JPH0250911B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an 8,9-epoxy derivative of antibiotic B-41 and a method for producing the same. Group B-41 antibiotics are derived from a culture of B-41-146 strain belonging to the Streptomyces strata (deposited with the Institute of Microbial Technology, Agency of Industrial Science and Technology as Microbiology Laboratory Deposit No. 1438), and have the following structure. A compound having the formula was isolated.

[Table] Among the above B-41 group antibiotics, A ₁ , A ₃ , A ₄ ,
A ₅ , B ₂ , B ₃ , C ₁ and C ₂ are described in Japanese Patent Application Laid-open No. 50-29742. In addition, B-41D is a special patent application made in 1972.
-B in No. 107550 (see Japanese Patent Application Laid-open No. 56-32481)
-41E and F are Patent Application No. 153141 (1982)
-77686), and B-41-G is Japanese Patent Application No. 56-7091 (see Japanese Patent Application Laid-open No. 57-120589).
The physical and chemical properties of each are described below. The above B-41 group antibiotic is prepared by adding the B-41-146 strain to a medium conventionally used for culturing Streptomyces bacteria under aerobic conditions at about 28°C for 5 to 50 minutes.
After culturing for 15 days, the culture was separated using a supernatant such as diatomaceous earth, and the resulting cake was extracted with methanol and then n-hexane to obtain an oily substance, which was subjected to silica gel column chromatography. Obtained by separation. The present invention provides a novel B having the following structural formula () obtained by chemical means from the compound of the above formula ().
-41 is an 8,9-epoxy derivative. (In the formula, R ₁ represents an isopropyl group, R ₂ represents a methyl group, R ₃ represents a hydrogen atom, and R ₄ and R ₅ together form a group -O-CH ₂ - (the oxygen atom is The compound of formula () has acaricidal and anthelmintic activity. Derivatives of formula () can be prepared by selectively reacting a compound of formula () with an alkyl hydroperoxide in the presence of a complex of a metal of group B or group B of the periodic table as a catalyst. 8,
A compound in which the 9-position is epoxidized is obtained. Examples of alkyl hydroperoxides include methyl-, ethyl-, n-propyl, n-butyl-
Alternatively, t-butyl hydroperoxide can be used, preferably t-butyl hydroperoxide. Further, as the catalyst, for example, vanadium acetylacetonate, molybdenum dioxide acetylacetonate or molybdenum hexacarbonyl is used, and vanadium acetylacetonate is preferably used. The reaction is preferably carried out in an inert solvent, such as aromatic hydrocarbons such as benzene, toluene, xylene, halogenated hydrocarbons such as methylene chloride, chloroform, ethers, ethers such as tetrahydrofuran, dioxane, etc. benzene is used. Reaction temperature is 0~100℃,
Preferably it is carried out at room temperature. In this reaction, other substituents and the basic skeleton remain unchanged. Example 8,9-epoxy derivative of B-41D To a solution of 330 mg of B-41D and 15 mg of vanadium acetylacetonate in 4 ml of benzene, a solution of 108 mg of t-butyl hydroperoxide in 3 ml of benzene was added dropwise under ice cooling, and the mixture was reacted at room temperature for 2 hours. I let it happen. The reaction mixture was cooled with ice, poured into an aqueous sodium sulfite solution, and extracted with ether. The extract was washed with water and then with saturated brine, and then dried over anhydrous magnesium sulfate.
The residue obtained by evaporating the solvent was purified by silica gel column chromatography (developing solvent, n-hexane: ethyl acetate = 100:100) to obtain 101 mg of the target product.
Obtained. Molecular weight: 572 IR (Nujol mull): 3500, 1745, 1715, 1165 cm ^-1 NMR (CDCl ₃ , 100MHz, δppm): 1.52 (14-CH ₃ , s), 1.82 (4-CH ₃ , s),
3.88 (26-CH ₂ -, d, J = 11.0Hz), 3.93 (7-
OH, s), 4.35 (26-CH ₂ -, d, J = 11.0
Hz), 5.84 (10-H, dd, J = 9.0, 15.0Hz) The derivative of formula () of the present invention is a two-spotted spider mite (Tetranychus) that parasitizes fruit trees, vegetables, and flowers.
It has excellent acaricidal activity against adults and eggs of apple spider mites, citrus spider mites (Panonychus), and rust mites, as well as against animals such as Ixodidac, Dermanysside, and Sarcoptidae. Furthermore, animal and bird ectoparasites such as sheep fly (Oestrus), golden fly (Lucilia), cow fly (Hypoderma), horse fly (Gautrophilus), chisels, and lice; sanitary pests such as cockroaches and house flies; other aphids, and lepidoptera. It is active against various agricultural and horticultural pests such as larvae. Furthermore, it is also active against root-knot nematodes (Meloidogyne), mites (Phizoglyphus), etc. during soil transfer. Furthermore, the derivatives of formula () according to the invention have excellent parasiticidal activity as anthelmintics for animals and humans. It is particularly effective against the following nematodes that infect livestock such as pigs, sheep, goats, cows, horses, dogs, cats, and chickens, poultry, and pets. Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Esophagostomum Oesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyocaulus, Capillaria, Heterakis , Toxocara, Ascaridia, Oxyuris, Ancylostoma, Uncinaria, Toxascaris and Parascaris. Certain members of the genera Nematodeilus, Cooperia and Esophagostomum attack the intestinal tract, while those of the genera Haemonchus and Ostertagia inhabit the stomach, and parasites of the genus Deictyokaurus are found in the lungs. However, it also shows activity against these. Parasites of the Filariidae and Setariidae families are also found in and active in other tissues and organs in the body, such as the heart and blood vessels, subcutaneous and lymphatic tissue. It is also useful against parasites that infect humans, and the most common parasites of the human gastrointestinal tract are Ancylostoma, Necator, Ascaris, and Strongyloides. The genera Strongyloides, Trichinella, Capillaria, Trichuris and Enterobius. Other medically important parasites found in the blood or other tissues and organs outside the gastrointestinal tract; members of the family Filariaceae such as Wuchereria, Brugia, Onchocerca;
and parasites of the genus Loa and the genus Dracunculus of the family Dracunculidae, as well as the spp. Strongyloides and Trichinella in the special extraintestinal parasitic state of intestinal parasites. show. When the derivatives of formula () are used as anthelmintics in animals and humans, they can be administered orally as a liquid drink. Beverages are usually solutions, suspensions or dispersions in a suitable non-toxic solvent or water with suspending and wetting agents such as bentonite or other excipients. Beverages generally also contain antifoaming agents. Beverage formulations generally contain about 0.01-0.5%, preferably 0.01-0.1% by weight of active compound. When oral administration in a dry, solid unit dosage form is desired, capsules, pills, or tablets containing the desired amount of active compound are commonly employed.
These use forms involve homogeneously admixing the active ingredient with suitable finely divided diluents, fillers, disintegrants and/or binders such as starch, lactose, talc, magnesium stearate, vegetable gums, etc. It is manufactured by Such unit use formulations can vary widely with respect to weight and content of anthelmintic agent depending on the type of host animal being treated, the degree of infection and the type of parasite and the weight of the host. When administered via animal feed, it is homogeneously dispersed in the feed, used as a top dressing, or used in the form of pellets. To achieve the normally desired antiparasitic effect, the active compound in the final feed should be between 0.0001 and 0.02
Contains %. Furthermore, a solution dissolved or dispersed in a liquid carrier excipient can be administered parenterally to animals by injection into the forestomach, intramuscularly, intratracheally, or subcutaneously. For parenteral administration, the active compound is preferably mixed with a suitable vegetable oil, such as peanut oil, cottonseed oil. Such formulations generally contain 0.05 of the active compound.
Contains ~50% by weight. They may also be administered topically by mixing with a suitable carrier such as dimethyl sulfoxide or a hydrocarbon solvent. The formulation is applied directly to the external surface of the animal by spray or direct injection. The optimum amount of active compound to be used to obtain the best results will depend on the type of animal being treated and the type and severity of the parasitic infection, but will generally be about 0.01 to 100 mg/kg of animal body weight, preferably 0.5 mg/kg of animal body weight. Obtained by oral administration of ~50.0 mg. Such dosages may be given at once or in divided dosages over a relatively short period of time, such as from 1 to 5 days.

[Brief explanation of the drawing]

Figure 1 shows the infrared absorption spectrum of the 8,9-epoxy derivative of B-41D, and Figure 2 shows the nuclear magnetic resonance spectrum of the same substance.

Claims (1)

[Claims] 1. An 8,9-epoxy derivative of B-41 having the following structural formula. (In the formula, R ₁ represents an isopropyl group, R ₂ represents a methyl group, R ₃ represents a hydrogen atom, and R ₄ and R ₅ together represent a group -O-CH ₂ -. 2 formula (In the formula, R ₁ represents an isopropyl group, R ₂ represents a methyl group, R ₃ represents a hydrogen atom, and R ₄ and R ₅ together represent a group -O-CH ₂ -.)
B-41 having the formula (In the formula, R ₁ , R ₂ , R ₃ , R ₄ and R ₅ are the same as above.) A method for producing an 8,9-epoxy derivative of B-41.