JPH041749B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a novel 3-acylamino-4-alkyl-2-azetidinone-1-sulfonic acid derivative, a method for producing the same, and a drug containing the derivative. 3-acylamino-4-alkyl-2 of the present invention
The -azetidinone-1-sulfonic acid derivative is a novel compound that has not been published in any literature, and is represented by the following general formula (). [In the formula, R ¹ represents an amino group or a protected amino group. R ² is 11 or more identical substituents AR ⁴
represents a lower alkyl group substituted with R ³ represents a lower alkyl group. R ⁴ represents a hydrogen atom, lower alkyl, lower alkenyl or lower alkynyl group. A represents an oxygen atom or a sulfur atom. ] In this specification, the protecting group for the protected amino group represented by R ¹ includes conventional amino protecting groups used in penicillin and cephalosporin compounds, such as acyl groups such as formyl, benzoyl, and tosyl, benzyl, and trityl. Examples include phenyl alkyl groups such as. R ² is 1
Methyl, ethyl, propyl, isopropyl, substituted with one or more of the same substituents AR ₄ as described below,
Lower alkyl groups such as butyl, pentyl, neopentyl, and hexyl. The lower alkyl group represented by ^R3 includes methyl, ethyl, propyl,
Examples include isopropyl, butyl, pentyl, neopentyl, hexyl, and the like. As R ⁴ ,
Hydrogen atoms, lower alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, pentyl, neopentyl, hexyl, vinyl, propenyl,
Examples include lower alkenyl groups such as isopropenyl, pentenyl, and hexenyl, and lower alkynyl groups such as acetylenyl and propargyl. In addition, the salts of the compound of the above general formula () include pharmaceutically acceptable salts, such as alkali metal salts (e.g., sodium salts, potassium salts, etc.),
Alkaline earth metal salts (e.g., calcium salts, magnesium salts, etc.), ammonium salts, organic amine salts (e.g., triethylamine salts, pyridine salts, etc.), inorganic acid addition salts (e.g., hydrochlorides, hydrobromide, etc.) ,
Organic acid addition salts (e.g., formate, trifluoroacetate,
methanesulfonate, etc.), and salts with basic or acidic amino acids (eg, arginine salt, aspartate, glutamate, etc.). In the compounds of the present invention () and the starting materials () and () in the processes described below, one or more stereoisomers, such as optical isomers, may exist due to the presence of asymmetric carbon atoms in these molecules. However, such isomers are included within the scope of the present invention. Furthermore, the compound () of the present invention has a syn isomer and an anti isomer, and the present invention includes both of these isomers. In the present invention, the syn isomer is particularly preferred. The compound () of the present invention and its salts can be produced by various methods, and one preferred example thereof can be produced by the method shown below. [In the formula, R ¹ , R ² and R ³ are the same as above. R _1a represents a protected amino group. ] Method 1 will be explained below. The compound ( ) of the present invention or a salt thereof can be produced by reacting the compound ( ) or a reactive derivative at an amino group or a salt thereof with a compound ( ) or a reactive derivative at a carboxyl group or a salt thereof. Suitable salts of compound () and () include the same salts exemplified for compound (). Examples of reactive derivatives at the amino group of the compound () include silyl derivatives formed by the reaction of the compound () with a silyl compound [eg, bis(trimethylsilyl)acetamide, trimethylsilylacetamide, etc.]; isocyanate; isothiocyanate; Examples include Schiff bases formed by the reaction of compound () with carbonyl compounds (e.g., aldehydes such as acetaldehyde and benzaldehyde, and ketones such as acetone and methyl ethyl ketone) or their enamine-type tautomers.Compound () Examples of reactive derivatives at the carboxyl group include acid halides such as acid chlorides and acid bromides; acid anhydrides and symmetrical acid anhydrides; activated acid amides with imidazole, dimethylpyrazole, etc.; P-nitrophenyl ester, phenylthioester, carboxymethylthioester or N-hydroxypiperidine, N-hydroxysuccinimide, N-hydroxy Examples include active esters such as esters with N-hydroxy compounds such as phthalimide.Solvents used in this reaction include, for example, water, acetone, dioxane, acetonitrile, chloroform, benzene, ethyl acetate, N-hydroxy compounds, etc.
Single or mixed solvents that do not adversely affect the reaction, such as N-dimethylformamide, pyridine, hexane, etc., can be used. The reaction temperature is not particularly limited, but it is usually carried out under cooling or heating, preferably at about 0 to 40°C. This reaction can be carried out in the presence of an organic or inorganic base. Such bases include, for example, alkali metals such as lithium, sodium, and potassium; alkaline earth metals such as calcium and magnesium; alkali metal hydroxides such as sodium hydroxide; alkali metal hydrides such as sodium hydride; Alkaline earth metal hydrides such as calcium, alkali metal carbonates such as sodium carbonate, alkali metal hydrogen carbonates such as potassium hydrogen carbonate, alkali metal alkoxides such as sodium ethoxide, trialkylamines such as triethylamine, pyridine, picoline, Examples include nitrogen-containing heterocyclic compounds such as quinoline. Among these, it is preferable to use trialkylamines and nitrogen-containing heterocyclic compounds. The amount of the base used is not particularly limited, but it is usually 25 equivalents or less, preferably 0.25 to 4 equivalents relative to the compound [].
It is best to use equivalent amounts. In the above reaction, compound () and compound ()
The ratio of the former to the latter is not particularly limited and can be selected from a wide range, but usually the ratio of the former to the latter is 1:5.
~5:1 (equivalent ratio), preferably 1:2~2:1. When compound () is used in the form of a free acid or its salt in this reaction, it is preferable to carry out the reaction in the presence of a condensing agent.As a condensing agent, a carbodiimide compound such as N,N'-dicyclohexylcarbodiimide , ketene imine compounds such as diphenylketene-N-cyclohexylimine, unsaturated alkyl ether compounds such as ethoxyacetylene and β-chlorovinylethyl ether, sulfonic acid esters of N-hydroxybenzotriazole derivatives [e.g., 1-(4-chlorobenzenesulfonyl)] 6-chloro-1H
-benzotriazole, etc.], trialkyl phosphite or triphenylphosphine, carbon tetrachloride, ethyl polyphosphate, phosphorus compounds such as phosphorus trichloride, thionyl chloride, and so-called Vilsmeier reagents (N,N-dimethylformamide, Formed by the reaction of an amide compound such as N-methylformamide with a halogen compound such as thionyl chloride, phosphoryl chloride, or phosgene)
can be mentioned. The amount of the condensing agent used is usually 25 equivalents or less, preferably 25 equivalents or less, based on the compound [].
The amount is preferably 0.25 to 4 equivalents. Method 2 will be explained below. Compound (-b) or a salt thereof can be produced by subjecting compound (-a) or a salt thereof to an elimination reaction of the amino protecting group in R ¹ _a .
This elimination reaction can be carried out by conventional methods such as hydrolysis and reduction as shown below. (a) Hydrolysis Hydrolysis is preferably carried out in the presence of an acid.
Suitable acids include, for example, hydrochloric acid, hydrobromic acid,
Inorganic acids such as sulfuric acid, and organic acids such as formic acid, acetic acid, trifluoroacetic acid, propionic acid, benzenesulfonic acid, and P-toluenesulfonic acid are used. For hydrolysis, a single or mixed solvent that does not adversely affect the reaction, such as water, methanol, tetrahydrofuran, N.N-dimethylformamide, dioxane, benzene, hexane, etc., can usually be used. In addition, if the above acid is a liquid,
The acid itself can also be used as a solvent. The reaction temperature for this hydrolysis is not particularly limited, but it is usually preferable to carry out the reaction under cooling or under heating. (b) Reduction Reduction is carried out by conventional methods such as chemical reduction and catalytic reduction. Chemical reducing agents include, for example, tin, zinc,
Metals or metal compounds such as iron, chromium chloride, and chromium acetate, and formic acid, acetic acid, trifluoroacetic acid, P-
Examples include those in combination with organic or inorganic acids such as toluenesulfonic acid, hydrochloric acid, and hydrobromic acid. The catalyst used in the catalytic reduction is, for example, a conventional catalyst containing heavy metals such as platinum, palladium, rhodium, nickel, copper, cobalt, and iron. Catalytic reduction typically involves water, methanol,
A single or mixed solvent that does not adversely affect the reaction, such as N.N-dimethylformamide, hexane, benzene, dioxane, etc., can be used. Moreover, when the above-mentioned acid is a liquid, it can also be used as a solvent. The reaction temperature of this catalytic reduction is not particularly limited, but it is usually preferable to carry out the reaction under cooling or heating. The compound () of the present invention has high antibacterial activity,
It is useful as a preventive or therapeutic agent for bacterial infections. Next, in order to demonstrate the usefulness of the target compound (2), in vitro antibacterial activity test data for representative compounds (2) of the present invention are shown below. All of the following compounds are syn isomers. Test: In vitro antibacterial activity test Compound A: 3-[2-(2-aminothiazol-4-yl)-2-(2-hydroxyethoxyimino)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid Potassium salt B: 3-[2-(2-aminothiazol-4-yl)-2-(2,3-dihydroxypropoxyimino)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt C: 3-[2-(2-aminothiazol-4-yl)-2-(2-vinyloxyethoxyimino)
potassium acetamide]-4-methyl-2-azetidinone-1-sulfonate D: 3-[2-(2-aminothiazol-4-yl)-2-methylthiomethoxyiminoacetamide]-4-methyl-2-azetidinone- 1-
Potassium sulfonate salt test method In vitro antibacterial activity was determined by the 2-fold agar plate dilution method described below. Each test bacterial species was cultured in susceptibility measurement broth for 20 hours (number of viable bacteria: approx.
10 ³ /ml) was inoculated onto a susceptibility measurement agar medium containing various concentrations of antibacterial agents, and after culturing at 37℃ for 20 hours, the nadir inhibitory concentration (MIC) was determined as mg/ml.
Measured in units of. The results are shown in Table 1. Test results

[Table] For comparison, the same test as above was conducted using the following comparative test compound in place of the compound of the present invention (). The results are shown in Table 2 below. Comparison test compound comparison 1...Compound of Example 102 of JP-A-56-125362 [3S-[3α(Z),4β]]-3-[[(2-amino-
4
-thiazolyl)(methoxyimino)acetyl]
Amino]-4-methyl-2-oxo-1-azetidine sulfonic acid potassium salt comparison 2...Compound of Example 103 of JP-A-56-125362 [3S-[3α(Z),4β]]-3-[ [(2-amino-
4
-thiazolyl)[1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-
Methyl-2-oxo-1-azetidinesulfonic acid dipotassium salt comparison 3...Compound (3S,4S)-3-[2-(2-amino-4-thiazolyl) of Example 8 of JP-A-59-1482 -2-(Z)-[(cyanomethoxy)imino]acetamide]-4-methyl-2-oxo-1-azetidinesulfonic acid triethylamine salt

【table】

[Table] As is clear from the comparison between Table 2 and Table 1 above, the compounds of Comparison 1 and Comparison 2 both have lower antibacterial activity against Gram-positive bacteria than the compounds of the present invention, and the compounds of Comparison 1 Furthermore, Pseudomonas
It also has low antibacterial activity against Aeruginosa. The compound of Comparative 2 has considerably poor antibacterial activity against the above-mentioned Gram-positive bacteria, and is considered to be almost ineffective. In addition, the compound of Comparison 3 is Staphylococcus spp.
Although antibacterial activity was observed against Pseudomonas aeruginosa, it was found to be ineffective against Pseudomonas aeruginosa. When administering the compound () of the present invention and its pharmaceutically acceptable salts for prophylactic and therapeutic purposes, it is preferable to use a compound containing the compound as an active ingredient and an organic compound suitable for oral, parenteral and external administration. or in conventional formulations mixed with pharmaceutically acceptable carriers such as inorganic, solid or liquid excipients. The preparation may be in solid form such as tablets, granules, powders, capsules, or as a solution, suspension,
It may be in liquid form such as syrup, emulsion or lemonade. If necessary, the above formulations may contain auxiliary substances, stabilizers, wetting agents, as well as other customary additives,
For example, lactose, magnesium stearate, white porcelain, cane sugar, cornstarch, talc, stearic acid, gelatin, agar, pectin, peanut oil,
Olive oil, cacao butter, ethylene glycol, etc. may be mixed. The dosage of the compound () depends on the patient's age, condition,
It is selected depending on the type of disease, the type of compound () to be administered, etc. Generally, from 1 mg to about
Amounts of 4000 mg or even more can be administered to patients. For the treatment of pathogenic bacterial infections, compound () 1
Approximately 50mg, 100mg, 250mg per dose
Amounts of mg, 500mg, 1000mg, and 2000mg are available. Next, the results of toxicity tests for the compounds of the present invention are shown. Acute toxicity test One group consisted of 10 ICR female mice (6 weeks old). Test compound A used in the above antibacterial activity test
When D was intravenously administered to each of the above mice, the LD ₅₀ values were all 7000 mg/Kg or more. Moreover, when these compounds A to D were orally administered to the above mice, the LD ₅₀ values were all 10,000 mg/Kg or more. Next, production examples of the present invention will be shown as examples. Example 1 3-amino-4-methyl-2-azetidinone-
1-Sulfonic acid (0.900 g), 2-(2-hydroxyethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (syn isomer) (2.365
g), and triethylamine (1.9 ml) N・N
1-Hydroxybenzotriazole (1.013 g) and then N.N'-dicyclohexylcarbodiimide (1.030 g) were added to a dimethylformamide (50 ml) solution with stirring under ice cooling. The mixture was stirred at ambient temperature for 5 hours and then left overnight. The reaction mixture was filtered and the resulting white solid was washed with a small amount of acetone. The liquid and washing liquid were combined and concentrated, and potassium bicarbonate (0.500 g) and water (6
ml) was added and nitrogen was bubbled through for 20 minutes. After lyophilization, the residue was eluted through a silica gel column with chloroform-acetone (volume ratio 1:2). The product-containing eluate was collected and then concentrated to give 3-[2-(2-hydroxyethoxyimino)
-2-(2-tritylaminothiazol-4-yl)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer)
(1.897g) was obtained. NMR δppm (acetone- _d6 ) 1.45 (3H, d, J=6.5Hz) 3.5~4.2 (5H, m) 4.42 (1H, dd, J=8.0, 4.0Hz) 6.67 (1H, s) 7.0~7.5 ( 15H, m) 7.85 (1H, s) 8.88 (1H, d, J=8.0Hz) Example 2 3-[2-(2-hydroxyethoxyimino)-
2-(2-tritylaminothiazol-4-yl)
Acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer)
(1500 g) in 75% acetic acid (30 ml) was heated to 35-40°C and stirred for 5 hours, then water (30 ml) was added to separate the precipitated solid. After washing the solution with benzene, the aqueous layer was freeze-dried to give 3-[2-(2-aminothiazole-4
-yl)-2-(2-hydroxyethoxyimino)
Acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer)
(0.860g) was obtained. NMR δppm (DMSO-d ₆ ) 1.41 (3H, d, J = 6.5Hz) 3.4 - 3.75 (3H, m) 3.9 - 4.15 (2H, m) 4.88 (1H, dd, J = 8.0, 2.5Hz) 6.67 ( 1H, s) 7.10 (2H, brs) 9.08 (1H, d, J=8.0Hz) Example 3 According to the method of Example 1, 3-amino-4-methyl-2-azetidinone-1-sulfonic acid ( 0.900g), 2-(2,3-dihydroxypropoxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (syn isomer) (2.515g), triethylamine (0.7ml), N・N- 3-[2-(2,3-dihydroxy propoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamide]-4
-Methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer) (2.480 g) was obtained. NMR δppm (DMSO-d ₆ ) 1.35 (3H, d, J = 6.5Hz) 3.2 ~ 4.0 (6H, m) 4.30 (1H, dd, J = 8.0, 2.0Hz) 6.65 (1H, s) 7.0 ~ 7.4 ( 15H, m) 8.68 (1H, brs) 9.05 (1H, d, J=8.0Hz) Example 4 According to the method of Example 2, 3-[2-(2,3-dihydroxypropoxyimino)-2-( 2-tritylaminothiazol-4-yl)acetamide]
Using -4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer) (1.100 g) and 75% acetic acid (30 ml), )-2-(2,3-dihydroxypropoxyimino)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer) (0.584 g) was obtained. NMR δppm (DMSO-d ₆ ) 1.40 (3H, d, J=6.5Hz) 3.50-4.05 (6H, m) 4.40 (1H, dd, J=8.0, 2.0Hz) 6.65 (1H, s) 7.10 (2H, brs) 9.10 (1H, d, J = 8.0Hz) Example 5 According to the method of Example 1, 3-amino-4-methyl-2-azetidinone-1-sulfonic acid (0.486 g), 2-(2 -vinyloxyethoxyimino)-2-(2-tritylaminothiazole-4-
yl) acetic acid (syn isomer) (1.497g), triethylamine (0.66ml), N・N-dimethylformamide (5ml), 1-hydroxybenzotriazole (0.603g), N・N′-dicyclohexylcarbodiimide (0.618g) , potassium bicarbonate (0.260
g) using 3-[2-(2-vinyloxyethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamido]-4-methyl-2
-Azetidinone-1-sulfonic acid potassium salt (syn isomer) (1.250 g) was obtained. NMR δppm (DMSO-d ₆ ) 1.34 (3H, d, J = 6.5Hz) 3.5-3.8 (5H, m) 4.14 (2H, t, J = 6.0Hz) 4.30 (1H, dd, J = 8.0, 2.0Hz ) 6.60 (1H, s) 7.80 (15H, m) 8.80 (1H, s) 9.20 (1H, d, J=8.0Hz) Example 6 According to the method of Example 2, 3-[2-(2- vinyloxyethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamide]-4
-Potassium methyl-azetidinone-1-sulfonate (syn isomer) (1.100 g) and 50% acetic acid (10 ml)
3-[2-(2-aminothiazole-4
-yl)-2-(2-vinyloxyethoxyimino)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer)
(0.490g) was obtained. NMR δppm ((DMSO-d ₆ ) 1.34 (3H, d, J=6.5Hz) 3.5-3.8 (5H, m) 4.14 (2H, h, J=6.0Hz) 4.30 (1H, dd, J=8.0, 2.0 Hz) 6.60 (1H, s) 7.20 (2H, s) 9.20 (1H, d, J=8.0Hz) Example 7 3-amino-4-methyl-2-azetidinone-
1-sulfonic acid (0.20 g), 2-(methylthiomethyloxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (syn isomer) (0.80
g) To a solution of triethylamine (0.23 ml) in N,N-dimethylformamide (2 ml) was added N,N'-dicyclohexylcarbodiimide (0.23 g) with stirring under ice cooling. Mixture at room temperature 20
Stir for an hour. The reaction was filtered and the resulting white solid was washed with a small amount of N,N-dimethylformamide. Combine the washing liquid and concentrate, add potassium hydrogen carbonate (0.11 g) and water (2 ml), and add 5 ml of nitrogen.
It lasted for a minute. After lyophilization, the residue was eluted through a silica gel column with chloroform-methanol (6:1 by volume). Furthermore, 3-[2-(methylthiomethyloximino)]-2-(2-tritylaminothiazol-4-yl)acetamide was purified by thin layer chromatography using ethyl acetate-methanol (volume ratio 6:1). ]-4-methyl-2
-Azetidinone-1-sulfonic acid potassium salt (syn isomer) (0.13 g) was obtained. NMR δppm (DMSO-d ₆ ) 1.35 (3H, d, J = 6.5Hz) 2.08 (3H, s) 3.59 (1H, dd, J = 6.5, 2.0Hz) 4.33 (1H, dd, J = 8.0, 2.0Hz ) 5.07 (2H, s) 6.67 (1H, s) 7.27 (15H, s) 8.68 (1H, s) 9.14 (1H, d, J=8.0Hz) Example 8 According to the method of Example 2, 3- [2-(Methylthiomethyloximino)-2-(2-tritylaminothiazol-4-yl)acetamide]-4-
Potassium methyl-2-azetidinone-1-sulfonate (syn isomer) (0.12 g) and 60% acetic acid (6 ml)
3-[2-(2-aminothiazole-4-
yl)-2-(methylthiomethyloxyimino)acetamide]-4-methyl-2-azetidinone-
1-sulfonic acid potassium salt (syn isomer) (0.06
g) was obtained. NMR δppm (DMSO-d ₆ ) 1.38 (3H, d, J = 6.5Hz) 2.22 (3H, s) 3.72 (1H, dd, J = 6.5, 2.0Hz) 4.34 (1H, dd, J = 8.0, 2.0Hz ) 5.25 (2H, s) 7.02 (1H, s) 7.10 (2H, s) 9.05 (1H, d, J=8.0Hz) Example 9 According to the method of Example 1, 3-amino-4-methyl- 2-azetidinone-1-sulfonic acid (0.180 g), 2-(1,3-dihydroxypropoxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (syn isomer) (0.503 g), triethylamine 3- [2-(1,3-dihydroxypropoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamide]-4
-Methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer) (0.48 g) was obtained. ¹ H NMR δppm (DMSO-d ₆ ) 1.35 (3H, d, J=6.5Hz) 3.2-4.0 (6H, m) 4.32 (1H, dd, J=8.0, J=2.0Hz) 6.68 (1H, s) 7.00～7.30 (15H, m) 8.70 (1H, brd) 9.10 (1H, d, J=8.0Hz) Example 10 According to the method of Example 2, 3-[2-(1,3-
dihydroxypropoxyimino)-2-(2-tritylaminothiazol-4-yl)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (syn isomer) (0.400 mg) and 60
3-[2-(2-aminothiazol-4-yl)-2-(1,3-dihydroxypropoxyimino)acetamido]-4-methyl-2-azetidinone-1-sulfonic acid using % acetic acid (10 ml). Potassium salt (syn isomer) (175 mg) was obtained. ¹ H NMR δppm (DMSO- _d6 ) 1.35 (3H, d, J=6.5Hz) 3.30~4.10 (6H, m) 4.30 (1H, dd, J=8.0, J=2.0Hz) 6.68 (1H, s) 7.10 (2H, brd) 9.10 (1H, d, J=8.0Hz)

Claims (1)

[Claims] 1. General formula [In the formula, R ¹ represents an amino group or a protected amino group. R ² is one or more identical substituents AR ⁴
represents a lower alkyl group substituted with R ³ represents a lower alkyl group. R ⁴ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group. A represents an oxygen atom or a sulfur atom. ] 3-acylamino-4-alkyl-2 represented by
-Azetidinone-1-sulfonic acid or salts thereof. 2. The compound according to claim 1, wherein R ¹ is an amino group and R ³ is a methyl group. 3. The compound according to claim 2, wherein A is an oxygen atom. 4 3-[2-(2-aminothiazol-4-yl)-2-(2-hydroxyethoxyimino)acetamide]-4-methyl-2-azetidinone-1
- The compound according to claim 3, which is a sulfonic acid. 5 3-[2-(2-aminothiazol-4-yl)-2-(2-vinyloxyethoxyimino)acetamide]-4-methyl-2-azetidinone-
The compound according to claim 3, which is 1-sulfonic acid. 6 formula [In the formula, R ³ represents a lower alkyl group. ] The general formula [In the formula, R ¹ represents an amino group or a protected amino group. R ² is one or more identical substituents AR ⁴
represents a lower alkyl group substituted with R ⁴ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group. A represents an oxygen atom or a sulfur atom. ] A compound represented by the formula or a reactive derivative of the carboxyl group or a salt thereof is reacted to form the general formula [In the formula, R ¹ , R ² and R ³ are the same as above. ] 3-acylamino-4-alkyl-2 represented by
-A method for producing a 3-acylamino-4-alkyl-2-azetidinone-1-sulfonic acid derivative, which comprises obtaining an azetidinone-1-sulfonic acid derivative or a salt thereof. 7 General formula [In the formula, R ^1a represents a protected amino group. ^R2
represents a lower alkyl group substituted with one or more identical substituents AR ⁴ . R ³ represents a lower alkyl group. R ⁴ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group. A represents an oxygen atom or a sulfur atom. ] 3-acylamino-4-alkyl-2 represented by
-Azetidinone-1-sulfonic acid derivatives or salts thereof are subjected to an amino-protecting group elimination reaction, and the general formula [In the formula, R ² and R ³ are the same as above. ] 3-acylamino-4-alkyl-2 represented by
-A method for producing a 3-acylamino-4-alkyl-2-azetidinone-1-sulfonic acid derivative, which comprises obtaining an azetidinone-1-sulfonic acid derivative or a salt thereof. 8 General formula [In the formula, R ¹ represents an amino group or a protected amino group. R ² is one or more identical substituents AR ⁴
represents a lower alkyl group substituted with R ³ represents a lower alkyl group. R ⁴ represents a hydrogen atom, a lower alkyl group, a lower alkenyl group or a lower alkynyl group. A represents an oxygen atom or a sulfur atom. ] 3-acylamino-4-alkyl-2 represented by
-A prophylactic or therapeutic agent for bacterial infections containing an azetidinone-1-sulfonic acid derivative or a salt thereof as an active ingredient.