JPH0227360B2 - SHINKIKOSEIBUTSUSHITSU - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula (In the formula, R ₁ and R ₄ are methyl groups or hydrogen atoms,
R ₂ means a hydroxyl group or a hydrogen atom, and R ₃ means an amino group or a hydroxyl group. However, when R ₄ is a methyl group, R ₂ is a hydroxyl group and R ₁ means a hydrogen atom, and when R ₄ is a hydrogen atom, R ₂ means a hydrogen atom. ) or an acid addition salt thereof. The above compound ( ₁ ) has kanamycin A or kanamycin B in which the amino group at the 3'' position is methylated and both the 3' and 4' positions are deoxylated, or the amino group at the 3'' position is N-methylated. and
This compound has a chemical structure characterized by being methylated at the 4″ position. Compound ( ₁ ) provided by the present invention exhibits excellent antibacterial activity and is promising as an antibacterial agent. Compound ( ₁ ) can be used as a raw material to produce various derivatives.For such derivatives, the amino group at position 1 is replaced with L(-)-γ-amino-α-hydroxybutyric acid by chemical synthesis means. Mention may be made of acylated compounds.
Other derivatives having significant antibacterial activity include various compounds produced by microbial transformation. Such compounds include compounds obtained by contacting compound ( ₁ ) with gentamine-producing strains and sisomicin-producing strains belonging to the genus Micromonospora, or mutant strains thereof, such as 1 3',4'-dideoxy -3″-N-methyl-4″-
C-Methyl-6'-N-methylkanamycin B or its 4" epimer [-B ₁ ] 2 3',4'-dideoxy-3"-N-methyl-4"-
C-Methylkanamycin B or its 4″ epimer [-B ₂ ] 3 3′,4′-dideoxy-3″-N-methyl-4″-
C-Methylkanamycin A or its 4″ epimer [-A ₂ ] 4 4′,5′-didehydro-3′,4′-dideoxy-
3″-N-methyl-4″-C-methylkanamycin A or its 4″ epimer [-SK-A ₁ ] 5 4′,5′-didehydro-3′,4′-dideoxy-
3″-N-methyl-4″-C-methylkanamycin B or its 4″ epimer [-SK-B ₁ ] 6 4′,5′-didehydro-3′,4′-dideoxy-
3″-N-Methylkanamycin B [-SK-B ₂ ].These derivatives have been disclosed in Japanese Patent Application No. 3188/1983 and Japanese Patent Application No. 1983-1989 (1989-1999), which are related to the inventors' earlier application.
147396. Next, the antibacterial activity of compound ( ₁ ) is shown in comparison with kanamycin A (hereinafter abbreviated as KM-A) and kanamycin B (hereinafter abbreviated as KM-B) as follows.

[Table] As is clear from the above table, compound ( ₁ ) has a wide range of strong antibacterial activity against various Gram-positive and Gram-negative bacteria, and is useful as a pharmaceutical. According to the present invention, compound ( ₁ ) is KM-A
Alternatively, it is produced by contacting KM-B with a gentamicin-producing strain belonging to the genus Micromonospora or a mutant strain thereof. The strains used in this production method are KM-A and
Deoxylation at the 3′ and 4′ positions of KM-B and C- at the 4′ position
There is no particular restriction as long as the strain can perform both methylation and N-methylation at the 6′ position depending on the case, and N-methylation at the 3″ position.Such strains include Micromonospora Echinospora NRRL.・
In addition to known strains such as Micromonospora purpurea NRRL.2985 (IFO-13149) and Micromonospora purpurea NRRL.2953 (IFO-13150), Micromonospora sp.K-6993 strain, which is a new strain of the Micromonospora genus, can be mentioned. This Micromonospora sp. K-6993 strain was newly isolated by the present inventors from the soil of Ishigaki Island, Okinawa Prefecture, and has been confirmed to produce gentamicin. In addition, the mutant strain is a gentamicin-producing strain belonging to the genus Micromonospora that has been exposed to ultraviolet irradiation, cobalt-60 irradiation, X-ray irradiation, nitroso compounds,
It can be obtained by ordinary artificial mutagenesis methods using mutagenic agents such as acridine dye compounds and nucleobase analogues. Suitable mutant strains include KM-A and KM-B, which have no ability to produce gentamicin or have an extremely reduced ability to produce gentamicin.
It has the property of being able to deoxylate and methylate. A representative example of these mutant strains is Micromonospora sp.K-6993, which was newly acquired by the present inventors.
-Y-41 strain and Micromonospora echinospora NRRL 2985-N-6 strain. Next, Micromonospora sp.K-6993 (hereinafter abbreviated as K-6993), its mutant strain Micromonospora sp.K-6993-Y-41 (hereinafter abbreviated as Y-41), and Micromonospora sp. The mycological properties of three strains of Spora echinospora NRRL 2985-N-6 (hereinafter abbreviated as N-6) will be described. These strains have been deposited with the Institute of Microbial Technology, Agency of Industrial Science and Technology under the National Institute of Microbiology Deposit No. 4304, No. 4305, and No. 4303, respectively. These strains are also listed in the American Type Culture Collection as ATCC No. 31348.
No. 31349 and No. 31350. Morphological characteristics The morphological characteristics of the above three strains are relatively similar. 3
Neither strain produces true aerial hyphae, but the diameter is 0.5~
Forms branched basal hyphae at 1.0μ. Only one spore settles on the tip of a sporophyte that branches from the basal hyphae. The shape of the spores is oblong or oval. All three strains, Tuapetsk agar, yeast extract,
It grows well on malt extract agar and shows a purple color on egg albumin agar. K-6993 and N
-6 strains are Micromonospora echinospora
It showed similar morphological characteristics to NRRL, 2985 (IFO-13149). Compared to the above two strains, Y-41 strain does not adhere well to spores, and the color tone of the growth is slightly lighter overall.

【table】

[Table] Assimilation of carbon sources Pridham Gottlieb (Pridham-
Gottlieb's medium was used as the basal medium, and 1.0% of each carbon source was added to examine the assimilation ability, and the results are shown in Table 2.

【table】

【table】 physiological properties

[Table] In Table 3, the results for milk and cellulose are shown after one month of culture at 37°C, and the results for gelatin liquefaction, nitrate reduction, and tyrosinase production are shown after two weeks at 29°C. . The K-6993 strain does not form true aerial hyphae, but attaches a single spore to the basal hyphae, and is therefore a strain related to the genus Micromonospora. The following strains of Micromonospora that produce gentamicin have already been reported. Micromonospora purpurea
NRRL・2953 (Micromonospora purpurea), Micromonospora varietus Echinospora NRRL・2985 (Micromonospora purpurea)
echinospora var.echinospora), Micromonospora echinospora varietus fuerginia
NRRL・2995 (Micromonospora echinospora
var.ferruginea), Micromonospora echinospora varietus pallida NRRL・2996
(Micromonospora echinospora var.pallida)
[The above, Antimicrobial Agents and Chemotherapy 1963, 116-124]
micromonospora sagamiensis MK-65
(Micromonospora sagamiensis), Micromonospora sagamiensis varietus nonreducans MK-62 (Micromonospora sagamiensis)
sagamiensis var.nonreducans), Micromonospora sagamiensis varietus flava Mm
−628 (Micromonospora sagamiensis var.
Flava)
6755] The taxonomic characteristics of these seven strains were compared with strain K-6993, and the differences are listed in Table 4. As a result, it is considered to be a new strain close to Micromonospora echinospora.

【table】

[Table] Next, combine KM-A and KM-B with compound ( ₁ )
In order to convert the above-mentioned bacterial strain into a culture medium containing KM-A and KM-B, the above-mentioned strain may be cultured.
In the culture of the present invention, conventional culture methods for producing antibiotics are used. Various sources of nutrients can be used for culture. As carbon sources, glucose, starch, soluble starch, dextrin, sucrose, molasses, etc. are used alone or in combination, and depending on the assimilation ability of the bacteria, hydrocarbons, alcohols, organic acids, etc. , animal and vegetable oils, etc. may also be used.
Nitrogen sources include inorganic salts such as ammonium chloride, ammonium sulfate, urea, ammonium nitrate, sodium nitrate, etc. Natural nitrogen sources include:
Soybean flour, defatted soybean flour, cottonseed meal, gluten meal,
Cornmeal, peptone, meat extract, yeast extract, dried yeast, corn steep liquor, etc. may be used alone or in combination. In addition, amino acids, nucleic acids, vitamins, and inorganic salts such as sodium chloride, calcium carbonate, phosphates, magnesium sulfate, and cobalt chloride can also be added as necessary. As a culture method, a liquid culture method, particularly a method using a deep stirring method, is suitable. The culture temperature is 25°C to 45°C, preferably 28°C to 32°C, and the pH is preferably around neutral. Furthermore, it goes without saying that culture conditions such as the liquid nature of the medium, the amount of additives, the temperature, the number of stirrings, and the amount of aeration must be appropriately selected depending on the bacterial strain used. To obtain compound ( ₁ ),
The raw materials KM-A and KM-B may be added at the start of the culture, or after the bacteria have grown after the start of the culture, but preferably by about 72 hours after the start of the culture. The amount to be added may be approximately 0.1 g to 10 g/at once, or may be added in portions. Also,
KM-A and KM-B may be in the form as they are, or may be in the form of a salt such as a sulfate. KM-A or
The contact time with KM-B is as follows:
₁ ) is selected at the time when it is accumulated the most. This can be done, for example, by using Escherichia coli K-12 ML-1629 as a test bacterium and tracking the amount of the compound in the culture solution using the paper disk method, but usually within 3 to 7 days after the addition of the raw materials. Compound ( ₁ ) can be collected using methods normally used for collecting aminoglycoside antibiotics, including isolation and purification from the culture solution. That is, an appropriate combination of adsorption/desorption methods using cation and anion exchange resins, adsorption/desorption methods using activated carbon, adsorption/desorption methods using cellulose column chromatography, silica gel column chromatography, etc. can be used. Specifically, for example, after adjusting the pH of the culture solution to 2 to 3, it is filtered to remove bacterial cells, the pH is neutralized to 6 to 7, and a carboxylic acid suitable for adsorption and elution of substances with this structure is added. , Amberlite 1RC-50 (trade name), which is a cation exchange resin, has a group such as sulfonic acid, etc.
(NH ₄ ⁺ type), Dowex 50W (product name) (NH ₄ ⁺
(type) and eluted with 1N ammonia water. This eluate was concentrated under reduced pressure to produce Amberlite.
Perform ion exchange chromatography using CG-50 (trade name) (NH ₄ ⁺ form) using a concentration gradient using aqueous ammonia. To further separate and purify these compounds ( ₁ ), for example, use silica gel column chromatography, and if necessary, use Amberlite CG-50 (NH ₄ ⁺ type) and Dowex 1.
Column chromatography using x2 (trade name) (OH ^- type) can also be performed repeatedly. Representative compounds ( ₁ ) obtained by the above method are as follows. 4″-C-Methyl-3″-N-methylkanamycin A or its 4″ epimer [-A ₃ ] 3′,4′-dideoxy-3″-N-methyl-6′-N
-Methylkanamycin B [-B ₃ ] 3',4'-dideoxy-3''-N-methyl-kanamycin B [-B ₄ ] This compound ( ₁ ), which is basic, can be used with inorganic or organic acids such as hydrochloric acid and sulfuric acid. , easily forms non-toxic salts with phosphoric acid, acetic acid, stearic acid, propionic acid, tartaric acid, maleic acid, etc. Next, the production method of the present invention will be further explained with examples.Example 1 Micromonospora sp. Production of target compound [-A ₃ ] using K-6993-Y-41 strain A loopful of Micromonospora sp. A seed culture medium was obtained by shaking at ℃ for 48 to 72 hours. Separately, prepare 100 ml of main culture medium in a 500 ml flask, and inoculate it with 1 ml of the above seed culture medium. The composition of this main culture medium is as follows: Dextrin 5%, defatted soybean flour Ssanmeat special grade 3.5%, calcium carbonate
0.7%, cobalt chloride 0.000025% (PH7.5),
Sterilize in an autoclave at 120℃ for 20 minutes before use.
24 hours after inoculation, separately sterilized KM-A was added to medium 1.
1000 mcg (potency) was added per ml. Flask 600 obtained by performing shaking culture at 29℃ for 120 hours after addition.
After adjusting the main culture solution 60 to pH 2.0 with 4N hydrochloric acid, the bacterial cells were separated by filtration. The filtrate was readjusted to pH 7.0 with 4N sodium hydroxide and passed through a column filled with Amberlite IRC-50 (NH ₄ ⁺ type) 4 to adsorb the target compound [-A ₃ ]. The resin was thoroughly washed with water and eluted with 1N ammonia water (12), and the eluate was concentrated under reduced pressure and dried to obtain a crude eluate. This crude eluate was added to Amberlite CG-50.
(NH ₄ ⁺ form) 1.6 is adsorbed on a column packed with
After washing the resin with water, perform a concentration gradient elution operation using water 7 and 0.7N ammonia water 7.
Each fraction (15 ml each) was subjected to paper disc method and silica gel thin layer chromatography (manufactured by Merck & Co., Ltd., Kieselgel) using Escherichia coli K-12 as the test bacteria.
Kieselgel 60F ₂₅₄ (trade name) 0.25 mm thick, developed with a developing solvent (A in Table 5) for 2 hours and detected by ninhydrin color development (Rf value 0.11). Target compound [-
A ₃ ] fraction is eluted together with added K-A prior to 3-N-methyl-KM-A. This eluate was concentrated to dryness, and the crude fraction of [-A ₃ ] obtained was applied to a silica gel column [Wakogel C-200 (trade name)] 20 mm x 1200 mm, and eluted with a developing solvent (A in Table 5). It was fractionated and detected by silica gel thin layer chromatography in the same manner as above, and fractions containing [-A ₃ ] were collected and concentrated to dryness to obtain 2 g of a crude fraction of [-A ₃ ]. This crude fraction still contains KM-A, so in order to remove it, it was again applied to a silica gel column (Wako Gel C-200) 20 mm x 1000 mm, and the eluted fraction was eluted with the same developing solvent as in the above silica gel column chromatography. and detected by the silica gel thin layer chromatography described above. The eluted [I-A ₃ ] fraction was collected, concentrated under reduced pressure, and then dried to obtain 462 mg of white coarse powder of [I-A ₃ ]. This coarse powder was converted into Amberlite CG-50 (NH ₄ ⁺ type) 20mm×
The mixture was adsorbed onto a 500 mm column, and concentration gradient elution was performed using 1 part of water and 1 part of 0.7N ammonia water, and each fraction (15 ml each) was detected by the thin layer chromatography described above. This [I-A ₃ ] elution fraction was concentrated to dryness to obtain 388 mg of crude powder. For further purification, 300 mg of this coarse powder was added to Dowex 1×2.
(OH ^- type) Charge to an 8 mm x 300 mm column and elute with water. The eluted [I-A ₃ ] fraction was detected and collected by the above-mentioned silica gel thin layer chromatography, and this was lyophilized to obtain 249 mg of pure target compound [I-A ₃ ] as a white powder. This [I-A ₃ ] free base (lyophilized product) exhibits the following physical and chemical properties. Basic white powder (vacuum dried at 80℃ for 18 hours) Solubility: Extremely soluble in water. It is poorly soluble in methanol and ethanol, and insoluble in organic solvents such as acetone, chloroform, benzene, ethyl acetate, butyl acetate, ether, and n-hexane. Elemental analysis value (as C ₂₀ H ₄₀ N ₄ O ₁₁・H ₂ O) C H N Theoretical value (%) 45.28 7.98 10.56 Experimental value (%) 45.33 7.93 10.39 Melting point: 168-170℃ Optical rotation: [α] ²⁵ _D +163.6゜(C=0.5%, in H ₂ O
) Ultraviolet absorption spectrum: Terminal absorption Infrared absorption spectrum (KBr): Figure 1 Absorption maximum (cm ^-1 ) 1045, 1145, 1360, 1450, 1595, 1635, 2910,
3375 NMR spectrum (in heavy water): Characteristic peaks
1.38ppm……Tertiary 4″-C-methyl, 2.72ppm…
…3″-N-methyl, 5.13ppm……1″-anomeric proton, 5.28ppm……1′-anomeric proton Mass spectrum: Main ion peaks (m/
e) 110, 125, 126, 128, 130, 145, 146, 162,
163, 174, 189, 190, 191, 192, 205, 233,
245, 246, 264, 275, 306, 334, 352, 362,
388, 446, 513 (M+1) Rf value by thin layer chromatography: 5th
Table (end) The above physical and chemical properties, especially typical fragment ion peaks and
Based on the results of MMR and derivation from KM-A, 4″-C-methyl-3″-
It is recognized to be N-methylkanamycin A or its 4'' epimer. Example 2 Production of target compound [I-B ₃ ] using Micromonospora sp. .5) Dispense 100ml into 500ml flasks and sterilize. Place the flask on Bennett's slant agar at 30 °C.
Micromonospora sp.
Seed culture was obtained by shaking at ℃ for 48-72 hours. Separately, prepare 100 ml of main culture medium in a 500 ml flask, and inoculate it with 1 ml of the above seed culture medium. The composition of the main culture medium is 5% dextrin, 3.5% defatted soybean flour Ssanmeat special grade, and 0.7% calcium carbonate.
%, cobalt chloride 0.000025% (PH7.5),
Sterilize at 120℃ for 20 minutes before use. 24 hours after inoculation, add 300mcg of separately sterilized KM-B per ml of culture medium.
(Titer) Added. After the addition, shaking culture was performed at 29°C for 120 hours to obtain 110 culture fluids. Add this culture solution to 4
After adjusting the pH to 2.0 with normal hydrochloric acid and filtering out the bacterial cells, the filtrate was returned to pH 7.0 with 4N sodium hydroxide, passed through a column of Amberlite IRC-50 (NH ⁺ ₄ type) 7, and washed with water. It was eluted with 21 ml of specified ammonia water and concentrated under reduced pressure to obtain a candy-like crude eluate. Divide this crude eluate into four equal parts and use Amberlite CG-50.
(NH ₄ type) was adsorbed onto four columns packed with 900 ml, and after thoroughly washing the resin with water, each column was subjected to concentration gradient fractionation elution using 3.5 ml of water and 3.5 ml of 0.8N ammonia water. (15 ml each) was detected using silica gel thin layer chromatography (Rf value 0.26) in the same manner as in Example 1, and the [-B ₃ ] segment was eluted before [-B ₄ ] from each column. Collect and concentrate to dryness
520 mg of [-B ₃ ] coarse powder was obtained. This crude powder was dissolved in 13 ml of methanol, insoluble matter was filtered off, and then concentrated to about 3 ml. A 0.1N methanol solution of sulfuric acid was gradually added to this concentrated solution to adjust the pH to 4.0, producing a white precipitate. After adding acetone to ensure further precipitation, this white precipitate was collected by filtration and vacuum dried to obtain 749 mg of [-B ₃ ] sulfate. This sulfate was dissolved in Dowex-1×2 (OH ^-
Type) Charge a 10mm x 500mm column and elute with water. The eluted [-B ₃ ] fraction was confirmed by silica gel thin layer chromatography in the same manner as above, and the eluted fraction was collected and concentrated to dryness to form [-B ₃ ].
284 mg of white powder was obtained. To further purify this platinum powder, we mixed it with Amberlite CG-50 (NH ⁺ ₄
Type) Adsorb onto a 13mm x 250mm column and add 200ml of water.
Concentration gradient elution was performed with 200 ml of 0.8N ammonia water, and each fraction (3 ml each) was confirmed using the silica gel thin layer chromatography described above [-B ₃ ].
The fractions were collected and lyophilized to obtain 98 mg of pure [-B ₃ ] white powder. This [-B ₃ ] free base (lyophilized product) exhibits the following physical and chemical properties. Basic white powder (vacuum dried at 80°C for 18 hours) Solubility: Extremely soluble in water and soluble in methanol. Slightly insoluble in ethanol and acetone,
It is insoluble in organic solvents such as chloroform, benzene, ethyl acetate, butyl acetate, ether, and n-hexane. Elemental analysis value (as C ₂₀ H ₄₁ N ₅ O ₈・0.5H ₂ O) C H N Theoretical value (%) 49.17 8.66 14.33 Experimental value (%) 48.95 8.59 14.35 Melting point: 112-116℃ Optical rotation: [α] ²⁵ _D +134.8゜ (C=1%, inH ₂ O) Ultraviolet absorption spectrum: Terminal absorption Infrared absorption spectrum (KBr): Figure 2 Absorption maximum (cm ^-1 ) 1035, 1110, 1140, 1335, 1375, 1475 , 1565,
1630, 2920, 3400 NMR spectrum (in heavy water): Characteristic peaks
2.51ppm……3″-N-methyl, 2.60ppm……
6′-N-methyl, 5.07PPm……1″-anomeric proton, 5.38ppm……1′-anomeric proton Mass spectrum: Main ion peaks (m/
e) 110, 112, 114, 125, 126, 130, 134, 142,
143, 144, 145, 158, 163, 176, 191, 272,
305, 320, 338, 366, 449, 479, 480 (M+1) Rf value by thin layer chromatography: 5th
Table The above physical and chemical properties, especially typical fragment ion peaks in mass spectra and
Based on the NMR results and derivation from KM-B, 3',4'-dideoxy-
3″-N-methyl-6′-N-methylkanamycin B
It is recognized that Example 3 Production of target compound [-B ₄ ] using Micromonospora sp.K-6993-Y-41 strain First Amberlite CG-50 of Example 2
(NH ⁺ ₄ type) column was used for concentration gradient elution of aqueous ammonia, [-B ₄ ] was eluted following [-B ₃ ] (silica gel thin layer chromatography, developing solvent A in Table 5). , detected at an Rf value of 0.19) was collected and concentrated to obtain 85 mg of [-B ₄ ] crude powder. This coarse powder was dissolved in 0.5 ml of water and placed on a silica gel plate (manufactured by Merck & Co., Ltd., Kieselgel).
Kieselgel 60PF ₂₅₄ (Product name) Thickness 0.3mm, 20cm×
It was charged into three strips (20 cm, activated at 150°C) and developed with a developing solvent (A in Table 5). After development, the position of the target compound was confirmed by ninhydrin coloring, and the position was scraped off along with the silica gel, and eluted from the silica gel with the same developing solvent. This eluate was concentrated to dryness under reduced pressure to obtain 56 mg of crude powder. To further purify this crude powder, it was dissolved in 20 ml of methanol, adjusted to pH 4.0 with a 0.1N methanol solution of sulfuric acid, and acetone was added. The resulting white precipitate was collected by filtration and vacuum-dried to give 95 mg B ₄ ] sulfate was obtained.
Add this sulfate to Dowex 1 x 2 (OH ^- type) 8 mm.
The column was charged to a ×300 mm column and eluted with water, and the eluted [-B ₄ ] fraction was confirmed by the silica gel thin layer chromatography described above and collected and concentrated.
This concentrate is converted into Amberlite CG-50 (NH ⁺ ₄ type).
Adsorb onto an 8 mm x 180 mm column, perform concentration gradient elution with 200 ml of water and 200 ml of 0.8N ammonia water, and confirm each fraction (2.5 ml each) using the silica gel thin layer chromatography described above [-B ₄ ].
The fractions were collected and lyophilized to obtain 52 mg of pure [-B ₄ ] white powder. This [-B ₄ ] free base (lyophilized product) exhibits the following physical and chemical properties. Basic white powder (vacuum dried at 80°C for 18 hours) Solubility: Extremely soluble in water and soluble in methanol. Slightly insoluble in ethanol and acetone, chloroform, benzene ethyl acetate,
It is insoluble in organic solvents such as butyl acetate, ether, and n-hexane. Elemental analysis value (as C ₁₉ H ₃₉ N ₅ O ₈・0.5H ₂ O) C H N Theoretical value (%) 48.09 8.50 14.76 Experimental value (%) 48.10 8.49 14.37 Melting point: 204-208℃ (browning) Optical rotation: [α] ²⁵ _D +131.1° (C=1%, in H ₂ O) Ultraviolet absorption spectrum: Terminal absorption Infrared absorption spectrum (KBr): Figure 3 Absorption maximum (cm ^-1 ) 1035, 1110, 1140, 1335 , 1380, 1480, 1565,
1630, 2920, 3400 NMR spectrum (in heavy water): 2.48ppm...
3″-N-methyl, 5.06 ppm……1″ anomeric proton 5.25 ppm……1′-anomeric proton Mass spectrum: Main ion peaks (m/
e) 112, 126, 130, 145, 158, 163, 176, 191,
242, 246, 258, 273, 302, 305, 320, 338,
366, 429, 438, 465, 466, (M+1) Rf value by thin layer chromatography: 5th
Table The above physical and chemical properties, especially typical fragment ion peaks in mass spectra and
Based on the NMR results and that derived from KM-B, 3',4'-dideoxy-
It is recognized to be 3″-N-methylkanamycin B.

【table】 [Brief explanation of drawings]

FIGS. 1 to 3 show the infrared absorption spectra of the target compounds [-A ₃ ], [-B ₃ ], and [-B ₄ ] of the present invention, respectively.

Claims (1)

[Claims] 1. General formula (In the formula, R ₁ and R ₄ are methyl groups or hydrogen atoms,
R ₂ means a hydroxyl group or a hydrogen atom, and R ₃ means an amino group or a hydroxyl group. However, when R ₄ is a methyl group, R ₂ is a hydroxyl group and R ₁ is a hydrogen atom,
Further, when R ₄ is a hydrogen atom, R ₂ means a hydrogen atom. ) or its acid addition salt. 2 formulas An aminoglycoside compound according to claim 1 or an acid addition salt thereof. 3 formulas An aminoglycoside compound according to claim 1 or an acid addition salt thereof. 4 formula An aminoglycoside compound according to claim 1 or an acid addition salt thereof.