinkowski, Pflanzenliche Virologie, Berlin 1967, S, 283), The primary aim is to stabilize the yields of virus-infected or virus-threatened crops in order to meet urgent economic needs. It is important to make the chemotherapy of cultivated plants more effective and safer.

In recent years, a larger number of preparations have become known which inhibit the multiplication of plant viruses. These include analogues of purine and pyrimidine bases or of corresponding nucleosides, and nucleotides (see review of the literature by HECHT and DIERCICS, Bayerisches Land? /. Jb.55, 433-457, -1978) and also analogues of intermediates of biosynthesis of the corresponding bases, nucleosides, etc., especially 1-.beta.-D-ribofuranosyl-1,2,4-t.riazoi-3-carboxamide (Sidwell et al., Science 1, pp. 205-206 , 1972, Schuster, Ber.d.Inst .. for Tobacco Research, Dresden, 23, 31-36, 1976). Been very common and some with good results are antibiotics -aus microorganisms or higher plants for those control used by plant viruses (see. Literature reviews in Bobyr, Chimioprofilaktika i terapija wirusnych bolesnei rastenii, IsdatelstwOj Naukowa aumka, Kiev 1976i Hecht et _al.} Bayerische Landw »Jb. 53, -135-180, 1976; Misra, Z ₁ f.'Pflanzenkrankh ', Ue. PflanzenschutZs 84, 244-252, 1977). Furthermore, antiviral effects and side effects of native and synthetic herbal or other growth regulators have been made therapeutically useful (Cheo,

Phytopathology, supra, 243-244 ,. 1969; Müo and Srivastava, Viro »logy 2§> 26-31, 1969? Schuster, Arch. Pflanzenschutz, £, 171 ™ 18 ?, 1971; Schuster, Arch. Pflanzenschutz 8 ₅ 89-102, 1972; Shoemaker, bioch. Physiol. Plants 166, 393-400, 1974? Schuster, Arch. Fnytopathol. tu Plant Protection IjIj 9-17 _s 1975; Schuster j Arch * Phytopath. u. Plant Protection IJ _-5 255 ~ 268 _S 1975). Interesting therapeutic effects have also been achieved with polyanions, especially with polyacrylic acid (Stein and Loebenstein, Phytopathology 62, 1461-1466, 1972. Kassanis and mLite, A.A., appl., Biol., 79s 215-220, 1975). Furthermore, it is increasingly being attempted to make antiphytoviral activities of herbicides, which are used in these cases at low, non-plant-damaging application rates, as well as of fungicides, especially of systemic fungicides and of insecticides, useful for antiviral chemotherapy. In this connection, especially the antiphytoviral effects of sublethal doses of herbicidal triazines (Bobyr, Chimioprofilactika i terapija wirusnych bolesnei rastenii, Isdatelstwo ITaukowadumka, Kiev 1976), ureas and carbamates (Schuster, Berd d. Inst. Dresden 20, 25-37} 1973)) of the systemic fungicides Oxycarboxin, Tridemorph (Schuster, Arch. Phytopathol. And Pflanzenschutz 1J3, 229-239, 1977) and Carbendazim (Fraser and Whenham, Physiological Plant Pathology 1J3, '51-64 , 1978) and organophosphorus insecticides (Schuster, Ber. Inst. For Tobacco Research 22, 22-29, 1975). Apart from some triazines and the antibiotic preparation Imanin isolated from Hypericum perforatum (Bobyr, Chimioprofilactika i terapija v / irusnych bolesnei rastenii, Isdatelstwo Naukowa dumka, Kyiv 1976), none of the cited plant protection products or antiviral preparations in the. became known in the literature mentioned above. The main reasons for the low practical application are, s [

1. too strong. : Pnytotoxicity.

2. too much warm-blooded toxicity

3 "- Uneconomical Substance Synthesis or Recovery 4» - too little effect

5c too small, difference between dose curativa and dose toxica. ,

Hydrogenated triazines alone, and especially 2,4 ™ dioxo-1,3,5-hexahydrotriazine (DD-F8 115 566), have withstood extensive tests (Schuster et al., - Acta virol. 23, 412-420 , Schuster et al., Journ Potato Res. 279-288s 1979). It has also been shown that not all viruses are equally well combated by 2,4-dioxohexahydrotriazine. In addition, the virus multiplication in the inoculated sheet is only relatively weakly affected by this substance. Although it has recently become possible »by arttiphytoviral thioureas (DD-PS 142,788) _s ureas (DD-PS 141 968) and guanidines (DD-PS 139 921) when used separately or in 'combination' with 2,4-Dioxohexahydr0 -1.3 "5 ~ t; riazinetrione. (DD-PS 115 566), some of the only in the case of treatment with dioxohexahydrotriazine only little influ- / flowable viruses, eg cucumber mosaic virus or the leaf roll virus of the potato, better, there are. still 'not a completely satisfactory solution to the chemotherapy of some so-called problem viruses, in particular the iPabak mosaic virus'. The same applies to the reduction of the virus concentration in the inoculated leaf. In addition, it is to be feared "that as a result of the relatively high degree of mi- litability of a large number of plant viruses", for example, the emergence of ever new, aggressive virus strains is recognizable, virus forms are formed and selected that are insensitive to certain antiviral preparations are so far only one or a few antiphytoviral preparations available »

^ i ⁶ -L JL? -LJiiSi iS ^ ESS

The aim of the invention is to further improve the possibilities of chemotherapy beyond the level reached and to remedy some of the deficiencies already mentioned. "

-5.

, .. hi 5 ~

Explanation of the essence of the invention

The object of the invention is to find chemical active substances which, by virtue of their chemical constitution, enable antiphytoviral therapy. They should be suitable. to expand the spectrum of chemotherapeutically detectable plant viruses and, in particular, to make the tobacco mosaic virus, which is difficult to combat but also cause severe harm in tobacco and tomato crops, chemically accessible, the new active substances or the preparations prepared therewith (= agents) help to prevent ¹ resistance to viruses in the presence of chemotherapeutic agents, as they have also appeared in antibacterial therapy very soon after the first antibiotics were found and must also be expected in antiphytoviral therapy in view of the strong mutability of the viruses the range of antiviral preparations available to them is the lower the risk of the emergence of resistant virus strains in their alternating application.

The object is achieved in that are used to combat PfIanzenvirösen agents, the oxazoles of the general.formula

R;

R-

-R,

contain.

Mean in it?

R = alkyl, hydroxyalkyl or "biphenyl groups R / j '= alkyl, Pheny3--, hydroxyl, carboxyl groups Rp = L ⁷ HP, guanyl, Alkylthiocarbamoylhydrazino-v N-substituted aminomethyl groups, further hydrazone from GIyoxy1 -. acid. Acetone, aldoses, N ~ alkylisatines, halogenate benzaldehydes, pyridine aldehydes, perrocene aldehydes, aminoacetophenone,! -Substituted acetophenones, polyhydroxyacetophenones, and methoxyacetophenone, as well as salts and adducts of these substances.

 '.'. -6-

In addition to one or more of the compounds of the general formula 1 according to the invention, the compositions contain diluents and / or solvents, moreover optionally surfactants, adhesives and / or further formulating agents and can be used together with plant hormones, synthetic waxy regulators and also aryl- and alkyl substituted ureas, thioureas and guanidines are used.

The agents of the invention show a pronounced anti-viral activity, in particular to economically important karteleviruses, e.g. various mosaic diseases (pathogens such as potato X, and potato A virus) and potato vascular disease (potato strains virus) "Furthermore, various viral diseases of tomato and tobacco can be combated, whereby for the first time a number of Preparations also the tobacco mosaic virus is detected. A number of preparations show a good effect in the inoculated Blatt.und can thus contribute to the desired, but so far only partially achieved Eliniinierung the foci of infection. The compounds according to the invention represent an extension of the previous range of antiphytoviral preparations. This makes it possible to expand the preparation rotation, i. successively, z.T. successively in different trial years, to use a larger number of preparations and thus to counteract the selection of virus strains that are resistant to certain antiphytoviral preparations. Also, by using preparations in which different preparations are used at the same time, this purpose can be achieved «

Sufficient to achieve an adequate for practical protection against yield losses by virus infection in general application rates of O _-.., 5 "to 10 kg / ha, the formulation and application of the compositions of the invention can be effected by the known and customary in practice methods Thus, the active compounds mixed with inert diluents and suitable Pormulierungsniitteln and processed into wettable powders, pastes, emulsion concentrates, etc. Become »It has

when the active ingredient content accounts for 10 to 90 % of the agent which is dispersed with water shortly before use with spray liquors. The spray mixtures can be sprayed with the usual spraying, spraying and fogging devices ^ "By granulating the active substances and auxiliaries with suitable substances which allow a gradual release of the active ingredients and auxiliaries in the soil, it is possible, with your own treatment, to order the Fields that provide comprehensive protection throughout the growing season «·

To indicate the increased antiphytoviral effects of oxazoles invention especially whole-plant tests were used to Solanaceae "As a test virus common plant viruses found using the one hand infect each weiligen host systemically and secondly a proper concentration determination allow on serological way .. In the basic experiment, using a Abrasives (carborundum powder, grain size 500) the two lower, intact leaves of plants of Nicotiana tabacum 'Samsun ¹ , the 5 to ? Leaves had formed, with the Kart inoculated X-virus. Each 2 days before and 2 days after the inoculation, the test plants with water or a solvent-water mixture, the active compounds of the invention in the determined in preliminary experiments, in the application examples concentration (usually 5 × 10 ^ mol / 1) and 0.2% Fekama adhesive (adhesive based on Buna latex) sprayed to drip point. This corresponds to an application of 600 l spraying solution or broth per hectare of field surface under practical conditions. As a control, a number of plants were inoculated with the same virus in the manner described. The spraying was carried out with the same solvent-water mixture with the addition of 0.2 % of Fekama adhesive, but without the active compounds according to the invention. The virus concentration was determined serologically in the precipitation drop test using the intervals of .the inoculation in leaves of the sheet insertion also indicated therein in the example series.

Dümungsendpuiikt determination (geometric dilution in each case in the ratio Is 1 with physiological saline until virus is no longer serologically detectable) plant and leaf by leaf separately determined (G. "Schuster, ¹ Archive Phytopath.-u. Pflanzenschutz 7, 1971, 171-187 and 1_3, 1977, 231-241). "Each experimental member comprised at least 10 individual plants.

The virus concentration found in the leaves of the individual plants was expressed in terms of value. In this case value 0 means that even in a ratio of 1 .s1 diluted (= starting) pressed juice no virus was detectable. The value plate 1 shows that after a single dilution in a ratio of 1 μg no more virus could be detected , the value 2, that after two dilution no virus precipitate occurred ,, etc. For comparison of the results obtained in the experimental elements with those of the control of the individual numerical values, which represent the basis of the scrambled test arrangement logarithms (exponents) to the base 2, the corresponding Antilogarithms formed ", the latter were averaged and found with the control plants. Mittelwerten'verglichen. The following tables show the percentage of virus concentration found in the control compared to the control (control = 100%), which is referred to as the reduction coefficient (RK) Virus concentration was reduced to 8 % of the virus concentration of the controls.

The significance of the differences found was tested in the t-test, after having undergone suitable transformation, 'z' B. appropriate Radiation, normal distribution of the measurements had been brought about. The test result was given in addition to the differences expressed in percentages in symbols.

2 ^% jfi rf «* · / H / K **» % ß ff *. J

Say this?

+. q στ > ·

ρ> 0.1 ^

* Ω 1% '- η

ρ. =:

The experiments carried out and evaluated in the manner described below yielded the oxazoles according to the invention selected as examples below on secondary infected leaves in the results summarized in example series 1 »

Beisgielsreihe Ij '.

"Reduction of potato X-virus concentration in secondary infected leaves of Nicotlana tabcum ^f Samsun ^f ( Virginian {Dabak) by the substituted oxazoles of the present invention Examination in the second leaf over the upper inoculated leaf ( Fig Cotyledons) 12 to 15 days (usually 13 days) after inoculation.

connection

Conc. (Mol / 1)

PvK and

u. Solvent significance

2-guanidino-4,5-di-n-propyl-oxazole hydrochloride

2-guanidino-4-carboxy-5- (1S 2, 3-trihydroxy-n-propyl) -oxazole

m-guanidino-acetophenone- (4,5-diphenyl-oxazol-2-yl-hydrazone) ~ hydrochloride

3- (D ~ ribosylimino) ~ aceto-phenone- (4, ^ -diphenyloxa -ol-2-yl-hydi'azone)

10 χ 10 ~ ²

H ₂ O

5 χ ΙΟ " ³

^Η 2 °

5 χ ΙΟ ™ ³

Methylglykor

5 χ 10 "" ³

.Methylglykol

43 ^Η

63 °

40 '

connection

, 2,4-dihydoxy (4j5-diphenyl-oxazol-2-yl-hydrazone)

 2,3,4-trihydroxyacetophenone (4,5-diphenyl-oxazol-2-yl-hydrazone)

5-phenyl-4-hydroxy-2-amino, oxazole

4,5-DIPB onyl-oxazol-2 ~ yl. Nydrazine salt of the _$ 2.4 6 ~ 'Tr ihy dr. oxy-aceto-t-ophenone ™ (4,5-diphenyl-oxazol-2-ylhydrazone) -

o-F.luorbenzaldehyd- (4,5-oxazol ~ 2 ~ yl-iiydrazon) '

diplienyl-oxazol-2-ylhydrazone)

N ~ n-Butylisatin- (4,5-diphenyl-oxazol-2-ylhydrazone)

N-Benzylisatin-3- (4,5-diphenyl-oxazol-2-yl-liydrazone)

Conc. (Mol / 1 RK and

U ₀ Jjösungsmittel significance

acetone

5 χ 10 acetone

-3

5 × 10 ^-3 methylglycol

2 χ 10 " J methyl glycol 2 χ 10"

"3

methylene glycol

• 2 χ ΙΟ " ³ methyl glycol

2 x 10 -3 metihylglycol

50 '

49 6O ⁺

2% each in water, 5% each in water -11-

A similar good reduction of the concentration of the Kartöffel-X virus as by the in Example series 1 'specified compounds is also by the following invention. Achieved Oxazole!

Acetone - (4, α-daphhexyl-oxazol-2-yl-hydrazone) 2,5-dihydroxybenzaldehyde d (4 ₎ 5-diphenyl-oxazol-2-yl-hy dr azon); m-guanylguanidino-acetophenone- (4,5-cl-plienyl-6xazGl-2-yl.

hydrazone) hydrochloride

4.5 ~ biphenyl-oxazol-2-yl-iminoglyoxylic acid Mefhoxyacetophenone ™ (4,5-diphenyl-oxazol-2-yl-hydrazone) 2,3j4-bis-hydroxy-acetophenone ~ (4,5-diptelenyl-oxa2ol-2 yl ~

•.: Hydrazone)

D ~ glucose- (4,5-diphenyl-oxazol-2-yl-hydrazone) 1- (4,5 "-diphenyl-oxazol-2-yl) -4-isopropyl-thiosemicarbazide

In example series 2 it is shown that a number of the invention. Oxazole also in inoculated leaves to reduce the virus concentration to a considerable extent, which has been achieved over the known preparations progress.

Reducing the concentration 'of Kartoffei-virus X in ^^ S ^ - ^^ l ^ l ^^ PSB (inoculated) Blättern..von Hiaotiana tabacum' Saiasun '(= Nicotiana tabacum) by the present invention, substituted oxazoles. Examination in the upper inoculated leaf (= 3 * leaf above the cotyledons) 5 - 7 days (usually 6 days) after inoculation.

connection

Conc. (Mol / 1) RK and

u. Solvent significance

m-Guanidino-acetophenone- (4,5-diphenyl-oxazol-2-yl-hydrazone) hydrochloride

2 ~ Diethanolaiomethyl-4,5-diphenyl-oxazole ·

oxazol-2-yr-hydrazone)

m-Guanylguanidinor-aceto- phenone • (4.5 ~ 2 ~ yl ~ a.iph.enyloxazol-hydrazone) hydrochloride

3 ~ (D-xylosylimino) ~ acetophenone ~ (4j5-diphenyloxazol-2-yl-hydrazone)

D-XyIose- (4, ^ - diphenyloxazol ~ 2-yl-hydrazone)

5-Pheny1-4-hydroxyi-2-amino-oxazole

 5-x 10 "acetone

• 3X)

5x; 1O ~ ³ Biethanoi 5 x 10 ~ ³ acetone

r3

5 x 10 'acetone

5 x 10 ^-3 acetone

5 OK "χ ³ -methanol

icr ² 46

35 ⁺⁺⁺

46 ¹

49 '

each 5% solvent in water

connection

Conc. (Mol / 1) RK and

u. Solvent significance

D ~ arate) ino5e ~ (4 »5- diptienyl-oxazol ~ 2 ~ yl hydrazone).

4,5-diphenyl-oxazol-2-yl-hydrazine salt of 2,4-dihydroxyacetophenone - (4,5-diphenyl-oxazol-2-yl-hydrazone

2- (β-phenylethylamino-ethyl) 4,5-diphenyl-3-oxazole

Ferrocene aldehyde ~ (4,5-diphenyl-oxazol-2-yl-hydrazone)

N-n- »butylisatin- (4,5-diphexyl-oxazol-2-yl ™ hydrazone)

N-Methylisatin- (4,5-diphenyl-oxazol-2-ylhydrazone

1 - (4, ^5- diphenyl-oxaz ol ~ 2-yl -) - 4 ~ ethyl-thiosemicarbazide

Guanidine salt of. · Glyoxylic acid (4 _S 5-diphenyloxazol-2-yl hydrazone)

5 χ 10 ethanol

5 χ 10 "acetone

, -3

5 x 10 ^-3 ethanol 2 x 10 ³ methylglycol

xx)

2 χ ΙΟ "* ³ methyl glycol

2 χ 10 ~ ³ methyl glycol

2 χ 10 ~ ' ³ methyl glycol

5 × 10 ^-3 acetone

63 ^Ί

30 '

58 '

40 '

63 ⁺

2% each in water

Similar good results can be obtained with the following compounds in-inoculated / leaves?

o-Atninoacet oplienone- 4-, 5-diphenyl - o: xazolyl - (2) hydrazone pyridine-2-aldehyde-4j5-diphe: ayl-oxazolyl- (2) -hydrazone «

In example series 3 it is shown that some of the oxazoles according to the invention also have a considerable effect on the extraordinarily difficult to control tobacco mosaic virus. Liese has been demonstrated in the inoculated leaf of Nieotiana glutinous a by the change of the number of local lesions. In example row 3 the percentage is the local lesions indicated in the respective test member compared to with Wasser.bzw. Solvents. without controls (control = 100%) - _:: . · was found (= .reduction coefficient = RE) _B The significance of the differences found was also tested in the t-test. Transformations of the measured values were not required «The symbols for the test results correspond to those already indicated.

Reduction of the number of local lesions of the tobacco mosaic virus on leaves of Ni-cotiana gl.utinosa by the substituted oxazoles according to the invention.

connection

Konz «(mol / 1) RK and

u. Solvent significance

2,3f4-trihydroxyaceto-5x10 'phenone (4,5-diphenyl-acetone-oxazol-2-yl-hydrazone)

m-guanylguanidino-aceto-5x10 'phenone (4,5-diphenyl-acetone oxazol-2-yl-hydrazone) hydrochloride

4,5-Diphenyl-oxazol-2-yl-yl hydrazine salt of 2,4-acetone dihydroxyacetone-4,5-diphenyl-oxazol-2-ylhydrazone

N-Methyl-isatin (4,5-dipheny1-oxazol-2 ~ yl hydrazone)

1- (4,5-diphenyl-oxazol-2-yl) -4-ethylthio-semicarbazide

Guanidine salt of gyoxyl 5 ^x

acid ~ (4,5 "diphenyloxazole ~ acetone

2-yl hydrazones '';

-3

, -3

-3

2 × 10 -3 methylglycol 2 × 10 ^-3 methylglycol

52 '

34 ¹

12

Claims (1)

invention claims 1. Composition for the chemotherapy of cropviruses, characterized in that together with customary excipients and carriers compounds of the general formula R- -R, be used, in which. RH or alkyl, hydroxyalkyl or phenyl group, R ^ H or alkyl, phenyl, hydroxyl, carboxyl, Rp H bzv /. KHp, 'guanyl, alkylthiocarbamoylhydrazino, ^ -substituted aminomethyl group, further hydrazone of glyoxylic acid ,. Acetone, aldoses, N-alkylisatines ,. halogenated benzaldehydes, Pyridinaldehyden, Ferrocenaldehyden, asinoacetophenone, N-substituted Ac'etöphenonen, Polyhydroxyacetophenonen and methoxyacetophenone, as well as salts and adducts of these substances mean and R ₅ R ^, Rp may occur in any variation. '. Means according to items 1 and 2, characterized in that the preparations used in addition to the 'active substance according to the invention also contain surfactants, adhesives and other formulating agents and optionally auxiliary substances for the formation of granules. Agents according to items 1 and 2, - characterized in that the active compounds according to the invention can be used together with plant hormones, synthetic plant growth regulators and aryl- and alkyl-substituted polyureas, thioureas and guanidines.