JPS6257199B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel antibiotic, more specifically, the following formula: In the formula, R represents a hydrogen atom or a methyl group. The present invention relates to a compound or a salt thereof, a method for producing the same, and a use as an antibacterial agent. The compound represented by the above formula () is an antibiotic that has a wide range of antibacterial activity against bacteria, yeast, filamentous fungi, etc., and also exhibits antitumor activity against murine leukemia L1210 cells and Sarccoma 180 ascites cancer. In the explanation, the compound represented by the above formula () is collectively referred to as "antibiotic 1907", and the compound represented by formula () when R represents a hydrogen atom is referred to as "antibiotic 1907".
1907" and the compound of formula () when R represents a methyl group is referred to as "antibiotic 1907". As is clear from the above formula (), antibiotic 1907 contains the novel amino acids 1 molecule of 2-amino-4-methyl-6-hydroxy-8-oxodecanoic acid, 2 molecules of leucine, 3 molecules of α-aminoisobutyric acid, and 4- The peptide chain is composed of one molecule of methylproline, one molecule of β-hydroxyleucine, and one molecule of β-alanine, and has 4-methyl-2-hexenoic acid at the N-terminus and N-methyl-1,2 at the C-terminus.
- A peptide derivative to which propanediamine (R=H) or N,N-dimethyl-1,2-propanediamine (R=CH ₃ ) is bound, and has basicity,
It can form salts with many inorganic or organic acids. Examples of such salts include inorganic acid salts such as hydrochlorides, phosphates, sulfates; acetates, propionates, oleates, citrates, tartrates, succinates, malates, glutamates. and organic acid salts such as pantothenate, among which salts with pharmaceutically acceptable acids are preferred. According to the present invention, the antibiotic 1907 can be used to kill filamentous fungi belonging to the genus Paecilomyces that have the ability to produce antibiotic 1907, with a PH value of about
It can be produced by a method consisting of culturing in a nutrient medium of 8.5 to about 11, and collecting antibiotic 1907 as a component having antibacterial activity from the culture solution. Antibiotics that can be used in the method of the invention 1907
The producing microorganism is not particularly limited as long as it is a microorganism capable of producing antibiotic 1907 having the physical and chemical substances and biological properties described below, but filamentous fungi belonging to the genus Pecilomyces are particularly suitable.
A search for antibiotic 1907-producing bacteria among filamentous fungi belonging to the genus Pecilomyces can be easily carried out, for example, as described below. The search for antibiotic 1907-producing bacteria can be carried out according to the conventional method as shown below: About 1 g of a soil sample is suspended in about 6 ml of sterile water. Spread the soil suspension onto the agar medium shown below. Medium composition is C
Both source and N source may be any source that can grow general filamentous fungi;
It is important to add 3% and bring the medium PH to 10.0-10.5. Medium: glucose 1%, asparagine 0.03%, peptone 0.02%, yeast extract
0.01%, dipotassium phosphate 0.1%, magnesium sulfate 0.01%, trace metals such as iron and manganese, and 2%
A medium containing agar and 1% sodium carbonate is used. When the above soil suspension is applied to this medium and cultured at 26.5℃ for about 5 to 10 days, a colony of the desired bacteria will be obtained.Then, it is further transferred to a slant medium prepared in a test tube and cultured at 26.5℃ for 10 days. save. The bacterial strain obtained as described above is subjected to liquid culture using a medium used for culturing general filamentous fungi.
At this time, adjust the initial pH of the medium using soda carbonate, etc.
It is important to adjust the pH to 10.0 to 10.5, and culture is carried out at 26.5°C aerobically for about 5 to 8 days. After culturing, mix the culture solution and acetone well in a ratio of 1:1, soak the supernatant liquid into a pulp disk, and place it on a test plate using the following test bacteria to examine the antibacterial activity. Using Staphylococcus aureus, Bacillus subtilis, Escherichia Coli, Candida albicans, etc. as test bacteria, the antibacterial activity was examined and each of the above test bacteria was tested. Strains that exhibit a strong antibacterial spectrum are selected as candidates for antibiotic 1907 production. Regarding candidate bacteria selected in this way,
Furthermore, paper chromatography and thin layer chromatography will be performed to confirm the productivity of antibiotic 1907. Accordingly, those skilled in the art can easily search for antibiotic 1907-producing bacteria that are suitable for the purpose of the present invention. Typical antibiotic 1907-producing bacteria searched as above include antibiotic 1907-producing bacteria belonging to the genus Pecilomyces, and a suitable example is An example of this strain is a filamentous fungus isolated from soil collected in a botanical garden and designated by the present inventors as strain No. 1907. The properties of strain No. 1907 isolated as above are as follows. (a) Growth status in each medium Malt extract agar medium Colonies grew well, with a diameter of 38 to 40 cm after being incubated at 26.5°C for 10 days, and no coloration of the medium was observed. The surface is rich in aerial mycelium, which grows woolly and forms a mountain in the center. The color is light reddish-purple, and there are 5 to 6 vertical wrinkles extending from the peak to the periphery. The growth on the underside is dense, with 5 to 6 wrinkles radiating from the center. The color is brown in the center and white in the periphery. Conidia are well formed, with nearly circular conidia attached in a chain at the tip of the conidiophore. Potato Glucose Agar Medium Colony growth was very good, at 26.5℃,
After 10 days of culture, the diameter was 40 to 41 cm, and no coloration of the medium was observed. The surface is rich in aerial mycelium, which grows woolly and forms a mountain in the center. The color tone is light gray-purple, and many vertical wrinkles are seen from the top of the mountain, and 6 to 7 wrinkles are observed radially. The growth on the underside is dense, with 2 to 3 wrinkles radiating from the center. The color is dark brown in the center and becomes white towards the periphery. Conidia are well formed, with almost circular conidia attached in a chain at the tip of the conidiophore. Tuapetsk agar medium Colonies grow well, with a diameter of 30.5 to 33.0 cm after 10 days of culture at 26.5°C, and no coloration of the medium is observed. The surface is rich in aerial mycelium, which grows in a fluffy manner and forms a mountain in the center. The color is white, but the center is pale gray-purple. There are 4 to 5 wrinkles radiating from the mountain. Water droplets can be seen in the center of the mountain. The growth on the underside is dense, with 3 to 4 annual ring-shaped wrinkles starting from the center, and 4 to 5 large radial wrinkles. The color is yellowish brown. Conidia formation is good, with almost circular conidia being formed in a chain at the tip of the conidiophore. The tips of the conidiophores are seen to be curved. (b) Physiological and ecological properties Physiological and ecological properties of the live bacteria were tested using Czapetsk liquid medium. Suitable growth temperature and growth temperature range Suitable growth temperature is 22.5℃~33.6℃, 26.5℃
It grows best at temperatures between 9°C and 35.2°C. Optimum PH for growth and PH range for growth Optimum PH for growth is PH7.5 to PH9.00, PH2.5
Can grow up to PH11.00. This bacterium was classified as Paecilomyces and Some Allied hyphomycetes by RASamson (1974).
Hyphomycetes)” and Agnes H.S.Brown and
George Smith’s text “The Genus”
Paecilomyces Bainier And It's Perfect Stage
Byssochlamys Westling” (Trans.Brit.mycol.
Soc., 40 (1), 17-89 (1957))
When compared with the description of Paecilomyces Iilacinus, it was found that the growth rate of the colonies, the morphology of the colony surface, and the color tone were very similar, and the morphology of the stalks and conidia were similar.
Furthermore, it was observed that many of the characteristics, such as the absence of chlamydospores, were consistent with the described characteristics of this bacterium and Paecilomyces Iilacinus. Therefore, this bacterium was classified as Paecilomyces lilacinus.
Iilacinus). However, Pecilomyces
Production tests were conducted on P. lilacinus ATCC10114 and IAM7002 as type cultures of P. lilacinus, but no production of antibiotic 1907 was observed, so the strain of the present invention was recognized as a physiological variety belonging to P. lilacinus. , and named it Pecilomyces lilacinus No.1907. This bacterium was deposited on September 26, 1981 at the Institute of Microbial Technology, Agency of Industrial Science and Technology under the microorganism accession number 5715. To produce antibiotic 1907 using the antibiotic 1907 producing bacteria described above, antibiotic 1907 producing bacteria,
For example, Pecilomyces lilacinus No. 1907 is cultivated under aerobic conditions in a suitable nutrient medium. As the nutrient source for the nutrient medium, those commonly used as nutrient sources for filamentous fungi are used, such as assimilable nutrient sources such as carbohydrates, nitrogen sources, and inorganic salts. For example, carbohydrates such as glucose, glycerin, maltose, sucrose, molasses, dextrin, and starch; carbon sources such as oils and fats such as soybean oil, peanut oil, and lard; peptone, meat extract, soybean flour, and cottonseed flour. , dried yeast, corn steep liquor, yeast extract, skim milk, casein, sodium nitrate, ammonium nitrate, ammonium sulfate, and other nitrogen sources; inorganic salts such as dipotassium phosphate, common salt, calcium carbonate, and magnesium sulfate can be used, and trace metals can be used if necessary. For example, cobalt, manganese, etc. can be added. As the nutrient source, any other nutrient source can be used as long as it produces antibiotic 1907 using antibiotic 1907-producing bacteria, and any culture material for known filamentous fungi can be used. Further, in order to suppress foaming during heat sterilization and culturing, an antifoaming agent such as silicone or vegetable oil may be added. The blending ratio of the nutrient sources as described above is not particularly restricted and can be varied over a wide range, and those skilled in the art will be able to determine the optimum nutrient source composition and blending ratio for the antibiotic 1907-producing bacteria to be used. If so, it can be easily determined by simple small-scale experiments. The nutrient medium can also be sterilized prior to cultivation, and the pH of the medium can be adjusted to approximately 8.5 to 8.5 before or after sterilization.
Adjust to a range of about 11, especially PH9.0 to 10.5,
It is important to maintain this PH range during culture. As a method to adjust and maintain the pH of the medium within the above range,
Examples include a method of appropriately adding basic substances such as sodium hydroxide, potassium hydroxide, sodium carbonate, sodium bicarbonate, and ammonia to the medium. Among them, sodium carbonate is added to the medium at the beginning of culture.
It is convenient to add it at a concentration of 0.5 to 3 g/dl. In principle, the cultivation of antibiotic 1907-producing bacteria in such a nutrient medium can be carried out according to the method commonly used in the production of antibiotics using general filamentous fungi. It is usually suitable to culture under aerobic conditions, usually with stirring or shaking and/or
Alternatively, it can be carried out with ventilation. In addition, as a culture method, static culture, shaking culture, and submerged culture with aeration and agitation can all be used.
Submerged culture is advantageous. The culture temperature that can be used is not particularly limited as long as the growth of antibiotic 1907-producing bacteria is not substantially inhibited and antibiotic 1907 can be produced, and it can be changed depending on the production strain used. but,
Generally temperatures within the range 20-35°C, preferably 25-30°C are suitable. In the case of large-scale mass cultivation, it is advantageous to perform a seed culture as appropriate, inoculate it into a nutrient medium, and perform liquid culture. Cultivation can normally be continued until sufficient antibiotic 1907 has accumulated. The culture time varies depending on the composition of the medium, culture temperature, production strain used, etc.
It usually ranges from 4 to 8 days. As for the culture conditions to be used, those skilled in the art can easily determine the optimal conditions through simple experiments, depending on the characteristics of the production strain used. The amount of antibiotic 1907 accumulated during culture can be quantified by bioassay and bioautography, thereby making it easy to determine the optimum amount of antibiotic 1907 accumulated. Thus, depending on the culture conditions used, the type of bacterial strain used, etc., antibiotics 1907- and
1907- is mainly produced, or both are produced at the same time. Since the antibiotic 1907 accumulated in the culture in this way exists mainly outside the bacterial cells, it is advantageous to
The bacterial cells are removed by a separation method known per se, such as centrifugation or extraction, and recovered from the resulting liquid, supernatant liquid, extract liquid, etc. Recovery can be carried out by various methods known per se, and in particular, methods commonly used for recovery of peptide-based substances are advantageously applied. For example, the culture solution is first made acidic with dilute mineral acids such as hydrochloric acid or sulfuric acid, and then the solid content is removed by filtration, centrifugation, etc., and the resulting solution or supernatant is added with sodium hydroxide, hydroxide, etc. Add an alkali such as potassium or sodium carbonate to make it alkaline with a pH value of about 8 to about 9.
Next, this liquid or supernatant liquid is extracted with a water-immiscible solvent such as ethyl acetate, chloroform, benzene, n-butanol, etc., and the extract is concentrated as necessary.・Manufactured by & Haas), Diamond Aeon HP
-20 (manufactured by Mitsubishi Chemical Corporation), etc., and elution with methanol water, acetone water, etc.; Sephadex
Gel filtration with LH-20 and G-10 (manufactured by Pharmacia), Bio-Gel P-2 (manufactured by Bio-Rad), etc.; with cellulose, Avicel SF (manufactured by American Viscose), silica gel, alumina, etc. The target antibiotic 1907 can be isolated by using column method or thin layer chromatography; forced precipitation method by adding a solvent such as petroleum ether; freeze-drying method, etc. alone or in appropriate combinations. can. For example, apply the above extract to silica gel column chromatography, first elute with a mixed solvent of benzene/methanol (10/1 υ/υ), then increase the proportion of methanol in sequence, and finally elute with benzene/methanol (1/1 υ/υ). ) Elute with mixed solvent. As a result, antibiotic 1907− was eluted as the second fraction, and antibiotic
1907- elutes as the 8th fraction. The above eluted fractions can be further purified, for example, by high performance liquid chromatography and/or column chromatography using Sephadex LH-20, thereby converting the antibiotics 1907- and 1907- into white powders. It can be recovered as Antibiotic 1907 thus obtained is a basic substance and forms acid addition salts with various acids. Formation of such acid addition salts can be easily carried out by treating the antibiotic with an acid using a salt-forming reaction known per se. Examples of acids that can be used to form such acid addition salts include inorganic acids such as hydrochloric acid, phosphoric acid, and sulfuric acid; acetic acid, propionic acid, oleic acid, citric acid, tartaric acid, succinic acid, malic acid, glutamic acid, and pantothenic acid. This includes organic acids such as. Antibiotics 1907- and
1907- has a wide range of antibacterial activity, and is effective against various microorganisms such as bacteria, yeast, and filamentous fungi, such as bacteria belonging to the genus Staphylococcus, Sarcina, Micrococcus, Serratia, etc.; Candida, Cryptococcus , Rhodotorula spp., Trichophyton spp.
Sporotrichum, Cosideioides, Penicillium, Alternaria, Pericularia,
It exhibits strong antibacterial activity against fungi belonging to the genus Pyricularia and Cladosporium. In particular, the antibiotic 1907 of the present invention exhibits excellent antibacterial activity against filamentous fungi, including Trichophiton Mentagrophytes and Trichophiton rubram, which are pathogens of athlete's foot, and Trichophiton rubram, which is a pathogen of pear blight. Alternaria Kikuchiana, Pellicularia Sasakii Hokko, a rice blast pathogen, and Pellicularia oryzae, a rice blast pathogen.
It shows remarkable antibacterial activity against (Piricularia Oryzae) etc. The antibacterial activity of the antibiotic 1907 of the present invention can be determined by measuring the minimum inhibitory concentration (MIC) against various pathogenic test bacteria using the agar dilution method (for bacteria: Heart Infusion Agar medium, for fungi: Sabouraud Agar medium). This can be proven by The measurement results of MI and C. of the antibiotic of the present invention against various test bacteria are shown in Table 1 below.

【table】

【table】

[Table] Furthermore, the antibiotic 1907 of the present invention exhibits excellent anti-malignant tumor activity, as is clear from the following in vitro and in vivo test results, and is considered for use as an anti-cancer agent. (1) The effects of antibiotics 1907- and 1907- of the present invention on cultured cells were investigated using L1210 mouse leukemia cells. i.e. L1210 cells containing 20% calf serum
RPMI medium (Japan Rosewell Memorialpark
Institute 1640), cultured in a carbon dioxide incubator at 37℃ for 3 days, and treated with various concentrations of antibiotics 1907.
- and 1907- and tracers and breaker surfers were added, and the degree of proliferation was expressed as the 50% inhibitory concentration (mcg/ml) of the drug. As shown in Table 2 below, by adding antibiotic 1907- to the medium at a concentration of 1 mcg/ml, nucleic acid biosynthesis and cell proliferation were suppressed by 50% or more. Antibiotic 1907- had a similar effect, with a 50% inhibitory concentration on nucleic acid biosynthesis of 2.0 mcg/ml. RNA, DNA, and protein synthesis in this experiment was performed at ¹⁴ C-
Examined the cellular uptake rate of thymidine, ¹⁴ C-uridine, and ¹⁴ C-leucine, and the rate was 50% compared to the control group.
It is expressed as inhibitory concentration (IC ₅₀ ).

[Table] (2) The antitumor effects of antibiotics 1907- and 1907- of the present invention on murine leukemia L1210 cells were investigated. i.e. CDF ₁ mice weighing 19 to 24 g.
1 x ¹⁰⁵ L1210 cells were transplanted intraperitoneally, and antibiotics 1907- and 1907- were administered 24 hours after transplantation.
It was administered intraperitoneally once daily for 10 consecutive days. The results are shown in Table 3 below. As is clear from Table 3, when antibiotic 1907- was administered at a dosage of 0.125 mg per kg of mouse body weight, it showed a survival rate of 158% compared to mice to which it was not administered. 146% compared to mice not treated with antibiotic 1907− at a dosage of 0.125 mg/Kg.
showed a life extension rate.

[Table] (3) Antibiotics 1907- and 1970-
The antitumor effect of Sarcoma180 on ascites cancer was investigated. 4 × ¹⁰⁶ Sarcoma180 cells were intraperitoneally transplanted into ICR mice weighing 22 to 25 g, and treated with antibiotic 1907.
- and 1907- were intraperitoneally administered once a day for 7 consecutive days starting 24 hours after transplantation. The results are shown in Table 4 below. As is clear from Table 4, antibiotics 1907- and 1907- were administered at a dosage of 0.063 mg/Kg of body weight, which was 161% and 168%, respectively, compared to mice not administered this drug.
% life extension rate.

[Table] (4) Toxicity Based on the experimental data in (2) and (3) above, the LD ₅₀ value for each mouse was calculated, and the LD ₅₀ value for antibiotics 1907- and 1907- was approximately 5 mg/
Estimated to be Kg. As mentioned above, the antibiotic 1907 provided by the present invention has strong antibacterial activity.
It can be used as an active ingredient of an antibacterial agent for the prevention, treatment, and/or treatment of infectious diseases caused by various pathogenic bacteria as mentioned above, and for the prevention, treatment, and treatment of infectious diseases in humans and non-human animals. can. For example, the antibiotic 1907 of the present invention has remarkable antibacterial activity against the pathogenic bacteria of athlete's foot, Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, so it is commonly used as a pharmaceutical agent for external use on athlete's foot. According to the law, it can be formulated into dosage forms such as ointments, creams, tinctures, lotions, etc. Furthermore, as mentioned above, the antibiotic 1907 of the present invention has remarkable bactericidal activity against plant pathogens, such as pear sheath blight pathogen, rice sheath blight pathogen, and rice blast pathogen, and is therefore useful as an agricultural chemical. It can be used for the prevention, treatment and/or treatment of infectious diseases of crops. The antibiotic 1907
When used as a plant fungicide, an effective amount of the antibiotic 1907 may be added to a solid or liquid inert carrier or diluent (e.g., starch, kaolin, talc, water, various organic solvents, etc.) according to customary practices in the field of agrochemicals. ), it can be formulated into dosage forms such as powders, concentrated emulsions, and aerosols. Further, the antibiotic 1907 of the present invention can be used in the industrial field, construction field, etc. by incorporating it into paints and plastics, or for sterilizing wood, leather, etc., by taking advantage of its excellent antibacterial activity. The present invention will be further explained below with reference to Examples. Examples Paecilomyces lilacinus
Iilacinus) No. 1907, both the seed medium and production medium had the following composition: glucose 0.5 g/dl, soluble starch 3.0 g/dl, soybean flour 1.5 g/dl, peptone 0.3
g/dl, dry yeast 0.2g/dl, K ₂ HPO ₄ 0.1g/
dl, NaCl0.1g/dl, _MgSO4・_7H2O0.05g /dl,
Fe ₂ (SO ₄ ) ₃・6H ₂ O0.001g/dl, CuSO ₄・
5H ₂ O0.0001g/dl, ZnSO ₄・7H ₂ O0.0001g/
dl, MnSO ₄・H ₂ O0.0001g/dl, Na ₂ CO ₃ 1.0g/
dl. For the seed culture medium, dissolve or suspend the raw materials other than Na ₂ CO ₃ in water, and add 100 ml of each to 500 ml.
The mixture was dispensed into Sakaguchi flasks and steam sterilized at 120°C for 15 minutes. On the other hand, a corresponding amount of Na ₂ CO ₃ was dissolved in a small amount of water, and separately from the above, it was sterilized at 120° C. for 15 minutes, and after cooling, it was poured into the Sakaguchi flask. This brought the pH of the medium to 10.25. In this seed medium, Pecilomyces lilacinus No.
1907 was inoculated and cultured with shaking at 28°C for 3 days. Next, as the second stage seed culture medium, one of the above raw materials is used.
Add 15 substances other than Na ₂ CO ₃ to a jar fermenter with a total capacity of 30, and add 0.05 of Nissan Daysform CB-442 (manufactured by NOF Corporation) as an antifoaming agent.
g/dl was added and steam sterilized at 120°C for 15 minutes. separately
After dissolving Na ₂ CO ₃ in a small amount of water, it was sterilized at 120° C. for 15 minutes and added to the jar fermentor. This brought the pH of the medium to 10.25. Add 100ml of the seed mother cultured in the Sakaguchi flask to this.
The cells were inoculated and cultured for 1 day at 28°C with aeration and stirring. 100 to 200 fermentation tanks as production medium
The culture medium was prepared in the same manner as in the preparation of the jar fermenter described above. The pH of the medium was 10.25.
One seed mother cultured using the above-mentioned jar fermentor was added to this, and cultured for 6 days at 28°C with aeration and stirring. The PH during culture was kept in the range of 10.25-9.00. Take out this culture solution (total volume 85) and add it with sulfuric acid.
After setting the pH to 4.0, pass it through a filter press,
A liquid of 80% was obtained. This was adjusted to pH 8.0 with caustic soda and extracted twice with 20 portions of benzene to obtain benzene extract 37. This was concentrated under reduced pressure to obtain about 15 g of a brown oily substance. Add this to silica gel [Wako
The mixture was subjected to column chromatography using gel C-200 (Wako Pure Chemical Industries, Ltd.) (φ7 cm x 52 cm) to separate the contained components. As the elution solvent, a mixture of benzene and methanol = 10:1 was initially used.
The ratio of methanol was gradually increased until the ratio of benzene:methanol was 1:1. As a result, 11 types of fractions were obtained. Each fraction was concentrated under reduced pressure and further dried under vacuum overnight. As a result, approximately 6 g is obtained from the fraction containing antibiotic 1907- according to the present invention (the second eluting fraction), and approximately 1.4 g from the fraction containing antibiotic 1907- (the eighth eluting fraction). A yellowish brown powder was obtained. Each of the above substances was again subjected to silica gel column chromatography. A column with a diameter of 5.0 cm x 77 cm was used, and purification was performed using a chloroform:methanol-based eluent. Antibiotic 1907- was obtained singly from the chloroform:methanol (10:1) elution section. Furthermore, antibiotic 1907- was obtained singly from the elution section of chloroform:methanol (1:1). The obtained eluted sections were each concentrated under reduced pressure, and finally purified by column chromatography using Sephadex LH-20 (manufactured by Pharmacia). In this case, a φ5 cm x 50 cm column was used and elution was performed with methanol. By concentrating this eluate under reduced pressure and further vacuum drying, antibiotic 1907
750 mg of white powder of - and 150 mg of white powder of antibiotic 1907- were obtained. Obtained antibiotic 1907- and antibiotic 1907-
The physical and chemical properties of are as follows. Physical and chemical properties of antibiotics 1907- and 1907- (1) Molecular weight Determined by spectral analysis using FD-mass (JEOL mass spectrometer model JMS-D300). 1907-:1203 1907-:1217 (2) Elemental analysis Molecular weight and In-Beam determined by FD-MS analysis
The following molecular formula was determined from the structure determined by mass spectrometry (Hitachi Mass Spectrometer Model M-80). 1907-: C ₆₁ N ₁₁ O ₁₃ H ₁₀₉ 1907-: C ₆₂ N ₁₁ O ₁₃ H ₁₁₁ (3) In-Beam mass spectra Attached are the In-Beam mass spectra of the acetyl form of 1907- and the acetyl form of 1907-, respectively. 1st of
As shown in FIG. From the fragmentation patterns shown in Figures 1 and 2, the antibiotic of the present invention
The sequences of 1907- and 1907- components have been determined. (4) Melting point 1907-: 125-133℃ 1907-: 113-120℃ (5) Specific rotation 1907-: [α] ²⁴ _D -38.1° (c=0.07, methanol) 1907-: [α] ²⁴ _D -38.0゜ (c=0.05, methanol) (6) Solubility in solvents 1907- and 1907-: Easily soluble in benzene, toluene, ethyl acetate, chloroform, lower alcohols, slightly soluble in petroleum ether, hexane, water (7) Color reaction 1907-: Ninhydrin reaction +; Buillets reaction +; Moritsch reaction -; Sakaguchi reaction - 1907-: Ninhydrin reaction -; Buillets reaction +; Moritshu reaction -; Sakaguchi reaction - (8) Basic, Neutral/acidic 1907-: Basic 1907-: Basic (9) Color of substance 1907-: White 1907-: White (10) Infrared absorption spectrum 1907-: Shown in attached Figure 3 (Nujiol) 1907 -: Shown in attached Figure 4 (KBr tablet) (11) Nuclear magnetic resonance spectrum (90 MHz, in deuterated chloroform) 1907-: Shown in attached Figure 5. 1907-: Shown in attached Figure 6. (12) Ultraviolet absorption spectrum (in methanol) Both 1907− and 1907− show terminal absorption.
A slight shoulder can be seen at 220nm.

[Brief explanation of the drawing]

FIGS. 1 and 2 are In Beam mass spectrograms of antibiotic 1907- and acetylated products of antibiotic 1907-, respectively. 3 and 4 are infrared absorption spectra of Antibiotic 1907- and Antibiotic 1907-, respectively. FIGS. 5 and 6 are proton nuclear magnetic resonance spectra of antibiotic 1907- and antibiotic 1907-, respectively.

Claims (1)

[Claims] 1 formula A compound or a salt thereof, wherein R represents a hydrogen atom or a methyl group. 2 formulas In the formula, R represents a hydrogen atom or a methyl group.
A method for producing a compound represented by the above formula (), which comprises culturing in a nutrient medium having a pH value of about 8.5 to about 11, and collecting the compound represented by the above formula () from the culture solution. 3 formulas An antibacterial agent characterized in that the active ingredient is a compound or a salt thereof, wherein R represents a hydrogen atom or a methyl group.