JPH021147B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to 5-methoxy and 5-lower alkanoyloxy derivatives of the new antibiotic B-41D, their production, and acaricides and anthelmintics containing them as active ingredients. A group of macrolide antibiotics isolated from Streptomyces strain B41-146 was published in
50-29742, designated as B-41, and A ₁ ,
Nine species were mentioned: _A2 , _A3 , _A4 , _B1 , _B2 , _B3 , _C1 , and _C2 . Four more compounds were isolated and the structures of all 13 compounds determined and published in The Journal of Antibiotics (J.
Antibiotics) 29(3) 76-14 to 76-16 and the same magazine 29
(6), pages 76-35 to 76-42. Furthermore, B-41D having the following structural formula was isolated and was published in Japanese Patent Application No. 54-107550 (see Japanese Patent Application Laid-open No. 56-32481).
It was stated in The present inventors newly isolated a 5-methoxy derivative of B-41D from a culture of B-41-146 strain belonging to the genus Streptomyces, and also obtained a 5-methoxy derivative of B-41D from B-41D by a chemical method. 5-methoxy and 5-lower alkanoyloxy derivatives were produced. The structural formulas of the 5-methoxy and 5-lower alkanoyloxy derivatives of B-41D of the present invention are as follows. In the formula, R is a methyl group or a lower alkanoyl group such as acetyl, propionyl, lobetryl, isobutyryl, especially an acetyl group. The 5-methoxy derivative of B-41D of the present invention can be obtained by aerobically cultivating a 5-methoxy derivative-producing bacterium of B-41D belonging to the genus Streptomyces, for example, strain B-41-146, and then producing a monomer from the culture. Manufactured by separating. The mycological properties of Streptomyces strain B-41-146 are described in detail in JP-A-50-29742, and Streptomyces strain B-41-146 has been deposited with the National Institute of Microbial Technology, Agency of Industrial Science and Technology. and
Its microbial accession number is FERM BP-1072. As is well known, actinomycetes are susceptible to mutations in nature and by artificial manipulation (e.g., ultraviolet irradiation, radiation irradiation, chemical treatment, etc.), and the B-41-146 strain of the present invention is also susceptible to mutations in this respect. It is. The B-41-146 strain referred to in the present invention includes all its mutant strains. That is, in the present invention, a 5-methoxy derivative of antibiotic B-41D is produced and B-41D is produced.
Bacteria that cannot be clearly distinguished from the 41-146 strain and its mutant strains are all included in the B-41-146 strain. To culture the B-41-146 strain, known nutritional sources that have been conventionally used for culturing Streptomyces bacteria can be used. For example, glycol, sucrose, starch, glycerin, starch syrup, molasses, soybean oil, etc. can be used as carbon sources. Further, as the nitrogen source, soybean flour, wheat germ, meat extract, peptone, yeast cells, corn steep liquor, ammonium sulfate, sodium sulfate, etc. can be used. In addition, inorganic salts such as calcium carbonate, common salt, potassium chloride, and phosphates may be added as necessary, as well as organic and inorganic substances that support the growth of bacteria and promote the production of 5-methoxy derivatives of B-41D. can be added appropriately. The most suitable culture method is the liquid culture method, especially the deep culture method, similar to the method for producing general antibiotics. Cultivation is carried out under aerobic conditions, and the appropriate temperature for cultivation is 22-30℃, but in many cases
Culture at around 28℃. The production of 5-methoxy derivatives of B-41D reaches its maximum value in 5 to 10 days in both shaking culture and tank culture. The following method is used to assay the 5-methoxy derivative of B-41D. i.e. culture
Place 3 g in a small test tube, add 10 ml of acetone, shake to extract, and centrifuge. Fill up the supernatant obtained here with acetone up to 10%. Transfer 10 to 20 μl of this sample to a TLC plate (Merck,
Kieselgel 60F ₂₅₄ ) was adsorbed at a predetermined position, developed with dioxane:carbon tetrachloride (18:82) for 4 hours, and then analyzed using a dual wavelength chromatography scanner.
Measure at a wavelength of 245 mμ (blank is 380 mμ), compare the absorption amount with that of the standard substance, and calculate. When collecting the 5-methoxy derivative of B-41D from the culture, adsorbents such as activated carbon, alumina, and silica gel, synthetic adsorbents such as Diaion Hp-20 (manufactured by Mitsubishi Kasei Corporation), and Avicel (manufactured by Asahi Kasei Corporation) are used. Although fixatives such as paper, ion exchange resins, and ion exchange gel filters can be used, the collection method described below is the most effective. The target product is dissolved in methanol water by separating the culture using a supernatant such as diatomaceous earth and extracting the resulting cake with methanol. After adding water to this, extraction is performed with n-hexane, and this is concentrated under reduced pressure to obtain an oily substance containing the target product. This was adsorbed on a column of silica gel (Wako Gel C-200), eluted with n-hexane:acetone (95:5), fractions containing the target product were collected, concentrated under reduced pressure, and made into an oil again. Add a small amount of n-hexane to this, apply it to a silica gel column, develop with n-hexane:acetone = 95:5, collect the fractions containing the target product, concentrate under reduced pressure, and leave the resulting residue. When dissolved in a small amount of n-hexane:ethyl acetate = 20:1 and allowed to stand at room temperature, the 5-methoxy derivative of B-41D is obtained in crystal form. Production example 1 Syucross 1%, polypeptone 0.35% and
_{Streptomyces B-}
One loopful of strain 41-146 was inoculated and cultured at 27°C for 48 hours, and the two 2-l Erlenmeyer flasks were transferred to a 30-l Jar Huamenta. For Jia Huamenta, a medium containing 8% glucose, 1% soybean flour, 0.5% corn starch, 1% skim milk, 0.2% corn steep liquor and 0.3% NAC _0.
20 liters was charged, the pH was adjusted to 7.2 to 7.5, and it was thoroughly sterilized. During the culture period, the temperature was 28℃ and the internal pressure was 0.5Kg/
held at ^cm2 . After culturing for 10 days, the pH of 20 liters of the culture was adjusted to 3 with sulfuric acid.
Approximately 1.8 kg by adding 1 kg of Celite and applying pressure.
of cake was obtained. This was extracted with 15 liters of methanol, separated, and 5 liters of water was added to the resulting 15 liters of methanol solution, followed by extraction with 20 liters of n-hexane. The obtained n-hexane layer was dehydrated with mirabilite and heated to 40-45℃.
Concentration under reduced pressure in a water bath gave 34 g of oil. This was dissolved in 50 ml of n-hexane, adsorbed onto a column packed with 800 g of silica gel in advance with n-hexane, and developed with n-hexane:acetone (95:5). As a result, 1.5 liters of fraction containing the target substance was obtained. This was concentrated under the same conditions as above to obtain 500 mg of oil.
Dissolve this in 5 ml of n-hexane and add 50 ml of n-hexane in advance.
ml of silica gel was applied to a column packed with n-hexane and developed with n-hexane:acetone=95:5. Here, 70 ml of fraction containing the target product was obtained. This was concentrated under reduced pressure at 45°C, and the resulting residue was mixed with 5 ml of n-hexane:
The mixture was dissolved in 20:1 acetone, added with 2 ml of water, and allowed to stand at room temperature to obtain 90 mg of 5-methoxy derivative of amorphous powder B-41D. The 5-methoxy derivative of B-41D has the following physical and chemical properties. 1 Appearance: Amorphous powder 2 Molecular weight: 570 3 Ultraviolet absorption spectrum: Shown in FIG. Maximum absorption: 237 mμ (shoulder, ε = 29400) 244 mμ (ε = 30500) 4 Infrared absorption spectrum: The spectrum measured with Nujol mull is shown in Figure 2. 3475, 1715 cm ^-1 5 NMR spectrum: The nuclear magnetic resonance spectrum (100 MHz) measured using TMS for internal groups in deuterated chloroform is shown in FIG. 1.50 (14-OH ₃ , s), 1.79 (4-CH ₃ , br, s),
3.44 (5-oCH ₃ , s), 4.59 (26-CH ₂ −, s),
4.89 (15-H, br-t, J=8Hz) The 5-methoxy derivative of B-41D of the present invention can also be produced by reacting B-41D with methyl halide. Production Example 2 568 mg of silver oxide was added to an ether solution of 278 mg of B-41D and 580 mg of methyl iodide, and 1
Stir for a day and add methyl iodide to this reaction.
580 mg and 568 mg of silver oxide were added, and the mixture was stirred at room temperature overnight. The reaction mixture was filtered through Celite, the mother liquor was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (developing agent: n-hexane to n-hexane:ethyl acetate = 8:2) to give a white amorphous powder. 258 mg of the 5-methoxy derivative of B-41D was obtained. The physicochemical properties of the obtained 5-methoxy derivative of B-41D were consistent with those of Production Example 1. The 5-lower alkanoyloxy derivative of B-41D of the present invention is produced by reacting B-41D with a reactive derivative of lower alkanoic acid. Acid halides or acid anhydrides can be used as reactive derivatives, and the reaction is carried out with bases such as pyridine, triethylamine, morpholine, 4-(N,
It is preferable to carry out the reaction in the presence of an organic base such as N-dimethylamino)pyridine or N,N-dimethylaniline, and the reaction is carried out in a solvent, and there is no particular restriction as long as it does not participate in the reaction, but benzene, Hydrocarbons such as toluene and n-hexane;
Halogenated hydrocarbons such as carbon tetrachloride, chloroform, methylene chloride are used. Furthermore, by using an excess of an organic base that is liquid at room temperature, such as pyridine or triethylamine, the reaction can be carried out without using a solvent. Reaction is 0-100℃
The temperature is preferably from ice-cooling to room temperature. Production Example 3 A solution of 102 mg of acetic anhydride in 1 ml of methylene chloride was added dropwise to a solution of 50 mg of B-41D, 122 mg of 4-(N,N-dimethylamino)pyridine, and 1 ml of methylene chloride under ice cooling, and the mixture was stirred at room temperature for 1 hour. After the reaction was completed, the reaction mixture was poured into ice-cold diluted hydrochloric acid and extracted with ether. The extract was washed successively with saturated sodium hydrogen carbonate, water and saturated brine, and then dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure is purified by silica gel column chromatography (developing solvent: n-hexane/ethyl acetate = 10/3) to obtain the desired 5-acetoxy derivative of B-41D. 45mg of was obtained. The 5-acetoxy derivative of B-41D has the following physical and chemical properties. 1 Appearance: White amorphous powder 2 Molecular weight: 598 3 Ultraviolet absorption spectrum: Shown in Figure 4. Maximum absorption: 244 mμ (ε=28600) 4. Infrared absorption spectrum: The spectrum measured with Nujol mull is shown in Figure 5. 3480, 1745,
1715, 1235, 1170 cm ^-1 5 NMR spectrum: The nuclear magnetic resonance spectrum (100 MHz) measured in deuterated chloroform using TMS as an internal standard is shown in FIG. 1.51 (14-CH ₃ , s), 1.72 (4-CH ₃ , br, s),
2.12 (5-OCOCH ₃ , s), 4.58 (26-CH ₂ ,
s), 4.91 (15-H, br.t, J=8.0Hz) Production Example 4 The 5-propionyloxy derivative of B-41D produced according to the method of Production Example 3 has the following physical and chemical properties. 1 Molecular weight: 612 2 IR spectrum: ν ^nujol _nax : 3490, 1740, 1720,
1170 3 NMR spectrum: (CDCl ₃ , δppm, 100M
Hz); 1.14 (5-OCOCH ₂ CH ₃ , t; J = 7.8
Hz), 2.37 (5-OCO CH ₂ CH ₃ , q; J = 7.8
Hz), 4.55 (26-CH ₂ , s), 4.90 (15-H, br.
t; J=7.8Hz) Production Example 5 The 5-n-butyryloxy derivative of B-41D produced according to the method of Production Example 3 has the following physical and chemical properties. 1 Molecular weight:: 626 2 IR spectrum: ν ^nujol _nax 3480, 1740, 1715,
1170cm ^-1 3 NMR spectrum: (CDCl ₃ , δppm) 2.37
(t, 2H; J=7.6Hz, 5-OCO CH ₂ CH ₂ CH ₃ ) Production Example 6 The 5-isobutyryloxy derivative of B-41D produced according to the method of Production Example 3 was subjected to the following physical and chemical process. have a property. 1 Molecular weight: 626 2 IR spectrum: ν ^nujol _nax 3490, 1745, 1720,
1160cm ^-1 3 NMR spectrum: (CDCl ₃ , δppm) 1.18
(d, 6H; J=7.6Hz,

[Formula]) The 5-methoxy and 5-lower alkanoyloxy derivatives of B-41D of the present invention can be used to treat adults and eggs of two-spotted spider mites (Tetranychus), apple spider mites, citrus mites (Panonychus), rust mites, etc. that parasitize fruit trees, vegetables, and flower petals. It has excellent acaricidal activity against Ixodidae, Dermanysside, Sarcoptidae, etc. that parasitize animals. Furthermore, the sheep fly (Oestrus) and the golden fly (Lu-
cilia), Hypoderma, Gautrophilus, etc., as well as ectoparasites of animals and birds such as chisels and lice; sanitary pests such as cockroaches and house flies; and various other agricultural and horticultural pests such as aphids and lepidopteran larvae. It is active against. Furthermore, it is also active against root-knot nematodes (Meloidogyne), mites (Phizoglyphus), etc. in the soil. For the use of the 5-methoxy and 5-lower alkanoyloxy derivatives of B-41D as acaricides, they can be prepared as powders, coarse powders, by diluting the active compound with carrier and, if necessary, adding other auxiliaries. It can be prepared and used as a dispersing agent such as granules, fine powders, wettable powders, emulsions, and oils. The carrier here refers to active ingredient plants, mites,
Refers to synthetic or natural inorganic or organic substances that are commonly mixed with insecticides to aid in their accessibility to the target to be treated, such as pests, or to facilitate the storage, transport, or handling of active ingredients. Suitable solid carriers include inorganic substances such as clay, talc, diatomaceous earth, kaolin, bentonite, calcium carbonate and synthetic calcium silicates, natural and synthetic resins such as coumaron resins, alkyd resins and polyvinyl chloride, carnauba wax, paraffin. Examples include waxes such as wax, shells of nuts such as walnuts and nuts, and soybean flour. Examples of suitable liquid carriers include, for example, water,
Alcohols such as ethanol, isopropanol, and ethylene glycol; glycol ethers such as ethylene glycol monophenyl ether and diethylene glycol monoethyl ether; ketones such as acetone, methyl isobutyl ketone, cyclohexanone, acetophenone, and isophorone;
Contains ethers such as tetrahydrofuran, dioxane, aromatic hydrocarbons such as benzene, toluene, xylene, methylnaphthalene, chlorinated hydrocarbons such as trichlorethylene, carbon tetrachloride, kerosene, light oil or aromatic hydrocarbons. Examples include low boiling point, medium and high boiling point petroleum fractions. Suitable propellants include, for example, chlorofluorocarbon gas, liquefied petroleum gas, methyl ether, and vinyl chloride monomer. Surfactants used for purposes such as emulsification, dispersion, wetting, and spreading may be ionic or nonionic. Suitable anionic surfactants include, for example, sodium or calcium salts of lignosulfonic acid, sodium or potassium salts of oleic acid, sodium laurylsulfonate,
Examples include sodium or calcium salts of dodecylbenzenesulfonic acid. Suitable cationic surfactants include, for example, higher aliphatic amines, higher aliphatic amine ethylene oxide condensates, and the like. Suitable nonionic surfactants include, for example, glycerol of fatty acids, sucrose esters of fatty acids, ethylene oxide condensates of higher aliphatic alcohols, ethylene oxide condensates of higher fatty acids, ethylene oxide condensates of alkylphenols or alkylnaphthols. and copolymers of ethylene oxide and propylene oxide. The acaricide of the present invention may also contain other ingredients, such as gelatin, gum arabic, casein, polyvinyl alcohol, protective colloid agents such as carboxymethyl cellulose, thixotropic agents such as sodium polyphosphate, bentonite, and the like. The acaricide of the present invention may contain other compounds having acaricidal activity, such as 0,0-diethyl 0-(5-
Phenyl-3-isoxazolyl) phosphorothioate (isoxathion), 0-ethyl 0-p-
Nitrophenyl, phenyl phosphonothioate (EPN), 0,0-diethyl 0-(2-isopropyl-4-methyl-6-pyrimidinyl) phosphorothioate (diazinon), 0-ethyl 0
-(4-cyanophenyl)benzenephosphonothioate (CYP), 0,0-diethyl S-(2,
5-dichlorophenylthiomethyl)phosphorodithioate (fenkapton), 0,0-diethyl 0-[2-chloro-1-(2,4-dichlorophenyl)vinyl]phosphate (CVP), 0,0
-diethyl S-(N-ethoxycarbonyl, N
-Methyl carbamoylmethyl)phosphorodithioate (mecarbam), 0,0,0',0'-tetraethyl S,S'-methylenebisphosphorodithioate (ethion), 0,0-diethyl S-(6
-Chloro-2-oxobenzoxazoline-3-
diethyl phosphate, diethyl phosphorothioate, diethyl phosphorodithioate, such as S-(2-chloro-1-phthalimidoethyl) 0,0-diethyl phosphorodithioate (diaryphor), methyl diethyl phosphorodithioate (phosalone), ate or ethylphosphonothioate organic phosphorus agent; 2-(1-methylpropyl)-
4,6-dinitrophenyl-β,β-dimethyl acrylate, di-(p-chlorophenyl)-cyclopropylcarbinol, N′-(2-methyl-
4-Chlorphenyl)-N,N-dimethylformamidine, 2,4,4',5-tetrachlorodiphenylsulfone, 1,1-bis-(P-chlorphenyl)2,2,2-trichloroethanol, 2-
By blending secondary butyl phenyl-N-methyl carbamate, m-tolyl-N-methyl carbamate, mineral oil, piperonyl butoxide, etc., the efficacy can be further increased, and in some cases, a synergistic effect can be expected. You can also do that. Of course, it can be used in combination with other fungicides, herbicides, plant growth regulators, attractants, fertilizers, etc. Next, the effects of the acaricide of the present invention will be shown using test examples. Test Example 1 Test Method 1 Two-spotted spider mite acaricidal test A 3% emulsion was prepared according to Formulation Example 3 described later, and diluted with water to a predetermined concentration to prepare a drug solution. This chemical solution was applied to cowpea leaves infested with female adult two-spotted spider mites for 5 c.c. using a Mizuho rotary sprayer (manufactured by Mizuho Rikagaku Kikai KK). The rate was calculated. The number of adult two-spotted spider mites tested was 60 to 70 in each treatment area. 2 Two-spotted spider mite ovicidal test Treated in the same manner as in 1) except that one-day old two-spotted spider mite eggs that had been laid on cowpea leaves in advance were used.
The unhatched rate was determined after two weeks. The number of eggs tested was approximately 100 in each treatment area. 3 Citrus citrus spider mite acaricidal test Same as 1) except that mulberry leaves infested with adult female citrus spider mites were used. Test results are shown in Tables 1 and 2.

【table】

[Table] Formulation example 1 Amorphous powder of 5-methoxy derivative of B-41D 10
1 part is uniformly mixed with 5 parts of white carbon, 50 parts of talc and 35 parts of clay are added thereto, mixed uniformly, crushed three times with an impact crusher, and mixed uniformly again to obtain a powder. Formulation example 2 Amorphous powder of 5-acetoxy derivative of B-41D
40 parts were uniformly mixed with 20 parts of white carbon, 5 parts of sodium dodecylbenzenesulfonate, 2 parts of polyvinyl alcohol, and 33 parts of clay were added and mixed uniformly, and the mixture was pulverized 3 times using an impact pulverizer, and then crushed again. Mix uniformly to obtain a wettable powder. Formulation example 3 Amorphous powder of 5-methoxy derivative of B-41D 3
parts, polyoxyethylene nonyl phenyl ether 7 parts, calcium dodecylbenzenesulfonate 3 parts
1 part and 87 parts of xylene were mixed and dissolved uniformly.
An emulsion is obtained by filtration. Formulation example 4 Amorphous powder of 5-methoxy derivative of B-41D 10
1 part of xylene and 80 parts of machine oil.
A strained oil solution is obtained. Furthermore, 5-methoxy and 5 of B-41D of the present invention
-Lower alkanoyloxy derivatives have excellent parasicidal activity as anthelmintics for animals and humans. Diseases commonly described as parasitic diseases are due to infection of animal hosts by parasitic protozoa known as helminths. Parasitic diseases are prevalent in livestock, poultry, and pets such as pigs, sheep, goats, cattle, horses, dogs, cats, and chickens, causing serious economic damage. A group of helminths described as nematodes infest a variety of animals and often cause serious infections. The most common genera of nematodes that infect the animals mentioned above are Haemonchus, Trichostrongylus, Ostertagia, Nematodirus, Cooperia, Ascaris, Bunostomum, Cesophagostomum, Chabertia, Trichuris, Strongylus, Trichonema, Dictyokaurus Dictyocaulus, Capillaria, Heterakis, Toxocara, Ascaridia, Oxyuris, Aucylostoma, Uncinaria, Toxascaris (Toxascaris) and Parascaris. Certain members of the genera Nematodeilus, Cooperia and Esophagostomum attack the intestinal tract;
On the other hand, parasites of the genus Haemonchus and Ostertagia are found in the stomach, and parasites of the genus Deictyokaurus are found in the lungs. Parasites of the Filariidae and Setariidae families are also found in other tissues and organs in the body, such as the heart and blood vessels, subcutaneous and lymphatic tissue. Furthermore, it has a broad spectrum of activity against many endoparasites in various animals, such as Dirofilaia in dogs, Nematospiroides in Cyphers, and Syphacia. ) and Aspiculuris. The 5-methoxy and 5-lower alkanoyloxy derivatives of B-41D are also useful against parasites that infect humans, and the most common parasites of the human gastrointestinal tract are Ancylostoma spp. They are Necator, Ascaris, Strongyloides, Trichinella, Capillaria, Trichuris, and Enterobius. Other medically important parasites found in the blood or other tissues and organs outside the gastrointestinal tract include the family Filariaceae, Wuchereria, Brugia, Onchocerca.
Besides the parasites of the genus Loa and the genus Dracunculus of the family Dracunculidae, the genus Strongyloides and Trichinella in a special extraintestinal parasitic state of intestinal parasites. It is. When the 5-methoxy or 5-lower alkanoyloxy derivatives of B-41D are used as anthelmintics in animals and humans, they can be administered orally as a liquid beverage. 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 active compounds from approximately 0.01 to
It contains 0.5% by weight, preferably 0.01-0.1% by weight. When it is desired to administer the 5-methoxy or 5-lower alkanoyloxy derivative of B-41D orally in a dry, solid unit dosage form, capsules, pills or tablets containing the desired amount of active compound are usually used. 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. Manufactured by Such unit use formulations can vary widely in weight and content of anthelmintic agent depending on the type of host animal being treated, the degree of infection and type of parasite, and the weight of the host. When the 5-methoxy or 5-lower alkanoyloxy derivative of B-41D is administered via animal feed, it must be homogeneously dispersed in the feed, used as a top dressing, or used in the form of pellets. be done. To achieve the desired anti-parasitic effect, the final feed usually contains 0.0001-0.02% of active compound. In addition, a 5-methoxy or 5-lower alkanoyloxy derivative of B-41D dissolved or dispersed in a liquid carrier excipient can be administered parenterally by injection into the proventriculus, intramuscularly, intratracheally, or subcutaneously. can be administered to animals. For parenteral administration, the active compound is preferably mixed with a suitable vegetable oil, such as peanut oil, cottonseed oil. Such formulations generally contain from 0.05 to 50% by weight of active compound. 5-methoxy or 5-lower alkanoyloxy derivatives of B-41D may also be administered topically by mixing with a suitable carrier such as dimethyl sulfoxide or a hydrocarbon solvent. This 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 for best results will depend on the type of animal being treated and the type and severity of the parasitic infection, but will generally be in excess of 1 kg of animal weight.
It can be obtained by oral administration of about 0.01 to 100 mg, preferably 0.5 to 50.0 mg. Such doses may be given at once or in divided doses over a relatively short period of time, such as from 1 to 5 days. The anthelmintic compounds of the invention have low toxicity to warm-blooded animals. For example, 5-methoxy and 5-acetoxy were administered to male mice weighing approximately 20 g (5-5 per group).
When each compound was orally administered at a dose of 1000 mg/Kg to mice, none of the mice in either compound group died. Further, no abnormality was observed in appearance until 24 hours after administration. Next, the effects of the anthelmintic agent of the present invention will be shown using test examples. Test Example 2 RFVL male mice, 4 weeks old and weighing 18 to 22 g, were injected with Nematospiroides doubias (Nemato-
The mice were orally infected with larvae of M. spiroides dubius, divided into groups of 5, fed with feed containing the test drug for 7 days after infection, then switched to regular feed, and dissected on the 14th day after infection. The number of worms in the small intestine was calculated and compared with the control group. The results are shown in the table below.

[Table] Derivatives
B-41D 5-acetyl 0.05 100
Shi derivative

Claims (1)

[Claims] 1. 5- of antibiotic B-41D having the following chemical formula:
Methoxy or 5-lower alkanoyloxy derivatives. (In the formula, R represents a methyl group or a lower alkanoyl group.) 2. The 5-methoxy derivative of B-41D according to claim 1, wherein R is a methyl group. 3. The 5-acetoxy derivative of B-41D according to claim 1, wherein R is an acetyl group. 4 An anthelmintic agent containing a 5-methoxy or 5-lower alkanoyloxy derivative of B-41D as an active ingredient. A miticide containing a 5-methoxy or 5-lower alkanoyloxy derivative of 5 B-41D as an active ingredient. 6 5- of B-41D belonging to the genus Streptomyces
A method for producing a 5-methoxy derivative of B-41D, which comprises culturing a methoxy derivative-producing bacterium aerobically and collecting the 5-methoxy derivative of B-41D from the culture.