Derivatives of 13-(substituted thio)acetoxypiperidine, the retrieval method, the insecticidal composition and method of plant protection

 

(57) Abstract:

Describes compounds having the formula (I):

< / BR>
where R1represents methyl, ethyl or isopropyl; R2alkyl, aralkyl, cycloalkyl, cycloalkenyl, aryl, heterocyclic group or a thio group, a substituted heterocyclic group; R3represents hydrogen, methyl or ethyl; or R2together with R3represents -(CH2)n-, where n represents 3, 4 or 5; and A represents an aromatic heterocyclic group; and their salts, which are valuable in agriculture and horticulture anthelmintic, acaricidal and insecticidal agents. 5 C. and 14 C.p. f-crystals, 4 PL.

The invention relates to a series of new derivatives of compounds known as "milbemycin", which are characterized by the presence of heterocyclic substituted mercaptoacetate group in the 13-position. The invention also provides new methods and compositions based on the use of these compounds for agricultural and horticultural use, and the processes of their production.

There are several classes of known compounds with the structure, which is a 16-membered macrolide ring, consist of by using chemical derivatization of such natural fermentation products, and who show acaricidal, insecticidal, anthelminthic and antiparasitics activity. Milbemycin and avermectins are examples of two such classes of known compounds, but there are also various other compounds and they are identified in the art by various names or code numbers. The names of these various macrolide compounds are usually taken on the basis of names or code numbers of microorganisms that produce naturally occurring representatives of each class, and these names were then distributed to chemical derivatives of the same class, resulting wasn't given a standardized systematic nomenclature for these compounds.

In order to avoid any misunderstanding here we will use a standardized system of nomenclature, which is followed in accordance with the normal rules of names derived organic compounds recommended by the International Union of pure and applied chemistry (IUPAC), Department of organic chemistry, Commission on nomenclature of organic chemistry, which is based primarily on a hypothetical initial (source) connection, called SDATA.

In the formula (II) shown also non system macrolide ring, which applied to those provisions that are most relevant to the compounds of the invention and the compounds of the prior art.

Produced by natural milbemycin are a number of macrolide compounds, which are known to exhibit anthelminthic, acaricidal and insecticidal activity. Milbemycin D was described in U.S. patent No. 4 346 171, where he was referred to as "Compound B-41D", and milbemycin A3and A4have been described in U.S. patent N 3 950 360. These compounds can be represented by the above formula (II) in which Rain position 13 represents a hydrogen atom, and Rbin position 25 represents methyl group, ethyl group or isopropyl group, and these compounds are referred to as milbemycin A3milbemycin A4and milbemycin D, respectively. Similar milbemycin having a hydrogen atom in position 13 and substituted in position 25 second-butilkoi group described in U.S. patent N 4 173 571, where it is known as the "13-deoxy-22,23-dihydroavermectin B1athe aglycone".

Were subsequently received various derivatives of the original milbemycin and the customers USA 4 201 861, 4 206 205, 4 173 571, 4 171 314, 4 203 976, 4 289 760, 4 457 920, 4 579 864 and 4 547 491, in European patent publications N 8 184, 102 721, 115 930, 180 539 and 184 989 and in Japanese patent applications Kokai (i.e., laid out for everyone to see) N 57-120 589 and 59-16 894.

Derivatives of 13-hydroxy-5-kelimelerin described in U.S. patent No. 4 423 209. Derivatives of 5-oxime milbemycin have been described in U.S. patent No. 4 547 520 and European publications N 203 832.

Milbemycin having ester bond at the 13-position, are particularly close to the invention, and the number of compounds in which the 13-hydroxy group in compounds of the above formula (II) sonoelasticity described in Japanese patent application Kokai N Sho 61-180787, which discloses esters of a wide variety of carboxylic acids, such as alcamovia acid. However carbonisation fragment in the 13-position of these known compounds do not include any heterocyclic rings. Other derivatives milbemycin having ester bond at the 13-position, described in Japanese patent application Kokai N Hei 1-104 078, which, in our opinion, is the closest known source for compounds of the invention. Herein disclosed compounds, in which the fragment carboxylic kislota classes related milbemycin macrolide compounds, referred to above, all described as having one or more types of activity as antibiotic, anthelmintic, ectoparasiticide, acaricide or other pesticide agents. However, there is still a continuing need to provide such agents with improved activity against one or more classes of agricultural and garden pests.

Now it was found that the activity of such related milbemycin derivatives can be improved through appropriate selection of the combination of the substituents in the macrolide ring system, especially of the substituents at the 13-position. In particular, it was found that the activity of these compounds can be improved with a suitable choice of some highly specific ester groups in the 13-position, as described below. In General, compounds of the invention have a tendency to be the best pesticide activity than known compounds, and many of the compounds show very much better activity.

Accordingly, an object of the invention is the provision of such macrolide compounds having improved activity. Another aim invented the etch pesticide compositions and methods of using such compounds.

In accordance with these objectives the invention provides compounds of formula (I):

< / BR>
where:

R1represents methyl, ethyl or isopropyl group;

R2is:

alkyl group having from 1 to 6 carbon atoms; phenylalkyl group in which an alkyl group having from 1 to 3 carbon atoms, substituted by at least one phenyl group, and specified the phenyl group is unsubstituted or substituted by at least one Deputy, selected from the group consisting of methyl and ethyl groups;

cycloalkyl group having from 3 to 6 carbon atoms;

cycloalkylation group, in which cycloalkyl part has from 3 to 6 carbon atoms;

carbocyclic aryl group which has from 6 to 10 ring carbon atoms and which is unsubstituted or substituted by at least one Deputy, selected from the group consisting of methyl groups, ethyl groups, haloalkyl groups having 1 or 2 carbon atoms, methoxy groups, ethoxy groups, halogen atoms and amino groups;

heterocyclic group, which 5 - or 6-membered alicyclic ring containing 2 oxygen atom, secondinternational heterocyclic group, containing 2 nitrogen atom;

R3represents a hydrogen atom, methyl group or ethyl group; or

R2together with R3represents a group of formula -(CH2)n-, where n represents the integer 3, 4, or 5; and

A represents A 6-membered aromatic heterocyclic group containing 2 or 3 nitrogen atom, which is unsubstituted or substituted by at least one Deputy, selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms, methoxypropyl, ethoxy groups and halogen atoms.

The invention further is insecticidal composition comprising an insecticidal compound in a mixture with acceptable in agriculture and horticulture carrier or diluent, in which the specified connection selected from the group consisting of compounds of the formula (I).

The invention is also a method of protecting plants from damage by parasites selected from the group consisting of insects, which comprises applying the active compounds to plants or their parts or to the beginning of the reproductive (e.g., seeds) of the said plants or to the locus, including the specified plants or parts of plants or player is ineni formula (I).

In the compounds of the invention, when R2represents an alkyl group containing from 1 to 6 carbon atoms, it can be a group with a straight or branched chain, having from 1 to 6 carbon atoms, and examples include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert-pentyl, 2-methylbutyl, 1-methylbutyl, 1-ethylpropyl, 4-methylpentyl, 3-mentality, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2, 2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, hexyl and isohexyl group. Of these preferred alkyl groups having 3 to 5 carbon atoms, more preferred ISO-propyl and 1-terbutaline group, and most preferred of the isopropyl group.

When R2is cycloalkyl group, this has from 3 to 6 carbon atoms, and examples of such groups include cyclopropyl, cyclobutyl, cyclopentyl and tsiklogeksilnogo groups, of which the preferred cycloalkyl group having 5 or 6 carbon atoms, and most preferred tsiklogeksilnogo group.

When R2is cycloalkylation group, this has from 3 to 6 atoms comfort cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl groups, of which the preferred cycloalkenyl group having 5 or 6 carbon atoms in cycloalkyl parts, and more preferred cyclohexylmethyl group.

When R2represents an aryl group, it represents a carbocyclic group having from 6 to 10 ring carbon atoms, and this group is unsubstituted or substituted by at least one Deputy, selected from the group consisting of methyl groups, ethyl groups, haloalkyl groups having 1 or 2 carbon atoms, methoxy groups, ethoxy groups, halogen atoms and amino groups. The number of these substituents do not have any particular limitations, except those that may be imposed by the number of positions of the substituents and possibly by steric or spatial constraints. However, it is generally preferred from 1 to 5 substituents, and a number from 1 to 3 is preferable, and 1 or 2 is preferable. Examples of such substituents include:

alkyl group having 1 or 2 carbon atoms, i.e. methyl and ethyl groups, preferably methyl group;

haloalkylthio, such as vermeil, chloromethyl, methyl bromide, deformity, trifluoromethyl, trichloromethyl, tribromoethyl, 2-foretel, 2,2,2-triptorelin, 2,2,2-trichlorethyl and 2,2,2-tribromoethanol groups, of which the preferred alkyl fluoride group having 1 or 2 carbon atoms, and more preferred triptorelin group;

alkoxy group having 1 or 2 carbon atoms, i.e., methoxy, ethoxy group, preferably a methoxy group; and

the halogen atoms which can be the atoms fluorine, chlorine, bromine or iodine, preferably bromine atoms and fluorine, and more preferably a fluorine atom.

Aryl groups represented by the radical R2can have from 6 to 10, preferably 6 or 10, ring carbon atoms, and examples include phenyl, 1-naftalina and 2-naftalina group, preferably phenyl group. The number of the substituents at these aryl groups is preferably 0.1 or 2, and more preferably 0. In the case of a phenyl group, if the number of substituents is 1, Deputy preferably is 2 - or 4-position, more preferably in the 2-position; on the other hand, if the number of substituents is 2, they are preferably in the 2 - and 4-, or 2 - and 6-positions; more predpochitala, having from 1 to 3, preferably 1 or 2, carbon atoms, substituted by one or two, preferably one phenyl group. Fenilalanina the group as a whole is preferably from 7 to 12 carbon atoms. The phenyl part of this phenylalaninol group may be unsubstituted or may be substituted by at least one and preferably 1 or 2 substituents selected from the group consisting of methyl and ethyl groups. Examples of the unsubstituted groups include the benzyl, -methylbenzyl, phenethyl, 1-naphthylmethyl, 2-naphthylmethyl and 2-(1-naphthyl)-ethyl group, of which the preferred benzyl group.

When R2represents a heterocyclic group, which 5 - or 6-membered alicyclic ring containing 2 oxygen atom (with the remaining ring atoms are carbon atoms), condensed with a benzene ring, it may be, for example, 1,3-benzodioxole-5-yl, 1,4-benzodioxan-6-yl or 1,3-benzodioxan-6-yl, of which the preferred heterocyclic group, which 5 - or 6-membered alicyclic ring containing 2 oxygen atoms condensed with a benzene ring. Most preferred of these groups is 1,3-benzodioxole-5-ilen, 1,4-benzodi the - S-, R4represents a 6-membered aromatic heterocyclic group containing 2 nitrogen atom (the remaining ring atoms are carbon atoms), and examples of such groups include 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-personilnya and 3-personilnya groups, of which the preferred 2-pyrimidinamine, 4-pyrimidinyl and 5-pyrimidinyl group, and more preferred 2-piramidalnaya group.

When A in the compound of formula (I) represents a 6-membered aromatic heterocyclic group containing 2 or 3 nitrogen atom (the remaining ring atoms are carbon atoms), this group can be unsubstituted or substituted by at least one Deputy, selected from the group consisting of alkyl groups having from 1 to 4 carbon atoms, alkoxy groups having 1 or 2 carbon atoms and halogen atoms. Examples of such substituents include:

alkyl groups having from 1 to 4 carbon atoms that can be alkyl groups with straight or branched chain such as methyl, ethyl, sawn, ISO-propyl, bucilina, isobutylene, second-bucilina and tert-bucilina groups, of which the preferred is si group, having 1 or 2 carbon atoms, i.e., methoxy or ethoxy group, preferably a methoxy group; and

the atoms of halogen, such as fluorine atoms, chlorine, bromine or iodine, preferably fluorine atoms or chlorine, and more preferably a chlorine atom.

The aromatic heterocyclic group has 6 atoms in the ring, of which 2 or 3 are nitrogen atoms and the remainder carbon atoms, and examples of the unsubstituted groups include 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 3-pyrazinyl, 2-(1,3,5)-triazine, 3-(1,2,4)-triazinyl, 5-(1,2,4)triazine and 6-(1,2,4)triazinyl group, of which the preferred 6-membered aromatic heterocyclic group, containing 2 nitrogen atom, more preferred pyrimidinyl group, and most preferred 2-pyrimidinyl group.

There are no particular restrictions on the number of substituents, except such which may be imposed by the number of substitutable positions and possibly by steric constraints. However, when the heterocyclic group is substituted, preferred from 1 to 3 substituents, and more preferably the presence of 0,1 or 2 substituents, and more preferably 0 or is subramania can contain several asymmetric carbon atoms in their molecules, and can thus form optical isomers. Although all these compounds represented here by a single molecular formula, the invention includes both the individual isolated isomers and mixtures thereof, including racemates. When applied techniques stereospecific synthesis or when source materials are used optically active compounds, can be obtained directly individual isomers; on the other hand, if the result is a mixture of isomers, an individual isomers can be obtained by using conventional separation techniques. In particular, the compounds of the invention may exist in alpha or beta configuration relative stereochemistry 13-position of the skeleton milbemycin. Although all such isomers and mixtures of them form part of the invention, preferred is a beta configuration.

Preferred classes of compounds of the invention are the compounds of formula (I) in which:

(a) R2is:

alkyl group having from 2 to 5 carbon atoms;

phenylmethylene group;

cycloalkyl group having 5 or 6 carbon atoms;

cycloalkylation group, in which cycloalkyl part has 5 or 6 carbon atoms;
the mi, selected from the group consisting of methyl groups, triptoreline groups, methoxy groups, fluorine atoms, chlorine atoms and amino groups;

benzene ring condensed with a 5 - or 6-membered alicyclic group containing 2 atoms of oxygen.

(b) R3represents a hydrogen atom, methyl group or ethyl group.

(c) instead of (A) or (B) a group of the formula -(CH2)nwhich is formed by the radical R2together with R3is trimethylene group.

(d) A represents A 6-membered aromatic heterocyclic group containing 2 or 3 nitrogen atom, which is unsubstituted or substituted by at least one Deputy, selected from the group consisting of methyl groups, ethyl, methoxy, ethoxy groups and halogen atoms.

In particular, from the above classes of compounds are preferred compounds in which R2matter specified in section (a) above, R3has the values defined in (b), or R2and R3together have the meanings given under (c), and A has the meanings given above in (d).

More preferred classes of compounds of the invention are those compounds formulae:

alkyl group having 3 to 5 carbon atoms; 1-methylbenzyl group; phenyl group which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of methyl groups, triptorelin, methoxy groups, fluorine atoms, chlorine atoms and amino groups; 2-naftalina group; 1,3-benzodioxole-5-ilen group; or 1,4-benzodioxan-6-ilen group.

(g) R3represents a hydrogen atom.

(h) A represents A 3-pyridazinyl group, 2-pyridazinyl, 4-pyrimidinyl, 2-personilnya or 1,3,5-triazine-2-ilen group, each of which is unsubstituted or substituted by 1 or 2 substituents selected from the group consisting of methyl groups, ethyl groups, methoxy groups, ethoxy groups and halogen atoms.

Of the above classes of compounds are particularly preferred those compounds in which R1has the values defined above in (e), R2has the values defined in (f), R3matter specified in (g), and A has the meanings specified above in (h).

Even more preferred classes of compounds of the invention are the compounds of formula (I) in which:

(i) R2ISO-propyl group or phenyl itelnych groups, triptoreline groups, fluorine atoms and chlorine atoms in the 2-position and/or 6-position of the phenyl group.

(j) A is 2-pyrimidinyl group.

In particular, of the above classes of compounds are preferred compounds in which R1has the values defined above in section (e), R2such as defined in (i), R3such as defined in (g), and A has the meanings as defined in (j), and from all classes of compounds (a) to(j) above, compounds in which the carbon atom at the 13-position is in the beta configuration.

The most preferred compounds are (k) compounds in which R2is ISO-propyl or phenyl group, and especially those in which R1has the values defined in (e), R2as defined in (g), and A has the meanings given above in section (j), and especially those in which the carbon atom at the 13-position is in the beta configuration.

Specific examples of compounds are those compounds of formula (I) in which R1, R2and A have the values listed in the table. 1. The number of each connection has the prefix K, L, M or N, which specifies the definition of the group R3. So, in those compounds, L, R3represents a methyl group; in those compounds in which the prefix is M, R3represents ethyl group; and compounds in which the console is N, R2together with R3represents a group of formula -(CH2)n- and in this case, specific examples of this group are shown in column R2.

In addition to this "optical isomer" is indicated in column R2when in column R2given the reference to "optical isomer", the corresponding connection can exist as optical isomers due to a carbon atom that is attached to R2and R3; for any connection for which to set the absolute configuration, also specify R or S. When the presence of optical isomers was confirmed, but the absolute configuration was not installed, the isomers are designated as "A" and "B".

From the following table.1 of the preferred compounds are the following: K-1, K2, K3, K4, K5, K-6, K-7, K-8, K-9, K-10, K-11, K-12, K-13, K-14, K-15, K16, K-17, K-18, K-19, K-20, K-21, K-22, K-23, K-24, K-25, K-26, K-27, K-28, K-32, K-33, K-34, K-38, K-39, K-40 K-42 K-43 K-44 K-45 K-46 K-47 K-48 K-49 K-50 K-51 K-52 K-53 K-54 K-56 K-57 K-59, K-60, K-61 K-62 K-63 K-64, K-66 K-67 K-68, K-69 K-70 K-71 K-72 K-73, K-74, K-75, K-76, K-77, K-78, N-79, M-80, N-81, K-82, K-83, K-85, K-88, K-90 and K-93, and more preferred is 6, K-67 K-68, K-69, K-74, K-77, K-78, K-79, M-80, N-81, K-84, and K-88.

Even more preferred individual connections are:

K-3. 13-[3-Methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4;

K-8. 13-[2-Phenyl-2-(2-pyrimidinyl)acetoxy]milbemycin A4;

K-40. 13-[3-Methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A3;

K-42. 13-[2-Phenyl-2-(2-pyrimidinyl)acetoxy]milbemycin A3;

K-67. 13-[(2S)-2-Phenyl-2-(2-pyrimidinyl)acetoxy]milbemycin A4;

K-68. 13-[(2R)-2-Phenyl-2-(2-pyrimidinyl)acetoxy]milbemycin A4;

K-77. 13-[(2R)-3-Methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4;

K-78. 13-[(2S)-3-Methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4,

and their salts.

Compounds of the invention can be obtained by using many different methods, which themselves are known to produce compounds of this type. For example, in General, they can be obtained by restoring the compounds of formula (VI)

< / BR>
(where R1, R3and A have the meanings defined above, and R2arepresents any of the groups or atoms represented by the radical R2except that any amino-substituted phenyl group substituted with a nitro-substituted facine, defined above), and when R2arepresents a nitro-substituted phenyl group, with the recovery of the compounds of formula (Ia) with a compound of formula (I) in which R2is amino-substituted phenyl group.

Learn more compounds of the invention can be obtained, as shown by reaction scheme A, is given at the end of the description.

In the above formulas, R1, R2a, R3and A have the meanings defined above, and X represents a halogen atom (e.g. chlorine atom or bromine) or sulfonyloxy group (for example, methanesulfonate group).

The compound of formula (III), which are among the source materials for use in this reaction scheme, can be obtained using the procedure described in Japanese patent application Kokai N Sho 61-103884, namely, by turning the hydroxy-group in the 5-position of the respective milbemycin in oxo group, and then by hydroxylation of methylene groups in the 13-position.

On A stage of this reaction scheme, the compound of formula (III) is subjected to interaction with the carboxylic acid of formula (IV) or its reactive derivative, giving the 13-lonefire, defined above).

Phase A consists of a complex reaction of esterification conventional type hydroxy group at the 13-position of compounds of formula (III) and a carboxylic acid of formula (IV), and, therefore, it may be implemented using well known in themselves complex ways of esterification using a carboxylic acid of formula (IM) or its reactive derivative. Examples of reactive derivatives of carboxylic acids include: galodamadruga acids (such as anhydrides of the acids, bromohydrin acids and iodohydrin acids, acid anhydrides, mixed acid anhydrides, active esters (such as n-nitrobenzyloxy ether), reactive amides and favorite other compounds commonly used for complex reactions of esterification.

When used by itself carboxylic acid of formula (IV), the reaction preferably is carried out in the presence of legitimised agent, such as dicyclohexylcarbodiimide (BCA), 2-chloro-1-methylpyridinium, n-toluensulfonate or sulphuric acid.

When using galoyanized carboxylic acid of formula (IV), the reaction preferably is carried out in the presence of a base. In relation PR is actvie on any part of the reactant molecules, and examples of preferred bases include: organic bases, such as triethylamine, N,N-dimethylaniline, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo(4.3.0)non-5-DBN and 1,8-diazabicyclo-(5.4.0)undec-7-ene (DBU); and inorganic bases such as sodium bicarbonate, potassium carbonate and sodium hydroxide.

The amount used galodamadruga carboxylic acid of formula (IV) is not particularly critical, and it usually is in the range from 1 to 10 equivalents per equivalent of compound of formula (III), and the number of used grounds usually ranges from 2 to 8 equivalents.

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions with regard to the nature of the employed solvent, provided that it has no adverse effect on the reaction or the reagents involved in the reaction, provided that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: hydrocarbons, which may be aliphatic or aromatic, such as, hexane, petroleum ether, benzene, toluene and xylene; halogenated hydrocarbons such as chloroform, methylene chloride and o-chlorobenzene; the e esters, such as acetate.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not important for the invention. Usually it is considered convenient to carry out the reaction at a temperature of from 0 to 100oC, more preferably from 2 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, namely the reaction temperature and the nature of the reagents and used solvents. However, provided that the reaction is carried out in the preferred conditions outlined above, is usually sufficient period of from 30 minutes to 3 hours

Reactions involving other reactive derivatives, usually carried out in similar conditions or other conditions, as is known in the technique for complex reactions of esterification.

At the stage B of the scheme of the reactions of A group or atom represented by X may be, for example, chlorine atom, bromine or methansulfonate group in alpha-position of the ester fragment in the 13-position in the compound of formula (V) is substituted by a group of the formula A-S-(in which A has the meanings as defined above) using the reaction of compounds of formula (V) with tilenum connection formula is Finance provided that it has no adverse effect on any portion of the reactant molecules, and the preferred examples of bases that can be used at this stage include organic tertiary amines such as triethylamine, tributylamine, diethylethanolamine, pyridine, 1,4-diazabicyclo(2.2.0)octane and 1,8-diazabicyclo ((5.4.0)undec-7-ene(DBU); metal hydrides, including hydrides of alkali metals and alkaline-earth metals, such as sodium hydride and calcium hydride; alkali metals such as sodium and lithium; alkyl compounds of alkali metals, such as utility; amides of alkali metals, such as diisopropylamide lithium bis(trimethylsilyl)amide lithium; an alkali metal alcoholate such as sodium methylate and tert-butyl potassium; other inorganic bases, especially carbonates of alkali metals and bicarbonates of alkali metals such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate and sodium bicarbonate.

The amount used of the base is not particularly significant, and it usually takes from 1 to 20 equivalents, preferably 1-5 equivalents, per equivalent of the compound of formula (V).

The reaction may proceed in a wide range rate is depending on the nature of the Foundation) and the reactivity of the compounds of formula (V) and Colnago connection used. Usually it is considered convenient to carry out the reaction at a temperature of from -70 to 90oC, more preferably from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, namely the reaction temperature and the nature of the reagents and solvent. However, if the reaction is carried out in the preferred conditions outlined above, is usually sufficient period of from 15 minutes to 24 hours

The reaction is normally and preferably carried out in the presence of a solvent. With respect to the applicable solvent has no particular restrictions, provided that it does not adversely affect the reaction or on the reagents involved in the reaction and can dissolve the reagents, at least to some extent. Examples of suitable solvents include: hydrocarbons, which may be aliphatic or aromatic, such as hexane, petroleum ether, benzene and toluene; halogenated hydrocarbons, especially halogenated aliphatic hydrocarbons, such as chloroform and methylene chloride; ethers, such as diethyl ether and tetrahydrofuran, amides such as dimethylformamide; sulfoxidov, such as dimethylsulfate is Tadei C reaction scheme A carbonyl group at the 5-position of the compounds of formula (VI) is restored to the hydroxy group by reaction of compounds of formula (VI) with a regenerating agent, giving the compound of formula (Ia).

There are no special restrictions with regard to the nature of the used reducing agent, provided that it is able to restore carbonyl group, and provided that it does not affect other functional groups in the compounds of formula (VI). Examples of such reducing agents include reducing agents, which operate using hydrogen anion, such as sodium borohydride or DIBORANE, preferably sodium borohydride.

The reaction is normally and preferably carried out in the presence of a solvent. There are no particular restrictions on the nature of the employed solvent, provided that it does not have a negative impact on the course of the reaction and can dissolve the reagents, at least to some extent. When used regenerating agent is sodium borohydride, the specific examples of preferred solvents include lower alcohols, such as methanol, ethanol and propanol.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not critical for the invention. Usually convenient to carry out the reaction at a temperature of about 0 to 50oC. Premature reaction and on the nature of the reagents and solvents. However, provided that the reaction is carried out at the preferred conditions outlined above, is usually sufficient period of from 5 minutes to 2 hours

At stage D scheme of the reaction of A compound of the formula (1b) in which R2brepresents a phenyl group, substituted amino group, can be obtained by restoring the nitro group of compounds of formula (1a) in which R2arepresents a phenyl group substituted by a nitro group. The restoration of the nitro group can be carried out using conventional means.

One example of such a reaction recovery is a catalytic reduction using a noble metal catalyst in the presence of gaseous hydrogen. Examples of preferred catalysts which may be used in this reaction include palladium on charcoal, palladium on barium sulfate, platinum oxide and similar.

The reaction is normally and preferably carried out in the presence of a solvent. There are no particular restrictions regarding the nature of the employed solvent, provided that it does not adversely affect the reaction or the participating agents, and that it can dissolve the reagents, at the end is; rostie ethers, such as tetrahydrofuran or dioxane; and esters such as ethyl acetate.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. Usually convenient to carry out the reaction at a temperature of from 10 to 80oC. the Time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents and solvent. However, if the reaction is carried out in the preferred conditions described above, is usually sufficient period of from 10 min to 5 h

As another example, the preferred response recovery recovery can be carried out using powdered zinc in the presence of acetic acid.

This reaction can occur in a wide temperature range, but the precise reaction temperature is not essential for the invention. Usually convenient to carry out the reaction at a temperature of from 0oC to about room temperature. The time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and the nature of the reagents and the m is the period from 30 minutes to 12 o'clock

Alternatively, the reactions shown in reaction scheme A, compounds of formula (V) can also be obtained by using the procedure summarized in reaction scheme B, is given at the end of the description.

In the above formulas, R1, R2a, R3and A have the meanings defined above.

Derived 15-hydroxybenzene formula (VII), which is the source material for this scheme of reactions, can be obtained using the method described in Japanese patent application Kokai SHo 60-158 191, the contents of which are included in this description for details.

Stage E this reaction scheme can be carried out by exposure of the formula (VII) reaction with a carboxylic acid of formula (IV) in the presence of acid, which acts as a catalyst.

There are no particular restrictions on the nature of the acid used as catalyst and here equally, you can use any acid commonly used in reactions of this type, including both inorganic acids and organic acids, for example hydrochloric, sulphuric, triperoxonane, trichloroacetic acid, triftormetilfullerenov, methanesulfonate, n-colorswith, triftoratsetata, methansulfonate or n-nitrobenzenesulfonate.

The applied amount of acid is usually a catalytic amount, and therefore, it is sufficient to use 1 equivalent or less equivalent to the compounds of formula (VI). However, this number can vary greatly depending on the reactivity of acid used, and can usually be used in amounts of from a catalytic amount to 5 equivalents.

In addition, if the reaction system is added to the powder of inorganic compounds, the reaction sometimes is accelerated, and thus, this technique can also be preferred. Examples of suitable inorganic compounds that can be used, if necessary, includes triftorbyenzola copper iodide, copper (1) iodide zinc, iodide, cobalt iodide Nickel, it is preferable to use a salt of copper, such as triftorbyenzola copper or copper iodide (1).

The reaction is normally and preferably carried out in the presence of a solvent. There are no special restrictions with regard to the nature of the employed solvent, provided that it has no adverse effect would serve as solvent, can be used even carboxylic acid of formula (IV). Examples of other suitable solvents include: aromatic hydrocarbons, such as benzene, toluene and xylene; halogenated hydrocarbons, especially halogenated aliphatic hydrocarbons, such as methylene chloride, 1,2 dichloroethane and chloroform; esters such as ethyl acetate and propyl; ethers, such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; such as dimethylsulfoxide; and NITRILES, such as acetonitrile.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not critical for the invention. Usually convenient to carry out the reaction at a temperature of from -10 to 100oC, more preferably from 0 to 50oC. the Time required for the reaction may also vary widely, depending on many factors, namely, the reaction temperature and on the nature of the reagents and solvent. However, with the reaction in the preferred conditions described above, is usually sufficient period of from 5 minutes to 6 hours, more preferably from 10 min to 2 h

Stage reaction scheme C is carried out by exposure of the compounds of formula (VII) interaction with the carboxylic acid of formula (VIII) in the presence of acid, which serves as a catalyst:

A-S-CR3(R2a)COOH

(in which R2a, R3and A have the meanings described above).

There are no particular restrictions on the acid used as catalyst, and any acid commonly used in reactions of this type can be used in this process, including both inorganic acids and organic acids, for example hydrochloric, sulphuric, triperoxonane, trichloroacetic acid, triftormetilfullerenov, methanesulfonate, n-toluensulfonate, n-nitrobenzenesulfonate or benzosulfimide acid, of which the preferred sulfuric acid, triftoratsetata, methansulfonate or n-nitrobenzenesulfonate.

The amount of acid used is usually the catalyst, and therefore, it is sufficient to use 1 equivalent or less equivalent to the compounds of formula (VII). However, this number may be varied within considerable limits, savienotajskava amount to 5 equivalents.

This reaction can be accelerated by adding powdered inorganic compounds to the reaction system, and this technique is therefore sometimes preferred. Examples of such inorganic compounds include metal salts, such as triftorbyenzola copper, copper iodide, modesty zinc, modesty cobalt or modesty Nickel; celite (trade mark); silica gel; alumina or aluminum oxide and similar; one of them we preferred salts of copper, such as triftorbyenzola copper and copper iodide; and most preferably triftorbyenzola copper or copper iodide.

The reaction is normally and preferably carried out in the presence of a solvent. There are no particular restrictions on the nature of the employed solvent, provided that it has no adverse effect on the reaction and the involved reagents, and can dissolve the reagents, at least to some extent. In some circumstances, as a solvent for this reaction can serve itself carboxylic acid of the formula (VIII). Examples of other suitable solvents include: aromatic hydrocarbons, such as benzene, toluene and xylene; halogenated hydrocarbons, especially halogenated alett and propyl; ethers, such as diethyl ether, tetrahydrofuran, dioxane and dimethoxyethane; amides, such as dimethylformamide, dimethylacetamide and hexamethylphosphoric triamide; sulfoxidov, such as dimethyl sulfoxide; and NITRILES, such as acetonitrile.

The reaction may proceed in a wide temperature range, but the precise reaction temperature is not critical for the invention. Usually convenient to carry out the reaction at a temperature of from -10 to 100oC, more preferably from 0 to 50oC.

The time required for the reaction may also vary depending on many factors, namely, the reaction temperature and the nature of the reagents and solvent. However, if the reaction is carried out in the preferred conditions described above, is usually sufficient period of from 5 minutes to 6 hours, more preferably from 10 min to 2 h

After completion of the reaction, the desired compound of formula (V), (VI), (Ia) and (Ib) may be released from the reaction mixture by conventional means. The product thus obtained can, if necessary, further purified using techniques such as various chromatography techniques, namely, chromatography on a column.

Milbemycin and similar the th formula (III) or (VII), usually obtained as mixtures with different ratios of the respective compounds, and they can be introduced in the reaction after they are divided into different factions, or they can be used in the above reactions in the form of mixtures, whether natural mixture or artificially obtained mixture. Therefore, the connection used at each stage of the above reactions may be either a single compound or a mixture of compounds. Accordingly, the compound of formula (I) may be in the form of a single compound or mixture of compounds, and, if they are obtained in the form of a mixture of compounds, they can be used for what they are, or may be separated before use on individual compounds.

Compounds of the invention possess strong insecticidal activity, and, therefore, they can be used as insecticides. Active compounds of the invention are apparent protective effect against harmful insects, but they do not exhibit phytotoxicity, and therefore agricultural plants never damaged these compounds. Compounds of the invention can be used to destroy a variety of harmful the insects, parasitic on plants, pests, which damage the materials being stored, household insects and similar.

Examples of harmful insects that are susceptible to compounds of the invention include insects of the orders: Coleopteza, for example, Callosobruchus chinensis, Sitophilus zeamais, Tribolium castaneum, Eplachna vigtioctomaculata, Agriotes fuscicollis, Anomala rufocuprea, Leptinotarsa decemkineata, Dibrotica spp. Monochamus alternatus, Lissorhoptrus oryzophilus and Lyctus bruneus; Lepidoptera, for example, Lymantria dispar, Malacosoma neustria, Pieris rapae, Spodoptera litura, Mamestra brassicae, Chilo suppressalis, Pyrausta nubilalis, Ephestia cautella, Adohophues ozana, Carpocapsa pomonella, Agrotis fucosa, Gallezia mellonella, Plutella mylostella and Phyllonistis citrella, Hemiptera, for example, Nephotettix cincticeps, Nilapavata lugens, Pseudococcus comstocki, Unaspis yanonensis, Myzus persicae, Aphis pomi, Aphis gossypii, Rhopalosiphum pseudobrassicas, Stephanitis nashi, Nazara spp. Cimex leotularius, Trialeurodes vaporariorum and Psylla spp. Ozthoptera, for example, Blatella germanica, Periplaneta americana, Gryllotalpa africana and Locusta migratoria, migratoriodes; Isoptera, for example, Deucotermes speratus and Coptotezma formosanus; and Diptera, for example, Musca domestica, Aedes aegypti, Hylemia platura, Culex pipiens, Anopheles Slnensis and Culex tritaeniorhynchus.

The composition of the invention, intended for agricultural use or for use in gardening, it is possible in many forms and ready-made forms of drugs. For example, it may be formed in the form of Farrukh Dustov, rough Farrukh Dustov, soluble powders, microgravity or oily suspensions or aqueous or oil solutions (which can be directly sprayed or can be used with dilution), aerosols or capsules in polymeric substances. Used media can be natural or synthetic and organic or inorganic, and it is usually applied in order to contribute to the achievement of an active compound of the processed substrate, and to facilitate storage, transportation or handling of the active connection. Solid, liquid and gaseous media can be selected from carriers, well known in the art for use with compositions of this type.

Such forms of drugs can be obtained using conventional techniques, for example by thorough mixing and/or grinding the active ingredient(s) with a carrier or diluent (solvent) or optional surface-active agent.

Examples of suitable solvents include: aromatic hydrocarbons, in particular, (8-12)C fraction from the distillation of crude oil, such as xylene mixtures or substituted naphthalenes; esters of phthalic acid, such as dibutil or dioctyl-phthalate; aliphatic or alicyclic hydrocarbons, such as cyclopentan or paraffins; alcohols, such as ethanol, ethylene glycol, etilenglikolevye ether or monotropy ether etilenglikolevye, dimethyl sulfoxide or dimethylformamide; optional epoxydecane vegetable oils, such as epoxydecane coconut oil or soybean oil; and water.

Examples of media that can be used, for example, in doctah and dispersible powders, include: natural mineral fillers such as calcite, talc, kaolin, montmorillonite or attapulgite. To improve the physical properties of the composition can also add high dispergirovannoyj silicic acid or highly dispersione absorbente polymers. An example of suitable granular adsorptive media includes: a porous material, such as pumice, brick grit, thick, bentonite; and non-porous materials, such as calcite or sand. Can be used with a wide variety of pre-granulated materials, organic or inorganic, examples of which include dolomite and crushed the remains of plants.

As surface-active agents can be used in cationic, anionic and non-ionic compounds having good emulsifying, dispersing and wetting properties, which are usually used. Can also be used one such agent or atarov, defoamers, viscosity regulators, binders and adhesives, or any combination thereof, as well as fertilizers or other active agents; to achieve special effects.

Insecticidal compositions typically contain from 0.01 to 99%, more preferably from 0.1 to 95% active compound; from 1 to 99.99% solid or liquid additive; and from 0 to 25%, more preferably from 0.1 to 25% surface-active agent. When industrially produced products are generally solid, in the form of concentrated compositions, they are usually diluted by the end user until the concentrations from 0.001 to 0.0001% by weight (10 to 1 parts per million).

In the above description, the percentages are given by weight.

Compounds of the invention can be formed in the form of a mixture or used in combination with other active compounds, for example, insecticide, poisonous food baits, bactericides, acaricides, nematicides, fungicides, plant growth regulators or herbicides. Examples of these insecticides include: organic phosphorus chemical compounds, urethane chemicals, carboxylate chemicals, chlorinated hydrocarbon chemicals and insecticidal substances produced to microorganis in combination with synergists. You want drugs such chemical substances and the form of the proposed industrial use were useful. A synergist is, regardless of activity, connection, is able to potentiate the effect of active compounds.

The connection is further illustrated by the following non-limiting examples which illustrate some of the compounds of the invention and the receipt of some agrochemical preparative forms containing compounds of the invention. In these examples, the "stage" refers to the stages preceding reaction schemes. Compounds of the invention are identified by numbers assigned to them in table.1.

Example 1 (stage A). 13-(2-bromo-phenylacetate)-5-kelimelerin AND4[(Y): R1=ethyl, R2a=phenyl, R3=hydrogen, X=bromine]

0.75 ml(9.3 mmole) of pyridine was added to a solution of 3.5 mg (6.3 mmole) 13-hydroxy-5-kelimelerin A4in 2 ml of dichloroethane, and then to the mixture was added with 2.93 g (12.6 mmole) of 2-bromo-2-phenylacetylamino. The resulting mixture was then stirred at room temperature for 12 hours after the end of this period the reaction mixture is poured into water and was extracted with ethyl acetate. The extract was filtered nassen what took place by distillation under reduced pressure. The resulting residue was then purified using chromatography on a column through silica gel, using 3:1 by volume mixture of hexane and ethyl acetate as eluent, giving to 2.41 g (yield of 51.0%) of target compound. Spectrum NMR (CD Cl3, 200 MHz mln. is 6.54 (1H, broad singlet); 5,72-5,90 (2H, multiplet); 4,96 (1H, doublet, J=10.4 Hz); of 3.85 (1H, singlet); 3,49-3,68 (2H, multiplet); totaling 3.04 (1H, triplet, J=8,8 Hz).

Example 2 (stage b). 13-[3-methyl-2-(5-methyl-2-pyrimidinyl)butyryloxy]-5-kelimelerin AND4< / BR>
[(VI):R1, R2a=isopropyl, R3=hydrogen, A=5-methyl-2-pyrimidinyl]

of 7.3 mg(0,087 mmole) of sodium bicarbonate were added to a solution of 33 mg (0,26 mmole) 5-methylpyrimidin-2-thiol in a mixture of 0.3 ml of water and 0.3 ml of N, N-dimethylformamide, and the resulting mixture was mixed at 80oC for 40 minutes After this mixture has been given the opportunity to cool and then was added 50 mg (0.07 mmole) 13-(2-bromo-3-methylbutoxy)-5-kelimelerin AND4(obtained as described in example 5), and the mixture is stirred at room temperature for 2 hours At the end of this period the reaction mixture is poured into water and was extracted with ethyl acetate. The extract was washed with saturated aqueous NaCl NAT the pressure. The resulting residue was purified using chromatography on a column over silica gel using a stepwise method, gradient elution with a mixture of hexane and ethyl acetate ranging from 3: 1 to 1:1 by volume as the eluent, giving 84 mg (yield 79%) of target compound.

An NMR spectrum (CDCl3, 200 MHz) d million dollars. is 6.54 (1H, multiplet); 5,74-5,91 (2H, multiplet); equal to 4.97 and 4,96 (together 1H, each doublet, J=a 10.6 Hz); at 4.75 (2H, broad singlet); 4,10 (1H, broad singlet); 3,50-3,68 (2H, multiplet).

Example 3 (stage C). 13-[3-methyl-2-(5-methyl-2-pyrimidinyl)butyryloxy]milbemycin AND4(the compound K-21)

[(Ia):R1=ethyl, R2a= isopropyl, R3=hydrogen, A=5 methyl-2-pyrimidinyl]

8,4 mg(0.22 mmole) of sodium borohydride was added to a solution of 84 mg (0.11 mmole) of 13-[3-methyl-2-(5-methyl-2-pyrimidinyl)-butyryloxy] -5-kelimelerin AND4(obtained as described in example 2) in 4 ml of methanol, and the resulting mixture stirred at room temperature for 30 minutes At the end of this period the reaction mixture is poured into water and was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. Restorationist chromatography on a column over silica gel, using the stepwise method, gradient elution with a mixture of hexane and ethyl acetate ranging from 3 to 7 1 1 by volume) as an element, giving 69 mg (yield 82%) of target compound.

Mass spectrum (m/z 766 (M+), 540, 522, 504, 412. Spectrum (CDCl3, 200 MHz) d million dollars. 4.97 and 4.96 (together 1H, each doublet, J=10.6 Hz); 4.68 (2H, broad singlet); 4.29 (1H, doublet, J=6. Hz); 3.95 (1H, doublet, J=6.0 Hz).

Example 4 (stage D). 13-[2-(4-aminofilina)-2-(2-pyrimidinyl)acetoxy] milbemycin A4(the compound K-12)

[(I) R1ethyl, R2b=AMINOPHENYL, R3A 2-pyrimidinyl]

18,5 mg of powdered zinc was added to a solution of 25 mg (0.03 mmole) of 13-[2-(4-nitrophenyl)-2-(2-pyrimidinyl)acetoxy] milbemycin A4(obtained in the same manner as described in examples 1-3) in 1 ml of 90% (weight/volume) aqueous solution of acetic acid, while cooling with ice, and the resulting mixture was mixed for 10 hours At the end of this period the reaction mixture was diluted with ethylacetate, and insoluble materials were filtered off. The filtrate was mixed with water, and the mixture was extracted with ethyl acetate. The extract was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous sulfate NAT the current was purified using chromatography on a column over silica gel, using the stepwise method, gradient elution with mixtures of hexane and ethyl acetate ranging from 1:3 to 100% hexane as eluent, yielding 14 mg (yield 58%) of target compound.

Mass spectrum (m/z): 760 (M+-41), 731, 690, 651. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,78 and 5.86 (2H, multiplet); 5.22-5.38 (4H, multiplet); 4.95 and 4.93 (together 1H, each doublet, J 10.0 Hz); 4.29 (1H, doublet, J 5.2 ); 3.95 (1H, doublet, J=6.4 Hz).

Example 5 (stage E). 13-(2-bromo-3-methylbutoxy)-5-kelimelerin A4< / BR>
[(Y):R1= ethyl, R2a=isopropyl, R3hydrogen, X is bromine]

3 drops triftormetilfullerenov acid at room temperature and in a stream of argon was added to a solution of 315 mg (0,666 mmole) of 15-hydroxy-5-kelimelerin A4and 510 mg and 2.83 mmole) of 2-bromo-3-methylmalonic acid in 6.3 ml of methylene chloride, and the resulting mixture was mixed for 1 h At the end of this period, the reaction mixture was poured into water and the mixture was extracted with ethyl acetate. The extract was filtered by 4% (weight/volume) aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride in that order, then dried over anhydrous magnesium sulfate; the solvent was then removed by means of negotiations is via silica gel using 7:3 by volume mixture of hexane and ethyl acetate as eluent, giving 288 mg (yield 71%) of target compound.

An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5.80-5.93 (2H, multiplet); 5.32-5.49 (4N, multiplet); 4.98 and 4.97 (together 1H, each doublet, J 10.5 Hz); 4.72 and 4.78 (2H, AB-Quartet, J 14.9 Hz); 4.03 and 4.00 (together 1H, each doublet, J 8.0 <); 3.86 (1H, singlet); 3,51 3.66 (2H, multiplet).

Example 6 (stage F). 13-[1-(2-pyrimidinamine)cyclopentanecarbonyl]-5-kelimelerin A4< / BR>
[(VI): R1ethyl, R2a+ R3-(CH2)4-, A 2-pyrimidinyl]

to 68.1 mg (0,358 mmole) iodide, copper (2), and then adding 79,1 ál (0,895 mmole) triftormetilfullerenov acid was added at room temperature and in a stream of gaseous nitrogen to 10 ml methylenechloride solution containing 100 mg (0,179 mmole) of 15-hydroxy-5-kelimelerin A4and 200 mg (0,895 mmole) 1-(2-pyrimidinyl)cyclopentanecarbonyl acid. The mixture was then stirred for 1 h at room temperature. At the end of this period of time, the reaction solution was poured into water and was extracted with ethyl acetate. The extract was filtered by 4% (weight/volume) aqueous solution of sodium bicarbonate and saturated aqueous sodium chloride, in that order. The resulting mixture over anhydrous magnesium sulfate, and the solvent Inoi column using the method of gradient elution with mixtures of hexane and ethyl acetate, ranging from 10: 1 to 1:1 by volume as the eluent, to obtain the 94.5 mg (yield 69,1%) of target compound.

Mass spectrum (m/z): 762 (M+), 538, 520. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 8.60 (2H, doublet, J 5.1 Hz); 6.92 (1H, triplet, J 1 Hz); 6.54 (1H, triplet, J 1.9 Hz); 5.70-5.90 (2H, multiplet); 5.26 5.46 (3H, multiplet); 4.93 (1H, doublet, J is 10.6 Hz); a 3.83 (1H, singlet).

Example 7 (stage E). 13-[(2s)-2-methansulfonate-2-phenylacetate]-5-ketones-Berezin A4< / BR>
[(Y): R1ethyl, R2a(S) - phenyl, R3hydrogen, X methansulfonate]

3 drops triftormetilfullerenov acid was added at room temperature and in a stream of nitrogen gas to 6,0 ml methylenchloride solution containing 300 mg (0.54 mmole) of 15-hydroxy-5-kelimelerin A4and 503 mg (2,28 mmole) of (2S)-methanesulfonamide-2-phenylacetic acid. The mixture was then stirred for 2 h at room temperature. At the end of this period the reaction solution was poured into water and was extracted with ethyl acetate. The extract was filtered by 4% (weight/volume) aqueous solution of sodium bicarbonate and then saturated aqueous sodium chloride, after which it was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation POI reduced by the use of stepwise method, gradient elution with mixtures of hexane and ethyl acetate, ranging from 7: 3 to 1:1 by volume as the eluent, to obtain 200 mg (yield 48%) of target compound.

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 6.53 (1H, multiplet); 5.70-5.92 (3H, multiplet); 4.95 (1H, doublet, J10.6 Hz); 3.99 (1H, singlet); 3.84 (1H, singlet).

Example 8 (stage B). 13-[(2R)-phenyl-2-(2-pyridylthio)acetoxy]-5-kelimelerin A4< / BR>
[(VI): R1ethyl, R2a(r)-phenyl, R3hydrogen, A 2-pyrimidinyl]

6.6 mg (0,078 mmole) of sodium bicarbonate were added to a mixture of 0.3 ml of water and 0.3 ml of N, N-dimethylformamide, containing 17.5 mg (0.16 mmole) pyrimidine-2-thiol. The mixture then was stirred for 10 min at room temperature, after which the reaction mixture was added 0.3 ml of N, N-dimethylformamide solution containing 30 mg (0,039 mmole) 13-[(2S)-2-methansulfonate-2-phenylacetate] -5-kelimelerin A4( obtained as described in example 7), and the mixture is stirred for 1 h at room temperature. At the end of this period the reaction solution was poured into water and was extracted with ethyl acetate. The extract was rinsed with water and then saturated aqueous sodium chloride. Then it was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure is of 7:3 by volume mixture of hexane and ethyl acetate as eluent, obtaining 13.2 mg (yield 43%) of target compound.

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 6.53 (1H, multiplet); 5.71-5.90 (1H, multiplet); 5.54 (1H, singlet); 4.96 (1H, doublet, J 10.6 Hz);4.04 (1H, singlet);of 3.85 (1H, singlet).

Example 9 (stage C). 13-[(2R)-2-phenyl-2-2-(2-pyrimidinyl)acetoxy] milbemycin A4(the compound K-68).

[(1a): R1ethyl, R2a(R)-phenyl, R3hydrogen, A 2-pyrimidinyl]

1.3 mg (0,034 mmole) sodium borohydride was added to 1 ml of methanol containing 13 mg (0,017 mmole) 13-[(2R)-2-phenyl(2-pyrimidinyl)acetoxy] -5-kantonilaisen A4(obtained as described in example 8), and the mixture is stirred for 30 min at room temperature. At the end of this period the reaction solution was poured into water and was extracted with ethyl acetate. The extract was rinsed with water and then saturated aqueous sodium chloride. Then it was dried over anhydrous magnesium sulfate, and the solvent is managed by distillation under reduced pressure. The resulting residue was purified using chromatography on silicagel column using a stepwise method, gradient elution with mixtures of hexane and ethyl acetate ranging from 7:3 to 1:1 by volume as pectr (CDCl3, 200 MHz) d million dollars. 5,74 - to 5.85 (2H, multiplet); of 5.53 (1H, singlet); the 5.25 - 5,41 (4H, multiplet); 4,96 (1H, doublet, J 10.5 Hz); 4,08 (1H, broad singlet); of 3.95 (1H, doublet, J 6.2 Hz).

Examples 10-99.

The following method, which were synthesized compounds of examples 10-99, similar to that described in the above examples.

To illustrate in more detail the methods used in the process of the invention, used stage and the output (in%) at each stage is indicated after each number of connections. The asterisk indicates that the obtained product was used in subsequent reactions without further purification, and thus, the output is not evaluated in this stage.

Example 10. 13-[2-(2-pyrimidinyl]butyryloxy]milbemycin A4< / BR>
[(the compound K-1: stage E(x) stage B (61%) stage C (71%)]

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,72 5,90 (2H, multiplet); 5,28-5,48 (4H, multiplet); and 5,00 4,95 (together 1H, each doublet, J 10.5 Hz); 4,06 (1H, singlet); of 3.97 (1H, doublet, J 5.8 Hz).

Example 11. 13-[2-(2-pyrimidinyl)pentanoyl]milbemycin A4< / BR>
[connection K-2: stage E (x) stage B (96%) stage C (49%)]

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,72 - 5,90 (2H, multiplet); from 5.29-5,44 (4H, multiplet); 4,94 4,99 (together 1H, each DN is milbemycin A4< / BR>
[connection K-3: stage E (x) phase B (50%) stage C (86%)]

Mass spectrum (m/z): 558 (M+194), 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,72 - 5,90 (2H, multiplet); 5,28-5,46 (4H, multiplet); 4,96 5,01 (together 1H, each doublet, J and 10.8 Hz); 4,07 (1H, singlet); 3,98 (1H, doublet, J 5,9 Hz).

Example 13. 13-[2-(2-pyrimidinyl)hexanoate)milbemycin A4< / BR>
[connection K-4: stage E (86%) phase B (100%) stage C (81%)]

Mass spectrum (m/z): 766 (M+), 637, 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,79 - 5,88 (2H, multiplet); 5,26-5,43 (4H, multiplet); 4,98 and 4.93, (together 1H, each doublet, J 10.5 Hz); the 4.29 (1H, doublet, J 6.4 Hz); of 3.96 (1H, doublet, J 6.5 Hz).

Example 14. 13-[3-methyl-2-(2-pyrimidinyl)pentanoic]milbemycin A4< / BR>
[connection K-5: stage E (88%) stage B (49%) stage C (82%)]

Mass spectrum (m/z): 766 (M+, 540, 522, 488. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,72 - of 5.89 (2H, multiplet); 5,26-5,46 (4H, multiplet); 4,99 4,96 (together 1H, each doublet, J 10.5 Hz); the 4.29 (1H, doublet, J 6.0 Hz); of 3.96 (1H, doublet, J 6.4 Hz).

Example 15. 13-[2-cyclopentyl-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-6: stage E (x) stage B (63%) stage C (65%)]

Mass spectrum (m/z): 778 (M+), 760, 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,71 - of 5.89 (2H, multiplet); 5,23-5,48 (4H, multiplet); 5,00-4,95 (is imaginally)acetoxy]milbemycin A4< / BR>
[connection K-7: stage E (x) stage B (97%) stage C (43%)]

Mass spectrum (m/z): 792 (M+), 734, 698, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,70 of 5.99 (2H, multiplet); 5,20 - 5,44 (4H, multiplet); to 4.92 4.99 together 1H, each doublet, J of 10.7 Hz); 4,19 (1H, singlet); of 3.95 (1H, doublet, J 5.8 Hz).

Example 17. 13-[2-phenyl-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-8: A stage (51%) stage B (70%) stage C (60%)]

Mass spectrum (m/z): 559 (M+2 227), 541, 523. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,72 - to 5.85 (2H, multiplet); 5,24-of 5.45 (4H, multiplet); 4,96 and 4,92 (together 1H, each doublet, J 10.5 Hz); 4,08 and of 4.05 (together 1H, each singlet); 3,23 - 3,29 (1H, multiplet).

Example 18. 13-[2-(2-were)-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-9: stage A (51%) stage B (49%) stage C (59%)]

Mass spectrum (m/z): 800 (M+), 652, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.68 of 5.84 (2H, multiplet); 5.23-5,48 (4H, multiplet); 4.92 and 4.98 (together 1H, each doublet, J 10.7 Hz); 4.08 (1H, doublet, J 4.8 Hz); 3.96 (1H, doublet, J 5.8 Hz).

Example 19. 13-[2-(4-chlorophenyl)-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-10: stage E (65%) stage B (66%) stage C (81%)]

Mass spectrum (m/z): 820 (M+), 710, 674. Spectrum (CDCl3, 200 MHz) d million dollars. 5.82-5.77 (2H, multiplet); 5.41-5.29 (4H, the mule is. 3-[2-(2-chlorphenyl)2-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-11: stage A (72%) stage B (49%) stage C (62%)]

Macc-spectrum (m/z): 711 (M+109), 652, 572, 588. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 6.06-6.16 (1H, multiplet); 5.71-5.86 (2H, multiplet); 5.20-5.43 (3H, multiplet); 4.97 and 4.94 (together 1H, each doublet, J 8.5 ); 4.28 (1H, doublet, J 5.2 Hz); 3.55 (1H, multiplet); 3.25 (1H, multiplet); 3.03 (1H, multiplet).

Example 21. 13-[2-(2-forfinal)-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-13: A stage (77%) stage B (60%) stage C (68%)]

Mass spectrum (m/z): 804 (M+), 766. An NMR spectrum (CDl3, 200 MHz) d million dollars. 5.93 (1H, doublet, J 5.5 Hz); 5.77-5.40 (3H, multiplet); 4.97 and 4.92 (together 1H, each doublet, J 10.3 Hz); 4.08 and 4.07 (together 1H, each singlet); 3.95 (1H, singlet, J 6.2 Hz); 3.43-3.70 (1H, multiplet); 3.24-3.27 (1H, multiplet); 2.95 - 3.10 (1H, multiplet).

Example 22. 13-[2-(2-pyrimidinyl)-2-(2-trifloromethyl)acetoxy] milbemycin A4< / BR>
[connection K-14: stage E (x) stage B (75%) stage C (72%)]

Mass spectrum (m/z): 854 (M+), 744, 726, 540. Spectrum NMR (CD Cl3, 200 MHz) d million dollars. 5.72 - 5.83 (2H, multiplet); 5.21-5.42 (4H, multiplet); 4.89 and 4.93 (together 1H, each doublet, d, 10.2 Hz); 4.08 (1H, doublet, J 4.3 Hz);

Example 23. 13-[2-(2,6-differenl)-2-(2-pyrimidinyl)acetoxy]milbemycin ANMR (CDCl3, 200 MHz) d million dollars. 5.68 - 5.82 (2H, multiplet); 5.27-5.46 (4H, multiplet); 4.92 and 4.99 (together 1H, each doublet, J 14.1 Hz); 4.07 (1H, singlet); 3.95 (1H, doublet, J 5.8 Hz).

Example 24. 13-[3-methyl-2-(4-methyl-2-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection K-16: stage E (71%) stage B (38%) stage C (79%)]

Mass spectrum (m/z): 766 (M+), 736, 706, 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.97 (1H, doublet, J 10.4 Hz); 4.68 (2H, broad singlet); 4.29 (1H, doublet, J 5.6 Hz); 4.06 (1H, broad singlet); 3.95 (1H, doublet, J 5.6 HZ);

Example 25. 13-[2-(4-methyl-2-pyrimidinyl)-2-phenylacetate]milbemycin A4< / BR>
[connection K-17: stage E (72%) stage B (76%) stage C (68%)]

Mass spectrum (m/z): 800 (M+), 782, 764. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.94 4.95 and (together 1H, each doublet, J 10.5 Hz); 4.05 and 4.04 (together 1H, each singlet); 3.95 (1H, doublet, J 6.2 Hz); 3.65-3.47 (1H, multiplet); 3.28-3.21 (1H, multiplet); 3.10-2.97 (1H, multiplet).

Example 26. 13-[2-(4-chlorophenyl)-2-(4-methyl-2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-18: stage E (61%) stage B (78%) stage C (65%)]

Mass spectrum (m/z): 834 (M+), 674, 628. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.81 - 5.77 (2H, multiplet); 5.39-5.28 (4H, multiplet); 4.95 and 4.93 (together 1H, each doublet, J 10.6 Hz); 4.28 (1H, doublet, J 5.9 Hz); 4.10-4.00 (1H, broad); 3.95 (1H, doubledayi K-19: stage A (70%) stage B (55%) stage C (88%)]

Mass spectrum (m/z): 834 (M+), 816, 798. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.96 (1H, doublet, J 10.3 Hz); 3.95 (1H, doublet, J 6.2 Hz); 3.68 3.43 (1H, multiplet); 3.28 3.21 (1H, multiplet); 3.11-2.95 (1H, multiplet).

Example 28. 13-[2-(2-forfinal)-2-(4-methyl-2-pyrimidinyl)acetoxy] milbemycin A4< / BR>
[connection K-20: stage A (88%) stage B (59%) stage C (60%)]

Mass spectrum (m/z): 540 (M+278), 505, 412, 279. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4,95 (IH, doublet, J 10.3 Hz); 4.60-4.70 (2H, multiplet); 4.27 (IH, doublet, J 4.6 Hz); 4.00 - 4.10 (IH, broad singlet); 3.95 (IH, doublet, J 6.2 Hz); 3.35 3.65 (IH, multiplet); 3.20 3.30 (IH, multiplet); 2.95-3.10 (IH, multiplet).

Example 29. 13-[2-(5-methyl-2-pyrimidinyl)-2-phenylacetate]milbemycin A4< / BR>
[connection K-22: stage E (72%) stage B (78%) stage C (84%)]

Mass spectrum (m/z): 801 (M++ 1), 783, 765. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.94 and 4.92 (along IH, each doublet, J 10.5 Hz); 4.09 and 4.05 (along IH, each singlet); 3.95 (IH, doublet, J 6.2 Hz); 3.63 3.43 (IH, multiplet); 3.29 3.21 (IH, multiplet; 3.11 - 2.95 (IH, multiplet).

Example 30. 13-[2-(2-were)-2-(5-methyl-2-pyrimidinyl)acetoxy] milbemycin A4< / BR>
[connection K-23: stage A (x) station B (x) stage C (12%)]

Mass spectrometer (m/z): 814 (M+). An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.95 (IH, duplicates the CLASS="ptx2">

Example 31. 13-[2-(4-chlorophenyl)-2-(5-methyl-2-pyrimidinyl)acetoxy] milbemycin A4< / BR>
[connection K-24: stage E (61%) stage B (45%) stage C (69%)]

Mass spectrum (m/z): 834 (M+), 816, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.82 - 5.77 (2H, multiplet); 5.39-5.28 (4H, multiplet; 4.94 and 4.92 (along IH, each doublet, J 10.6 Hz); 4.29 (IH, doublet, J 5.2 Hz); 3.95 (IH, doublet, J 6.2 Hz).

Example 32. 13-[2-(2-chlorophenyl)-2-(5-methyl-2-pyrimidinyl)acetoxy] milbemycin A4< / BR>
[connection K-25: stage A (70%) stage B (77%) stage C (79%)]

Mass spectrum (m/z): 834 (M+), 540. An NMR spectrum (CDCl3, 200 MHz) million dollars. 4.96 - 4.92 (along IH, each doublet, J 10.5 Hz); 4.29 (IH, doublet, J 5.1 Hz); 3.95 (IH, doublet, J 6.2 Hz); 3.63-3.48 (IH, multiplet); 3.28 3.21-in (IH, multiplet); 3.10-2.97 (IH, multiplet).

Example 33. 13-[2-(2-forfinal)-2-(5-methyl-2-pyrimidinyl)acetoxy] milbemycin A4< / BR>
[connection K-26: stage A (88%) stage B (47%) stage C (37%)]

Mass spectrum (m/z): 818 (M+), 800, 704. An NMR spectrum (CDCl3, 200 MHz) million dollars. 4.98 and 4.91 (along IH, each doublet, J 5.8 Hz); 4.65-4.70 (2H, multiplet); 4.28 (IH, doublet, J 4.5 Hz); 3.90-4.10 (IH, broad singlet); 3.95 (IH, doublet, J 5.1 Hz); 3.44-3.68 (IH, multiplet); 3.20 - 3.30 (IH, multiplet); 2.90 3.10 (IH, multiplet).

Example 34. 13-[2-(4,6-dimethyl-2-pyrimidinyl)-3-methylbutyrate]milbee the NMR Spectrum (CDCl3, 200 MHz) d million dollars. 5.71 - 5.89 (2H, multiplet); 5.27-5.44 (4H, multiplet); 4.95 4.99 and (together 1H, each doublet, J 10.5 Hz); 4.29 (1H, doublet, J 5.8 Hz); 4.08 (1H, broad singlet); 4.03 (1H, broad singlet); 3.96 (1H, doublet, J 5.8 Hz).

Example 35. 13-[2-(4,6-dimethyl-2-pyrimidinyl)-2-phenylacetate)milbemycin A4< / BR>
[connection K-28: stage E (72%) stage B (78%) stage C (85%)]

Mass spectrum (m/z): 814 (M+), 676. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.90 and 4.85 (together 1H, each doublet, J 10.5 Hz); 3.95 (1H, broad singlet); 3.88 (1H, doublet, J 6.2 Hz); 3.63-3.40 (1H, multiplet); 3.20-3.23 (1H, multiplet); 3.00-2.90 (1H, multiplet).

Example 36. 13-[2-(4.6-dimethyl-2-pyrimidinyl)-2-(2-were)acetoxy]milbemycin A4< / BR>
[connection K-29: stage E (x) stage B (x) stage C (8%)]

Mass spectrum (m/z): 828 (M+), 810, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4.99 and 4.92 (together 1H, each doublet, J 10.6 Hz); 4.03 (1H, broad singlet); 3.94 (1H, doublet, J 6.2 Hz); 3.63-3.47 (1H, multiplet); 3.28-3.22 (1H, multiplet); 3.10-2.97 (1H, multiplet).

Example 37. 13-[2-(4-chlorophenyl)-2-(4,6-dimethyl-2-pyridylthio)acetoxy] milbemycin A4< / BR>
[connection K-30: stage E (61%) stage B (60%) stage C (58%)]

Mass spectrum (m/z): 848 (M+), 804, 582. An NMR spectrum (CDCl3, 200 MHz) million dollars. 5.81-5.76 (2H, multiplet); 5.43-5.28 (4H, multiplet); 4.9

Example 38. 13-[2-(2-chlorophenyl)-2-(4,6-dimethyl-2-pyrimidinyl)acetoxy] milbemycin A4< / BR>
[connection K-31: stage A (70%) stage B (71%) stage C (80%)]

Mass spectrum (m/z): 830(M+18), 810. An NMR spectrum (CDCl3, 200 MHz) d million dollars. equal to 4.97 and 4.93 (together 1H, each doublet, J=a 10.6 Hz); 4,07 (1X, broad singlet); a 4.03 (1H, broad singlet); of 3.95 (1H, doublet, J=6.2 Hz); 3,63-3,49 (1X, multiplet); 3.27 to up 3.22 (1H, multiplet); 3,09 - 2,95 (1H, multiplet).

Example 39. 13-[2-(4,6-dimethyl-2-pyrimidinyl)-2-(2-forfinal)acetoxy] milbemycin A4< / BR>
[connection K-32: stage A (88%) stage B (58%) stage C (77%)]

Macc-spectrum (m/z): 706 (+-126), 670, 626. An NMR spectrum (CDCl3, 200 MHz) d million dollars. equal to 4.97 and 4,94 (together 1H, each doublet, J=10.5 Hz); 4,50-4,70 (2H, broad singlet); to 4.28 (1H, broad doublet, J=5.6 Hz); of 4.05 (1H, broad singlet); of 3.94 (1H, doublet, J=6.2 Hz); 3.45 points-of 3.65 (1H, multiplet); 3,20-3,30 (1H, multiplet); 2.95 and - 3,10 (1H, multiplet).

Example 40. 13-2-(5-chloro-2-pyrimidinyl)-3-methylbutyrate milbemycin A4< / BR>
[connection K-33: stage E (71%) stage B (63%) stage C (42%)]

Mass spectrum (m/z): 786 (M+, 768, 750, 720, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. equal to 4.97 and 4,96 (together 1H, each doublet, J=10.5 Hz); and 4.68 (2H, broad singlet); the 4.29 (1H, doublet, J=6,1=Hz); of 3.95(1H, doublet, J=6,1 Hz); 3,48 - 3,66 (1H, multiplet); 3,26 (1H, multiplet); 3,02 (Ndiaye K-34: stage E (72%) stage (79%) stage C (69%)]

Mass spectrum (m/z): 820 (M+), 802, 692. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4,94 and 4,92 (together 1H, each doublet, J=a 10.6 Hz); 4,10 (1H, broad singlet); Android 4.04(1H, broad singlet); of 3.96 (1H, doublet, J=6.2 Hz); 3,64 3,47 (1H, multiplet); 3,20 of 3.12 (1H, multiplet); 3,10 of 2.97 (1H, multiplet).

Example 42. 13-[2-(4-chlorophenyl)-(5-chloro-2-pyrimidinyl)-2-acetoxy] milbemycin A4< / BR>
[connection K-35: stage E(61%) stage B (52%) stage C (50%)]

Mass spectrum (m/z): 709 (M+145), 600, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. of 5.83 is 5.77 (2H, multiplet); 5,44-of 5.26 (4H, multiplet); 4,94 and 4.93 (together 1H, each doublet, J=10.0 Hz); 4,68 (25N, singlet; the 4.29 (1H doublet, J=6.3 Hz); of 3.95 (1H, doublet, J=6,6 Hz).

Example 43. 13-[2-(2-chlorophenyl)-2-(chlor-2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[compound K-36: stage A (70%) stage B (73%) stage C (64%)]

Mass spectrum (m/z: 854 (M+), 836, 710. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4,96 and 1,93 (together 1H, each doublet, J=10,6 ); of 4.05 (1H, broad singlet); 3.96 points 1H, doublet, J=6.2 Hz); 3,60-3,47 (1H, multiplet); 3,28-is 3.21 (1H, multiplet); 3,10 3,00 (1H, multiplet).

Example 44. 13-[3-methyl-2-(4-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection K-37: stage E (71%) stage B (38%) stage C (62%)]

Mass spectrum (m/z): 752 (M+), 723, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4,91 N, doublet, J=6.2 Hz); 3,48-3,68 (1H, multiplet).

Example 45. 13-[2-phenyl-2-(4-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-38: stage A (31%) stage B (x) stage C (58%)]

Mass spectrum (m/z): 786 (M+), 768, 750, 692. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,75 of 5.84 (2H, multiplet); 5,24-of 5.45 (4H, multiplet); 4,92 and to 4.98 (together 1H, each doublet, J=10,2 Hz); of 3.95 and 3.97 (together 1H, each doublet, J=6.4 Hz).

Example 46. 13-[3-methyl-2-(2-personilty)butyryloxy]milbemycin A4< / BR>
[connection K-39: stage E (71%) stage B 46%) stage C (43%)]

Mass spectrum (m/z): 752 (M+), 540, 504, 460. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,70 - 5,80 (2H, multiplet); the 5.25 to 5.45 (4h, multiplet); 4,96 and equal to 4.97 (together 1H, each doublet, J=10.5 Hz); and 4.68 (2H, broad singlet); the 4.29 (1H, doublet, J=5.3 Hz); of 4.05 (1H, broad singlet); of 3.95 (1H, doublet, J=6.2 Hz); 3.45 points-of 3.65 (1H, multiplet); 3,20-3,30 (1H, multiplet); 3,03 (1H, triplet, J=9.5 Hz).

Example 47. 13-[3-methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection K-40: stage E (91%) stage B (34%) stage C (76%)]

Mass spectrum (m/z): 739 (M+1), 526, 508, 398. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,75 - of 5.82 (2H, multiplet); 5,30 is 5.38 (2H, multiplet); 4,98 and 4,96 (together 1H, each doublet, J=10.5 Hz); 4,28 (1H, triplet, J=6.5 Hz); 4,06 (1H, doublet, J=1.6 Hz); 3,90 (1H, doublet, J=6.5 Hz).

An example is C (90%)]

Mass spectrum (m/z 733 (M+ 1), 726, 712, 526. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5.73-5.80 (2H, multiplet); 5.24-5.41 (4H, multiplet); 4.95 and 4.92 (together 1H, each doublet, J=10.5 Hz); 4.28 (1H, triplet, J=6.4 Hz); 3.95 and 3.94 (together 1H, each doublet, J=6.4 Hz).

Example 49. 13-[2-phenyl-2(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-43: stage E(44%) stage B (x) stage C (19%)]

Mass spectrum (m/z): 800 (M+), 756, 554, 516. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5.77-5.80 (2H, multiplet); 5.28-5.39 (4H, multiplet); 4.95 and 4.93 (together 1H, each doublet, J=10.5 Hz); 4.29 (1H, broad singlet); 4/06 (1H, doublet, J=4.4 Hz); 3.97 (doublet, J=6.5 Hz) and 3.95 (doublet, J=6.0 Hz), together 1H.

Example 50. 13-[2-cyclopentyl-2-(5-methyl-2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-44: stage E (68%) stage B (71%) stage C (75%)]

Mass spectrum (m/z): 792 (M+), 756, 630, 540, 504. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.77-5.84 (2H, multiplet); 5.28-5.40 (4H, multiplet); 4.97 4.94 (together 1H, each doublet, J=10.5 Hz); 4.29 (1H, doublet, J=6.0 Hz); 3.96 (1H, doublet, J=6.0 Hz).

Example 51. 13-[2-5-chloro-2-pyrimidinyl)-2-cyclopentylacetic]milbemycin A4< / BR>
[connection K-45: stage E (68%) stage B (67%) stage C (64%)]

Mass spectrum (m/z): 722 (M+40), 730, 681, 631, 520, 502. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.80-5.85 (2H, ASS="ptx2">

Example 52. 13-[2-cyclopentyl-2-(4,6-dimethyl-2-pyrimidinyl)acetoxy] -milbemycin A4< / BR>
[connection K-46: stage E (68%) phase B (50%) stage C (40%)]

Macc-spectrum (m/z): 782 (M+24), 752, 552, 516. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.77 - 5.82 (2H, multiplet); 5.30-5.40 (4H, multiplet); 4.95 (1H, doublet, J=10.3 Hz); 4.68 (1H, singlet); 3.96 (1H, doublet, J 6.2 Hz).

Example 53. 13-[2-cyclopentyl-2-(4-methyl-2-pyrimidinyl)acetoxy milbemycin A4< / BR>
[connection K-47: stage E (68%) stage B (47%) stage C (74%)]

Mass spectrum (m/z): 791 (M+), 756, 724, 504, 486. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.78-5.83 (2H, multiplet); 5.30-5-40 (4H, multiplet); 4.96 and 4.95 (together 1H, each doublet, J 10.5 Hz); 4.69 (1H, broad singlet); 3.96 (1H, doublet, J=6.2 Hz).

Example 54. 13-[2-cyclohexyl-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-48: stage E (86%) stage B (37%) stage C (36%)]

Mass spectrum (m/z):820 (M+), 504, 413, 315. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 6.66 (1H, singlet); 5.78-5.83 (2H, multiplet); 5.29-5.39 (4H, multiplet); 4.97 and 4.94 (together 1H, each doublet, J 10.4 Hz); 4.30 (1H, doublet, J 6/0 Hz); 3.63 (1H, doublet, J 6.0 Hz).

Example 55. 13-[2-cyclohexyl-2-(4-methyl-2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-49: stage E (86%) stage B (29%) stage C (21%)]

Mass spec is 2H, multiplet); 5.28-5.39 (4H, multiplet); 4.96 (1H, doublet, J 10.5 Hz); 4.29 (1H, doublet, J 6.0 Hz); 3.96 (1H, doublet, J 6.0 Hz).

Example 56. 13-[2-(5-chloro-2-pyrimidinyl)-2-(2,6-differenl)acetoxy] milbemycin A4< / BR>
[connection K-50: stage E (40%) stage B (40%) stage C (16%)]

Mass spectrum (m/z): 724 (M+132), 540, 504, 279. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.73-5.79 (2H, multiplet); 5.26-5.39 (4H, 'multiplet); 4.98 and 4.93 (together 1H, each doublet, J 11.0 Hz); 4.28 (1H, multiplet); 4.07 (1H, singlet); 3.95 (1H, doublet, J 6.2 Hz.

Example 57. 13-[2-(2,6-differenl)-2-(5-methyl-2 - pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-51: stage E (X) stage B (25%) stage C (25%)]

Mass spectrum (m/z): 605(M+231), 540, 412, 301. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.73-5.78 (2H, multiplet); 5.27-5.38 (4H, multiplet); 4.93 and 4.98 (together 1H, each doublet, J and 12.4 Hz); 4.25-4.31 (1H, multiplet); 4.07 (1H, singlet); 3.95 (1H, doublet, J 6.2 Hz).

Example 58. 13-[2-(2,6-differenl)-2-(4-methyl-2 - pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-52: stage E (37%) stage B (74%) stage C (24%)]

Mass spectrum (m/z): 724 (M+112), 522, 307, 279. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.74-5.78 (2H, multiplet); 5.29-5.38 (4H, multiplet); 4.94 and 4.99 (together 1H, each doublet, J 11.4 Hz); 4.56 (2H, singlet); 3.95 (1H, doublet, J 6.02 Hz).

Pride E (43%) stage B (44%) stage C (19%)]

Mass spectrum (m/z): 540 (M+310), 522, 311, 293. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.75-5.79 (2H, multiplet); 5.29-5.45 (4H, multiplet); 4.94 and 5.00 (together 1H, each doublet, J 10.4 Hz); 4.66 (2H, singlet); 3.95 (1H, doublet, J 6.3 Hz).

Example 60. 13-[2-cyclohexyl-2-(methyl-2-pyrimidinyl)acetoxy milbemycin A4< / BR>
[connection K-54: stage E (86%) stage B (37%) stage C (47%)]

Mass spectrum (m/z): 806 (M+), 540, 504, 440. An NMR spectrum (CDCl3, 270 MHz) million dollars. 8.30 (2H, singlet); 5.77-5.88 (2H, multiplet), 5.32-5.40 (4H, multiplet), 4.96 and 4.95 (together 1H, each doublet, J 10.5 Hz), 4.30 (1H, et, J 6.0 Hz), 3.96 (1H, doublet, J 6.0 Hz).

Example 61. 13-[2-(5-chloro-2-pyrimidinyl)-2-cyclohexylacetate]milbemycin A4< / BR>
[connection K-55: stage E (86%) phase B (50%) stage C (32%)]

Mass spectrum (m/z:826 (M+), 540, 504, 412. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 8.41 (2H, multiplet), 5.35-5.39 (4H, multiplet), 4.97 (1H, doublet, J 10.5), 4.30 (1H, doublet, J 6.4 Hz), 3.97 (1H, doublet, J 6.4 Hz).

Example 62. 13-[2-cyclohexyl-2-(2-personilty)acetoxy]milbemycin A4< / BR>
[connection K-56: stage E (86%) phase B (50%) stage C (16%)]

Mass spectrum (m/z): 792 (M+), 756,504. An NMR spectrum (DCl3, 270 MHz) d million dollars. 5.76-5.87 (2H, multiplet), 5.29 5.39 (4H, multiplet), 4.95 (1H, doublet, J 10.5 Hz), 4.29 (1H, doublet, J 6.4 Hz), 3.95 (1H, doublet, J 6.4).


Mass spectrum (m/z): 786 (M+, 540, 504. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.77 5.81 (2H, multiplet), 5.30 5.38 (4H, multiplet), 4.94 and 4.29 (together 1H, each doublet, J 10.6 Hz), 4.67 (1H, singlet), 3.95 (1H, doublet, J 6.2 Hz).

Example 64. 13-[2-phenyl-2-(2-personilty)acetoxy]milbemycin A4< / BR>
[connection K-58: stage E (68%) stage B (68%) stage C (84%)]

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.79 5.84 (2H, multiplet), 5.30 5.39 (4H, multiplet), 4.96 and 4.94 (together 1H, each doublet, J 10.6 Hz), 4.29 (1H, doublet, J 6.3 Hz), 3.96 (1H, doublet, J 6.3 Hz).

Example 65. 13-[3-cyclopentyl-2-(2-pyrimidinyl)propionyloxy]milbemycin A4< / BR>
[connection K-59: stage E (*) stage B (55%) stage C (58%)]

Mass spectrum (m/z): 792 (M+), 758, 541, 504, 412. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.78-5.83 (2H, multiplet); 5.28-5.42 (4H, multiplet), 4.94 and 4.97 (together 1H, each doublet, J 10.6 Hz), 4.27 (1H, multiplet), 4.07 (1H, doublet, J 1.6. Hz), 3.96 (1H, doublet, J 6.2 Hz).

Example 66. 13-(3-cyclohexyl-2-(2-pyrimidinyl)propionyloxy]milbemycin A4< / BR>
[connection K-60:stage E (*) stage B (*) stage C (47%)]

Mass spectrum (m/z):806 (M+), 678, 540, 522, 460, 412. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5.79-5.98 (2H, multiplet), 5.29-5.48 (4H, multiplet), 4.94 (doublet, J 10.6 Hz) and 4.98 (doublet, J 10.5 Hz), together 1H, 4/06 (1H, broad singlet), EDINENIE K-61: stage E (58%) stage (58%) stage C (84%)]

Mass spectrum (m/z): 780(M+), 540, 412, 249, 223. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,77 of 5.84 (2H, multiplet); 5,28-5,43 (4H, multiplet), equal to 4.97 4.99 (together 1H, each doublet, J=10.3 Hz), 4.26 deaths-4033 (1H, multiplet), 4,05-4,08 (1H, broad singlet), of 3.96(1H, doublet, J=6.0 Hz).

Example 68. 13-[2-phenyl-2-(3-pyrimidinyl)acetoxy milbemycin AND4< / BR>
[connection-62: stage E (72%) stage (66%)-stage (51%)]

Mass spectrum (m/z):786 (M+), 672, 540, 522. An NMR spectrum (CDCl3, 70 MHz) d million dollars. 5,77-of 5.83 (2H, multiplet), 5,28 is 5.38 (4H, multiplet), 4,95 and 4,87 (together 1H, each doublet, J= 10.5 Hz), 4.09 to (1H, singlet), 3,95 and 3,94 (together 1H, each doublet, J=6,04 Hz).

Example 69. 13-[3-methyl-2-(3-pyridazinyl)botorelax]milbemycin AND4< / BR>
[connection-63: stage E (*) stage (18%) stage C (52%)]

Mass spectrum (m/z): 752 (M+), 706, 540, 412. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,76-of 5.82 (2H,multiplet); 5,30 of 5.39 (4H, multiplet), 4,89 and 4,87 (together 1H, each doublet, J=6.85 Hz), 4.09 to (1H, singlet), of 3.96 (1H, doublet, J=6.0 Hz).

Example 70. 13-[2-(1,3-benzodioxol-5-yl)-2-(pyrimidinyl)acetoxy] milbemycin AND4< / BR>
[connection K-64: stage (*) stage C(7%)]

Mass spectrum (m/z):830 (M+), 652, 592, 540. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,74-of 5.83 (2H, multiplet); 5,28-5,41 (4H, multiplet),4,94 and 4,96 (together 1H, each d)acetoxy]milbemycin AND4< / BR>
[connection-65: stage E (*) stage (60%) stage (83%)]

Mass spectrum (m/z): 536 (M+), 800, 540, 412, 279. An NMR spectrum (CDCl3, 200 MHz) d million dollars. to 4.98 and 5,00 (together 1H, each doublet, J=10.4 Hz), 4,25-to 4.23 (1H, multiplet); 4,04 and of 4.05 (together 1H, each singlet), of 3.94 and 3.96 points (together 1H, doublet, J=6.2 Hz).

Example 72. 13-[2-(4,6-dimethoxy-1,3,5-triazine-2-yl)-2-phenylacetate]milbemycin AND4< / BR>
[connection K-66: stage E (68%) stage B (*) stage (27%)]

Mass spectrum (m/z):847(M+, 811, 753, 676, 638, 596, 540, 504. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,76-of 5.82 (2H, multiplet); 5,30 of 5.39 (4H, multiplet), 4,95 and 4,94 (together 1H, each doublet, J=10.5 Hz), the 4.29 (1H, triplet, J=7,1 Hz).

Example 73. 13-[[2S)-2-phenyl-2-(2-pyrimidinyl)acetoxy]milbemycin AND4< / BR>
[connection-67: stage E (50%) stage (70%)- stage (61%).

Mass spectrum (m/z): 786(M+), 658, 540, 522, 504. An NMR spectrum (CDCl3, 270 MHz) d million dollars. of 4.95 (1H, doublet, J=10.5 Hz), 4,28 (1H, doublet, J=6.3 Hz), of 4.05 (1H, broad singlet); of 3.95 (1H, doublet, J=6.3 Hz).

Example 74. 13-[2-(1,4-benzodioxan-6-yl)-2-pyrimidinyl)acetoxy]milbemycin AND4< / BR>
[connection-69: stage (34%) stage C (41%)]

Mass spectrum (m/z):844 (M+, 810, 606, 540, 412.

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,73-of 5.82 (2H, multiplet); the 5.25-5,42 (4H, multiplet); 4,93 and 4.95 (VM is ylthio)-2-phenylacetate]milbemycin AND4< / BR>
[connection To-70: stage E (72%) stage b (*) stage (22%)]

Mass spectrum (m/z): 816 (M+, 702, 654, 60. An NMR spectrum (CDCl3, 70 MHz) d million dollars. 5,77-of 5.89 (2H, multiplet), 5,28 is 5.38 (4H, multiplet), 4,93 and 4,89 (together 1H, each doublet, J=10,5 ), 3,95 3,94 (together 1H, doublet, J=6.4 Hz).

Example 76. 13-[2-(6-methoxy-3-pyridazinyl)-3-methylbutyrate]milbemycin AND4< / BR>
[connection-71: stage E (58%) stage b (*) stage C (2%)

Mass spectrum (m/z): 782 (M+), 540, 412. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,76-of 5.83 (2H, multiplet); 5,34 of 5.39 (4H, multiplet), equal to 4.97 and 4,94 (together 1H, each doublet, J=10.1 Hz); the 4.29 (1H, doublet, J=5,2 Hz), 4,96 (1H, doublet, J=6.4 Hz).

Example 77. 13-[2-(6-chloro-3-pyridazinyl)-2-phenylacetate]milbemycin AND4< / BR>
[connection-72: stage E (86%) stage (54%)- stage (57%)

Mass spectrum (m/z): 540 (M+- 280), 522,504. Mass spectrum (m/z) 820 (M+- 63), 706, 672, 640. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,76-5,79 (2H, multiplet), 5,28 is 5.38 (4H, multiplet); 4,92 and 4,89 (together 1H, each doublet, J=10.5 Hz), 4,28 (1H, broad singlet), 4,07 (1H, singlet), 3,95 and 3,94 (together 1H, each doublet, J=6.5 Hz).

Example 78. 13-[2-(6-chloro-3-pyridazinyl)-3-methylbutyrate]milbemycin AND4< / BR>
[connection K-73: stage E (58%) stage B (*) stage C (24%)]

Mass spectrum (m/z): 786 (M+), 540, 522, 412.t, J 10.5 Hz), the 4.29 (1H, triplet, J 6.4 Hz), 4,07 (1H, singlet), of 3.96 (1H, doublet, J 6,4).

Example 79. 13-[2-(6-methyl-3-pyridazinyl)-2-phenylacetate]-milbemycin A4< / BR>
[connection K-74; stage E (86%) stage B (*) stage C (28%)]

Mass spectrum (m/z): 768 (M+32), 666, 522. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,75 - 5,79 (2H, multiplet), 5,28 of 5.39 (4H, multiplet), 4,94 and 4,88 (together 1H, each doublet, J 10.5 Hz), 4,27 (1H, triplet, J 6.5 Hz), of 4.05 (1H, broad singlet), 3,95 and 3,94 (together 1H, each doublet, J 6.5 Hz).

Example 80. 13-[3-methyl-2-(6-methyl-3-pyridazinyl)butyryloxy]milbemycin A4< / BR>
[connection K-75: stage E (58%) stage B (*) stage C (2%)]

Mass spectrum (m/z): 766 (M+), 540, 412. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,78 of 5.82 (2H, multiplet), and 5.30-5,3 (4H, multiplet), 4,98 (doublet, J 10.3 Hz) and 4,90 (doublet, J 9.3 Hz), together 1H, 4,06 (1H, singlet), of 3.96 (1H, doublet, J 6.0 Hz).

Example 81. 13-[2-Methyl-2-(2-pyrimidinyl)propionyloxy]milbemycin A4< / BR>
[connection L-76: stage E (72%) stage B (11%) stage C (36%)]

Mass spectrum (m/z): 739 (M+), 704, 626, 540. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 4,94 (1H, b et, J 10.5 Hz), the 4.29 (1H, doublet, J 6.0 Hz), was 4.02 (1H, broad singlet), of 3.95 (1H, doublet, J 6.0 Hz).

Example 82. 13-[(2R)-3-methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection K-77: SLn.the Dol. at 4.99 (1H, doublet, J 10.5 Hz), and 4.40 (1H, doublet, J 3.4 Hz), the 4.29 (1H, triplet, J 6.0 Hz), 4,06 (1H, singlet), of 3.96 (1H, doublet, J 6.0 Hz).

Example 83. 13-[(2S)-3-methyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection K-78: stage E (52%) phase B (50%) stage C (91%)]

Mass spectrum (m/z): 752 (M+), 716, 540, 522, 504. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 4,96 (1H, doublet, J 10.5 Hz), 4,43 (1H, doublet, J 6.5 Hz), the 4.29 (1H, doublet, J 5.8 Hz), a 4.03 (1H, broad singlet), of 3.96 (1H, doublet, J 5.8 Hz).

Example 84. 13-[1-(2-pyrimidinyl)cyclopentanecarboxylate]milbemycin A4< / BR>
[the compound N-79: stage F (69%) stage C (51%)]

Mass spectrum (m/z): 656 (M+110), 638, 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4,95 and to 4.98 together 1H, each doublet, J 10.5 Hz), the 4.29 (1H, doublet, J 6.0 Hz), a 4.03 (1H, broad signet), of 3.96 (1H, doublet, J 6.0 Hz).

Example 85. 13-[2-ethyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection M-80: stage F (49%) stage C (53%)

Mass spectrum (m/z): 656 (M+110), 638, 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 4,95 and to 4.98 (together 1H, each doublet, J 10.5 Hz), the 4.29 (1H, doublet, J 3.0 Hz), a 4.03 (1H, broad singlet), of 3.96 (1H, doublet, J 6.0 Hz).

Example 86. 13-[1-(2-pyrimidinyl)cyclobutanecarbonyl]milbemycin A4< / BR>
[the compound N-81: stage F (24%) stage (45%)

Mass spectra (1H, broad singlet), of 3.95 (1H, doublet, J 6.0 Hz).

Example 87. 13-[2-(2-chlorophenyl)-2-(3-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection K-82: stage E (75) stage B (*) stage C (5,2%)]

Mass spectrum (m/z): 766 (M+44), 726, 522. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,76 - 5,79 (multiplet), 5,26 of 5.39 (4H, multiplet), 4,89 (1H, doublet, J 10.5 Hz), 4,27 (12H, broad singlet), of 3.94 (1H, doublet, J 6,04 Hz).

Example 88. 13-[2-(2-chlorophenyl)-2-(3-pyridazinyl)acetoxy]milbemycin A4< / BR>
[connection K-83: stage E (72%) stage B (*) stage C (4%)]

Mass spectrum (m/z): 770 (M+50), 724, 706, 540. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,72 5,80 (2H, multiplet), 5,30 is 5.38 (4H, multiplet), to 4.98 (1H, doublet, J 10.5 Hz), 1,28 (1H, broad singlet), to 4.01 (1H, singlet), of 3.95 (1H, doublet, J 6.5 Hz).

Example 89. 13-[2-(2-chlorophenyl)-2(6-methyl-3-pyridazinyl)-acetoxy]milbemycin A4< / BR>
[connection K-84: stage E (75%) stage B (*) stage C (6%)]

Mass spectrum (m/z): 796 (M+38), 755, 540, 522. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 5,71-5,80 (2H, multiplet), a 5.25-5,38 (4H, multiplet), equal to 4.97 4,90 (together 1H, each doublet, J 10.5 Hz), 4,28 (1H, broad singlet), 4,07 (1H, broad singlet), 3,95 and 3,94 (together 1H, each doublet, J 6.4 Hz).

Example 90. 13-[1-(2-pyrimidinyl)cyclohexanecarboxylate]milbemycin A4< / BR>
[connect is. the Dol. 5,73-by 5.87 (2H, multiplet), 5,22-5,41 (H, multiplet), 4,94 (1H, doublet, J of 10.7 Hz), of 3.95 (1H, doublet, J 6,3).

Example 91. 13-[2-(3,6-dimethyl-2-pyridazinyl)-2-phenyl-acetoxy]milbemycin A4< / BR>
[connection-86: stage E (57%) phase B (100%) stage C (67%)]

Mass spectrum (m/z): 814 (M+), 779, 676, 540, 412. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,74-5,79 (2H, multiplet), 5,24 lower than the 5.37 (4H, multiplet), 4,90 4.99 (together 1H, each doublet, J 10.4 Hz), 4.09 to (1H, singlet), 3,92 3,93 and (together 1H, each doublet, J 6,1 Hz).

Example 92. 13-[2-(5-ethyl-2-pyrimidinyl)-2-phenylacetate]milbemycin A4< / BR>
[connection-87: stage E (68%) stage (51%) stage C (57%)]

Mass spectrum (m/z): 774 (M+40), 692, 646, 564, 540, 522, 504.

An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,76-5,80 (2H, multiplet), 5,20-5,44 (4H, multiplet); 4,98 and equal to 4.97 (together 1H, each doublet, J 10.5 Hz), and 4.68 (1H, doublet, J 6.2 Hz), the 4.29 (1H, triplet, J 7.0 Hz), of 3.97 (1H, doublet, J 6,2).

Example 93. 13-[2-(5-bromo-2-pyrimidinyl)-2-phenylacetate]milbemycin A4< / BR>
[connection-88: stage E (35%) stage (68%) stage C (45%)]

Mass spectrum (m/z): 864 (M+), 736, 615, 540, 522, 504. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,72-5,80 (2H, multiplet), 5,23 is 5.38 (4H, multiplet), 4,94 and 4,92 (together 1H, each doublet, J is 10.6 Hz), 4,08 (1H, doublet, J 7.0 Hz), of 3.95 (1H, doublet, J 5,9 Hz).

Example 95. 13-[3-phenyl-2-(2-pyrimidinyl)butyryloxy]milbemycin A4< / BR>
[connection To 90: stage (*) stage C (9,0%)]

Mass spectrum (m/z): 814 (M+), 776, 686, 563, 540, 412. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,68 of 5.84 (2H, multiplet), 5,16-of 5.45 (4H, multiplet), 4,28 (1H, multiplet), Android 4.04 (1H, broad singlet), of 3.95 (1H, doublet, J 6.2 Hz).

Example 96. 13-[2-(2-methoxyphenyl)-2-(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection-91: stage F (*) stage C (11,0%)]

Mass spectrum (m/z): 816 (M+), 786, 540, 522, 412. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,69 of 5.84 (2H, multiplet), 5,19-5,43 (4H, multiplet); 4,94 and to 4.98 (together 1H, each doublet, J 10.4 Hz), 4,28 (1H, broad singlet), 4,06 (1H, singlet), of 3.95 (1H, doublet, J 6.2 Hz).

Example 97. 13-[2-(6-methyl-1,2,4-triazine-5-ylthio)-2-phenylacetate]milbemycin A4< / BR>
[connection To-92: stage F (70%) stage C (60%)

Mass spectrum (m/z): 801 (M+), 676, 540. An NMR spectrum (CDCl3, 270 MHz), each doublet, J 10.5 Hz), the 4.29 (1H, doublet, J 6.0 Hz), 3,59 vs. 3.96 (together 1H, each doublet, J 6.0 Hz).

Example 98.13-[2-(5-m is the Mass spectrum (m/z): 801 (M+), 676, 617, 540, 522. An NMR spectrum (CDCl3, 270 MHz) d million dollars. 4,96 and 4,87 (together 1H, each doublet, J 10.4 Hz), the 4.29 (1H, doublet, J 6.0 Hz), 3,95 vs. 3.96 (together 1H, each doublet, J 6.0 Hz).

Example 99. 13-[2,2-bis(2-pyrimidinyl)acetoxy]milbemycin A4< / BR>
[connection-94: stage E (38%) stage B (41%) stage C (43%)]

Mass spectrum (m/z): 598 (M+222), 540, 522. An NMR spectrum (CDCl3, 200 MHz) d million dollars. 5,73-of 5.82 (2H, multiplet), 5,27 of 5.39 (4H, multiplet), to 4.98 (1H, doublet, J 10.5 Hz), 4.26 deaths-to 4.33 (1H, multiplet), of 4.05 (1H, singlet), of 3.96 (1H, doublet, J 6.2 Hz).

Agrochemical finished drugs

When the compounds of this invention are intended for agricultural and horticultural purposes of applying possibly a great variety of forms and ready-made forms of drugs or preparative forms, and below are their examples. In these examples, all percentages are expressed by weight and the compounds of the invention are identified by numbers assigned to them in table. 1.

Example 100. Wettable powders.

A mixture comprising 10% of the compound K-10, 2.5 percent dodecylbenzenesulfonate sodium 2,5% ligninsulfonate sodium and 85% of diatomaceous earth, thoroughly mixed and pulverizadores, giving wettable powder.

Example 101. Emulsifiable conc the chemical Inc.) and 85% of xylene, thoroughly mixed, giving emulsifiable concentrate.

Example 102. Granules.

A mixture comprising 3% of the compound K-17, 1% white black, 5% ligninsulfonate sodium and 91% of clay were thoroughly mixed and pulverizadores. To the resulting mixture, water was added, and the mixture was mixed, granulated and dried, giving pellets.

Example 103. Emulsifiable concentrates.

A mixture comprising 5% of compound (K-6, 45% of cyclohexanone, 11% of polyoxyethylene-nonylphenylether ether, 4% of dodecylbenzenesulfonate calcium and 35% of methylnaphthalene is homogeneous, dissolved, giving emulsifiable concentrate.

Example 104. Emulsifiable concentrates.

A mixture comprising 5% of the compound K-8, 10% socola SM100 (brand emulsifying agent, Toho chemical Inc.) and 85% of xylene, were thoroughly mixed, giving emulsifiable concentrate.

Example 105. Wettable powders.

A mixture comprising 10% of the compound K-22, 5% ligninsulfonate sodium, 3% lauryl potassium, 5% highly dispersed silicic acid and 77% of kaolin, thoroughly mixed and pulverizadores, giving wettable powder.

Example 106. Emulsifiable concentrates.

A mixture comprising 5% soedineniya oil polyglycolic ether (36 moles of ethylene oxide), 35% of cyclohexanone and 50% xylene, homogeneous dissolved, giving emulsifiable concentrate.

Example 107. Dusty.

A mixture comprising 5% of the compound K-31 and 95% of talc were thoroughly mixed and pulverizadores, giving the dust.

Example 108. Emulsifiable concentrates.

A mixture comprising 1% of the compound K-3, 20% parakala KPS (emulsifying agent, Nippon Nyukazai To. Ltd.) and 79% of xylene, were thoroughly mixed, giving emulsifiable concentrate.

Biological activity.

The activity of compounds of the invention is further illustrated by the following biological tests. In table. 2, 3 and 4, all of the compounds (C1), (C2) and (C3), which are used as the control for comparison purposes disclosed in Japanese patent application Kokai Hei 1-104 078 and have the formula shown below. Connection (C4), (C5) and (C6) are all included in the scope of Japanese application Kokai Hei 1-104 078, but does not describe it. These compounds were first synthesized by us and have the formula shown in scheme D, presented at the end of the description.

Experiment 1. Insecticidal activity against Plutella mylostella.

Emulsifiable concentrates are obtained as described in example 108, and containing 1% active is Alice in the resulting mixture for 10 s, and then were dried in air, and then each sheet was placed in a polyethylene Cup with a diameter of 8 see each Cup was placed larvae in the amount of 10 pieces at the age of 3 days, and the Cup was then covered with a lid. The Cup was left to stand in a thermostat supported at a temperature of 25oC, for 3 days, after which we determined the percentage of mortality (including individuals with symptoms of various disorders). Each test was carried out in double repetition in parallel. The results are shown in table. 2, in which the compounds of the invention are identified by numbers assigned to them in table. 1.

Experiment 2. Insecticidal activity against Spodoptera fitura.

Emulsifiable concentrates are prepared as described in example 108 and containing 1% of active ingredient was diluted with water to bring the final concentration to 10 ppm million 5 g of artificial feed (Insecta L), were immersed in each of the obtained mixtures at 20 C, and the feed was then dried in air. Then he was placed in a polyethylene Cup with a diameter of 8 see each Cup was placed 10 three-day larvae of Spodoptera fitura, and the Cup was covered with a lid. The Cup was left to stand in a thermostat at 25oC for 3 days, after which it was determined pray shown in the table. 3.

Experiment 3. Insecticidal activity against Adoxophyes orana.

Emulsifiable concentrates are obtained as described in example 108, and containing 1% of active ingredient was diluted with water to bring the final concentration to 10 ppm million 5 g of artificial feed (Insecta L), were immersed in each of the obtained mixtures for 20 min, and the feed was then dried in air. Then he was placed in a polyethylene Cup having a diameter of 8 see each Cup was placed 10 four-day larvae of Adoxophyes orana, and the Cup was covered with a lid. The Cup was left to stand in a thermostat supported 25oC, for 5 days, after which we determined the percentage of mortality (including individuals with disorders). Each test was carried out with a double repetition in parallel. The results are shown in table. 4.

1. Derivatives of 13-(substituted thio)acetoxypiperidine General formula I

< / BR>
where R1represents methyl, ethyl or isopropyl group;

where R2is1WITH6-alkyl; phenylalkyl, in which alkyl has 1 to 3 carbon atoms; C3WITH6-cycloalkyl,3WITH6-cycloalkenyl, carbocyclic aryl group which has 6 to 10 calzavarini, ethyl, halogen(C1WITH2)-alkyl, methoxy - or taksigrup, halogen atoms and amino group, heterocyclic group, which 5 - or 6-membered alicyclic ring containing 2 oxygen atom, condensed with benzene ring, or a group R4-S-, in which R4represents a 6-membered aromatic heterocyclic group containing 2 nitrogen atom;

R3represents a hydrogen atom, a methyl or ethyl group, or R2and R3together represent a group of the formula -(CH2)n-, in which n is 3, 4 or 5, an integer;

A represents A 6-membered aromatic heterocyclic group containing 2 or 3 nitrogen atom, which is unsubstituted or substituted by at least one Deputy, selected from alkyl groups having 1

4 carbon atoms, methoxypropyl, taksigrup and halogen atoms.

2. Connection on p. 1, in which R2is2- C5is an alkyl group, phenylmethylene group, cycloalkyl group having 5 or 6 carbon atoms, cycloalkenyl group, in which cycloalkyl part has 5 or 6 carbon atoms, phenyl or 2-naftalina group, which is unsubstituted or Samusenko the ora and amino groups, or benzene ring condensed with a 5 - or 6-membered alicyclic group containing 2 atoms of oxygen.

3. Connection on p. 1, in which R2and R3together represent trimethylene group.

4. Connection on p. 1, in which A represents A 6-membered aromatic heterocyclic group containing 2 or 3 nitrogen atom, which is unsubstituted or substituted by at least one Deputy, selected from methyl groups, ethyl groups, methoxy-, taksigrup and halogen atoms.

5. Connection on p. 1, in which R2is2- C5is an alkyl group, phenylmethylene group5- C6-cycloalkyl group5WITH6-cycloalkylation group, phenyl group or 2-naftalina group, which is unsubstituted or substituted by one or two substituents selected from methyl groups, triptorelin, methoxypropyl, fluorine atoms and chlorine and amino group, or a benzene ring condensed with a 5 - or 6-membered alicyclic group containing 2 oxygen atom; R3represents a hydrogen atom, a methyl or ethyl group, R2and R3together represent trimethylene group and A camping unsubstituted or substituted by at least one Deputy, selected from methyl, ethyl groups, methoxy-, taksigrup and halogen atoms.

6. Connection on p. 1, in which R1represents a methyl or ethyl group.

7. Connection on p. 1, in which R2represents an alkyl group having 3 to 5 carbon atoms, 1-methylbenzyl, phenyl group which is unsubstituted or substituted by 1 or 2 substituents selected from methyl, triptoreline groups, methoxypropyl, fluorine atoms, chlorine and amino groups, 2-naftalina group, 1,3-benzodioxole-5 - ilen group or 1,4-benzodioxan-6-ilen group.

8. Connection on p. 1, in which R3represents a hydrogen atom.

9. Connection on p. 1, in which A represents A 3-pyridazinyl, 2-pyridazinyl, 4-pyrimidinyl, 2-personilnya group or a 1,3,5-triazine-2-ilen group, each of which is unsubstituted or substituted by one or two substituents selected from methyl, ethyl groups, methoxy-, taksigrup and halogen atoms.

10. Connection on p. 1, in which R1represents a methyl or ethyl group, R2represents an alkyl group having 3 to 5 carbon atoms, 1-methylbenzyl group, phenyl group, which methoxypropyl, of fluorine atoms and chlorine and amino groups, 2-naftalina, 1,3-benzodioxole-5-ilen or 1,4-benzodioxan-6-ilen group, R3represents a hydrogen atom and A 3-pyridazinyl, 2-pyridazinyl, 4-pyrimidinyl, 2-piratininga group or a 1,3,5-triazine-2-ilen group, each of which is unsubstituted or substituted by one or two substituents selected from methyl, ethyl groups, methoxy-, taksigrup and halogen atoms.

11. Connection on p. 1, in which R2is ISO-propyl or phenyl group, which is asamasinda or substituted by 1 or 2 substituents selected from methyl, triptoreline groups, methoxypropyl, fluorine atoms and chlorine in the 2 - and/or 6-position of the phenyl group.

12. Connection on p. 1, in which A represents A 2-pyrimidinyl group.

13. Connection on p. 1, in which R1represents a methyl or ethyl group, R2is ISO-propyl or phenyl group which is unsubstituted or substituted by 1 or 2 substituents selected from methyl, triptoreline groups, methoxypropyl, fluorine atoms and chlorine in the 2 - and/or 6-position of the phenyl group, R3represents a hydrogen atom, and A represents 2 is niloy group.

15. Connection on p. 1, in which R1represents a methyl or ethyl group, R2is ISO-propyl group or phenyl group, R3represents a hydrogen atom and A represents A 2-pyrimidinyl group.

16. Connection on p. 1, representing a 13-[3-methyl-2-(2 - pyrimidinyl)butyryloxy]milbemycin AND4; 13-[2-phenyl-2- (2-pyrimidinyl)acetoxy] milbemycin AND4; 13-[3-methyl-2- (2-pyrimidinyl)butyryloxy]milbemycin AND3; 13-[2-phenyl-2-(2 - pyrimidinyl)acetoxy]milbemycin AND3; 13-[(2S)-2-phenyl-2-(2 - pyrimidinyl)acetoxy] milbemycin AND4; 13-[(2R)-2-phenyl-2-(2 - pyrimidinyl)acetoxy] milbemycin AND4; 13-[(2R)-3-methyl-2-(2 - pyrimidinyl)butyryloxy]milbemycin AND4; 13-[(2S)-3-methyl-2-(2 - pyrimidinyl)butyryloxy]milbemycin AND4.

17. Insecticidal composition comprising a derivative milbemycin as the active ingredient and additives target, characterized in that as a derived milbemycin it contains a compound of the formula I according to any one of paragraphs.1 16 in an effective amount.

18. Method of protecting plants from damage by insects by processing plants derived milbemycin, characterized in that as about the/P> 19. A method of obtaining a compound according to any one of paragraphs.1 to 16, characterized in that the compound of General formula II

< / BR>
where R1, R3and A matter under item 1;

R2arepresents any of groups represented by R2except that aminosilane phenyl group substituted nitrosamines phenyl group,

restore with obtaining the compounds of formula Ia

< / BR>
in which R1, R2a, R3and A have the meanings defined above,

and, when R2ais nitrosamino phenyl group, restore the connection formula Ia with obtaining the compounds of formula I in which R2is aminosilane phenyl group.

 

Same patents:

The invention relates to certain 13-alkyl-23-imino - 13-halogen-23-imino-LL-F28249-compounds and to their use for combating endo - and ectoparasitic infections and infestations in warm-blooded animals

The invention relates to a series of new macrolide compounds that are chemically related to some well-known classes of macrolides, including milbemycin and avermectins

The invention relates to a method of obtaining new macrolide compounds of the formula I

The invention relates to methods of producing a range of new macrolide compounds that are chemically related to some well-known classes of macrolides, including milbemycin and avermectins

The invention relates to a method of obtaining new compounds with antibiotic

The invention relates to certain 13-alkyl-23-imino - 13-halogen-23-imino-LL-F28249-compounds and to their use for combating endo - and ectoparasitic infections and infestations in warm-blooded animals

The invention relates to new 2-imidazolin-2-yl)thieno - foroperational compounds, to intermediates used to obtain these compounds, and the way of dealing with these compounds with unwanted annual and perennial plants, namely 6-(2-imidazolin-2-yl)thieno - and furo[2,3-b] and 5-(2-imidazolin-2-yl)thieno - and furo[3,2-b]the pyridine compounds and the corresponding 2,3-dihydrothieno and 2,3-dihydropyrimidine with structural formulas (Ia) and (Ib):

< / BR>
whererepresents a single or double bond; R1represents a C1-C4alkyl; R2represents a C1-C4alkyl or C3-C6cycloalkyl; R1and R2together with the carbon atom to which they are joined, can form WITH3-C6cycloalkyl, optionally substituted stands; And represents СООR3CHO, CH2OH, COCH2HE, CONHCH2CH2OH, CONHOH or

R3hydrogen, C1-C12alkyl, which can be broken od is alkoxy, halogen, hydroxyl, C3-C6cycloalkyl, benzyloxy, fullam, phenyl, furfuryl, galopera, lower alkylphenyl, lower alkoxyphenyl, nitrophenyl, carboxyla, lower alkoxycarbonyl, cyano, C1-C4alkylthio or three (lower) alkylammonium; C3-C6alkenyl, optionally substituted by one of the following groups:1-C3alkoxy, phenyl, halogen or two WITH1-C3alkoxygroup or two halogen groups; C3-C6cyclooctyl, optionally substituted by one or two1-C3alkyl groups; C3-C10quinil, optionally substituted by phenyl, halogen or CH2IT; or the cation of an alkali metal or alkaline-earth metal (CA, BA) manganese, copper, iron, ammonium, or organic ammonium; RWITHand RDrepresent N or CH3; Represents N; COR4or SO2R5provided that when a represents a COR4or SO2R5and is a СOOR3the radical R3cannot be hydrogen or a salt-forming cation; R4represents a C1-C11alkyl, chloromethyl or phenyl, optionally substituted A5 alkyl or phenyl, optionally substituted one metalno, chloro - or nitro-group; W represents 0 or S; X represents 0, S or whenis a single bond, the group S 0; Y and Y', Z and Z' represent hydrogen, halogen, C1-C6alkyl, C1-C4hydroxy (lower) alkyl, C1-C6alkoxy, C1-C6acyloxy, benzoyloxy, optionally substituted by one or two1-C4alkyl, C1-C4alkoxygroup or halogen; C1-C4alkylthio, phenoxy,1-C4haloalkyl,1-C4haloalkoxy, nitro, cyano, C1-C4alkylamino,1-C4dialkylamino,1-C4alkylsulfonyl or phenyl, optionally substituted by one or more1-C4the alkyl, C1-C4alkoxy, halogen, or any combination of these two groups, where Y and Z are the same provided that Y and Z represent hydrogen, halogen, alkyl or alkoxy, and when Y and Y' or Z and Z' are the same group they are hydrogen or alkyl; and taken together, Y and Z form a ring in which YZ has the structural formula -(CH2)n- where n являе/www.fips.ru/fullimg/rupat2/19962/004.dwl/2058313-8t.gif" ALIGN="ABSMIDDLE">-=where L, M, Q, and R7each represent hydrogen, halogen, nitro, C1-C4lower alkyl, C1-C4lower alkoxy, methoxy, phenyl, phenoxy, provided that only one of the radicals L, M, Q or R7may have a value different from hydrogen, halogen, C1-C4the alkyl or C1-C4alkoxy; or a pyridine-N-oxides, when W represents oxygen or sulfur and a is COOR3; and when R1and R2not the same, the optical isomers of these compounds, except for the case when R3represents a salt-forming cation, their salts kislotoustoichivam

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R(I) where R1hydrogen, alkyl or hydroxyl radical;

R2hydrogen, linear or branched C1-C4-alkyl, foralkyl, cycloalkyl, alkyloxyalkyl or alkylamino radical;

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or R3hydrogen or alkyl, or cycloalkyl and R4and R5individually, each means hydrogen;

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FIELD: agriculture.

SUBSTANCE: invention describes a method for feeding potato and tomato with 6-benzylaminopurine an aqueous solution taken in the concentration 10-4 M and growing pants up to preparing harvest according to technology accepted for the culture crop. Invention proposes 3-fold treatment of plants for vegetation: at the lateral branching phase, at onset of forming economically value organs and immediately after the growth termination. Method provides the effective enhancing the productivity of the most important vegetable crops - tomato and potato.

EFFECT: improved enhancing method.

6 tbl, 4 ex

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

FIELD: organic chemistry, herbicides, agriculture.

SUBSTANCE: invention describes a synergistic composition of herbicides comprising components (A) and (B) wherein (A) represents herbicide taken among the group of the formula (I):

wherein R1 means (C1-C4)-alkyl; R2 means (C1-C4)-alkyl; R3 means hydrogen atom; X and Y mean (C1-C4)-alkoxy-group; (B) represents one or two herbicides taken among the group of compounds or their acceptable forms: alachlor, metolachlor, acetochlor, dimetenamide, atrazine, cyanasin, metribusin, fluthiamide, nicosulfuron, rimsulfuron, primisulfuron, pendimetalin, sulcotrion, dicamba, mesotrion, isoxachlortol, metosulam, anilofos, fenoxaprop-ethyl, setoxydim, diclofop-methyl, MCPA, bromoxynil, pyridat, clopyralid, iodosulfuron-methyl, ethoxysulfuron, amidosulfuron, gluphosinat-amminium, isopropylammonium-glyphosate, imasetapir wherein components (A) and (B) are taken in the effective doses. Also, invention describes a method for control of weeds by using above indicated herbicide composition. Invention provides the development of the synergistic herbicide composition eliciting high activity.

EFFECT: improved method for control, valuable properties of composition.

6 cl, 26 tbl, 3 ex

FIELD: agriculture, plant science, plant protection.

SUBSTANCE: the suggested herbicidal composition of selective action contains, except generally accepted additional substances for the composition, a mixture as an active substance including a) herbicidally efficient quantity of compound of formula (I) , where R1 and R3 each independently means ethyl, ethynyl, C1- or C2alkoxy; R4 and R5 forms together the group Z2-CR14(R15)-CR16(R17)-O-CR18(R19)-CR20(R21)-(Z2); R14, R15, R16, R17, R18, R19, R20 and R21 means hydrogen; G means hydrogen, -C(X1)-R30, -C(X2)-X3-R31; X1, X2, X3 means oxygen; R30, R31 each independently means C1-C10alkyl, or salts or diastereoisomer of compound of formula (I), and b) efficient quantity of antidote of formula IIa to prevent harmful action of herbicide, where R22 means hydrogen, alkaline-earth metal or ethyl, or of formula IIb , where R23 means hydrogen, alkaline-earth metal or ethyl, and method for selective control for weed plants and grasses in cultivated plants. Thus, the antidote decreases the damage of cultivated plants induced by herbicide of formula (I).

EFFECT: higher efficiency of plant protection.

3 cl, 4 ex, 4 tbl

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