Compound, its manufacturing method, antibacterial agent and medicine

Abstract

The present invention provides a compound represented by formula (1), formula (2), or formula (3), a salt thereof, or a solvate of these. (In the formulas, R1, R2, and R3 may be the same or differ, and represent a hydrazine group, an N-hydroxy-acetylamino group, or an N-hydroxy-formylamino group.)

Description

[Technical Field]

[0001] The present invention relates to a novel compound having antibacterial activity and a method for producing the same. The present invention also relates to an antibacterial agent and a medicine containing the compound. [Background technology]

[0002] To date, physiologically active substances such as antibiotics have been found from metabolites of actinomycetes. Non-Patent Document 1 describes that the P07101 strain of actinomycetes belonging to the genus Kitasatospora produced Hajimycin A and its related compounds, and that Hajimycin A had antibacterial activity against Gram-positive bacteria. [Prior art documents] [Non-patent literature]

[0003] [Non-Patent Document 1] Acta Pharmaceutica Sinica B Volume 5, Issue 6, 2015, Pages 564-568 Summary of the Invention [Problem to be solved by the invention]

[0004] The present invention aims to provide a novel compound having antibacterial activity and a method for producing the same, as well as to provide an antibacterial agent and a medicine containing the compound. [Means for solving the problem]

[0005] The compound of the present invention is a compound represented by the following general formula (1), the following general formula (2), or the following general formula (3), or a salt thereof, or a solvate thereof.

[0006] [ka]

[0007] (In the above formula, R 1 , R 2 and R 3 are the same or different and represent a hydrazine group, an N-hydroxy-acetylamino group, or an N-hydroxy-formylamino group.

[0008] The manufacturing method of the present invention is a method for manufacturing the above-mentioned compound or a salt thereof, or a solvate thereof, and includes a culturing step of culturing Kitasatospora purpeofusca HV058 strain (accession number NITE BP-03475), and a harvesting step of harvesting the above-mentioned compound or a salt thereof, or a solvate thereof from the culture obtained in the culturing step.

[0009] The antibacterial agent of the present invention includes the above-mentioned compound or a salt thereof, or a solvate thereof.

[0010] The pharmaceutical of the present invention includes the above-mentioned compound or a salt thereof, or a solvate thereof. [Effects of the Invention]

[0011] According to the present invention, it is possible to provide a novel compound having antibacterial activity and a method for producing the same, and also to provide an antibacterial agent and a medicine containing the compound. DETAILED DESCRIPTION OF THE INVENTION

[0012] The compounds of the present invention, their production methods, antibacterial agents, and pharmaceuticals are described below. The present invention is not limited to the following structures, and may be modified as appropriate within the scope of the present invention. In addition, a combination of multiple individual preferred structures described below also constitutes the present invention.

[0013] [Compounds with antibacterial activity] The compound of the present invention is a compound represented by the following general formula (1), the following general formula (2), or the following general formula (3), or a salt thereof, or a solvate thereof.

[0014] [ka]

[0015] In general formula (1), R 1 represents a hydrazine group, an N-hydroxy-acetylamino group, or an N-hydroxy-formylamino group. 1 is preferably a hydrazine group (-NH-NH2).

[0016] In general formula (2), R 2 represents a hydrazine group, an N-hydroxy-acetylamino group, or an N-hydroxy-formylamino group. 2 is preferably a hydrazine group.

[0017] In general formula (3), R 3 represents a hydrazine group, an N-hydroxy-acetylamino group, or an N-hydroxy-formylamino group. 3 is preferably a hydrazine group.

[0018] In this specification, the compound represented by the general formula (1) is also referred to as compound (1). The same applies to compounds of other formula numbers; for example, the compounds represented by the general formulas (2) to (3) are also referred to as compounds (2) to (3), respectively. In the following description, the compound represented by the above general formula (1), general formula (2) or general formula (3), a salt thereof, or a solvate thereof will also be referred to as compound (I).

[0019] In the above general formula (1), the carbon atom to which the isonitrile group (-NC) is bonded and R 1 The carbon atom to which is attached is an asymmetric carbon. In the above general formula (2), the carbon atom to which the nitrile group (-CN) is bonded and R 2 The carbon atom to which is attached is an asymmetric carbon. In the above general formula (3), the carbon atom to which the nitrile group is bonded and R 3 The carbon atom to which is attached is an asymmetric carbon. Compounds (1), (2), and (3) include compounds in which each asymmetric carbon atom is in the R-configuration, compounds in which each asymmetric carbon atom is in the S-configuration, and any combination thereof. In addition, the compounds of the present invention also include their racemates, racemic mixtures, single enantiomers, and diastereomeric mixtures.

[0020] Compound (1), compound (2), and compound (3) are preferably compounds in which the absolute configurations of the two asymmetric carbon atoms are both S-configuration (SS) or R-configuration (RR), and more preferably compounds in which the absolute configurations of the two asymmetric carbon atoms are both S-configuration (SS).

[0021] A preferred embodiment of the compound represented by general formula (1) is a compound represented by the following general formula (1a). A preferred embodiment of the compound represented by general formula (2) is a compound represented by the following general formula (2a). A preferred embodiment of the compound represented by general formula (3) is a compound represented by the following general formula (3a).

[0022] [ka]

[0023] R 1 , R 2 and R 3 is the same as above, and is preferably a hydrazine group.

[0024] The compound (I) of the present invention is preferably a compound represented by general formula (1) or a salt thereof, or a solvate thereof, and more preferably a compound represented by general formula (1a) or a salt thereof, or a solvate thereof. In general formula (1a), R 1 is a hydrazine group, or a salt thereof, or a solvate thereof is more preferred.

[0025] [ka]

[0026] The salt of the above compound is not particularly limited as long as it is a pharmaceutically acceptable salt. Both acidic and basic salts can be used as the salt. Examples of acidic salts include inorganic acid salts such as hydrochloride, sulfate, nitrate, hydrofluoride, hydrobromide, and phosphate; and organic acid salts such as acetate, tartrate, lactate, citrate, fumarate, maleate, malate, succinate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate, naphthalenesulfonate, and camphorsulfonate. Examples of basic salts include alkali metal salts such as sodium salt and potassium salt; alkaline earth metal salts such as calcium salt and magnesium salt; salts with ammonia; and salts with organic amines such as morpholine, piperidine, pyrrolidine, monoalkylamine, dialkylamine, trialkylamine, mono(hydroxyalkyl)amine, di(hydroxyalkyl)amine, and tri(hydroxyalkyl)amine.

[0027] The solvate of the above compound or its salt is not particularly limited as long as it is a solvate of the above compound or its salt with a solvent. Examples of the solvent include water; alcohols such as ethanol and glycerol; and acetic acid. Among these, preferred solvates are hydrates and alcohol solvates, with hydrates being more preferred.

[0028] [Manufacturing method] The method for producing Compound (I) of the present invention is not particularly limited and can be selected appropriately. Compound (I) of the present invention can be produced, for example, by a method including a culture step of culturing Kitasatospora purpeofusca HV058 strain (Accession No. NITE BP-03475) and a collection step of collecting the compound or a salt thereof, or a solvate thereof from the culture obtained in the culture step. The present invention also includes a method for producing the above-mentioned compound or a salt thereof, or a solvate thereof, which comprises the above-mentioned culturing step and collecting step. The compound represented by general formula (1), general formula (2), or general formula (3), or a salt thereof, or a solvate thereof can be produced by the production method of the present invention. The production method of the present invention may include steps other than the culturing step and the harvesting step, if necessary.

[0029] Kitasatospora purpeofusca HV058 strain (HV058 SIID34879-01) (hereinafter, sometimes simply referred to as HV058 strain) has been deposited at the Patent Microorganisms Depositary of the National Institute of Technology and Evaluation (Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan, 292-0818) (Deposit date: April 23, 2021, Accession No. NITE BP-03475). The HV058 strain is an actinomycete belonging to the Kitasatospora genus. The HV058 strain can produce at least one of the above-mentioned compounds (I). The HV058 strain is suitable for use, for example, in producing the compound represented by the above-mentioned formula (1a-1).

[0030] The culturing in the above-mentioned culturing step can be carried out according to a known method used for culturing actinomycetes. The medium is not particularly limited as long as it allows the HV058 strain to grow and the target substance to be produced. A known medium typically used as a medium for actinomycetes belonging to the genus Kitasatospora can be used as is, or an appropriately modified version can be used. Either a liquid medium or a solid medium can be used, but a liquid medium is preferred.

[0031] The medium may contain components selected from, for example, a carbon source, a nitrogen source, other inorganic salts, and the like, as needed. Examples of carbon sources include glucose, sucrose, lactose, galactose, mannose, and glycerol. One or a combination of two or more of these can be used as the carbon source. The carbon source is preferably glucose. The concentration of the carbon source in the medium is preferably 0.1% by weight to 10% by weight, more preferably 1% by weight to 5% by weight.

[0032] Examples of nitrogen sources include peptone, yeast extract, meat extract, soybean flour, ammonium sulfate, and urea. One or a combination of two or more of these can be used as the nitrogen source. The concentration of the nitrogen source in the medium is preferably 0.1% by weight to 10% by weight, more preferably 1% by weight to 5% by weight. The concentrations of the carbon source and nitrogen source may be the above concentrations at the start of the culture.

[0033] Other components include inorganic salts such as dipotassium hydrogen phosphate, potassium phosphate, magnesium sulfate, zinc sulfate, iron, manganese, molybdenum, sodium chloride, potassium chloride, magnesium chloride, etc. One or a combination of two or more of these may be used.

[0034] In one embodiment, it is preferable to add a porous adsorbent to the culture medium. Adding a porous adsorbent to the culture medium accelerates the growth of the HV058 strain. As a result, the amount of compound (I) produced in the culture increases. Furthermore, the porous adsorbent adsorbs compound (I) produced during the culture. Therefore, by separating the porous adsorbent from the culture after the culture, compound (I) can be easily purified.

[0035] Examples of porous adsorbents include synthetic adsorbents, ion exchange resins, activated carbon, etc. Among these, synthetic adsorbents are preferred. Examples of synthetic adsorbents include synthetic adsorption resins such as aromatic resins (e.g., styrene-based resins (styrene-divinylbenzene copolymers, etc.)). Among these, styrene-based resins are preferred. As the styrene-based resin, for example, commercially available products such as Diaion (trademark) HP20 (manufactured by Mitsubishi Chemical Corporation) can be used. The amount of synthetic adsorbent used in the culture medium is preferably 1% by weight to 10% by weight, more preferably 2% by weight to 5% by weight.

[0036] The pH of the liquid medium is, for example, preferably 6.0 to 9.0, more preferably 7.0 to 8.0. Known acidic or alkaline substances can be used to adjust the pH. The pH is measured at 25°C.

[0037] The culture may be divided into a preculture and a main culture. The medium used for the preculture is not particularly limited, and may be the same as or a different liquid medium used for the main culture. During the culture, for example, the HV058 strain may be precultured in a liquid medium and then inoculated into the liquid medium for the main culture, or the HV058 strain may be cultured in a solid medium such as an agar medium and then directly inoculated into the liquid medium.

[0038] The culture temperature is not particularly limited as long as it is a temperature at which actinomycetes belonging to the genus Kitasatospora can be cultured, and can be, for example, from 15° C. to 45° C., and preferably from 20° C. to 40° C. When the culture temperature is within this temperature range, the HV058 strain grows rapidly, resulting in a large amount of production of the above-mentioned compound (I).

[0039] The culture time is not particularly limited as long as the compound (I) can be produced. The culture time can be, for example, from 10 hours to 4 weeks, preferably from 1 day to 4 weeks, and more preferably from 5 days to 2 weeks.

[0040] In the culturing step, the HV058 strain is preferably cultured aerobically. The method for aerobic culturing is not particularly limited, and a liquid medium inoculated with the HV058 strain may be cultured, for example, by shaking or stirring. The shaking or stirring speed is not particularly limited, but may be, for example, 30 rpm to 500 rpm, preferably 50 rpm to 300 rpm. The culture format may be batch culture, fed-batch culture, or continuous culture, with batch culture being preferred. In the production method of the present invention, static culture may also be used.

[0041] By the above-mentioned cultivation, the compound (I) can be accumulated in the culture. The culture contains a medium and cells of the HV058 strain. The compound (I) accumulates in the medium and / or cells of the HV058 strain.

[0042] In the harvesting step, the compound (I) is harvested from the culture obtained in the culturing step. The compound (I) may be in the form of any of the compound or a salt thereof, or a solvate thereof.

[0043] The method for collecting the compound (I) is not particularly limited, and any known method used for separating and purifying compounds can be used. To collect the compound (I) accumulated within the bacterial cells, for example, the bacterial cells are disrupted by ultrasonication, autolysis, or the like, and the resulting disrupted bacterial cells are centrifuged, filtered, or the like to remove bacterial cell residues to obtain a supernatant. The resulting supernatant of the disrupted bacterial cells can be further purified to obtain the compound of the present invention. Purification can be performed using known separation and purification methods, such as separation using a porous adsorbent such as a synthetic adsorbent, reversed-phase high-performance liquid chromatography, or chromatography using an ion-exchange resin, either alone or in combination as appropriate. The method for separating the cells from the medium is not particularly limited, and known methods such as centrifugation and filtration can be used.

[0044] When compound (I) is collected from the medium, it can be collected by extracting it from the culture medium after cultivation using an organic solvent such as methanol, ethyl acetate, etc. In addition to the above extraction methods, compound (I) can be purified by known separation and purification methods, such as separation using a porous adsorbent such as a synthetic adsorbent, reversed-phase high performance liquid chromatography, chromatography using an ion-exchange resin, etc., either alone or in appropriate combination.

[0045] When the porous adsorbent is added to a medium and cultured, the compound (I) is adsorbed to the adsorbent. Therefore, the compound (I) can be extracted from the culture by recovering the porous adsorbent from the culture. The porous adsorbent can be extracted with an organic solvent such as methanol or ethyl acetate, or a mixture of the organic solvent and water, to obtain an extract containing the compound (I). The compound (I) can be purified from this extract by applying the known separation and purification methods, either alone or in combination. The compound (I) obtained by the production method of the present invention may be one type of compound or a mixture of two or more types of compounds.

[0046] The compound represented by the general formula (1), general formula (2), or general formula (3), or a salt thereof, or a solvate thereof, can also be produced by known chemical synthesis methods. Furthermore, for example, the compound obtained by culturing the HV058 strain (e.g., the compound represented by the formula (1a-1)) can be used as a starting material to undergo a known synthetic reaction or a synthetic reaction analogous thereto to obtain the compound (I). The target compound obtained by synthesis can be purified by a conventional purification method, such as reverse-phase high-performance liquid chromatography, chromatography using an ion exchange resin, or a synthetic adsorption resin.

[0047] Whether the desired compound has been obtained can be confirmed by known methods (for example, mass spectrometry, nuclear magnetic resonance spectroscopy (NMR), high performance liquid chromatography (HPLC), etc.).

[0048] [Use of the compound] The compounds represented by the above general formula (1), (2), or (3), or salts thereof, or solvates thereof, have antibacterial activity, and therefore can be used, for example, as antibacterial agents, medicines, etc.

[0049] The compound (I) can be used alone or in the form of a composition by blending it with other ingredients in various fields such as medicines (including quasi-drugs), foods and beverages (including general foods and beverages, health foods, functional foods, foods for specified health uses, health supplements, nutritional supplements, foods and beverages for the sick, food additives, etc.), reagents, cosmetics, daily necessities, etc.

[0050] The present invention also encompasses an antibacterial agent comprising a compound represented by the above general formula (1), general formula (2), or general formula (3), or a salt thereof, or a solvate thereof. The antibacterial agent of the present invention typically comprises the above compound (I) as an active ingredient. The antibacterial agent of the present invention can be used in various fields requiring antibacterial properties, such as pharmaceuticals, food and beverages, cleaning products, and daily necessities. In one embodiment, the antibacterial agent of the present invention can be provided in the form of a pharmaceutical.

[0051] The present invention also includes a pharmaceutical comprising a compound represented by the above general formula (1), general formula (2), or general formula (3), or a salt thereof, or a solvate thereof. The pharmaceutical of the present invention usually comprises the above compound (I) as an active ingredient.

[0052] The antibacterial agent or medicament of the present invention can be used for eradicating, disinfecting, sterilizing, or inhibiting the growth of microorganisms such as bacteria and fungi. Target microorganisms for the antibacterial agent or medicament include bacteria such as gram-positive bacteria and fungi such as yeast. The target microorganisms may be one type or two or more types. Examples of Gram-positive bacteria include Mycobacterium bacteria (e.g., Mycobacterium smegmatis), Staphylococcus aureus (e.g., Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), etc.), Bacillus bacteria (e.g., Bacillus subtilis), Micrococcus bacteria (e.g., Micrococcus luteus), Kocuria bacteria (e.g., Kocuria rhizophila), vancomycin-resistant enterococci (VRE), etc. Examples of yeast include Candida yeast (e.g., Candida albicans), etc.

[0053] In one aspect, the antibacterial agent or medicament of the present invention can be used for the prevention or treatment of infectious diseases. The medicament of the present invention may be, for example, an agent for the prevention or treatment of infectious diseases. Examples of infectious diseases include bacterial infections and fungal infections. Examples of bacterial infections include bacterial infections caused by the above-mentioned gram-positive bacteria. Specific examples include sepsis, meningitis, endocarditis, osteomyelitis, pneumonia, etc. Examples of fungal infections include infections caused by yeast (e.g., Candida yeast).

[0054] As used herein, prophylaxis means delaying or preventing the onset of a symptom or disease or reducing a subject's risk of developing a symptom or disease. Treatment means alleviating a symptom or disease, preventing or delaying the worsening of a symptom or disease, or curing a symptom or disease.

[0055] The form of the antibacterial agent or medicament of the present invention is not particularly limited, and may be in a form commonly used depending on the application. The above-mentioned compound or a salt thereof, or a solvate thereof may be used as it is or in various formulation forms.

[0056] The antibacterial agent or medicament may contain any additive in addition to the above-mentioned compound or a salt thereof, or a solvate thereof. The additive is not particularly limited as long as it is a pharmaceutically acceptable component, and examples thereof include a carrier, excipient, binder, disintegrant, lubricant, antioxidant, colorant, etc. In one aspect, the antibacterial agent or medicament of the present invention is provided as an antibacterial composition or pharmaceutical composition containing the above-mentioned compound or a salt thereof, or a solvate thereof, and an additive such as a pharmaceutically acceptable carrier.

[0057] The route of administration of an antibacterial agent or a pharmaceutical to a subject is not particularly limited, and may be either oral administration or parenteral administration (transdermal, transmucosal, enteral, injection, etc.). Dosage forms for oral administration include liquids, tablets, powders, fine granules, granules, sugar-coated tablets, capsules, suspensions, emulsions, chewable preparations, etc. Dosage forms for parenteral administration include injections, infusions, and topical skin preparations (patches, creams, ointments, etc.).

[0058] The target subjects (also referred to as administration subjects) of the antibacterial agent or medicament of the present invention are not particularly limited and include mammals such as humans, monkeys, mice, rats, rabbits, dogs, cats, pigs, cows, horses, sheep, and goats, with humans being preferred. Further, target subjects of the antibacterial agent or medicament include, for example, patients with infectious diseases, and subjects who wish to or require prevention or treatment of infectious diseases.

[0059] The content of the compound (I) in the antibacterial agent or medicament of the present invention can be adjusted appropriately depending on the mode of use, etc. The content in the antibacterial agent or medicament can be, for example, 0.0001% by weight or more and 100% by weight or less, preferably 0.001% by weight or more and 50% by weight or less. The antibacterial agent or medicament may contain only one type of the compound (I) or may contain two or more types. When two or more types of compounds are used as compound (I), the amount of compound (I) is the total amount of those compounds.

[0060] When administering the compound (I) to a subject, the dosage can be appropriately determined depending on the administration route, the subject, the subject's weight, the disease, etc., and is not particularly limited. For example, when administered to an adult, the compound (I) can be administered in a range of 0.001 mg / kg to 100 mg / kg per day. The number of administrations can be, for example, once, twice, or three times per day.

[0061] [Preventive or therapeutic methods, etc.] The present invention also encompasses a method for preventing or treating an infectious disease, which comprises administering the aforementioned compound (I). The present invention also encompasses use of the aforementioned compound (I) for preventing or treating an infectious disease. The infectious disease is preferably a bacterial infection or a fungal infection.

[0062] The present invention also encompasses the use of compound (I) for the manufacture of an antibacterial agent or a medicament. In one embodiment, the antibacterial agent or medicament may be an agent for the prevention or treatment of an infectious disease. [Example]

[0063] EXAMPLES Hereinafter, examples will be given that more specifically disclose the present invention, but the present invention is not limited to these examples.

[0064] [Example 1] (Cultivation of HV058 strain) Kitasatospora purpeofusca HV058 strain was inoculated and cultured on the following medium. Kitasatospora purpeofusca HV058 strain has been deposited at the Patent Microorganisms Depositary Center, National Institute of Technology and Evaluation (Room 122, 2-5-8 Kazusa Kamatari, Kisarazu City, Chiba Prefecture, Japan, 292-0818) (Deposit date: April 23, 2021, Accession number: NITE BP-03475).

[0065] Culture medium specifications: 1 L of ISP medium 4 supplemented with 4% Diaion (registered trademark) HP20 (manufactured by Mitsubishi Chemical Corporation) Culture conditions: 30℃, 7 days, 140rpm ISP medium 4 was prepared with the following composition and used. Ingredients (per 1L): Soluble starch (10.000g), K2HPO4 (1.000g), MgSO4·7H2O (1.000g), NaCl (1.000g), (NH4)2SO4 (2.000g), CaCO3 (2.000g), FeSO4·7H2O (0.001g), MnCl2·7H2O (0.001g), ZnSO4·7H2O (0.001g) Final pH (25℃):7.2±0.2

[0066] After the above-mentioned cultivation, the culture medium containing the bacterial cells was filtered to separate the Diaion HP20. The Diaion HP20 was washed with five times its volume of water. Next, five times its volume of methanol was added to the Diaion HP20, and the adsorbed substances were extracted for 1 hour. The methanol extract containing the Diaion HP20-adsorbed substances was vacuum-dried to obtain a brown powder. The obtained brown powder was fractionated by ODS column chromatography (Cosmosil 140C18-PREP (Nacalai Tesque, Inc.)). A solution of the above powder dissolved in 10% methanol was applied to an ODS column, and the methanol content was increased stepwise by 10% starting from 10% methanol, and finally eluted with 100% methanol. As a result, the target compound was detected in the 40% methanol fraction, and this fraction (referred to as fraction (A)) was analyzed by LC-MS.

[0067] The fraction (A) obtained above was dried under vacuum, and the resulting powder was dissolved in methanol and purified using high performance liquid chromatography (HPLC) under the following conditions to fractionate the water-soluble fraction.

[0068] Equipment: High-performance liquid chromatograph system Prominence (Shimadzu Corporation) System controller: CBM-20Alite Pump: LC-20AD Detector: SPD-M20A Column: Cosmosil 5C 18MS-II 2.0mm ID x 250mm (Nacalai Tesque, Inc.) Elution conditions: Solution A: H2O 0.1% formic acid Solution B: Acetonitrile 0.1% formic acid B liquid concentration: 10vol% (0-5min), 10-100vol% (5-30min), 100vol% (30-40min) Flow rate: 0.2mL / min Temperature: 30℃ Detection: 210nm

[0069] Under the above conditions, the target peak was detected at an elution time of 10 minutes.

[0070] (Structural analysis of compounds) The molecular weight of the compound contained in the target peak was 5 Da larger than that of Hazimycin A (Non-Patent Document 1). Analysis of the fragment ions by LC-MS / MS revealed that the cleavage mode from one side chain was the same as that of Hazimycin A, but the fragment ion cleaved from the other side chain, m / z = 352.27, which is specific to this compound, was detected, revealing the presence of hydrazine as a side chain functional group in place of the isonitrile group.

[0071] The compound contained in the target peak was found to be a compound represented by the following formula (1a-1) (compound (1a-1)).

[0072] [ka]

[0073] The antibacterial activity of compound (1a-1) was evaluated by the following method. (Antibacterial test) Using a paper disk (6 mm, manufactured by ADVANTEC) containing compound (1a-1), an antibacterial test was carried out against the following bacteria. (1) Gram-positive bacteria Mycobacterium smegmatis Bacillus subtilis Staphylococcus aureus Micrococcus luteus (2) Gram-negative bacteria Escherichia coli Pseudomonas aeruginosa (3) Yeast Candida albicans

[0074] Antibacterial tests were conducted using the culture medium of the above bacteria at 10 μg / 6 mm disc. The test method followed the method described in Koyama et al., "Calpinactam, a new antimycobacterial agent, produced by Mortierella alpina FKI-4905," The Journal of Antibiotics (2010) 63, 183-186. The results (inhibition zone (mm)) are shown in Table 1.

[0075] [Table 1]

[0076] Compound (1a-1) exhibited antibacterial activity against Gram-positive bacteria and yeast, and is useful as an antibacterial agent or an active ingredient of a medicine.

Claims

1. A compound represented by the following formula (1a-1), a salt thereof, or a solvate thereof: 【Chemical 1】

2. A culturing step of culturing Kitasatospora purpeofusca HV058 strain (accession number NITE BP-03475); and A method for producing the compound according to claim 1 or a salt thereof, or a solvate thereof, comprising a collection step of collecting the compound according to claim 1 or a salt thereof, or a solvate thereof from the culture obtained in the culture step.

3. An antibacterial agent comprising the compound according to claim 1 or a salt thereof, or a solvate thereof.

4. A pharmaceutical comprising the compound according to claim 1 or a salt thereof, or a solvate thereof.

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