JP2021178793A - Novel aminoglycoside antimicrobial agents effective against super-multidrug-resistant gram-negative bacteria - Google Patents

Abstract

To provide novel compounds with excellent antimicrobial action, particularly on gram-negative bacteria producing 16S rRNA methylase or NDM, or pharmaceutically acceptable salts thereof, or solvates thereof; and compositions, antimicrobial agents and pharmaceutical compositions that contain the novel compounds.SOLUTION: The invention provides: compounds represented by general formula (A) or pharmaceutically acceptable salts thereof, or solvates thereof; and compositions, antimicrobial agents and pharmaceutical compositions that contain the compounds or pharmaceutically acceptable salts thereof or solvates thereof.SELECTED DRAWING: None

Description

The present invention relates to novel amino glycoside compounds, or pharmaceutically acceptable salts thereof, or solvates thereof, and the novel amino glycoside compounds, or pharmaceutically acceptable salts thereof, or The present invention relates to a composition, an antibacterial agent, and a pharmaceutical composition containing the solvate thereof.

Conventionally, methicillin-resistant Staphylococcus aureus (hereinafter, may be referred to as "MRSA") has become a clinically problematic causative agent of serious infectious diseases, and therapeutic agents thereof have been studied.

In recent years, the number of multidrug-resistant bacteria has increased among Gram-negative bacteria, and multidrug-resistant Gram-negative bacteria have become a problem all over the world. Many of the multidrug-resistant Gram-negative bacteria are also resistant to existing amino glycoside antibacterial agents, β-lactam antibacterial agents, and new quinolone antibacterial agents, which often cause intractable infections. There is.

According to the World Health Organization (WHO), bacteria of high importance for research and development of new antibacterial agents include Acinetobacter baumannii, Pseudomonas aeruginosa, and enterobacteriaceae. .. The Centers for Disease Control and Prevention (CDC) has also listed 15 important pathogens associated with drug resistance that are urgently needed to develop corresponding antibacterial agents.

In addition, it is estimated that more than 8,000 people are lost annually due to drug-resistant bacteria (methicillin-resistant Staphylococcus aureus, fluoroquinolone-resistant Escherichia coli) in Japan, according to the National Center for Global Health and Medicine Hospital.

Under such circumstances, exploratory research on new antibacterial agents is being enthusiastically conducted (see, for example, Non-Patent Document 1). Among existing antibacterial agents, the degree of resistance to amino glycoside antibacterial agents is relatively low compared to other major antibacterial agents. Expectations are high.

Two main resistance mechanisms of aminoglycoside antibacterial agents include (1) inactivation with a modified inactivating enzyme and (2) modification of the site of action with 16S rRNA methylase (methyltransferase).

The above (1) is found in both Gram-positive and Gram-negative bacteria, and there are three types of modification: acetylation by acetyltransferase, phosphorylation by phosphotransferase, and adenylylation by nucleotidyltransferase.

The 16S rRNA methylase in (2) is an enzyme that methylates a specific base of 16S rRNA present in the 30S subunit that constitutes the ribosome responsible for bacterial protein synthesis. When the methylation occurs, the aminoglycoside antibacterial agent cannot bind to 16S rRNA, which is the site of action, and cannot exert antibacterial activity. The 16S rRNA methylase has been found only in Gram-negative bacteria so far, and about 10 types such as ArmA and RmtA are known.

In recent years, the emergence of highly resistant bacteria that produce the 16S rRNA methylase has become apparent. For example, it has been reported that the majority of aminoglycoside antibacterial agent-resistant bacteria isolated in Southeast Asia and Central Asia are already 16S rRNA methylase-producing bacteria.
Also, carbapenem-resistant Enterobacteriaceae that produce the metallo-β-lactamase, New Delhi metallo-β-lactamase (NDM), often simultaneously carry 16S rRNA methylase, resulting in a wide range of aminoglycolytic antibacterial agents. There is also the problem of showing high resistance to the drug.

16S rRNA methylase and NDM are used for Acinetobacter baumannii, Pseudomonas aeruginosa, and enterobacteriaceae, which are considered to be the most important bacteria for the research and development of the above-mentioned new antibacterial agents. It contains resistant bacteria to be produced, and the current situation is that existing aminosaccharide antibacterial agents are almost ineffective against these resistant bacteria.

Therefore, there is a strong demand for the development of a novel aminoglycoside antibacterial agent that is effective against ultramultidrug-resistant Gram-negative bacteria that produce 16S rRNA methylase and NDM.

Masayuki Igarashi, Yoshiaki Takahashi, Search for Next-Generation New Antibiotics from Natural Products, Journal of Japan Society of Chemotherapy, Vol. 67, No. 3, 308-323 (2019)

The present invention has been made in view of the above prior art, and an object of the present invention is to achieve the following object. That is, the present invention is a novel compound having an excellent antibacterial activity, particularly a novel compound having an excellent antibacterial activity against Gram-negative bacteria producing 16S rRNA methylase and NDM, or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable salt thereof. It is an object of the present invention to provide a composition, an antibacterial agent, and a pharmaceutical composition containing a solvate and the novel compound.

As a result of diligent studies to achieve the above object, the present inventors have found that the compound represented by the general formula (A) has antibacterial activity against gram-positive and gram-negative bacteria, and 16S rRNA. It was also found to be effective against Gram-negative bacteria that produce methylase and NDM. The compound represented by the general formula (A) is the first kanamycin derivative that exhibits antibacterial activity against Gram-negative bacteria that produce 16S rRNA methylase and NDM.

前記一般式（Ａ）中、Ｒ^１は、Ｈ、又はＯＨを表し、
Ｒ^２は、Ｈ、又はＯＨを表し、
Ｒ^３は、Ｈ、又はＯＨを表し、
Ｒ^４は、Ｈを表し、
Ｒ^５は、Ｈ、又はＯＨを表し、
Ｒ^６は、ＮＨ_２、又はＣＨ_２ＮＨ_２を表す。
＜２＞ 前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物を含有することを特徴とする化合物含有組成物である。
＜３＞ 前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物を含有することを特徴とする抗菌剤である。
＜４＞ 前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物を含有することを特徴とする医薬組成物である。 The present invention is based on the above-mentioned findings of the present inventors, and the means for solving the above-mentioned problems are as follows. That is,
<1> A compound represented by the following general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof.

In the general formula (A), R ¹ represents H or OH.
R ² represents H or OH.
R ³ represents H or OH.
R ⁴ represents H,
R ⁵ represents H or OH.
R ⁶ represents a NH _2, or _CH 2 NH _2.
<2> A compound-containing composition comprising the compound according to <1>, a pharmaceutically acceptable salt thereof, or a solvate thereof.
<3> An antibacterial agent comprising the compound according to <1>, a pharmaceutically acceptable salt thereof, or a solvate thereof.
<4> A pharmaceutical composition comprising the compound according to <1>, a pharmaceutically acceptable salt thereof, or a solvate thereof.

According to the present invention, the above-mentioned problems in the prior art can be solved, the above-mentioned object can be achieved, and an excellent antibacterial activity, particularly, an excellent antibacterial activity against gram-negative bacteria producing 16S rRNA methylase and NDM. A novel compound, a pharmaceutically acceptable salt thereof, or a solvate thereof, and a composition, an antibacterial agent, and a pharmaceutical composition containing the novel compound can be provided.

前記一般式（Ａ）中、Ｒ^１は、Ｈ、又はＯＨを表し、
Ｒ^２は、Ｈ、又はＯＨを表し、
Ｒ^３は、Ｈ、又はＯＨを表し、
Ｒ^４は、Ｈを表し、
Ｒ^５は、Ｈ、又はＯＨを表し、
Ｒ^６は、ＮＨ_２、又はＣＨ_２ＮＨ_２を表す。 (New compounds, or pharmaceutically acceptable salts thereof, or solvates thereof)
The compound of the present invention, or a pharmaceutically acceptable salt thereof, or a solvate thereof is a compound represented by the following general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof. It is a solvate, a novel compound found by the present inventors, a pharmaceutically acceptable salt thereof, or a solvate thereof.

In the general formula (A), R ¹ represents H or OH.
R ² represents H or OH.
R ³ represents H or OH.
R ⁴ represents H,
R ⁵ represents H or OH.
R ⁶ represents a NH _2, or _CH 2 NH _2.

Examples of the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof include the following compounds (I) to (VIII), or their pharmaceutical use. Acceptable salts, or solvates thereof are preferred.
-Compound (I): 1-N-[(S) -3-amino-2-hydroxypropionyl] -3', 4'-dideoxyneamine-Compound (II): 1-N-[(S) -4 -Amino-2-hydroxybutyryl] -3', 4'-dideoxy-5-epineamine-Compound (III): 1-N-[(S) -3-amino-2-hydroxypropionyl] -3', 4 '-Dideoxy-5-Epineamine-Compound (IV): 1-N-[(S) -4-Amino-2-hydroxybutylyl] -5,3', 4'-Trideoxyneamine-Compound (V) : 1-N-[(S) -3-Amino-2-hydroxypropionyl] -5,3', 4'-Trideoxyneamine-Compound (VI): 1-N-[(S) -4-Amino -2-Hydroxybutyryl] -5,6,3', 4'-Tetradeoxyneamine-Compound (VII): 1-N-[(S) -3-Amino-2-hydroxypropionyl] -5,6 , 3', 4'-Tetradeoxyneamine-Compound (VIII): 1-N-[(S) -4-Amino-2-hydroxybutyryl] -3', 4'-Dideoxy-2-hydroxyneamine

The salt is not particularly limited as long as it is a pharmaceutically acceptable salt, and can be appropriately selected depending on the intended purpose. For example, fluorinated acid salt, hydrochloride, hydrobromide acid salt, and iodine. Hydrohalogenates such as hydrides; Inorganic acid salts such as sulfates, nitrates, phosphates, perchlorates, carbonates; acetates, trichloroacetates, trifluoroacetates, hydroxyacetates, Carborates such as lactate, citrate, tartrate, oxalate, benzoate, mandelate, butyrate, maleate, propionate, nitate, malate; arginate, asparagine Amino acid salts such as acid salts and glutamates; sulfonates such as methanesulfonates and paratoluenesulfonates may be mentioned.

The solvate is not particularly limited and may be appropriately selected depending on the intended purpose. Examples thereof include hydrates and ethanol solvates.

<Compound manufacturing method>
The method for producing the compound represented by the general formula (A) is not particularly limited and may be appropriately selected depending on the intended purpose. For example, it can be produced by chemical synthesis.

The compound (I), which is an example of the compound represented by the general formula (A), can be produced, for example, by the following method.

Specifically, using 3', 4'-dideoxyneamine as a starting material, the method described in Takagi, Y. et al., Bull. Chem. Soc. Japan 47, 3139-3141 (1974), 3 , 2', 6'-tri-N- (benzyloxycarbonyl) -3', 4'-dideoxyneamine (hereinafter, may be referred to as "compound (1)") is obtained.
Next, the compound (1) is dissolved in N, N-dimethylformamide, and triethylamine and N-hydroxysuccinimide ester of (S) -3-benzyloxycarbonylamino-2-hydroxypropionic acid are added thereto for reaction. 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino-2-hydroxypropionyl] -3', 4'- Dideoxyneamine (hereinafter, may be referred to as "compound (2)") is obtained.
Then, the compound (2) can be treated by a catalytic reduction reaction to obtain the compound (I).
In the structural formulas of the above compounds (1) and (2), "Cbz" represents a benzyloxycarbonyl group.

The compounds (II) and (III), which are examples of the compounds represented by the general formula (A), can be produced, for example, by the following methods.

Specifically, 3,2', 6'-tri-N- (benzyloxycarboni) -1-N: 6-O-carbonyl-3', 4'-dideoxyneamine (hereinafter, "compound (3)" ) ”. It can be produced by the method described in Umezawa.S. et al., J. Antibiot. 26, 304-306 (1973).) This compound (3) is used as a starting material. ) Is dissolved in pyridine, and benzylsulfonyl chloride is added thereto to react, and 3,2', 6'-tri-N- (benzyloxycarboni) -5-O-benzylsulfonyl-1-N: 6- O-carbonyl-3', 4'-dideoxyneamine (hereinafter, may be referred to as "compound (4)") is obtained.
Next, the compound (4) is dissolved in N, N-dimethylformamide, and cesium acetate is added thereto for reaction to cause 5-O-acetyl-3,2', 6'-tri-N- (benzyloxycarbonyl). ) -1-N: 6-O-carbonyl-3', 4'-dideoxy-5-epineamine (hereinafter, may be referred to as "compound (5)") is obtained.
Next, the compound (5) is dissolved in a mixed solution of 1,4-dioxane-water (2: 1), and a 1M potassium hydroxide aqueous solution is added thereto for reaction to cause 3,2', 6'-tri-N. -(Benzyloxycarbonyl) -3', 4'-dideoxy-5-epineamine (hereinafter, may be referred to as "compound (6)") is obtained.

Then, when the compound (II) is produced, the compound (6) is dissolved in N, N-dimethylformamide, and triethylamine and (S) -4-benzyloxycarbonylamino-2-hydroxybutyric acid are used therein. N-Hydroxysuccinic acid imide ester was added and reacted, and 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -4- (benzyloxycarbonyl) amino-2. -Hydroxybutyryl] -3', 4'-dideoxy-5-epineamine (hereinafter, may be referred to as "compound (7)") is obtained.
Then, the compound (7) can be treated by a catalytic reduction reaction to obtain the compound (II).

When the compound (III) is produced, the compound (6) is dissolved in N, N-dimethylformamide, and triethylamine and (S) -3-benzyloxycarbonylamino-2-hydroxypropionic acid are dissolved therein. N-Hydroxysuccinic acid imide ester was added and reacted, and 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino- 2-Hydroxypropionyl] -3', 4'-dideoxy-5-epineamine (hereinafter, may be referred to as "compound (8)") is obtained.
The compound (8) can then be treated with a catalytic reduction reaction to give the compound (III).

In the structural formulas of the above compounds (3) to (8), "Cbz" represents a benzyloxycarbonyl group and "Ac" represents an acetyl group.

The compounds (IV) and (V), which are examples of the compounds represented by the general formula (A), can be produced, for example, by the following methods.

Specifically, the compound (4) is used as a starting material, this compound (4) is dissolved in N, N-dimethylformamide, sodium iodide is added thereto, and the reaction is carried out to cause 3,2', 6'. -Tri-N- (benzyloxycarbonyl) -1-N: 6-O-carbonyl-5,3', 4'-trideoxy-5-epi-5-iodoneamine (hereinafter referred to as "Compound (9)") There is.).
Next, the compound (9) is dissolved in 1,4-dioxane, and tributyltin hydride and 2,2-azobisisobutyronitrile are added thereto for reaction to cause 3,2', 6'-tri-N. -(Benzyloxycarbonyl) -1-N: 6-O-carbonyl-5,3', 4'-trideoxyneamine (hereinafter, may be referred to as "compound (10)") is obtained.
Next, the compound (10) was dissolved in 50% 1,4-dioxane water, and sodium carbonate was added thereto for reaction to cause 3,2', 6'-tri-N- (benzyloxycarbonyl) -5, 3', 4'-Trideoxyneamine (hereinafter, may be referred to as "compound (11)") is obtained.

Then, when the compound (IV) is produced, the compound (11) is dissolved in N, N-dimethylformamide, and triethylamine and (S) -4-benzyloxycarbonylamino-2-hydroxybutyric acid are used therein. N-Hydroxysuccinic acid imide ester was added and reacted, and 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -4- (benzyloxycarbonyl) amino-2. -Hydroxybutyryl] -5,3', 4'-Trideoxyneamine (hereinafter, may be referred to as "Compound (12)") is obtained.
The compound (12) can then be treated with a catalytic reduction reaction to give the compound (IV).

When the compound (V) is produced, the compound (11) is dissolved in N, N-dimethylformamide, and triethylamine and (S) -3-benzyloxycarbonylamino-2-hydroxypropionic acid are dissolved therein. N-Hydroxysuccinic acid imide ester was added and reacted, and 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino- 2-Hydroxypropionyl] -5,3', 4'-trideoxyneamine (hereinafter, may be referred to as "compound (13)") is obtained.
Then, the compound (13) can be treated by a catalytic reduction reaction to obtain the compound (V).

In the structural formulas of the above compounds (9) to (13), "Cbz" represents a benzyloxycarbonyl group.

The compounds (VI) and (VII), which are examples of the compounds represented by the general formula (A), can be produced, for example, by the following methods.

Specifically, 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N- (tert-butoxycarbonyl) -3', 4'-dideoxyneamine (hereinafter, "Compound (14)" ) ”. It can be produced by the method described in Minowa, N. et al., Bioorg. Med. Chem. Lett. 16, 6351-6354 (2006).) As a starting material. This compound (14) is dissolved in dichloromethane, and methanesulfonyl chloride and 4-dimethylaminopyridine are added thereto for reaction, and 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N- (tert-Butyloxycarbonyl) -3', 4'-dideoxy-5,6-di-O-methanesulfonylneamine (hereinafter, may be referred to as "compound (15)") is obtained.
Next, the compound (15) was dissolved in N, N-dimethylformamide, potassium iodide and zinc powder were added thereto for reaction, and 3,2', 6'-tri-N- (benzyloxycarbonyl)-. To obtain 1-N- (tert-butoxycarbonyl) -5-eno-5,6,3', 4'-tetradeoxyneamine (hereinafter, may be referred to as "compound (16)").
Then, the compound (16) was dissolved in 95% trifluoroacetic acid water and reacted to cause 3,2', 6'-tri-N- (benzyloxycarbonyl) -5-eno-5,6,3', A trifluoroacetic acid salt of 4'-tetradeoxyneamine (hereinafter, may be referred to as "compound (17)") is obtained.

Then, in the case of producing the compound (VI), the trifluoroacetate salt of the compound (17) is dissolved in N, N-dimethylformamide, and triethylamine and (S) -4-benzyloxycarbonylamino- N-Hydroxysuccinimide ester of 2-hydroxybutyric acid is added and reacted to: 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -4- (benzyl). Oxycarbonyl) Amino-2-Hydroxybutyryl] -5-eno-5,6,3', 4'-tetradeoxyneamine (hereinafter, may be referred to as "Compound (18)") is obtained.
The compound (18) can then be treated with a catalytic reduction reaction to give the compound (VI).

When the compound (VII) is produced, the trifluoroacetate salt of the compound (17) is dissolved in N, N-dimethylformamide, and triethylamine and (S) -3-benzyloxycarbonylamino- N-Hydroxysuccinimide ester of 2-hydroxypropionic acid was added and reacted, and 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyl) was added. Oxycarbonyl) Amino-2-hydroxypropionyl] -5-eno-5,6,3', 4'-tetradeoxyneamine (hereinafter, may be referred to as "Compound (19)") is obtained.
The compound (19) can then be treated with a catalytic reduction reaction to give the compound (VII).

In the structural formulas of the compounds (14) to (19), "Cbz" represents a benzyloxycarbonyl group, "Boc" represents a tert-butoxycarbonyl group, and "Ms" represents a mesyl group.

The compound (VIII), which is an example of the compound represented by the general formula (A), can be produced, for example, by the following method.

Specifically, 2-hydroxyarbekacin (which can be produced by the method described in Document J. Antibiot. 71, 345-347 (2018) of 2-OH-ABK, Takahashi, Y., etc.) is used as a starting material. 2-Hydroxyarbekacin is dissolved in 2 M aqueous hydrochloric acid solution and reacted to obtain a mixture of compound (VIII) and 2-hydroxyarbekacin.
Then, a mixture of the above compound (VIII) and 2-hydroxyarbekacin is dissolved in 50% methanol water, and triethylamine and di-tert-butylcarbonate are added thereto for reaction, and N-tert-butoxy of the compound (VIII) is reacted. Obtain a carbonyl derivative.
Then, the N-tert-butoxycarbonyl derivative of the compound (VIII) can be dissolved in 95% trifluoroacetic acid water and reacted to obtain the compound (VIII).

The above-mentioned method for producing a compound is an example. Further, the reaction conditions such as the reaction temperature and the reaction time in the chemical synthesis, the compound to be used, the amount used thereof, the solvent and the like are not particularly limited and may be appropriately selected depending on the intended purpose.

The compound of the present invention and the above-mentioned compound obtained in the production process thereof can be purified and isolated by a normal purification operation.
The purification isolation method is not particularly limited and may be appropriately selected depending on the intended purpose. For example, a liquid separation method, a distillation method, a sublimation method, a precipitation method, a crystallization method, a normal phase or a reverse phase silica gel. Examples thereof include a silica gel column chromatography method using a filler, a column chromatography method using an ion exchange resin, a column chromatography method using cellulose and the like, a preparative thin layer chromatography method, and a high-speed liquid chromatography method. These may be used alone or in combination of two or more. The compound obtained in the above-mentioned production step can be appropriately used in a subsequent step without isolation and purification.

Whether or not the obtained compound has a structure represented by the general formula (A) can be confirmed by various analytical methods selected as appropriate. The analysis method is not particularly limited and may be appropriately selected depending on the intended purpose. For example, mass spectrometry, ultraviolet spectroscopy, infrared spectroscopy, proton nuclear magnetic resonance spectroscopy, carbon 13 nuclear magnetic resonance spectroscopy. Analytical methods such as methods and elemental analysis methods can be mentioned. The analysis method may be used alone or in combination of two or more. Although some errors may occur in the measured values by each of the analysis methods, those skilled in the art can easily identify that the compound has a structure represented by the general formula (A). Is possible.

<Use>
The compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof has excellent antibacterial activity, particularly, to Gram-negative bacteria producing 16S rRNA methylase and NDM. On the other hand, it has an excellent antibacterial effect. Therefore, the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof is, for example, a compound-containing composition, an antibacterial agent, or a pharmaceutical composition of the present invention described later. It can be suitably used as an active ingredient of a substance or the like. Further, it can be suitably used for therapeutic purposes, for use in the prevention or treatment of infectious diseases, and for the production of drugs for the purpose of prevention or treatment of infectious diseases.

(Compound-containing composition)
The compound-containing composition of the present invention contains at least the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, and if necessary, further other components. Contains ingredients.
The compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof may be used alone or in combination of two or more. good.

<Compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof>
The compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof is the compound represented by the above-mentioned general formula (A) of the present invention, or a compound thereof. A pharmaceutically acceptable salt or a solvate thereof.
The total content of the compound represented by the general formula (A), the pharmaceutically acceptable salt thereof, or the solvate thereof in the compound-containing composition is not particularly limited and depends on the purpose. Can be selected as appropriate. The compound-containing composition may consist only of the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof.

<Other ingredients>
The other components are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected depending on the intended purpose. Examples thereof include additives described in the item of <formation form> described later. Will be.

The content of the other components in the compound-containing composition is not particularly limited, and is the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof. It can be appropriately selected according to the purpose within the range that does not impair the effect of.

-Usage-
Since the compound-containing composition contains the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, excellent antibacterial activity, particularly 16S rRNA methylase. It has an excellent antibacterial activity against gram-negative bacteria that produce NDM and, and can be suitably used for, for example, antibacterial agents and pharmaceutical compositions.
The compound-containing composition may be used alone or in combination with a drug containing another ingredient as an active ingredient. Further, the compound-containing composition may be used in a state of being blended in a medicine containing another ingredient as an active ingredient.

The pharmaceutical containing the other ingredients as an active ingredient is not particularly limited and may be appropriately selected depending on the intended purpose. For example, existing clinically useful antibacterial agents (for example, β-lactam antibacterial agents (for example, β-lactam antibacterial agents) Carbapenems, cephalosporins, cephamycins, penicillins), glycopeptide antibacterial agents, ansamycin antibacterial agents, aminoglycoside antibacterial agents, quinolone antibacterial agents, monobactam antibacterial agents, macrolide antibacterial agents, tetracycline Antibacterial agents, chloramphenicol antibacterial agents, lincomycin antibacterial agents, streptogramin antibacterial agents, oxazolidinone antibacterial agents, phosphomycins, novobiocins, cycloserines, moenomycins, etc. ) Inhibitors, existing antibacterial degrading enzyme (β-lactamase, etc.) inhibitors, drugs for treating complications, etc. may be mentioned. These may be used alone or in combination of two or more.

(Antibacterial agent)
The antibacterial agent of the present invention contains at least the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, and further contains other components, if necessary. include.
The compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof may be used alone or in combination of two or more. good.

<Compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof>
The compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof is the compound represented by the above-mentioned general formula (A) of the present invention, or a compound thereof. A pharmaceutically acceptable salt or a solvate thereof.
The total content of the compound represented by the general formula (A), the pharmaceutically acceptable salt thereof, or the solvate thereof in the antibacterial agent is not particularly limited, and is appropriately appropriate depending on the purpose. You can choose. The antibacterial agent may consist only of the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof.

<Other ingredients>
The other components are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected depending on the intended purpose. Examples thereof include additives described in the item of <formation form> described later. Will be.

The content of the other components in the antibacterial agent is not particularly limited, and the effect of the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof. Can be appropriately selected according to the purpose within a range that does not impair.

-Usage-
Since the antibacterial agent contains the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, excellent antibacterial activity, particularly 16S rRNA methylase or NDM. It has an excellent antibacterial action against Gram-negative bacteria that produce, and can be suitably used as an antibacterial agent against various bacteria.

The bacterium is not particularly limited and may be appropriately selected depending on the intended purpose, but at least one selected from the group consisting of Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumani is selected. Bacteria that produce at least one of 16S rRNA methyltransferase and Nudely metallo-β-lactamase are more preferred. The bacterium may or may not have resistance to conventional antibacterial agents, but the antibacterial agent is a compound represented by the general formula (A) or a pharmaceutical agent thereof. Because it contains an acceptable salt or a solvate thereof, it is also excellent against resistant bacteria showing resistance to conventional amino glycoside antibacterial agents, as shown in the items of Examples described later. Shows antibacterial activity.

The antibacterial agent may be used alone, or may be used in combination with a medicine containing another ingredient as an active ingredient as described in the above-mentioned (compound-containing composition) -use-item. May be good. Further, the antibacterial agent may be used in a state of being blended in a medicine containing another ingredient as an active ingredient.

Since the antibacterial agent contains the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, the growth of bacteria in an individual by administration to the individual And at least one of bacterial infections to an individual can be suppressed. Therefore, the present invention also relates to a method for suppressing at least one of bacterial growth and bacterial infection to an individual, which comprises administering the antibacterial agent to an individual.

(Pharmaceutical composition)
The pharmaceutical composition of the present invention contains at least the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, and if necessary, further components. including.
The compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof may be used alone or in combination of two or more. good.

<Compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof>
The compound represented by the general formula (A), or a pharmaceutically acceptable salt thereof, or a solvate thereof is the compound represented by the above-mentioned general formula (A) of the present invention, or a compound thereof. A pharmaceutically acceptable salt or a solvate thereof.
The total content of the compound represented by the general formula (A), the pharmaceutically acceptable salt thereof, or the solvate thereof in the pharmaceutical composition is not particularly limited and may vary depending on the intended purpose. It can be selected as appropriate. The pharmaceutical composition may consist only of the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof.

<Other ingredients>
The other components are not particularly limited as long as the effects of the present invention are not impaired, and can be appropriately selected depending on the intended purpose. Examples thereof include additives described in the item of <formation form> described later. Will be.

The content of the other components in the pharmaceutical composition is not particularly limited, and is the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof. It can be appropriately selected according to the purpose within a range that does not impair the effect.

-Usage-
Since the pharmaceutical composition contains the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, it has excellent antibacterial activity, particularly 16S rRNA methylase and the like. It has an excellent antibacterial effect against Gram-negative bacteria that produce NDM, and can be suitably used as a pharmaceutical composition for preventing or treating infectious diseases.

The infectious disease is not particularly limited and may be appropriately selected depending on the intended purpose, and examples thereof include bacterial infectious diseases. The bacterial infection is not particularly limited and may be appropriately selected depending on the intended purpose, but is septicemia, infectious endocarditis, dermatological area infection, surgical infection, orthopedic area infection, and respiration. At least one selected from the group consisting of organ infections, urinary tract infections, intestinal infections, peritonitis, meningitis, ophthalmic area infections, and otolaryngology area infections is preferred.

The cause of the infectious disease is not particularly limited and may be appropriately selected depending on the intended purpose, but at least selected from the group consisting of Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumani. Those caused by one species are preferably mentioned, and those caused by bacteria producing at least one of 16S rRNA methyltransferase and Nudely metallo-β-lactamase are more preferably mentioned.

The pharmaceutical composition may be used alone, or may be used in combination with a pharmaceutical having another ingredient as an active ingredient as described in the above-mentioned (compound-containing composition) -use-item. You may. Further, the pharmaceutical composition may be used in a state of being blended in a medicine containing another ingredient as an active ingredient.

Since the pharmaceutical composition contains the compound represented by the general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof, administration to an individual prevents infectious diseases. Or it can be treated. Accordingly, the present invention also relates to a method for preventing or treating an infectious disease, which comprises administering the pharmaceutical composition to an individual.

In the present invention, prevention of infectious disease means suppression of bacterial infection to an individual, suppression of bacterial growth before the onset of symptoms, suppression of the occurrence of symptoms after bacterial infection, and suppression of recurrence after treatment. And so on.
Further, in the present invention, the treatment of an infectious disease means alleviation of symptoms or prevention of exacerbation of symptoms, suppression of bacterial growth after symptoms occur, and the like.

<Form of formulation>
The pharmaceutical composition form of the compound-containing composition, antibacterial agent, and pharmaceutical composition is not particularly limited and may be appropriately selected depending on the administration route. For example, an injection mainly used for intravenous injection, intramuscular injection, or the like. Oral preparations such as capsules, tablets, granules, powders, rounds, fine granules, syrups, troches; ointments, eye drops, ear drops, nasal drops, eye ointments, mucocutaneous absorbents , External preparations for parenteral administration such as skin preparations, inhalants, suppositories; other dry powders; atomized aerosol formulations and the like.

The above-mentioned preparations include excipients, bulking agents, binders, wetting agents, disintegrants, surfactants, lubricants, dispersants, buffers, preservatives, solubilizing agents, preservatives, flavoring agents, etc. It can be produced by a conventional method using additives such as a pain-relieving agent and a stabilizer.
Specific examples of the additive include, for example, injectables, eye drops, ear drops, and nasal drops, which are solubilizers or solubilizing agents (distillation for injection) that can form an aqueous or on-use soluble form. Water, physiological saline, ethanol, glycerin, propylene glycol, corn oil, sesame oil, etc.), pH adjuster (inorganic acid addition salt such as trisodium ortholynate, sodium hydrogen carbonate; organic acid salt such as sodium citrate; L- Organic basic salts such as lysine and L-arginine), tonicity agents (sodium chloride, glucose, glycerin, etc.), buffers (sodium chloride, benzalconium chloride, sodium citrate, etc.), surfactants (mono) Sorbitane oleate, polysorbate 80, etc.), dispersants (D-mannitol, etc.), stabilizers (antioxidants such as ascorbic acid, sodium chloride, sodium pyrosulfate; chelating agents such as citric acid, tartrate acid, etc.), etc. Be done.
For example, in the case of an ointment, a skin-mucosal absorbent, and an outer skin agent, examples thereof include an ointment, a cream, and a pharmaceutical component suitable as a patch (white petrolatum, macrogol, glycerin, liquid paraffin, cotton cloth, etc.).
For example, for liquid inhalants, pH adjusters (sodium citrate, sodium hydroxide, etc.), isotonic agents (sodium chloride, benzalconium chloride, sodium citrate, etc.), buffers (sodium chloride, benzalco chloride, etc.) Nium, sodium citrate, etc.) and the like.
For example, in the case of powder inhalers, lactose as a carrier and the like can be mentioned.
For example, in oral administrations and suppositories, excipients (lactose, D-mannitol, corn starch, crystalline cellulose, etc.), disintegrants (carboxymethyl cellulose, carboxymethyl cellulose calcium, etc.), binders (hydroxypropyl cellulose, hydroxypropylmethyl cellulose, etc.) , Polyvinylpyrrolidone, etc.), lubricants (magnesium stearate, talc, etc.), coating agents (cerac, hydroxypropylmethyl cellulose, sucrose, titanium oxide, etc.), plasticizers (glycerin, polyethylene glycol, etc.), substrates (cacao fat, polyethylene, etc.) Glycol, hard fat, etc.).

<Administration>
The administration route, dose, administration time, and administration target of the compound-containing composition, antibacterial agent, and pharmaceutical composition are not particularly limited and may be appropriately selected depending on the intended purpose.
The administration route is not particularly limited, and can be administered orally or parenterally depending on the type of pathogen or disease, the nature of the individual to be administered, and the like. Examples of the parenteral injection include intravenous injection, intramuscular injection, subcutaneous administration, rectal administration, transdermal administration, topical ocular administration, and transpulmonary administration.
The dose is not particularly limited, and the usage, the type of pathogen, the age, sex, body weight, constitution, severity of the disease, and the presence or absence of administration of drugs or drugs containing other ingredients as active ingredients It can be selected as appropriate in consideration of various factors such as. For example, in the case of oral administration to humans, for example, it is within the range of 0.1 mg / kg to 1,000 mg / kg per adult per day, and in the case of intravenous administration, it is also in the range of 0.01 mg / kg to 100 mg / kg. Can be administered at.
The administration time is not particularly limited and may be appropriately selected depending on the intended purpose.
The animal species to be administered is not particularly limited and may be appropriately selected depending on the intended purpose. For example, humans, monkeys, pigs, cows, sheep, goats, dogs, cats, mice, rats, birds and the like. However, among these, it can be preferably used for humans.

Hereinafter, the present invention will be specifically described with reference to Examples and Test Examples of the present invention, but the present invention is not limited to these Examples and Test Examples.

上記化合物（１）及び化合物（２）の構造式中、「Ｃｂｚ」はベンジルオキシカルボニル基を表す。 (Example 1: Production of 1-N-[(S) -3-amino-2-hydroxypropionyl] -3', 4'-dideoxyneamine (compound (I)))
1-N-[(S) -3-amino-2-hydroxypropionyl] -3', 4'-dideoxyneamine (Compound (I)) was produced as follows.

In the structural formulas of the compound (1) and the compound (2), "Cbz" represents a benzyloxycarbonyl group.

<Example 1- (i): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino-2-hydroxypropionyl] Synthesis of -3', 4'-dideoxyneamine (compound (2))>
3,2', 6'-tri-N- (benzyloxycarbonyl) -3', 4'-dideoxyneamine (Compound (1)) (Takagi, Y. et al., Bull.Chem.Soc.Japan 47 , 3139-3141 (1974)) Dissolve 200 mg in N, N-dimethylformamide (2 mL), where triethylamine (88 mg) and (S) -3-benzyloxycarbonylamino-2-hydroxypropion The acid N-hydroxysuccinimide ester (173 mg) was added and reacted at room temperature for 2 hours with stirring. The reaction mixture was concentrated, and the residue was extracted with 1-butanol, and then the extract was washed with water and concentrated. The obtained solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 12: 1: 0.1), and the title compound (2) of a colorless solid was 176.8 mg (67%). Got
The identification data of the compound (2) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₇ H ₅₅ N ₅ NaO ₁₄ (M + Na) ⁺ 936.36, found 936.46.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 1.36 (1H, q, J = 13 Hz, H-2ax), 1.46 (1H, br d, J = ~ 13 Hz, H-4'eq), 1.82 (1H, apparent dt, J = ~ 4, ~ 4 and ~ 13 Hz, H-2eq), 3.51 (1H, m, H-1), 3.79 (1H, br, H-5'), 3.92 (1H) , apparent quintet, J = ~ 4Hz, H-2'''), 4.84 (1H, d, J = 5 Hz, HO-6), 5.25 (1H, d, J = 4 Hz, HO-5), 5.61 (1H, d, J = 5.5 Hz, HO-2'''), 7.10 (1H, t, J = 6 Hz, HN-3''') and 7.63 (1H, d, J = 8 Hz, HN- 1).

<Example 1- (ii): Synthesis of 1-N-[(S) -3-amino-2-hydroxypropionyl] -3', 4'-dideoxyneamine (compound (I))>
230 mg of compound (2) obtained in Example 1- (i) was dissolved in a mixed solution (12 mL) of 1,4-dioxane-water-acetic acid (15:10: 1), and palladium black was added thereto. Contact reduction was performed at room temperature in a hydrogen atmosphere. The reaction solution was filtered, the filtrate was concentrated, and the obtained residue was _{subjected to ion exchange chromatography using CG-50 (NH 4} ⁺ type) (developed by gradually changing the aqueous ammonia concentration to 0.1 to 1 M). Purification gave the title compound (I) 89.8 mg (71%) as a colorless solid.
The identification data of the compound (I) by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
ESI-MS: m / z calculation for C ₁₅ H ₃₁ N ₅ NaO ₆ (M + Na) ⁺ 400.22, found 400.26.
¹ H NMR (500 MHz, DCl-D ₂ O, pD 3): δ 1.56 (1H, m, H-4'ax), 1.73 (1H, q, H-2ax), 1.87 (1H, apparent dq, J) = ~ 3, ~ 3, ~ 3 and 14 Hz, H-4'eq), 1.93 ~ 2.03 (2H, H-3'), 2.24 (1H, apparent dt, H-2eq), 3.05 (1H, dd, H-6'a), 3.14 (1H, dd, H-3'''a), 3.20 (1H, dd, H-6'b), 3.33 (1H, dd, H-3'''b), 3.45 (1H, ddd, H-3), ~ 3.49 (1H, H-2'), 3.51 (1H, t, H-6), 3.60 (1H, t, H-5), 3.85 (1H, apparent t) , H-4), ~ 3.87 (1H, H-1), 4.12 (1H, m, H-5'), 4.41 (1H, dd, H-2''') and 5.71 (1H, d, H- 1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3} = 13 Hz, J _1,2eq = 4.5 Hz, J _{2eq, 3} = 4 Hz, J _3,4 = 10 Hz, J _4,5 = J _5,6 = 9.5 Hz, J _1,6 = ~ 10 Hz, J _{1', 2'} = 3.5 Hz , J _{5', 6'a} = 7 Hz, J _{5', 6'b} = 3.5 Hz, J _{6'a, 6'b} = 13.5 Hz, J _{2''', 3''' a} = 8 Hz, J _{2''', 3'''b} = 4 Hz and J _{3'''a, 3'''b} = 13 Hz.
Anal. calc. For C ₁₅ H ₃₁ N ₅ O ₆ 2H ₂ CO ₃ : C 40.72, H 7.04, N 13.97. Found: C 41.04, H 7.19, N 13.74.

上記化合物（３）〜化合物（８）の構造式中、「Ｃｂｚ」はベンジルオキシカルボニル基を表し、「Ａｃ」はアセチル基を表す。 (Example 2: 1-N-[(S) -4-amino-2-hydroxybutyryl] -3', 4'-dideoxy-5-epineamine (Compound (II)) and 1-N-[(S) ) -3-Amino-2-hydroxypropionyl] -3', 4'-dideoxy-5-epineamine (Production of compound (III)))
1-N-[(S) -4-amino-2-hydroxybutyryl] -3', 4'-dideoxy-5-epineamine (Compound (II)) and 1-N-[() as follows. S) -3-Amino-2-hydroxypropionyl] -3', 4'-dideoxy-5-epineamine (Compound (III)) was produced.

In the structural formulas of the above compounds (3) to (8), "Cbz" represents a benzyloxycarbonyl group and "Ac" represents an acetyl group.

<Example 2- (i): 3,2', 6'-tri-N- (benzyloxycarboni) -5-O-benzylsulfonyl-1-N: 6-O-carbonyl-3', 4' -Synthesis of dideoxyneamine (compound (4))>
3,2', 6'-tri-N- (benzyloxycarboni) -1-N: 6-O-carbonyl-3', 4'-dideoxyneamine (Compound (3)) (Umezawa.S., etc.) (Described in J. Antibiot. 26, 304-306 (1973)) 1.50 g was dissolved in pyridine (30 mL), to which benzylsulfonyl chloride (787 mg) was added under ice-cooling. After reacting at 45 ° C. for 12 hours with stirring, a small amount of water was added to the reaction solution, concentrated, and the residue was extracted with chloroform. The organic layer was washed successively with 5% aqueous potassium hydrogen sulfate solution, 10% aqueous sodium hydrogen carbonate solution and water, dried over anhydrous sodium sulfate and concentrated. The obtained solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-acetone = 5: 1) to obtain 1.61 g (88%) of the title compound (4) as a colorless solid.
The identification data of the compound (4) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₄ H ₄₈ N ₄ O ₁₃ SNa (M + Na) ⁺ 895.28, found 895.28.
¹ H NMR (500 MHz, DMSO-d ₆ ): δ 2.05 (1H, m, H-2eq), 3.03 (2H, m, H-6'), 3.49 (1H, m, H-2'), 3.77 (1H, br, H-5'), 4.08 (1H, t, J = 11 Hz, H-6), 4.68 (2H, ABq, J = 14 Hz, PhCH ₂ SO ₂ ), 4.89 ~ 5.04 [6H, m, PhCH ₂ OC (O) × 3], 5.11 (1H, d, J = 3.5 Hz, H-1'), 5.25 (1H, dd, J = 7 and 10 Hz, H-5), 6.18 (1H) , d, J = 9 Hz, HN-2'), 7.05 (1H, t, J = 5.5 Hz, HN-6') and 7.95 (1H, s, HN-1).

<Example 2- (ii): 5-O-acetyl-3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N: 6-O-carbonyl-3', 4'-dideoxy -Synthesis of 5-Epineamine (Compound (5))>
Compound (4) 400 mg obtained in Example 2- (i) was dissolved in N, N-dimethylformamide (6 mL), cesium acetate (470 mg) was added thereto, and the mixture was stirred at 60 ° C. 37. I made it react for time. The reaction mixture was concentrated, the residue was extracted with ethyl acetate, the extract was washed with water, dried over anhydrous sodium sulfate, and concentrated. The obtained solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 50: 1: 0.1), and the title compound (5) of a colorless solid was 131 mg (38%). Got
The identification data of the compound (5) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₃₉ H ₄₄ N ₄ NaO ₁₂ (M + Na) ⁺ 783.28, found 783.40.
¹ H NMR (400 MHz, DMSO-d ₆ ): δ 1.99 (3H, s, CH ₃ CO), 2.06 (1H, apparent dt, J = 4, 4 and 12 Hz, H-2eq), 3.04 (2H, br s, H-6'), 3.46 (1H, m, H-2'), 4.75 (1H, slightly br d, J = 2.5 Hz, H-1'), 5.69 (1H, apparent s, H-5) ), 6.46 (1H, d, J = 8 Hz, HN-2'), 7.08 (1H, brt, J = 5 Hz, HN-6'), 7.21 (1H, d, J = 8.5 Hz, HN- 3) and 7.68 (1H, s, HN-1).

<Example 2- (iii): Synthesis of 3,2', 6'-tri-N- (benzyloxycarbonyl) -3', 4'-dideoxy-5-epineamine (compound (6))>
Compound (5) 577 mg obtained in Example 2- (ii) was dissolved in a mixed solution (18 mL) of 1,4-dioxane-water (2: 1), and a 1 M aqueous potassium hydroxide solution (6 mL) was dissolved therein. Was added and reacted at room temperature for 4 hours with stirring. Ethyl acetate (150 mL) was added to the reaction mixture, the organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated. The obtained solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 20: 1: 0.1), and the title compound (6) of a colorless solid was 300 mg (57%). Got
The identification data of the compound (6) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₃₆ H ₄₄ N ₄ NaO ₁₀ (M + Na) ⁺ 715.29, found 715.36.
¹ H NMR (500 MHz, DMSO-d ₆ : D ₂ O = ~ 30: 1, 70 ° C): δ 1.10 (1H, q, J = 13 Hz, H-2ax), 1.28 (1H, m, H- 4'ax), 1.41 (1H, m, H-4'eq), 1.53 (1H, m, H-3'ax), 1.81 (1H, dt, J = 4.5, 4.5 and 13 Hz, H-2eq) , 2.84 (1H, apparent dt, J = 4.5, 10.5 and 10.5 Hz, H-1), 2.91 (1H, dd, J = 2.5 and 10 Hz, H-6), 3.03 (2H, m, H-6' ), 3.49 (1H, apparent dt, J = 4, 4 and 12 Hz, H-2'), 3.75 (1H, m, H-5'), 3.86 (1H, m, H-3), 3.95 (1H) , apparent t, J = ~ 2 Hz, H-5) and 4.81 (1H, d, J = 3 Hz, H-1').

<Example 2- (iv): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -4- (benzyloxycarbonyl) amino-2-hydroxybutyryl) ] -3', 4'-Dideoxy-5-Epineamine (Compound (7)) Synthesis>
Compound (6) 146 mg obtained in Example 2- (iii) was dissolved in N, N-dimethylformamide (1.5 mL), and triethylamine (64 mg) and (S) -4-benzyloxycarbonylamino- N-Hydroxysuccinimide ester of 2-hydroxybutyric acid (89.3 mg) was added and reacted at room temperature for 30 minutes with stirring. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 7: 1: 0.1) to obtain 180 mg of the title compound (7) as a colorless solid. 90%) was obtained.
The identification data of the compound (7) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₈ H ₅₇ N ₅ NaO ₁₄ (M + Na) ⁺ 950.38, found 950.44.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 3.02 (2H, br s, H-6'), 3.10 (2H, apparent q, J = 7 Hz, H-4'''), 3.47 (1H) , br, H-2'), 3.75 (1H, br, H-5'), 3.86 (1H, apparent quintet, J = ~ 4 Hz, H-2'''), 3.96 (1H, apparent s, H -5), 4.47 (1H, d, J = 7.5 Hz, HO-6), 4.76 (1H, slightly br s, HO-5), 4.78 (1H, slightly br d, J = ~ 2.5 Hz, H-1 '), 5.48 (1H, d, J = 5.5 Hz, HO-2'''), 7.07 (1H, br t, J = ~ 4.5 Hz, HN-6') and 7.19 (1H, t, J = 5.5 Hz, HN-4''').

<Example 2- (v): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino-2-hydroxypropionyl] Synthesis of -3', 4'-dideoxy-5-epineamine (compound (8))>
144 mg of compound (6) obtained in Example 2- (iii) was dissolved in N, N-dimethylformamide (1.5 mL), and triethylamine (64 mg) and (S) -3-benzyloxycarbonylamino- N-Hydroxysuccinimide ester of 2-hydroxypropionic acid (102 mg) was added and reacted at room temperature for 30 minutes with stirring. The reaction mixture was concentrated, and the residue was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 7: 1: 0.1) to obtain 202 mg of the title compound (8) as a colorless solid. 92%) was obtained.
The identification data of the compound (8) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₇ H ₅₅ N ₅ NaO ₁₄ (M + Na) ⁺ 936.36, found 936.40.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 1.24 (1H, q, J = 12.5 Hz, H-2ax), 1.30 (1H, m, H-4'ax), 1.38 (1H, br d, J = ~ 11 Hz, H-4'eq), 1.49 ~ 1.59 (2H, H-3'), 1.81 (1H, apparent dt, J = 4.5, 4.5 and 12.5 Hz, H-2eq), 3.02 (2H, br s, H-6'), 3.07 (1H, ddd, J = 6, 7 and 14 Hz, H-3'''a), ~ 3.35 (1H, H-4), 3.47 (1H, m, H -2'), 3.76 (1H, br, H-5'), 3.87 (1H, m, H-3), 3.93 (1H, m, H-2'''), 3.96 (1H, apparent s, H -5), 4.50 (1H, d, J = 7 Hz, HO-6), 4.75 (1H, slightly br s, HO-5), 4.78 (1H, slightly br d, J = ~ 2.5 Hz, H-1 '), 5.64 (1H, d, J = 5.5 Hz, HO-2'''), 6.90 (1H, d, J = 8.5 Hz, HN-2'), 6.92 (1H, d, J = 9.5 Hz, HN-3), 7.08 (1H, br t, J = ~ 5.5 Hz, HN-6'), 7.09 (1H, t, J = 6 Hz, HN-3''') and 7.57 (1H, d, J = 8 Hz, HN-1).

<Example 2- (vi): Synthesis of 1-N-[(S) -4-amino-2-hydroxybutyryl] -3', 4'-dideoxy-5-epineamine (compound (II))>
174 mg of compound (7) obtained in Example 2- (iv) was dissolved in a mixed solution (15 mL) of 1,4-dioxane-water-acetic acid (40:10: 1), and palladium black was added thereto. Contact reduction was performed at room temperature in a hydrogen atmosphere. The reaction was treated in the same manner as in Example 1- (ii) to give 52.4 mg (58%) of the title compound (II) as a colorless solid.
The identification data of the compound (II) by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
ESI-MS: m / z calculation for C ₁₆ H ₃₃ N ₅ NaO ₆ (M + Na) ⁺ 414.23, found 414.27.
¹ H NMR (600 MHz, DCl-D ₂ O, pD 3): δ 1.55 (1H, ddt, H-4'ax), 1.62 (1H, q, H-2ax), 1.85 (1H, dq, H- 4'eq), 1.94 (1H, ddt, J = 6.5, 8, 8 and 14.5 Hz, H-3'''a), 1.96 to 2.06 (2H, H-3'), 2.10 (1H, dddd, J = 4, 7, 8 and 14.5 Hz, H-3'''b), 2.21 (1H, dt, H-2eq), 3.02 (1H, dd, H-6'a), 3.09 (2H, m, H) -4'''), 3.19 (1H, dd, H-6'b), 3.53 (1H, ddd, H-2'), 3.68 (1H, ddd, H-3), 3.71 (1H, dd, H -6), 3.96 (1H, dd, H-4), 4.02 (1H, dddd, H-5'), 4.11 (1H, ddd, H-1), 4.25 (1H, dd, H-2''' ), 4.45 (1H, t, H-5) and 5.39 (1H, d, H-1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3 = 12.5} Hz, J 1,2eq = J _{2eq, 3} = 4.5 Hz, J _3,4 = J _1,6 = 10.5 Hz, J _4,5 = J _{5, 6} = 2.5 Hz, J _{1', 2'} = 3.5 Hz, J _{2', 3' ax} = 11.5 Hz, J _{2', 3'eq} = 5.5 Hz, J _{3'ax, 4'ax} = 12 Hz, J _{3'ax, 4'eq} = 3 Hz, J _{3'eq, 4'ax} = 5 Hz, J _{3'eq, 4'eq} = 3 Hz, J _{4'ax, 4'eq} = 13.5 Hz, J _{4'ax, 5'} = 12 Hz, J _{4'eq, 5'} = 3 Hz, J _{5 ', 6'a} = 7.5 Hz, J _{5', 6'b} = 3.5 Hz, J _{6'a, 6'b} = 13.5 Hz, J _{2''', 3''' a} = 8 Hz, J _2''',3'''b = 4 Hz and J _{3'''a, 3'''b} = 14.5 Hz.
Anal. calc. For C ₁₆ H ₃₃ N ₅ O ₆ H ₂ CO ₃ 1.5H ₂ O: C 42.49, H 7.97, N 14.57. Found: C 42.68, H 7.90, N 14.26.

<Example 2- (vii): Synthesis of 1-N-[(S) -3-amino-2-hydroxypropionyl] -3', 4'-dideoxy-5-epineamine (compound (III))>
191 mg of compound (8) obtained in Example 2- (v) was dissolved in a mixed solution (12 mL) of 1,4-dioxane-water-acetic acid (30:10: 1), and palladium black was added thereto. Contact reduction was performed at room temperature in a hydrogen atmosphere. The reaction was treated in the same manner as in Example 1- (ii) to give 58 mg (57%) of the title compound (III) as a colorless solid.
The identification data of the compound (III) by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
ESI-MS: m / z calculation for C ₁₅ H ₃₁ N ₅ NaO ₆ (M + Na) ⁺ 400.22, found 400.28.
¹ H NMR (600 MHz, DCl-D ₂ O, pD 3): δ 1.55 (1H, ddt, H-4'ax), 1.62 (1H, q, H-2ax), 1.85 (1H, dq, H- 4'eq), 1.96 ~ 2.06 (2H, H-3'), 2.22 (1H, dt, H-2eq), 3.03 (1H, dd, H-6'a), 3.15 (1H, dd, H-3) '''a), 3.19 (1H, dd, H-6'b), 3.32 (1H, dd, H-3'''b), 3.53 (1H, ddd, H-2'), 3.68 (1H, ddd, H-3), 3.73 (1H, dd, H-6), 3.96 (1H, dd, H-4), 4.02 (1H, dddd, H-5'), 4.12 (1H, ddd, H-1) ), 4.40 (1H, dd, H-2'''), 4.45 (1H, t, H-5) and 5.39 (1H, d, H-1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3 = 12. 5 Hz,} J 1,2eq = J 2eq, 3 = 4.5 Hz, J 3,4 = J 1,6 = 10.5 Hz, J 4,5 = J 5, 6 = 2.5 Hz, J 1 _{', 2'} = 3.5 Hz, J _{2', 3'ax} = 11.5 Hz, J _{2', 3'eq} = 5.5 Hz, J _{3'ax, 4'ax} = 12 Hz, J _{3'ax, 4'eq} = 3 Hz, J _{3'eq, 4'ax} = 5 Hz, J _{3'eq, 4'eq} = 3 Hz, J _{4'ax, 4'eq} = 13.5 Hz, J _{4'ax, 5'} = 12 Hz , J _{4'eq, 5'} = 3 Hz, J _{5', 6'a} = 7.5 Hz, J _{5', 6'b} = 3.5 Hz, J _{6'a, 6'b} = 13.5 Hz, J _2''',3'''a = 8 Hz, J _{2''', 3'''b} = 4 Hz and J _{3'''a, 3'''b} = 13 Hz.
Anal. calc. For C ₁₅ H ₃₁ N ₅ O ₆ 1.5H ₂ CO ₃ H ₂ O: C 40.57, H 7.43, N 14.34. Found: C 40.75, H 7.66, N 14.57.

上記化合物（９）〜化合物（１３）の構造式中、「Ｃｂｚ」はベンジルオキシカルボニル基を表す。 (Example 3: 1-N-[(S) -4-amino-2-hydroxybutyryl] -5,3', 4'-trideoxyneamine (Compound (IV)) and 1-N-[( S) -3-Amino-2-hydroxypropionyl] -5,3', 4'-Trideoxyneamine (Production of Compound (V)))
1-N-[(S) -4-amino-2-hydroxybutyryl] -5,3', 4'-trideoxyneamine (Compound (IV)) and 1-N- [ (S) -3-Amino-2-hydroxypropionyl] -5,3', 4'-trideoxyneamine (Compound (V)) was produced.

In the structural formulas of the above compounds (9) to (13), "Cbz" represents a benzyloxycarbonyl group.

<Example 3- (i): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N: 6-O-carbonyl-5,3', 4'-trideoxy-5-epi -5-Synthesis of iodoneamine (compound (9))>
Compound (4) 268 mg obtained in Example 2- (i) was dissolved in N, N-dimethylformamide (6 mL), sodium iodide (2.31 g) was added thereto, and the reaction solution was prepared at 100 ° C. 3 Stirred for hours. The concentrated residue was extracted with chloroform, and the organic layer was washed successively with 10% aqueous sodium thiosulfate solution and water, dried over anhydrous sodium sulfate, and concentrated. The obtained solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 20: 1: 0.1) to give the title compound (9) 212 mg (83%). ..
The identification data of the compound (9) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₃₇ H ₄₁ IN ₄ NaO ₁₀ (M + Na) ⁺ 851.18, found 851.13.
¹ H NMR (500 MHz, DMSO-d ₆ ): δ 1.63 (1H, q, J = 12 Hz, H-2ax), 2.02 (1H, m, H-2eq), 3.05 (2H, br s, H- 6'), 3.48 (1H, m, H-2'), 3.69 (1H, m, H-5'), 4.90 (1H, slightly br d, J = 2.5 Hz, H-1'), 5.12 (1H) , apparent s, H-5), 6.23 (1H, d, J = 8Hz, HN-2'), 7.10 (1H, brt, J = 6 Hz, HN-6'), 7.22 (1H, d, J = 9.5 Hz, HN-3) and 7.76 (1H, s, HN-1).

<Example 3- (ii): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N: 6-O-carbonyl-5,3', 4'-trideoxyneamine ( Synthesis of compound (10))>
Compound (9) 2.9 g obtained in Example 3- (i) was dissolved in 1,4-dioxane (60 mL), and tributyltin hydride (1.53 g) and 2,2-azobisisobutyronitrile were dissolved therein. (172 mg) was added and the mixture was stirred at 90 ° C. for 1 hour. The concentrated residue was extracted with acetonitrile (150 mL) and the extract was washed 3 times with hexane (150 mL). Then, the acetonitrile solution is concentrated, and the obtained residue is purified by silica gel column chromatography (developing while gradually changing the mixing ratio of the mixed solution of hexane-chloroform-ethyl acetate to 1: 1: 1 to 1: 1: 8). The title compound (10) was obtained in an amount of 2.0 g (81%).
The identification data of the compound (10) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₃₇ H ₄₂ N ₄ NaO ₁₀ (M + Na) ⁺ 725.28, found 725.25.
¹ H NMR (500 MHz, DMSO-d ₆ ): δ 1.43 (1H, q, J = 12 Hz, H-2ax), 1.61 (1H, q, J = 11 Hz, H-5ax), 2.04 (1H, 1H, dt, J = 4, 4 and 12 Hz, H-2eq), 2.46 (1H, br, H-5eq), 3.02 (2H, br t, J = ~ 5 Hz, H-6'), 3.44 (1H, m, H-2'), 4.87 (1H, d, J = 3 Hz, H-1'), 6.81 (1H, d, J = 8 Hz, HN-2'), 7.04 (1H, br t, J = ~ 5 Hz, HN-6'), 7.20 (1H, d, J = 9 Hz, HN-3) and 7.61 (1H, s, HN-1).

<Example 3- (iii): Synthesis of 3,2', 6'-tri-N- (benzyloxycarbonyl) -5,3', 4'-trideoxyneamine (compound (11))>
1.4 g of compound (10) obtained in Example 3- (ii) was dissolved in 50% 1,4-dioxane water (42 mL), sodium carbonate (1.23 g) was added thereto, and the mixture was mixed at 90 ° C. 2 Stir for hours. After neutralization by adding 1M hydrochloric acid water, the concentrated residue was extracted with 1-butanol (70 mL). The extract was washed with water and the solid obtained by concentration was gradually changed to silica gel column chromatography (chloroform-methanol-28% aqueous ammonia mixture ratio of 20: 1: 0.1 to 10: 1: 0.1). Purification by (while developing) gave 760 mg (56%) of the title compound (11) as a colorless solid.
The identification data of the compound (11) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₃₆ H ₄₄ N ₄ NaO ₉ (M + Na) ⁺ 699.30, found 699.26.
¹ H NMR (500 MHz, DMSO-d ₆ ): δ 1.13 (1H, q, J = 12 Hz, H-2ax), 1.18 (1H, q, J = 11.5 Hz, H-5ax), 1.79 (1H, 1H, apparent dt, J = ~ 4, ~ 4 and ~ 12 Hz, H-2eq), 2.09 (1H, br d, J = ~ 12 Hz, H-5eq), 2.41 (1H, apparent ddd, ~ 4, ~ 9 and ~ 12 Hz, H-1), 2.94 (1H, m H-6), 3.02 (2H, m, H-6'), 3.74 (1H, m, H-5'), 4.83 (1H, slightly br d, J = ~ 2.5 Hz, H-1'), 6.84 (1H, d, J = 8 Hz, HN-2'), 6.95 (1H, d, J = 9 Hz, HN-3) and 7.08 (1H) , br t, J = ~ 5 Hz, HN-6').

<Example 3- (iv): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -4- (benzyloxycarbonyl) amino-2-hydroxybutyryl) ] -5,3', 4'-Synthesis of trideoxyneamine (compound (12))>
200 mg of compound (11) obtained in Example 3- (iii) was dissolved in N, N-dimethylformamide (2 mL), and triethylamine (90 mg) and (S) -4-benzyloxycarbonylamino- N-Hydroxysuccinimide ester of 2-hydroxybutyric acid (155 mg) was added and reacted at room temperature for 1.5 hours with stirring. Water was added to the reaction mixture, concentrated, and the residue was extracted with chloroform. The solid obtained by concentrating the extract was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 12: 1: 0.1) to obtain the title compound (12) as a colorless solid. 245 mg (91%) was obtained.
The identification data of the compound (12) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₈ H ₅₇ N ₅ NaO ₁₃ (M + Na) ⁺ 934.38, found 934.46.
¹ H NMR (500 MHz, DMSO-d ₆ ): δ 2.17 (1H, br d, J = ~ 12 Hz, H-5eq), 3.03 (2H, br, H-6'), 3.10 (2H, apparent q) , J = 7 Hz, H-4'''), 3.74 (1H, br, H-5'), 3.87 (1H, apparent quintet, J = ~ 4 Hz, H-2'''), 4.82 (1H) , d, J = 5.5 Hz, HO-6), 4.84 (1H, slightly br d, J = ~ 2.5 Hz, H-1'), 5.47 (1H, d, J = 5.5 Hz, HO-2''' ), 6.95 (1H, d, J = 7.5 Hz, HN), 7.01 (1H, d, J = 9 Hz, HN), 7.08 (1H, brt, J = ~ 5.5 Hz, HN-6'), 7.20 (1H, t, J = 5.5 Hz, HN-4''') and 7.52 (1H, d, J = 7.5 Hz, HN).

<Example 3- (v): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino-2-hydroxypropionyl] -5,3', 4'-Synthesis of trideoxyneamine (compound (13))>
310 mg of compound (11) obtained in Example 3- (iii) was dissolved in N, N-dimethylformamide (3 mL), and triethylamine (139 mg) and (S) -3-benzyloxycarbonylamino- N-Hydroxysuccinimide ester of 2-hydroxypropionic acid (230 mg) was added and reacted at room temperature for 2 hours with stirring. The reaction was treated in the same manner as in Example 3- (iv) to give 177 mg (43%) of the title compound (13) as a colorless solid.
The identification data of the compound (13) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₇ H ₅₅ N ₅ NaO ₁₃ (M + Na) ⁺ 920.37, found 920.41.
¹ H NMR (500 MHz, DMSO-d ₆ ): δ 1.84 (1H, apparent dt, J = ~ 4, ~ 4 and ~ 13 Hz, H-2eq), 2.16 (1H, br d, J = ~ 12 Hz) , H-5eq), 3.09 (1H, ddd, J = 6, 8 and 13 Hz, H-3'''a), 3.73 (1H, br, H-5'), 3.93 (1H, ddd, J = 4, 5.5 and 8 Hz, H-2'''), 4.80 (1H, d, J = 5 Hz, HO-6), 4.83 (1H, slightly br d, J = ~ 2.5 Hz, H-1') , 5.61 (1H, d, J = 5.5 Hz, HO-2'''), 6.95 (1H, d, J = 7.5 Hz, HN), 7.01 (1H, d, J = 9 Hz, HN), 7.07 ( 1H, br t, J = ~ 5 Hz, HN-6'), 7.10 (1H, t, J = 6 Hz, HN-3''') and 7.60 (1H, d, J = 8 Hz, HN).

<Example 3- (vi): Synthesis of 1-N-[(S) -4-amino-2-hydroxybutyryl] -5,3', 4'-trideoxyneamine (compound (IV))>
320 mg of compound (12) obtained in Example 3- (iv) was treated in the same manner as in Example 1- (ii) to give 78.1 mg (49%) of the title compound (IV) as a colorless solid. rice field.
The identification data of the compound (IV) by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
ESI-MS: m / z calculation for C ₁₆ H ₃₃ N ₅ NaO ₅ (M + Na) ⁺ 398.24, found 398.28.
¹ H NMR (500 MHz, DCl-D ₂ O, pD 3): δ 1.42 (1H, q, H-5ax), 1.54 (1H, m, H-4'ax), 1.65 (1H, q, H- 2ax), 1.85 (1H, apparent dq, J = ~ 3, ~ 3, ~ 3 and 14 Hz, H-4'eq), 1.90 ~ 2.04 (3H, H-3'and H-3'''a) , 2.10 (1H, m, H-3'''b), 2.22 (1H, dt, H-2eq), 2.62 (1H, dt, H-5eq), 3.03 (1H, dd, H-6'a) , 3.09 (2H, m, H-4'''), 3.20 (1H, dd, H-6'b), 3.43 (1H, ddd, H-3), 3.50 (1H, m, H-2') , 3.70 (1H, apparent dt, H-6), 3.81 (1H, ddd, H-1), 3.95 (1H, apparent dt, H-4), 4.01 (1H, m, H-5'), 4.26 ( 1H, dd, H-2''') and 5.35 (1H, d, H-1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3} = 12.5 Hz, J _1,2eq = J _{2eq, 3} = 4.5 Hz, J _3,4 = 10 Hz, J _4,5ax = J _{5ax, 5eq} = J _{5ax, 6} = 12 Hz, J _4,5eq = J _{5eq, 6} = 4 Hz, J _1,6 = 10 Hz, J _{1', 2'} = 3.5 Hz, J _{5', 6'a} = 7.5 Hz, J _{5', 6'b} = 3 Hz, J _{6'a, 6'b} = 13.5 Hz, J _2''',3'''a = 8 Hz and J _{2''', 3'''b} = 4 Hz.
Anal. calc. For C ₁₆ H ₃₃ N ₅ O ₅ H ₂ CO ₃ H ₂ O: C 44.83, H 8.19, N 15.38. Found: C 44.98, H 8.00, N 15.01.

<Example 3- (vii): Synthesis of 1-N-[(S) -3-amino-2-hydroxypropionyl] -5,3', 4'-trideoxyneamine (compound (V))>
230 mg of compound (13) obtained in Example 3- (v) was treated in the same manner as in Example 1- (ii) to give 67 mg (56%) of the title compound (V) as a colorless solid. rice field.
The identification data of the compound (V) by specific rotation, HRESI-MS, ¹ H NMR, and elemental analysis were as follows.
[α] _D ²⁴ + 104 ° (c 1.0, H ₂ O).
HRESI-MS: m / z calculation for C ₁₅ H ₃₁ N ₅ NaO ₅ (M + Na) ⁺ 384.2217, found 384.2216.
¹ H NMR (500 MHz, DCl-D ₂ O, pD 3): δ 1.42 (1H, q, H-5ax), 1.55 (1H, m, H-4'ax), 1.65 (1H, q, H- 2ax), 1.85 (1H, apparent dq, J = ~ 3, ~ 3, ~ 3 and 14 Hz, H-4'eq), 1.94 ~ 2.04 (2H, H-3'), 2.23 (1H, dt, H -2eq), 2.62 (1H, dt, H-5eq), 3.03 (1H, dd, H-6'a), 3.15 (1H, dd, H-3'''a), 3.20 (1H, dd, H -6'b), 3.33 (1H, dd, H-3'''b), 3.43 (1H, ddd, H-3), 3.50 (1H, m, H-2'), 3.72 (1H, apparent dt , H-6), 3.83 (1H, ddd, H-1), 3.95 (1H, apparent dt, H-4), 4.01 (1H, m, H-5'), 4.41 (1H, dd, H-2) ''') and 5.35 (1H, d, H-1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3} = 12.5 Hz, J _1,2eq = 4.5 Hz, J _{2eq, 3} = 4 Hz , J _3,4 = 10 Hz, J _4,5ax = J _{5ax, 5eq} = J _{5ax, 6} = 12 Hz, J _4,5eq = J _{5eq, 6} = 4 Hz, J _1,6 = 10 Hz, J _{1 ', 2'} = 3.5 Hz, J _{5', 6'a} = 7.5 Hz, J _{5', 6'b} = 3 Hz, J _{6'a, 6'b} = 13.5 Hz, J _{2''', 3''' a} = 8 Hz, J _{2''', 3'''b} = 4 Hz and J _{3'''a, 3'''b} = 13 Hz.
Anal. calc. For C ₁₅ H ₃₁ N ₅ O ₅ 1.5H ₂ CO ₃ 0.5H ₂ O: C 42.76, H 7.61, N 15.11. Found: C 42.78, H 7.82, N 14.72.

上記化合物（１４）〜化合物（１９）の構造式中、「Ｃｂｚ」はベンジルオキシカルボニル基を表し、「Ｂｏｃ」はｔｅｒｔ−ブトキシカルボニル基を表し、「Ｍｓ」はメシル基を表す。 (Example 4: 1-N-[(S) -4-amino-2-hydroxybutylyl] -5,6,3', 4'-tetradeoxyneamine (compound (VI)) and 1-N- [(S) -3-Amino-2-hydroxypropionyl] -5,6,3', 4'-Tetradeoxyneamine (Production of Compound (VII)))
1-N-[(S) -4-Amino-2-hydroxybutylyl] -5,6,3', 4'-tetradeoxyneamine (Compound (VI)) and 1-N as follows. -[(S) -3-Amino-2-hydroxypropionyl] -5,6,3', 4'-tetradeoxyneamine (Compound (VII)) was produced.

In the structural formulas of the above compounds (14) to (19), "Cbz" represents a benzyloxycarbonyl group, "Boc" represents a tert-butoxycarbonyl group, and "Ms" represents a mesyl group.

<Example 4- (i): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N- (tert-butoxycarbonyl) -3', 4'-dideoxy-5,6- Synthesis of di-O-methanesulfonylneamine (compound (15))>
3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N- (tert-butoxycarbonyl) -3', 4'-dideoxyneamine (Compound (14)) (Minowa, N. et al.) (1), Bioorg. Med. Chem. Lett. 16, 6351-6354 (2006)) Dissolve 100 mg in dichloromethane (30 mL), where methanesulfonyl chloride (63 mg) and 4-dimethylaminopyridine ( 92.5 mg) was added, and the mixture was allowed to react at room temperature for 3 hours. After adding a small amount of water to the reaction solution, the mixture was diluted with chloroform, and the organic layer was washed successively with 5% aqueous potassium hydrogensulfate solution, 10% aqueous sodium hydrogencarbonate solution and water, and concentrated. The solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-methanol-28% aqueous ammonia = 10: 1: 0.1) to obtain 91.1 mg (76%) of the title compound (15) as a colorless solid. ..
The identification data of the compound (15) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₃ H ₅₆ N ₄ NaO ₁₆ S ₂ (M + Na) ⁺ 971.30, found 971.30.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 1.37 [9H, s, (CH ₃ ) ₃ COC (O)], 1.59 (1H, q, J = 13 Hz, H-2ax), 3.20 and 3.24 (3H, each s, CH ₃ SO ₂ O), 3.51 (1H, m, H-2'), 3.59 (1H, t, J = 9.5 Hz, H-4), 3.81 (1H, br, H-5) '), 4.45 (1H, t, J = 10 Hz, H-6), 5.08 (1H, br s, H-1'), 6.18 (1H, d, J = 9 Hz, HN-2'), 7.11 (1H, br t, J = ~ 5.5 Hz, HN-6') and 7.41 (1H, d, J = 9 Hz, HN-3).

<Example 4- (ii): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N- (tert-butoxycarbonyl) -5-eno-5,6,3', 4 '-Synthesis of tetradeoxyneamine (compound (16))>
200 mg of the compound (15) obtained in Example 4- (i) was dissolved in N, N-dimethylformamide (4 mL), and potassium iodide (1.05 g) and zinc powder (163 mg) were added thereto. The mixture was heated and stirred at 100 ° C. for 2 hours. Ethyl acetate (16 mL) and water (4 mL) were added, filtration was performed using cerite, and the filtrate was washed successively with 5% aqueous sodium thiosulfate solution and water, and concentrated. The obtained solid was purified by silica gel column chromatography (developed with a mixed solution of chloroform-acetone = 10: 1) to obtain 109 mg (68%) of the title compound (16) as a colorless solid.
The identification data of the compound (16) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₁ H ₅₀ N ₄ NaO ₁₀ (M + Na) ⁺ 781.34, found 781.43.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 1.39 [9H, s, (CH ₃ ) ₃ COC (O)], 1.54 (1H, q, J = ~ 12 Hz, H-2ax), 1.91 ( 1H, br d, J = ~ 12 Hz, H-2eq), 3.03 (2H, br t, J = ~ 5 Hz, H-6'), 3.43 (1H, m, H-2'), 3.74 (1H) , br, H-5'), 4.91 (1H, slightly br d, J = ~ 2 Hz, H-1'), 5.51 (2H, s, H-5 and 6) and 7.06 (1H, br t, J = ~ 6 Hz, HN-6').

<Example 4- (iii): 3,2', 6'-tri-N- (benzyloxycarbonyl) -5-eno-5,6,3', 4'-tetradeoxyneamine (Compound (17)) ) Synthesis>
515 mg of the compound (16) obtained in Example 4- (ii) was dissolved in 95% trifluoroacetic acid water (5 mL) and allowed to stand at room temperature for 15 minutes. The reaction mixture was concentrated, and diethyl ether was added to the obtained syrup. The resulting precipitate was thoroughly washed with diethyl ether to give 502 mg of the trifluoroacetic acid salt of the title compound (17) as a colorless solid.
The identification data of the compound (17) by ESI-MS were as follows.
ESI-MS: m / z calculation for C ₃₆ H ₄₂ N ₄ NaO ₈ (M + Na) ⁺ 681.29, found 681.38.

<Example 4- (iv): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -4- (benzyloxycarbonyl) amino-2-hydroxybutyryl) ] -5-Eno-5,6,3', 4'-Synthesis of tetradeoxyneamine (compound (18))>
64.4 mg of the trifluoroacetic acid salt of the compound (17) obtained in Example 4- (iii) was treated in the same manner as in Example 3- (iv), and the title compound (18) 49 mg (compound) of a colorless solid was treated. 63%) was obtained from (16).
The identification data of the compound (18) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₈ H ₅₅ N ₅ NaO ₁₂ (M + Na) ⁺ 916.37, found 916.49.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 1.79 (1H, m, H-3'''b), 1.90 (1H, br, H-2eq), 3.04 (2H, br t, J = ~ 5 Hz, H-6'), 3.08 (2H, apparent q, J = ~ 7 Hz, H-4'''), 3.44 (1H, m, H-2'), 3.63 (1H, m, H- 3), 3.75 (1H, br, H-5'), 3.87 (1H, apparent quintet, J = ~ 4 Hz, H-2'''), 4.10 (1H, slightly br d, J = 8 Hz, H -4), 4.44 (1H, m, H-1), 4.92 (1H, slightly br d, J = ~ 2 Hz, H-1'), 5.44 (1H, d, J = 5.5 Hz, HO-2'''), 5.46 (1H, d, J = ~ 10 Hz, H-6), 5.56 (1H, d, J = ~ 10 Hz, H-5), 7.05 (1H, d, J = 7 Hz, HN -2'), 7.07 (1H, br t, J = 5.5 Hz, HN-6'), 7.19 (1H, t, J = 5.5 Hz, HN-4''') and 7.78 (1H, d, J = 8.5 Hz, HN-1).

<Example 4- (v): 3,2', 6'-tri-N- (benzyloxycarbonyl) -1-N-[(S) -3- (benzyloxycarbonyl) amino-2-hydroxypropionyl] -5-Synthesis of eno-5,6,3', 4'-tetradeoxyneamine (compound (19))>
100 mg of the trifluoroacetic acid salt of the compound (17) obtained in Example 4- (iii) was treated in the same manner as in Example 3- (v), and the title compound (19) 94 mg (compound) of a colorless solid was treated. 79%) was obtained from (16).
The identification data of the compound (19) by ESI-MS and ¹ H NMR were as follows.
ESI-MS: m / z calculation for C ₄₇ H ₅₃ N ₅ NaO ₁₂ (M + Na) ⁺ 902.36, found 902.49.
¹ H NMR (600 MHz, DMSO-d ₆ ): δ 1.90 (1H, br, H-2eq), 3.04 (2H, br t, J = ~ 4 Hz, H-6'), 3.11 (1H, dt, J = 6.5, 6.5 and 13.5 Hz, H-3'''a), 3.44 (1H, m, H-2'), 3.63 (1H, m, H-3), 3.75 (1H, br, H-5) '), 3.92 (1H, m, H-2'''), 4.11 (1H, slightly br d, J = 8.5 Hz, H-4), 4.44 (1H, m, H-1), 4.92 (1H, slightly br d, J = ~ 3 Hz, H-1'), 5.48 (1H, d, J = 10 Hz, H-6), 7.05 (1H, d, J = 7.5 Hz, HN-2'), 7.07 (1H, br t, J = ~ 6 Hz, HN-6'), 7.14 (1H, t, J = 6 Hz, HN-3''') and 7.84 (1H, d, J = 8.5 Hz, HN- 1).

<Example 4- (vi): 1-N-[(S) -4-amino-2-hydroxybutyryl] -5,6,3', 4'-tetradeoxyneamine (compound (VI)) Synthesis>
The compound (18) 158 mg obtained in Example 4- (iv) was treated in the same manner as in Example 1- (ii) to obtain 39.5 mg (46%) of the title compound (VI) as a colorless solid. ..
The identification data of the compound (VI) by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
ESI-MS: m / z calculation for C ₁₆ H ₃₃ N ₅ NaO ₄ (M + Na) ⁺ 382.24, found 382.30.
¹ H NMR (600 MHz, DCl-D ₂ O, pD 3): δ 1.32 (1H, apparent dq, J = 3.5, 〜13, 〜13 and 〜13 Hz, H-5ax), 1.44 (1H, dq, H-6ax), 1.53 (1H, m, H-4'ax), 1.61 (1H, q, H-2ax), 1.83 (1H, apparent dq, J = ~ 3, ~ 3, ~ 3 and ~ 14 Hz , H-4'eq), 1.88 (1H, ddt, J = 6.5, 8.5, 8.5 and 14.5 Hz, H-3'''a), 2.08 (1H, dddd, J = 4, 7, 8 and 14.5 Hz , H-3'''b), 2.25 (1H, m, H-2eq), 2.34 (1H, apparent dq, J = ~ 4, ~ 4, ~ 4 and ~ 13 Hz, H-5eq), 3.02 ( 1H, dd, H-6'a), 3.07 (2H, m, H-4'''), 3.18 (1H, dd, H-6'b), 3.37 (1H, ddd, H-3), 3.48 (1H, m, H-2'), 3.84 (1H, H-4), 4.00 (1H, m, H-5'), 4.20 (1H, dd, H-2''') and 5.33 (1H, m, H-2''') and 5.33 (1H, m, H-2'') d, H-1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3} = 12 Hz, J _{2eq, 3} = 4 Hz, J _3,4 = 10 Hz, J _{5ax, 6ax} = J _{5ax, 5eq} = J _{6ax, 6eq} = J _1,6ax = 13 Hz, J _{5ax, 6eq} = J _{5eq, 6ax} = 3.5 Hz, J _{1', 2'} = 3.5 Hz, J _{5', 6'a} = 7.5 Hz, J _{5', 6'b} = 3.5 Hz, J _{6'a, 6'b} = 13.5 Hz, J _{2''', 3'''a} = 8.5 Hz and J _{2''', 3''' b} = 4 Hz.
Anal.calc. For C ₁₆ H ₃₃ N ₅ O ₄ 2H ₂ CO ₃ : C 44.71, H 7.71, N 14.48. Found: C 44.64 H 7.96, N 14.62.

<Example 4- (vii): Synthesis of 1-N-[(S) -3-amino-2-hydroxypropionyl] -5,6,3', 4'-tetradeoxyneamine (compound (VII)) ＞
The compound (19) 292 mg obtained in Example 4- (v) was treated in the same manner as in Example 1- (ii) to obtain 68.3 mg (49%) of the title compound (VII) as a colorless solid. ..
The identification data of the compound (VII) by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
ESI-MS: m / z calculation for C ₁₅ H ₃₁ N ₅ NaO ₄ (M + Na) ⁺ 368.23, found 368.31.
¹ H NMR (600 MHz, DCl-D ₂ O, pD 3): δ 1.33 (1H, apparent dq, J = 3.5, 〜13, 〜13 and 〜13 Hz, H-5ax), 1.46 (1H, dq, H-6ax), 1.53 (1H, m, H-4'ax), 1.63 (1H, q, H-2ax), 1.84 (1H, apparent dq, J = ~ 3.5, ~ 3.5, ~ 3.5 and ~ 14 Hz , H-4'eq), 2.26 (1H, m, H-2eq), 2.35 (1H, apparent dq, J = ~ 4, ~ 4, ~ 4 and ~ 13 Hz, H-5eq), 3.02 (1H, dd, H-6'a), 3.08 (1H, dd, H-3'''a), 3.19 (1H, dd, H-6'b), 3.31 (1H, dd, H-3'''b ), 3.38 (1H, ddd, H-3), 3.49 (1H, m, H-2'), 3.86 (1H, H-4), 4.01 (1H, m, H-5'), 4.36 (1H, dd, H-2''') and 5.34 (1H, d, H-1'); J _1,2ax = J _{2ax, 2eq} = J _{2ax, 3} = 12 Hz, J _{2eq, 3} = 4 Hz, J _{3 , 4} = 10 Hz, J _{5ax, 6ax} = J _{5ax, 5eq} = J _{6ax, 6eq} = J _1,6ax = 13 Hz, J _{5ax, 6eq} = J _{5eq, 6ax} = 3.5 Hz, J _{1', 2'} = 3.5 Hz, J _{5', 6'a} = 7.5 Hz, J _{5', 6'b} = 3.5 Hz, J _{6'a, 6'b} = 13.5 Hz, J _{2''', 3''' a} = 8.5 Hz , J _{2''', 3'''b} = 4 Hz and J _{3'''a, 3'''b} = 13.5 Hz.
Anal. calc. For C ₁₅ H ₃₁ N ₅ O ₄ H ₂ CO ₃ 0.5H ₂ O: C 46.14, H 8.23, N 16.82. Found: C 46.02, H 7.93, N 16.56.

(Example 5: Production of 1-N-[(S) -4-amino-2-hydroxybutyryl] -3', 4'-dideoxy-2-hydroxyneamine (compound (VIII)))
1-N-[(S) -4-amino-2-hydroxybutyryl] -3', 4'-dideoxy-2-hydroxyneamine (Compound (VIII)) was produced as follows.

2-Hydroxyarbekacin (described in J. Antibiot. 71, 345-347 (2018) in 2-OH-ABK, Takahashi, Y. et al.) 1.80 g (2.5H ₂ SO ₄ addition salt) in 2 M hydrochloric acid ( It was dissolved in 36 mL) and heated at 95 ° C for 2.5 hours. The syrup obtained by concentrating the reaction solution was dissolved in water (50 mL) and neutralized by adding 0.5 M aqueous sodium hydroxide solution. The concentrated residue was treated in the same manner as in the ion exchange chromatography described in Example 1- (ii) to give 248 mg of 3', 4'-dideoxy-2-hydroxyneamine and 2-hydroxygibberellin. (Takahashi, Y. & Umemura, International Publication No. 2017/078097 A1 (2017)) 202 mg and a mixture of compound (VIII) and 2-hydroxyalbecasin 790 mg were obtained as colorless solids, respectively.

A mixture of the above compound (VIII) and 2-hydroxyarbekacin is dissolved in 50% methanol water (24 mL), triethylamine (804 mg) and di-tert-butylcarbonate (1.69 g) are added thereto, and the mixture is added at room temperature for 18 hours. Stirred. After adding a small amount of concentrated aqueous ammonia to the reaction solution, it is concentrated, and the obtained residue is separated by silica gel column chromatography (developed with a mixed solution of chloroform-1-propanol-20% acetate solution = 8: 1: 0.1). Purification gave 381 mg of N-tert-butoxycarbonyl derivative of compound (VIII). 215 mg of this solid was dissolved in 95% trifluoroacetic acid water (50 mL) and left at room temperature for 1 hour. The reaction mixture was concentrated, diethyl ether was added to the syrup, and the resulting precipitate was treated in the same manner as in the ion exchange chromatography described in Example 1- (ii) to obtain 107 mg of the title compound (VIII) as a colorless solid. (15% from 2-hydroxyalbecasin) was obtained.

The identification data of the compound (VIII) and 3', 4'-dideoxy-2-hydroxyneamine by ESI-MS, ¹ H NMR, and elemental analysis were as follows.
[Compound (VIII)]
ESI-MS: m / z calculation for C ₁₆ H ₃₃ N ₅ NaO ₇ (M + Na) ⁺ 430.23, found 430.37.
¹ H NMR (500 MHz, DCl-D ₂ O, pD 3): δ 1.57 (1H, dq, H-4'ax), 1.88 (1H, apparent dq, J = ~ 3, ~ 3, ~ 3 and ~ 14 Hz, H-4'eq), 2.13 (1H, m, H-3'''b), 3.05 (1H, dd, H-6'a), 3.10 (2H, m, H-4''' ), 3.21 (1H, dd, H-6'b), 3.36 (1H, t, H-3), 3.47 (1H, apparent t, H-6), 3.50 (1H, apparent ddd, J = 3.5, 6 and ~ 11 Hz, H-2'), 3.69 (1H, t, H-5), 3.71 (1H, t, H-2), 3.85 (1H, t, H-1), 3.91 (1H, apparent t) , H-4), 4.14 (1H, m, H-5'), 4.32 (1H, dd, H-2''') and 5.74 (1H, d, H-1'); J _1,2 = J _2,3 = J _3,4 = J _1,6 = 10.5 Hz, J _4,5 = J _5,6 = 9.5 Hz, J _{1', 2'} = 3.5 Hz, J _{3'ax, 4'ax} = J _{4'ax, 4'eq} = J _{4'ax, 5'} = 12.5 Hz, J _{3'eq, 4'ax} = 5.5 Hz, J _{5', 6'a} = 7.5 Hz, J _{5', 6'b} = 3.5 Hz, J _{6'a, 6'b} = 13.5 Hz, J _{2''', 3'''a} = 8 Hz, J _{2''', 3'''b} = 4 Hz.
Anal. calc. For C ₁₆ H ₃₃ N ₅ O ₆ 1.5H ₂ CO ₃ H ₂ O: C 40.54, H 7.39, N 13.51. Found: C 40.33, H 7.38, N 13.66.
[3', 4'-dideoxy-2-hydroxyneamine]
ESI-MS: m / z calculation for C ₁₂ H ₂₆ N ₄ NaO ₅ (M + H) ⁺ 329.18, found 329.36.
¹ H NMR (500 MHz, DCl-D ₂ O, pD 3): δ 1.57 (1H, dq, H-4'ax), 1.88 (1H, apparent dq, J = ~ 3, ~ 3, ~ 3 and ~ 14 Hz, H-4'eq), 1.93 to 2.06 (2H, H-3'), 3.06 (1H, dd, H-6'a), 3.20 (1H, t, H-1), 3.21 (1H, H-6'b), 3.39 (1H, t, H-3), 3.50 (1H, ddd, H-2'), 3.56 (1H, apparent t, H-6), 3.71 (1H, t, H- 5), 3.86 (1H, t, H-2), 3.96 (1H, apparent t, H-4), 4.14 (1H, m, H-5') and 5.76 (1H, d, H-1'); J _1,2 = J _2,3 = J _3,4 = J _1,6 = 10.5 Hz, J _4,5 = J _5,6 = 9.5 Hz, J _{1', 2'} = 3.5 Hz, J _{2', 3'ax} = 11 Hz, J _{2', 3'eq} = 5.5 Hz, J _{3'ax, 4'ax} = J _{4'ax, 4'eq} = J _{4'ax, 5'} = 12 Hz, J _{3' eq, 4'ax} = 4.5 Hz, J _{5', 6'a} = 7 Hz and J _{6'a, 6'b} = 13.5 Hz.
Anal. calc. For C ₁₂ H ₂₆ N ₄ O ₅ H ₂ CO ₃ H ₂ O: C 40.41, H 7.83, N 14.50. Found: C 40.27, H 7.58, N 14.56.

The identification data of the compounds (I) to (VIII) produced in the above Examples by ¹³ C NMR (in DCl-D ₂ O (pD3)) are as shown in Table 1 below.

(Test Example 1: Antibacterial spectrum)
The antibacterial spectra of the compounds (I) to (VIII) produced in the above examples against the following bacteria including amino glycoside-resistant bacteria were obtained from the Mueller-Hinton agar medium (manufactured by Becton Dickinson) based on the standard method of the Japan Society of Chemotherapy. ) Above, measured by the multiple dilution method. In addition, the antibacterial spectra of the currently used aminoglycoside antibiotics amikacin and gentamicin C ₁ were measured in the same manner against the following bacteria. Table 2 shows the measurement results of the minimum inhibitory concentration (MIC).
[Bacteria used in the test]
・ Staphylococcus aureus
・ Enterobacteriaceae (Escherichia coli: Escherichia coli, Klebsiella pneumoniae, Providencia rettgeri)
・ Pseudomonas aeruginosa
・ Acinetobacter baumannii

From the results in Table 2, the compounds of the present invention, and 16S rRNA methyltransferase producing bacteria resistant to amikacin and gentamicin C _1, an existing aminoglycoside antibiotics, often simultaneously produce the 16S rRNA methyltransferase It was confirmed that it has antibacterial activity against New Delhi metallo-β-lactamase-producing bacteria. In addition, the compound of the present invention has antibacterial activity against aminoglycoside phosphotransferase-producing bacteria, which is a modified inactivating enzyme, and further, it also has antibacterial activity against not only Gram-negative bacteria but also Staphylococcus aureus, which is a Gram-positive bacterium. It was confirmed to have antibacterial activity.

前記一般式（Ａ）中、Ｒ^１は、Ｈ、又はＯＨを表し、
Ｒ^２は、Ｈ、又はＯＨを表し、
Ｒ^３は、Ｈ、又はＯＨを表し、
Ｒ^４は、Ｈを表し、
Ｒ^５は、Ｈ、又はＯＨを表し、
Ｒ^６は、ＮＨ_２、又はＣＨ_２ＮＨ_２を表す。
＜２＞ 前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物を含有することを特徴とする化合物含有組成物である。
＜３＞ 前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物を含有することを特徴とする抗菌剤である。
＜４＞ 細菌の増殖及び個体への細菌の感染の少なくともいずれかを抑制する方法であって、個体に、前記＜３＞に記載の抗菌剤を投与することを特徴とする方法である。
＜５＞ 前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物を含有することを特徴とする医薬組成物である。
＜６＞ 感染症を予防又は治療するためのものである前記＜５＞に記載の医薬組成物である。
＜７＞ 前記感染症が、敗血症、感染性心内膜炎、皮膚科領域感染症、外科感染症、整形外科領域感染症、呼吸器感染症、尿路感染症、腸管感染症、腹膜炎、髄膜炎、眼科領域感染症、及び耳鼻科領域感染症からなる群から選択される少なくとも１種である前記＜６＞に記載の医薬組成物である。
＜８＞ 前記感染症が、黄色ブドウ球菌、腸内細菌科細菌、緑膿菌、及びアシネトバクターバウマニからなる群から選択される少なくとも１種によって引き起こされるものである前記＜６＞から＜７＞のいずれかに記載の医薬組成物である。
＜９＞ 前記感染症が、１６Ｓ ｒＲＮＡメチルトランスフェラーゼ及びニューデリー・メタロ−β−ラクタマーゼの少なくともいずれかを産生する菌によって引き起こされるものである前記＜６＞から＜８＞のいずれかに記載の医薬組成物である。
＜１０＞ 感染症を予防又は治療するための方法であって、個体に、前記＜５＞から＜９＞のいずれかに記載の医薬組成物を投与することを特徴とする方法である。
＜１１＞ 療法に使用するための、前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物である。
＜１２＞ 感染症の予防又は治療において使用するための、前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物である。
＜１３＞ 感染症の予防又は治療を目的とする薬剤の製造のための、前記＜１＞に記載の化合物、又はそれらの薬学的に許容可能な塩、又はそれらの溶媒和物である。 Examples of aspects of the present invention include the following.
<1> A compound represented by the following general formula (A), a pharmaceutically acceptable salt thereof, or a solvate thereof.

In the general formula (A), R ¹ represents H or OH.
R ² represents H or OH.
R ³ represents H or OH.
R ⁴ represents H,
R ⁵ represents H or OH.
R ⁶ represents a NH _2, or _CH 2 NH _2.
<2> A compound-containing composition comprising the compound according to <1>, a pharmaceutically acceptable salt thereof, or a solvate thereof.
<3> An antibacterial agent comprising the compound according to <1>, a pharmaceutically acceptable salt thereof, or a solvate thereof.
<4> A method for suppressing at least one of bacterial growth and bacterial infection to an individual, which comprises administering the antibacterial agent according to <3> to the individual.
<5> A pharmaceutical composition comprising the compound according to <1>, a pharmaceutically acceptable salt thereof, or a solvate thereof.
<6> The pharmaceutical composition according to <5>, which is for preventing or treating an infectious disease.
<7> The infectious diseases include septicemia, infectious endocarditis, dermatological area infection, surgical infection, orthopedic area infection, respiratory infection, urinary tract infection, intestinal infection, peritonitis, and spinal cord. The pharmaceutical composition according to <6>, which is at least one selected from the group consisting of a membrane inflammation, an ophthalmic area infection, and an otolaryngology area infection.
<8> The infection is caused by at least one selected from the group consisting of Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumani. The pharmaceutical composition according to any one.
<9> The pharmaceutical agent according to any one of <6> to <8>, wherein the infectious disease is caused by a bacterium that produces at least one of 16S rRNA methyltransferase and New Delhi metallo-β-lactamase. It is a composition.
<10> A method for preventing or treating an infectious disease, which comprises administering to an individual the pharmaceutical composition according to any one of <5> to <9>.
<11> The compound according to <1> above, or a pharmaceutically acceptable salt thereof, or a solvate thereof for use in therapy.
<12> The compound according to <1> above, a pharmaceutically acceptable salt thereof, or a solvate thereof for use in the prevention or treatment of infectious diseases.
<13> The compound according to <1> above, or a pharmaceutically acceptable salt thereof, or a solvate thereof for producing a drug for the purpose of preventing or treating an infectious disease.

Claims (8)

Compounds, characterized by being represented by the following general formula (A), or pharmaceutically acceptable salts thereof, or solvates thereof:

In the general formula (A), R ¹ represents H or OH.
R ² represents H or OH.
R ³ represents H or OH.
R ⁴ represents H,
R ⁵ represents H or OH.
R ⁶ represents a NH _2, or _CH 2 NH _2. A compound-containing composition comprising the compound according to claim 1, a pharmaceutically acceptable salt thereof, or a solvate thereof. An antibacterial agent comprising the compound according to claim 1, a pharmaceutically acceptable salt thereof, or a solvate thereof. A pharmaceutical composition comprising the compound according to claim 1, a pharmaceutically acceptable salt thereof, or a solvate thereof. The pharmaceutical composition according to claim 4, which is for preventing or treating an infectious disease. The infectious diseases include septicemia, infectious endocarditis, dermatological area infection, surgical infection, orthopedic area infection, respiratory infection, urinary tract infection, intestinal infection, peritonitis, meningitis, The pharmaceutical composition according to claim 5, which is at least one selected from the group consisting of an infectious disease in the ophthalmic region and an infectious disease in the otolaryngology region. The pharmaceutical according to any one of claims 5 to 6, wherein the infectious disease is caused by at least one selected from the group consisting of Staphylococcus aureus, Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumani. Composition. The pharmaceutical composition according to any one of claims 5 to 7, wherein the infectious disease is caused by a bacterium that produces at least one of 16S rRNA methyltransferase and New Delhi metallo-β-lactamase.