JPS6124592A - 3-acylamino-2-azetidinone-1-sulfonic acid derivative, its preparation and drug containing said derivative - Google Patents

Abstract

NEW MATERIAL:The compound of formula I [R<1> is (protected) amino; R<2> is H, (substituted) phenyl, heterocyclic group, alkyl, cycloalkyl, (esterified) carboxyl or halogen; R<3> is H or lower alkyl; R<4> is H or methoxy] or its salt. EXAMPLE:3-[2-( 2-Aminothiazol-4-yl )-2-benzylideneacetamido]-4-methyl-2-azetidinone-1-sulfonic acid. USE:Preventive and remedy for bacteriosis. PREPARATION:The objective compound can be prepared by reacting 3-amino-2- azetidinone-1-sulfonic acid of formula II or its reactive derivative at the amino group or their salts with the compound of formula III or its reactive derivative at the carboxyl group or their salts, in an inert solvent preferably at 0-40 deg.C.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a novel 3-acylamino-2-azetidinone-1-sulfonic acid derivative, a method for producing the same, and a drug containing the derivative.

111'' The 3-acylamino-2-azetidinone-1-sulfonic acid derivative of the present invention is a novel compound that has not been described in any literature, and
It is represented by the following general formula (I).

[In the formula, R1 represents an amine group or a protected amino group; aR2 represents a hydrogen atom, a substituted or unsubstituted phenyl group,
□ indicates a heterocyclic group, a saturated or unsaturated alkyl group, a cycloalkyl group, a carboxyl group that may be esterified, or a halogen atom. R3 represents a hydrogen atom or a lower alkyl group.

R4 represents a hydrogen atom or a methoxy group. ] In Akira Mizukawa's Q book, the protecting group for the protected amino group represented by R1 includes the conventional amino groups used in penicillin and cephalosporin compounds, such as formyl,
Examples include acyl groups such as benzoyl and tosyl, and phenylalkyl groups such as benzyl and trityl. Each fIi group represented by R2 includes a halogen, a nitro group, an amino group, a hydroxyl group, a cyano group, a carboxyl group,
A phenyl group, a heterocyclic group, a saturated or unsaturated alkyl group, a cycloalkyl group, which may be substituted with a lower alkyl group, a lower alkoxy group, a lower alkylthio group, etc.
Examples include a carboxyl group that may be esterified, a hydrogen atom, and a halogen atom. Examples of the lower alkyl group represented by R3 include methyl, ethyl, propyl, isopropyl, and hexyl.

In addition, the salts of the compound of general formula (I) 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 salt, pyridine salt, etc.), inorganic acid addition salts (e.g., hydrochloride, hydrobromide, etc.), organic acid addition salts (e.g., screw salt, trichloride salt, etc.) oral acetate,
methanesulfonate, etc.), and salts with basic or acidic amino acids (eg, arginine salt, aspartate, glutamate, etc.).

In the compound (I) of the present invention and the starting materials II (II) and (III) in the method described below, optical isomers such as 1 due to the presence of asymmetric carbon atoms in these molecules
Although multiple stereoisomers may exist, such isomers are included within the scope of this invention. Further, the compound (I) of the present invention includes J.

A ser, Ct bes, S oc,,90,5
E/Z nomenclature as described in 09 (1968).
There are compounds with the -configuration and compounds with the 2-configuration, and the present invention includes both of these. In the present invention, a 2-configuration structure is particularly suitable.

Compound (I) and its salts of the present invention can be produced by various methods, and one preferred example thereof is the method shown below.

(1) Method 1: (II> (I
[[)(II)...or a reactive derivative at an amino group or a salt thereof (DI)...or a reactive derivative at a carboxyl group or a salt thereof (2) Method 2: (Ia) or a salt thereof R2 (Ib') or a salt thereof [wherein RI, R2, R3 and R4 are the same as above. R
a' represents a protected amino group. ] Method 1 will be explained below.

Compound (I) or a salt thereof of the present invention is compound (I[)
Alternatively, it can be produced by reacting compound (I[I) or a reactive derivative with a carboxyl group or a salt thereof with a reactive derivative with an amino group or a salt thereof.

Suitable salts of compounds (U) and <l1l) include the same salts exemplified for compound (I).

Examples of reactive derivatives at the 7-mino group of compound (I[) include compound (It) and silyl compounds [e.g.
Bis(trimethylsilyl)acetamide, trimethylsilylacetamide, etc.] formed by reaction with silylill! Conductor; Isocyanate; Isothiocyanate; Schiff base formed by the reaction of compound (II) with a carbonyl compound [e.g., aldehydes such as acetaldehyde and benzaldehyde, and ketones such as acetone and methyl ethyl ketone] or its enamine-type tautomer Examples include.

Examples of reactive derivatives at the carboxyl group of the compound (nl[) include acid halides such as acid chlorides and acid bromides; substituted phosphoric acids, dialkyl phosphorous acids, sulfurous acids,
Acid anhydrides and symmetrical acid anhydrides with acids such as thiosulfuric acid, sulfuric acid, alkyl carbonates, and organic carboxylic acids; active acid amides with imidazole, dimethylpyrazole, etc.; p-nitrophenyl ester, phenyldioester, carboxymethylthioester Alternatively, active esters such as esters with N-hydroxy compounds such as N-hydroxypiperidine, N-hydroxyphthalimide, and N-hydroxyphthalimide can be mentioned.

Examples of the solvent used in this reaction include water, acetone, dioxane acetonitrile, chloroform, benzene, ethyl acetate, N.

Single or mixed solvents that do not adversely affect the reaction, such as N-dimethylformamide, pyridine, and hexane, 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, potassium, calcium,
Alkaline earth metals such as magnesium, alkali metal hydroxides such as sodium hydroxide, alkali metal hydrides such as sodium hydride, alkaline earth metal hydrides such as calcium hydride, 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, and nitrogen-containing heterocyclic compounds such as lysine, picoline, and quinoline.

Among these, it is preferable to use trialkylamines and nitrogen-containing heterocyclic compounds. The amount of the base to be used is not particularly limited, but it is usually 25 equivalents or less, preferably 0.25 to 4 equivalents, relative to compound (I()).

In the above reaction, the ratio of compound (II) and compound (Iff) to be used is not particularly limited and can be selected from a wide range, but usually the former:the latter is 1:5 to 5:1 (equivalent ratio), The ratio is preferably 1:2 to 2:1.

When compound (III) is used in the form of vista or a salt thereof in this reaction, it is preferable to carry out the reaction in the presence of a condensing agent. As a condensing agent, N, N'-
Carbodiimide compounds such as dicyclohexylcarbodiimide, ketene imine compounds such as diphenylketene-N-cyclohexylimine, ethoxyacetylene, β-
Unsaturated alkyl ether compounds such as chlorovinylethyl ether, sulfonic acid esters of N-hydroxybenzotriazole derivatives [e.g., 1-(4-chlorobenzenesulfonyloxy)-6-rirollo-penzotriazole, etc.], In addition to alkyl phosphites or triphenylphosphine and carbon tetrachloride, ethyl polyphosphate, phosphorus compounds such as phosphorus trichloride, thionyl chloride, and so-called Vilsmey V-reagents (N, N-dimethylformamide, N--methylformamide, etc.) (formed by the reaction of an amide compound with a halogen compound such as thionyl chloride, phosphoryl chloride, or phosgene). The amount of the condensing agent used is usually compound (II
), preferably 0.25 to 4 equivalents C
It is better to

Method 2 will be explained below.

Compound (Ib) or a salt thereof can be produced by subjecting Compound (Ia) or a salt thereof to an elimination reaction of the amino protecting group in Ra1. This IB2gt reaction can be carried out by conventional methods such as hydrolysis and reduction as shown below.

(b) Hydrolysis Hydrolysis is preferably carried out in the presence of an acid.

Suitable acids include, for example, inorganic acids such as hydrochloric acid, hydrobromic acid, and sulfuric acid, and inorganic acids such as formic acid, acetic acid, trifluoroacetic acid, butionic acid, benzenesulfonic acid, and l)-trienesulfonic acid.

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. Moreover, when the above-mentioned acid is a liquid, this acid itself can 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, metals or metal compounds such as tin, zinc, iron, chromium chloride, chromium acetate, and
B, acetic acid, trifluoroacetic acid, pt-toluenesulfonic acid, hydrochloric acid, hydrobromic acid and other organic or l1Irn-free combinations.

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. Contact reduction is
Usually, a single or mixed solvent that does not adversely affect the reaction, such as water, methanol, 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.

Compound (I) of the present invention has high antibacterial activity and is useful as a prophylactic or therapeutic agent for bacterial infections.

Next, to demonstrate the usefulness of the compound (I) of the present invention.

In vitro antibacterial activity test data for representative compounds of the compound (I) of the present invention are shown below.

All of the following compounds are Z isomers.

Translation: In vitro antibacterial activity Translation: Compound A: 3-(2-(2-7minothiazol-4-yl)-
2-Benzylizolineacetamide]-4-methyl-2-
7zetidinone-1-sulfonic acid potassium salt B: 3-(2-(2-aminothiazol-4-yl)-
2-(2-tenylidene)acetamido)-4-methyl-
2-Azetidinone-1-sulfonic acid potassium salt C: 3- (2-(2-7minothiazol-4-yl)
-2-(2-furfurylidene)acetamido-4-methyl-2-fuzetidinone-1-sulfonic acid potassium salt In vitro antibacterial activity was determined by the following 2x agar plate dilution method. Each test type i was cultured in susceptible fenestration broth for 20 hours.
005 Ura, each f! The cells were inoculated onto an agar medium for susceptibility measurement containing a certain concentration of antibacterial agent, and after culturing at 37° C. for 20 hours, the minimum inhibition rate (MIG) was measured in units of tZal4. The results are shown in Table 1.

Table 1 When administering the compound (I) of the present invention and its salts for prophylactic and therapeutic purposes, organic or They are used in conventional formulations mixed with pharmaceutically acceptable carriers such as inorganic, solid or liquid excipients. The formulation may be in solid form such as tablets, granules, powders, capsules, or in liquid form such as solutions, suspensions, syrups, emulsions, lemonades, etc. If necessary, the above formulations may be supplemented with auxiliary substances, stabilizers, wetting agents, as well as other customary additives, such as lactose, magnesium stearate, china clay,
Sucrose, cornstarch, talc, stearic acid, gelatin, agar, pectin, peanut oil, olive oil, cocoa butter, ethylene glycol, and the like may be mixed.

The method of administering compound (I) is selected depending on the patient's age, condition, type of disease, type of compound (I) to be administered, etc. Generally, between 1 rAg and about 40,001!1 grams or even more can be administered to a patient per day. For the treatment of pathogenic bacterial infections, the average dosage per dose of compound (I) is about 50Il1g, 10011117.25011g,
500II1g, 10001110.2000mo M
can be used.

K-”L”1 Next, production examples of the present invention will be shown as examples.

Example 1 Preparation of potassium 3-[2-benzylidene-2-(2-tritylaminothiazol-4-yl)ace1-amide]-4-methyl-2-azetidinone-1-sulfonate (2-isomer) 3 -amino-4-methyl-2-azetidinone-1-sulfo',/m (0,1511), triethylamine <0.12 m) and 1-hydroxybenzotriazole (0,17 g) in N,N-dimethylformamide (5
1119) N,N-dicyclohexylcarbodiimide (0,17a) was added to the solution with stirring. After 5 minutes, 3-phenyl-2-(2-tritylaminothiazol-4-yl)propenoic acid (0,31
g) (Z isomer) was gradually added and the mixture was stirred at room temperature for 15 minutes.
Stir for hours. The reaction mixture was filtered, and the white solid obtained was washed with a small amount of N,N-dimethylformamide.
7a) and water (0,65-) were added and nitrogen was bubbled through.

After freeze-drying this, the residue was evaporated into ethyl acetate-methanol (
0.40 g (89.6%) of 3-(2-benzylidene-2-(2-tridelaminodeazol-4-yl)acetamido-4) was obtained by thin layer chromatography using a volume ratio of 3:1. -Methyl-2-azetidinone-1-potassium sulfonate (M (Z-isomer)) was obtained.

NMR6ppm (DMSOd6)1.35 (3
1-1, d 1J=6.5Hz), 3.63(IH,
翰), 4, 35 (I H, d, do, J=2.OH2.

J-8,0H2), 6.28 (IH,s), 6.64 (IH,s), 7.25 (5H,s), 7.30 (15H,s), 8, 57 (IH,s ), 9.00 (
IH,d, J-8,0Hz,).

Example 2 Preparation of potassium 3-(2-(2-aminothiazol-4-yl)-{2-benzylideneacetamide]-4-methyl-2-azetidinone-1-sulfonate (Z-isomer) 3-[ 2-benzylidene-2-(2-tritylaminothiazol-4-yl)acetamido-4-methyl-2
-Potassium azetidinone-1-sulfonate (2 isomers)
(0,181 J') in aqueous acetic acid (volume ratio 60%, 5
m> was stirred at room temperature for 3 hours. A small amount of water was added, and the precipitated white crystals were removed by filtration. The mother liquor was freeze-dried, and the obtained yellow crystals were purified using a Sephadex LH-20 column (methanol) to give 3-(2-(2-7
0.95 g (82%) of potassium minothiazol-4-yl)-2-benzylideneacetamide)-4-methyl-2-azetidinone-1-sulfonate (Z-isomer) was obtained.

NMR609m (DMSOds) 1.37
(3H, d, J=6.5H2), 3.62
(IH,m), 4.39 (1H,d,dl,J=2.0H2.

J-8,OH2), 6.33 (1H,s), 7.02 (2H,s), 7, 10 (IH,s), 7, 29
(5H,s), 9.02 (IH,d,
J-8,0Hz).

Example 3 Potassium 3-(2-(2-tenylidene)-2-(2-tridelaminodeazol-4-yl)acetamide]-4-medy-2-azetidinone-1-sulfonate (Z
-isomer) 3-amino-4-methyl-2-azetidinone-1-sulfonic acid (0,11 g), triethylamine (0,091
11) and 1-hydroxybenzotriazole (0,
N,N-dicyclohexylcarbodiimide (0,13a) was added to a solution of N,N-dimethylformamide (119) with stirring.After 5 minutes, 3-(2- chenyl)-2-(2-tritylaminothiazol-"4-yl)propenoic acid (0,21
a) was added slowly and the mixture was stirred at room temperature for 38 hours.

The reaction was filtered and the resulting white solid was treated with a small amount of N.

Washed with N-dimethylformamide. The furnace liquor and washing liquor were combined and concentrated, potassium bicarbonate (0.15 g) and water (1.5111 f2) were added, and nitrogen was bubbled through. After freeze-drying, the residue was purified with a silica gel column using chloroform-methanol (volume ratio 5:1).
(2-(2-tenylidene)-2-(2-tritylaminothiazole"-4-nor)acetamido-4-methyl-2-azetidinone-1-potassium sulfonate (Z-
isomer) 0.090 (30.9%) was obtained.

NMR15+) DI (DMSOd g )1.38
(3H,d, J-6,5Hz), 3.62 (1
81m), 4.37 (1H, d, do, J-2, 5H2.

J=8.0Hz), 6, 21 (IH,S), 6.90-7.
58 (4H, m), 7, 26 (15
H1s), 8.54 (IH,s)
, 9.15 (it-1, d% J-8, OH2).

Example 4 3-(2-(2-aminothiazol-4-yl)-2
-(2-tenylidene)acetamido-4-meb-ru Preparation of potassium 2-azetidinone-1-sulfonate (Z-isomer) 3-(2-(2-tenylidene)-2-(2-tridelamino) Potassium thiazol-4-yl)acetamido-4-methyl-2-azetidinone-1-sulfonate (Z
isomer) (0,085a) in acetic acid aqueous solution (volume ratio 70
%, 3 Peng) was stirred at 35-40°C for 1 hour. A small amount of water was added and the precipitated white crystals were removed by filtration.

The mother liquor was freeze-dried, and the resulting yellow powder was purified using a Sephadex LH-20 column (methanol) to obtain 3-(
2-(2-aminothiazol-4-yl)-2-(2-
Potassium (Z-isomer) 0.0
16 g (29.9%) were obtained.

NMR6pD! l (DMSOds) 1.44 (3H
1d, J-6,5Hz), 3.55 (IH, bending)
, 4, 45 (1H, d, d,, J=2.5Hz.

J=8.0H2''), 6.28 (IHSs), 7.02 (2H,s), 7.15 (2H,m), 7.25 (IH,s), 7.52 (1H,d, J-5,5Hz>,9.1
8 (1H, d, J=8.0Hz).

Example 5 3-(2-(2-furfurylidene)-2-(2-tritylaminothiazol-4-yl)acetamide 4
-Production of potassium methyl-2-azetidinone-1-sulfonate (Z-isomer) 3-amino-4-methyl-2-azetidinone-1-sulfone M (0,14(+), triethylamine (0,11 m2) ) and 1-hydroxybenzotriazole (0,14o) in N,N-dimethylformamide (3 m2) Fin' with stirring.
N-dicyclohexylcarbodiimide (0,16o) was added. After 5 minutes, while stirring, add 3-(2-geryl)-2-(2-tritylaminothiazol-4-yl).
Propenone IT! (0,249) (Z isomer) was added slowly and the mixture was stirred at room temperature for 15 hours. The reaction was filtered and the resulting white solid was washed with a small amount of N,N-dimethylformamide.

The SP solution and washing solution were combined and concentrated, and potassium hydrogen carbonate (0
, 159) and water (1,54) were added and nitrogen was bubbled through.

After freeze-drying, the residue was purified using a silica gel column using chloroform-methanol (volume ratio 5:1).
0.19 g (56.0%) of potassium tritylaminothiazol-4-yl)acetamido]-4-methyl-2-azetidinone-1-sulfonate (Z-isomer) was obtained.

NMR61) Dll (DMSOds) 1.33
(3H, d, J=6.5Hz), 3.54 (1H
, rp ), 4.35 (IH, d, d, , J=2.5H7.

J=8.0Hz), 6.42 (2H, s), 7.27 (17H, s), 7.53 (I Hls), 8.55 (IH, s), 8.93 (IHld, J=8.0Hz).

Actual journey example 6 3-(2-(2-aminothiazol-4-yl)-2
-(2-furfurylidene)acetamide]-4-Methyl-2-azetidinone-1-potassium sulfonate (Z-isomer) 3-(2-(2-furfurylidene)-2-(2-tritylaminothiazole-4) -i, l) acetamide) -4
An aqueous acetic acid solution (volume ratio 70%, 2%) of potassium -methyl-2-azetidinone-1-sulfonate (Z isomer) (0,18<1) was stirred at 35 to 40°C for 1.5 hours. A small amount of water was added, and the precipitated white crystals were removed by i-filtration. The mother liquor was condensed and dried, and the yellow crystals obtained were transferred to a Sephadex L 1-1-20 column (methanol).
M@ and 3-(2-(2-aminothiazole-4
-yl)-2-(2-furfurylidene)acetamide)
= Potassium 4-methyl-2-azetidinone-1-sulfonate (ZlN form>0.02J (17.5%))
! ? Ta.

NMRδppm (DMSOd6)1.44 (
3H, d, J=6.5Hz), 3.78 <18.
m), 4.45 (IH, d, do, J=2.5Hz.

J=8.0Hz), 6.34 (IH13), 6.55 (21-1, m), 6.95 (IH,S), 7.04 (2H,S), 7.64 (IHls) , 9.05 (I
H, d, J-8,0Hz>.

Example 7 3-(2-(4-methoxybenzylidene)-2-(2
Preparation of potassium tritylaminothiazol-4-yl)acetamide]-4-methyl-2-azetidinone-1-sulfonate (Z-isomer) 3-amino-4-methyl-
2-azetidinone-1-sulfone II (0.14 g),
N,N, was added to a solution of triethylamine (0,111d) and 1-hydroxybenzotriazole (0,1412) in N,N-dimethylformamide (3Peng) with stirring.
N-dicyclohexylcarbodiimide (0.16 g) was added. After 5 minutes, 3-(4-methoxyphenyl)-2-(2-tritylaminothiazole-
4-yl)propenone (0,260) (Z isomer) was slowly added and the mixture was stirred at room temperature for 5 hours. The reaction was filtered and the resulting white solid was washed with a small amount of N,N-dimethylformamide. The furnace liquid and washing liquid were combined and concentrated, and potassium hydrogen carbonate (0, -15 (]) and water (1,5
) was added and nitrogen was passed through. After freeze-drying, the residue was purified by silica gel column chromatography using chloroform-methanol (volume ratio 5:1).
- (2-(4-methoxybenzylidene)-2-(2-
0.16% (44.6%) of tritylaminothiazole-4-,yl)acetamido]-4-methyl-2-azetidinone-1-sulfonic acid potassium salt (2-isomer) was obtained.

NMR6rll)III (DMSOds)1.3
7 (3H, d, J=6.5Hz), 3.62 (
IH,m), 3.75 (3H,s), 4.35 (IH,d,d,, J-2,0Hz.

J=8.0) (z), 6.32 (IH,S), 6.65 (1H,S), 6.81 (2H,d, J=9.0Hz), 7.1
7 (2H,d, J-9,0Hz), 7.30 (
15H,s), 8, 52 (IH,s), 8.96 (
1H, d Mi J=8.0Hz) a Example 8 3-(2-(2-aminothiazol-4-yl)-2-
Potassium (4-methoxybenzylidene)acetamide)-4-methyl-2-azetidinone-1-sulfonate (Z
-isomer) 3- (2-(4-methoxybenzylidene)-2-(2
-tritylaminothiazol-4-yl)acetamido-4-methyl-2-azetidinone-1-potassium sulfonate (Z isomer) '(0,15o) in acetic acid aqueous solution (volume ratio 70%, 3.5p) 1 at 35-40℃
After stirring for an hour, a small amount of water was added, and the precipitated white crystals were removed by filtration. The mother liquor was freeze-dried, and the resulting slightly yellow powder was purified using a Sephadex LH-20 column (methanol) to obtain 3-(2-(2-aminothiazol-4-yl)-2-(4-methoxybenzylidene)). Potassium acetamido-4-methyl-2-azetidinone-1-sulfonate (Z-isomer) 8.2 mo (8.2%)
I got it.

NMR, 6ppm (DMSOdr, )1.3
8 (3H, d, J = 6.5Hz)
, 3.66<IH,m), 3, 74 <38. s ), 4.37 (
IHl d, d,, J=2. OH2.

J=8-OH2), 6, 25 (IH=s), 6.84
(2H,d, J-9,0Hz), 6.9
6 (IHls), 7.04 (2H,
s), 7.32 (2H, d, J-9,0Hz)
, 8.98 (IH, d 1 J-8,0Hz
>.

Example 9 3-(2-(4-carboxybenzylidene)-2-(
Preparation of potassium 2-t-ditylaminothiazol-4-yl)acetamido-4-methyl-2-azetidinone-1-sulfonate (2-isomer) 3-amino-4-methyl-2-azetidinone-1- Sur, Hong ff1 (0,1
2o), triethylamine (0,09mG) and 1
- In a solution of hydroxybenzo I lyazole (0,13a) in N,N-dimethylformamide (2,5 mG),
N while stirring.

N-dicyclohexylcarbodiimide (0.14 g) was added. After 5 minutes, while stirring, 3--(4-carboxyphenyl)-2-(2-tritylaminothiazol-4-yl)propenoic acid (0,35+II) (Z
isomer) was added gradually and the mixture was stirred at room temperature for 15 hours. Reactants! P'iAt... The resulting white solid was washed with a small amount of N,N-dimethylformamide. )P
The liquid and washing liquid were combined and concentrated, and potassium hydrogen carbonate (0.3
0g> and water (3,01112) were added and nitrogen was bubbled through. After freezing and drying this, the residue was separated using Sephadex LH-2.
Purified with 0 column (methanol) and purified with 3-(2-(4-
carboxybenzylidene)-2-(2-tritylaminothiazol-4-yl)acetamido-4-methyl-
0.17o (33.5%) of 2-azetidinone-1-sulfone-12 potassium (Z-isomer) was obtained.

NMRδl>13 (DMSOd6>1.3
9 (3H1d, J=6.5H2), 3, 69
<IH, m ) , 4, 52 (IH, d
,d,,J=2. OH2.

J=8.0Hz), 6, 47 (IH,S), 6, 75
(IH,S), 7.27 (2H,dS
J=8.0Hz), 7, 28 (15H
1s ), 7, 79 (2H,d, J=
'8.0Hz)8, 62 (1H,S)
, 9.11 (IH,d, J=8.0Hz
).

Real example 10 3- (2-(2-aminothiazol-4-yl)-2
-(4-carboxybenzylidene)acetamido-4
-Preparation of dipotassium methyl-2-azetidinone-1-sulponate (2-isomer) 3, -(2-(4-carboxybenzylidene)-2-(2-1-ditylaminothiazol-4-yl)acetamide ]-4-Methyl-2-azetidinone-1-sulfone m2 potassium (Z isomer) (0
, 16 o) acetic acid aqueous solution (volume ratio 70%, 3 ml)
Stirred at ~40°C for 4 hours. Water with a low R content was added, and the precipitated white crystals were removed by filtration. The mother liquor was freeze-dried, and the resulting yellow powder was purified using a Sephadex LH-20 column (methanol) to obtain 3-(2-(2-7minothiazol-4-yl)-2-(4-carboxybenzylidene)acetamide). )-4-Methyl-2-7zetidinone-1-sulfonic acid dipotassium (Z-isomer) 211
! J (19.1%) was obtained.

NMR6ppm (DMSOda) 1.34 (3H, d 1J-6,5Hz), 3.6
4 (IH, ll1), 4, 24 (I H, d, do, J=2.OH2.

J-8,0Hz), 6.35 (181s), 6.60 (IH,s), 6.77 (2H,s), 7.48 (2H1d 1J-8,0Hz), 7,
68 <28. d, J=8.0Hz),
7, 69 (IH, (+,'J=8.0Hz
).

Example 1゛1 3-, (2-1 carboxymethylene, -2-(2-tridelaminodeazol-4-yl)acetamide)-4
-Production of potassium methyl-2-azetidinone-1-sulfonate (Z-isomer) 3-amino-4-methyl-2-azetidinone-1-sulfone YJ (0,79o), triethylamine (0,6
1110) and 1-hydroxybenzotriazole (
0,89u) of N,N-dimethylformamide (151
1G) N into the solution with stirring.

N-dicyclohexylcarbodiimide (0,910) was added. After 5 minutes, while stirring, add 2-(2-1-lythylaminothiazol-4-yl)
Og) (Z isomer) was gradually added and the mixture was stirred at room temperature for 7 hours.
Stirred for 0 hours. The reaction was filtered and the resulting white solid was washed with a small amount of N,N-dimethylformamide. t
Pn and washing liquid were combined to condense 8I, and potassium hydrogen carbonate (0
, 5a) and water (5a) were added and nitrogen was passed through. After freeze-drying, the residue was purified by silica gel column chromatography using chloroform-methanol (volume ratio 5:1), and 3-(2-carboxymethylene-2
-(2-tritylaminothiazol-4-yl)acetamido-4-methyl-2-azetidinone-1-sulfonic acid dipotassium (Z-isomer) 0.09o (3,0
%) was obtained.

Purification also isolated 0.11 o of 3-[2-carboxy-2-(2-tritylaminothiazol-4-yl)methyleneacetamido-4-methyl-2-azetidinone-1-sulfone R2 potassium.

NMRδppm (DMSOd6) 1.27 (3H,d, J-6,5Hz), 3.4
8 (IH%l), 4, 13 (IH%d, d,, J-2,0Hz.

J-8,0Hz), 5.58 (IH, s), 6. 57 (IHLs), 7.22 (15H, s), 8.31 (IH, s), 9.94 (IH, d, J=8.0Hz).

Example 12 3-(2-,12-aminothiazol-4-yl)-2
-carboxymethyleneacetamide]-4-methyl-2
-7 Preparation of zetidinone-1-sulfonic acid dipotassium (2-isomer) 3-[2-carboxymethylene-2-(2-trideraminothiazol-4-yl)acetamido-4-methyl-2-azetidinone-1 - Dipotassium sulfonate (2
isomer) (0,09o) in vinegar m water in mM (WfJI ratio 70%, 31M>) was stirred at 35-40°C for 2 hours. A small amount of water was added and the precipitated white crystals were removed by filtration. Mother liquor The yellow crystals obtained were purified using a Sephadex L) l-20 column (methanol) to give 3-(2-(2-7minothiazol-4-yl)-
2-Carboxymethyleneacetamide]-4-methyl-2-azetidinone-1-sulfone W12 potassium (Z
-isomer) 14.6 mg (24.8%) was obtained.

NMRδ11pif (DMSOda) 1.37 (
3H, d%J=6.5Hz), 3, 62 (IH, l
it), 4.25 (IH, d, dl, J=2.0Hz, J=8
．． 0Hz), 6.07 (IH%S), 6.68 (IH,s), 6.83 (2H%S), 9.85 (1H,d, J=8.0Hz).

Example 13 3-(2-<4-bromobenzylidene)-2-(2-
Preparation of potassium tritylaminothiazol-4-yl)acetamido-4-methyl-2-azetidinone-1-sulfonate (Z-isomer) 3-amino-4-methyl-2
-7 Zetidinone-1-sulfonic acid (0.18 g), triethylamine (0.14 mQ) and 1-hydroxybenzotriazole (0.202 Q) were added to a solution of N,N-dimethylformamide (3 parts) without stirring. .

N-dicyclohexylcarbodiimide (0,206 (J )) was added. After 5 minutes, while stirring, 3-(4-bromophenyl)-2-(2-trideraminothiazol-4-yl)propenoic acid was added. (0,56
7o) (Z isomer) was added slowly and the mixture was stirred at room temperature for 15 hours. The reaction was filtered and the resulting white solid was washed with a small amount of N,N-dimethylformamide. The furnace liquid and washing liquid were combined and concentrated, and potassium hydrogen carbonate (0,
1 g) and water (1 raQ) were added and nitrogen was bubbled through. After lyophilization, the residue was subjected to silica gel column chromatography using edyl acetate-methanol (volume ratio 3:1) to obtain 0.19c+ (25%) of 3- (2-
Potassium (4-bromobenzylidene)-2-(2-tritylaminothiazol-4-yl)acetamido-4-medy-2-azetidinone-1-sulfonate FA (Z
-isomer) was obtained.

NMR6ppm (DMSOda)1.35 (3
HSd, J-6,5Hz'), 3.56 (1H,
rn), 4, 37 (I H16, do,
J=2.0Hz.

J=8.0Hz>, 6.37 (1H1s), 7.10 (IH1s), 7.25-7.
35 (19H%I'l'), 8.50 (I
HS s ), 9.02 (1HS d ,
J=8.0Hz>.

Example 14 3-(2-(2-aminothiazol-4-yl)-2-
(4-bromobenzylidene)acetamide)=potassium 4-methyl-2-azetidinone-1-sulfonate (Z-
Production of 3-(2-(4-bromobenzylidene)-2-(2-
Tritylaminothiazol-4-yl) acetamido-4-methyl-2-azetidinone-1-potassium sulfonate (2 isomers) (0,180) in acetic acid aqueous solution (volume ratio 80%, 5 relatives) was added to Stir for hours. A small amount of water was added and the precipitated white crystals were removed by filtration. The mother liquor was freeze-dried, and the resulting pale yellow crystals were purified using a Sephadex LH-20 column (methanol), and then purified again.
! By drying, 3-(2-(2-aminodeazol-4-yl)-2-(4-bromobenzylidene)acetamido-4-methyl-2-azededinone-
Potassium 1-sulfonate (Z-isomer) 0.047a
(40%).

NMR6ppm (DMSOds)1.38 (3
H, d, J=6.5H7), 3, 5 b
(1H, m), 4, 35 < I H, d, d
,,J=2. OH2.

, No-8. 0Hz), C3,40('IH,S), 7.05 (2H, S), 7.25 <18. s), 7.40 (4H1ta), 9.05 (IH, d, J-8, 0H2).

Example 15 3-(2-(4-hydroxybenzylidene)-2-(
Preparation of potassium 2-t-ditylaminothiazol-4-yl)acetamido-4-methyl-2-azetidinone-1-sulfonate (2-isomer) 3-amino-4-methyl-2-azetidinone-1-sulfone Acid (0,18g)
, triethylamine (0,14Tl12) and 1-hydroxybenzotriazole (0,202(] )]
N,N-dimethylformamide (3 mG) solution with stirring.

N-dicyclohexylcarbodiimide (0,206o) was added. After 5 minutes, 3-(4-hydroxyphenyl)-2-(2-tritylaminothiazol-4-yl)propenoic acid (0,4
88(] ) (Z isomer) was gradually added and the mixture was ul
The mixture was stirred for 18 hours. Reactants? The resulting white solid was washed with a small amount of N,N-dimethylformamide. The iP solution and washing solution were combined and concentrated, and potassium bicarbonate (
0,1) and water (14) were added and nitrogen was bubbled through. After freeze-drying this, the residue was converted into ethyl acetate-benzene (volume ratio: 1
:3) was purified by silica gel column chromatography using -Azetidinone-
1-sulfonic acid potassium salt (7-isomer) 0.21+1
(28%) was obtained.

N M RδI)Dllll (DMSOd e )1
．． 3[3(3H,d, J=6.5F-1z,), 3
．． 57 (IH, m), 4.38 (IH, d, do, J=2.0H7.

J=8.0Hz), 0.15 (IH,s), 6.50 (21-1, d, J=7.0Hz), 7.
05 <28. d, J-7,0Hz), 7.15(
IH,s), 7.25 (15H,,m), 8.40 (IH,s), 8.87 (IH,d, J=8.0Hz>.

Example 16 3-(2-(2-aminothiazol-4-yl)-2
-14-hydroxybenzylidene)acetamide)-4
-Methyl-2-azetidinone-1-potassium sulfonate (Z-isomer) In3- (2-(4-hydroxybenzylidene) = 2-(2-trideraminothiazole-
Potassium 4-yl)acetamido)-4-methyl-2-7zetidinone-1-sulfonate (2 isomers) (0,
2g) @ acid aqueous solution 311' (volume ratio 60%, 101!1
12) was stirred at room temperature for 3 hours. A small amount of water was added, and the precipitated white crystals were removed by filtration. The mother liquor was freeze-dried, and the resulting white crystals were purified using a Sephadex LH-20 column (water), freeze-dried again, and 3-(
2-(2-aminothiazol-4-yl)-2-(4-
0.07 g (50%) of potassium 4-methyl-2-azetidinone-1-sulfonate (Z-isomer) was obtained.

NMRδDDIn (DMSOds) 1.40
<38. d, J-6,5Hz), 3.60 (IH
, m ), 4.34 (IHld, d, , J-2, OH2, J=8
．． 0H2), 6, 13 (IH,S), 6.50 (2
H, d, J-T7. OHz >, 6.90 (2H
,S), 7.05 (2H,d, J=7.0f-1z)
7.10 (IHlS), 8.85 (IH, d, J=8.0Hz)
.

Example 17 3-(2--monochloromethylene-2-(2-tri1-
Ruminodeazol-4-yl)acetamido)-4-
Potassium methyl-2-azetidinone-1-sulfonate (
Preparation of 3-amino-4-methyl-2-azetidinone-1-sulfonic acid (0,09!If ), triethylamine (0
,07vQ> and 1-hydroxybenzotriazole (0,101 g) in N,N-dimethylformamide (2
112> N into the solution while stirring.

N-dicyclohexylcarbodiimide (0°1021J) was added. After 5 minutes, 2-monochloromethylene-2-(2-t-lytylaminodiazol-4-yl)acetic acid (0,223 (J)
Z isomer) was added slowly and the mixture was stirred at room temperature for 16 hours. The reaction was filtered and the resulting white solid was washed with a small amount of N,N-dimethylformamide. The tP solution and washing solution were combined and condensed by 3, and potassium hydrogen carbonate (0.05 (J
) and water (0,5-) were added and nitrogen was bubbled through. After freeze-drying this, the residue was converted into ethyl acetate-benzene (volume ratio: 1
3-[2-monochloromethylene-2-(2-tritylaminothiazol-4-yl)acetamide 4-
0.23 g (60%) of methyl-2-azetidinone-1-sulfonic acid potassium salt (Z-isomer) was obtained.

NMR6ppm (DMSOd6) 1.34 (3H,d, J-6,5Hz), 3.5
6 (IH,m>, 4.32(1)(,d,do,J=2.0Hz.

J-8,0H2), 6.22 (IHLs), 6.95 (2HSs), 7.12 (IH,s) 7.25 (15H, 1° heat, 8.42 (1H,s), 8 , 8/l (1t1, tJ,
J=8. 0Hz, ).

Example 18 3-(2-(2-aminothiazol-4-yl)-2
-monochloromethyleneacetamide)-4-nobu-ru-2-azetidinone-1-potassium sulfonate (Z-isomer) 3- (2-monochloromethylene-2-(2-trideraminothiazol-4-yl) Potassium acetamido-4-methyl-2-azetidinone-1-sulfonate (Z
isomer) (0.21 g) in acetic acid aqueous solution (volume ratio 70%,
5Wl(1) in the groove for 2 hours fi I! I did l'-.

A small amount of water was added, and the precipitated white crystals were filtered off. The mother liquor was freeze-dried, and the resulting pale yellow crystals were purified using a Sephadex LH-20 column (methanol) and freeze-dried again to give 3-(2-(2
-aminothiazol-4-yl)-2-monochloromethyleneacetamide]-4-methyl-2-azetidinone-
1-sulfone n potassium (Z-isomer) 0.03(](
2196) was obtained.

NMRI5D11m <DMSOd a ) 1.36
(3H, d, J=6.5Hz), 3.55 (I
H, m ), 4.30 (I H, d, d, , J=2.0Hz.

J=8. OH2), 6.20 (1H, s), 6.95 (2H, s), 7.10 (IH,s), 8.85 (IH, d, J=8.0Hz).

Example 19 3-[2-Butylidene-2-(2-tritylaminodeazol-4-yl)acetamidocy4-methyl-2-
Potassium azetidinone-1-sulfonate (2-isomer)
Preparation of 3-amino-4-methyl-2-azetidinone-1-sulfone I? ! (0,o9o), l'ethylamine (0
,0711J2) and 1-hydroxybenzotriazole (0,101 g) into N,N-dimethylborumamide (2+++Q) r81 with stirring.

N-dihexylcarbodiimide (0.103(+)) was added. After 5 minutes, the mixture was stirred in the same manner.
Then 3-propyl-2-(2-tritylaminothiazol-4-yl)propenone (0.229 J) (Z isomer) was slowly added and the mixture was stirred at room temperature for 30 hours. Filter.+
The white solid obtained was washed with a small amount of N,N-dimethylformamide. The tP'a and washing liquid were combined and condensed, potassium bicarbonate (0.05o) and water (0.5mQ) were added, and nitrogen was bubbled through. After freeze-drying, the residue was purified by silica gel column chromatography using ethyl acetate-benzene (volume ratio 1:3), and 3-[2-butylidene-2-(2-t-lythylaminothiazole-4
-yl)aceI-amide]-4-methyl-2-azetidinone-1-potassium sulfonate (Z-i form) 0, 11
5o (29%) was obtained.

NMR δDial (DMSO de )1,
10 (31-1,t, J=7.0Hz)
, 1. 23 (2H,t, J==7.,,
OHz), 1.34 (3H,d, J=
6.5Hz), 1, 75 <2H, m
> 3, 55 (IH,,m), 4, 38
(IH, d, do, J-2, OH2, J=8. O
H2), 6, 22 (IHS s), 7, 10
(IH,s) , 7, 25 (158%r
a), 9.00 (1H, d, J=8.
0Hz).

Example 20 3-(2-(2-aminothiazol-4-yl)-2
-Butylideneacetamide]4-Methyl-2-azetidinone-1-potassium sulfonate (Z-isomer) 3-[2-Butylidene-2-(2-tritylaminothiazol-4-yl)acetamide2-4- Methyl-2-
Potassium azetidinone-1-sulfonate (Z isomer) (
An acetic acid aqueous solution (volume 70%, 5 g) of 0.11 g) was stirred at room temperature for 4 hours. A small amount of water was added, and the precipitated white crystals were removed by filtration. 1(
2-(2-aminothiazol-4-yl)-2-butylideneacetamide]-4-methyl-2-1 zedidinone-
Potassium 1-sulfonate (Z-isomer) 0.023c+
(31%) was obtained.

N tvl Rδ111118 (DMSOd 6
)1.10 <38. t, J=7.0Hz), 1.
23 (2H, t%J=7.0Hz), 1.36
(3H, d, J=6.5Hz), 1.75 (2H
,m) 3,54 (11-1,ffl), 4,40 (IH,d,d,,J=2.0Hz.

J=8.0H2), 6.25 (IH, s), 6.95 (2H, s), 7.10 (IH, S), 9.15 (IH, d, J=8.0Hz).

Example 21 3-[2-ethoxycarbonylmethylene-2-(2-1
~Preparation of potassium lytylaminothiazol-4-yl) acetamidocou 4-methyl-2-azetidinone-1-sulfonate (2-isomer) 3-amino-4-methyl-2
-Azetidinone-1-sulfonic acid (0,51), triethylamine (0,401w12) and 1-hydroxybenzotriazole (0,58a) were added to a solution of N,N-dimethylformamide (70g) with stirring.
-dicyclohexylcarbodiimide (0,59!J)
added. After 5 minutes, while stirring, add 3-(2-tritylaminothiazol-4-yl)malein]-1-
Monoethyl ester (1,OOo) was added slowly and the mixture was stirred at room temperature for 15 hours.

The reaction was filtered and the resulting white solid was treated with a small amount of N.

Washed with N-dimethylformamide. The furnace liquid and washing liquid were combined and concentrated, and potassium hydrogen carbonate (0.3 g) and water (
3-) was added and nitrogen was bubbled through. After drying this for n volumes, the residue was analyzed by thin layer chromatography using ethyl acid-methanol ('fFfi ratio 8:1).
(16,9%) of 3-(2-1toxyluponylmethylene-2-(2-tritylaminodeazol-4-yl)acetamidocou 4-methyl-2-azetidinone-1
-Sulfone n-potassium (Z-isomer) was obtained.

NMRδpDII (DMSOds) 1.08
(3H1t, J=7.0.Hz), 1.37 (3
HSd, J-6,,5H2), 3.57 (IHlm
), 4.08 (2H,Q, J=7.0H2)4,,20
(I H, d, d,, J=2.0H7.

J=8. OH7), 5.66 (IH, s), 6.65 (IH18), 7.31 (15H, s), 8.30 <18. s), 9.91 (1H, d, J-8,0Hz).

Example 22 3-(2-(2-aminothiazol-4-yl)-2
-ethoxycarbonylmethyleneacetamide]-4-methyl-2-azetidinone-1-potassium sulfonate (Z
-Production of (isomer) 3-[2-ethoxycarbonylmethylene-2-(2-tritylaminothiazol-4-yl)acetamide]-
Potassium 4-methyl-2-azededinone-1-sulfonate (Z isomer) (0,509) in acetic acid aqueous solution (volume ratio 7
0%, 1011! (1) was stirred at 35-40°C for 15 hours. Shomon water was added, and the precipitated white crystals were removed by filtration.

The mother liquor was sintered and dried, tetrahydrofuran-dimethylformamide was added to the obtained yellow crystals, insoluble materials were removed by t-filtration, and the solvent was distilled off under reduced pressure to give 125 m138
．． 7%) of 3-(2-(2-aminothiazole-4-
yl)-2-ethoxycarbonylmethyleneacetamide]-4-methyl-2-azetidinone-1-potassium sulfonate (Z-isomer) was obtained.

NMRlaI! l(DMSOda) 1.15-(3H,t, J=7.0Hz), 1.4
6 (3H, d, J=6.5Hz), 3.60
(1f-1,m), 4.16 (21-1,t
1 J=7.0Hz), 4.24 (IH, d,
clo, J=2.0) (Z.

J-8,0Hz), 6.02 (IH,S), 6.74 (IHlS), 7, Ol (2H,s), 9, 83 (1t1, d1J
=8. 0)(z).

(Above) Procedures written by Masaru Shiga, August 15, 1980, Director General of the Patent Office;
%71 Indication of the case 1982 Patent Application No. 145798 2 Title of the invention 3-Acylamino-2-azetidinone-1-sulfonic acid derivative, its manufacturing process and mulberry agent containing the derivative 3 Person making the amendment Related Patent Applicant Otsuka Chemical Co., Ltd. 4 Agent 2-10 Hirano-cho, Higashi-ku, Osaka City Sawanotsuru Building Sponsored by 6 Contents of the amendment to the “Detailed Description of the Invention” section in the specification subject to amendment 1 Specification Cylinder 21 In Table 1 on page 1, the item ``Pseudomonas cepacica'' with 0 and 8 blanks has been corrected to ``Pseudomonas cepacia j''.

2. On page 40, line 11 of the specification, rO, 89 mgJ is corrected to IQ, 890 J.

(that's all) -79'shi

Claims (9)

[Claims] (1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R^1 represents an amino group or a protected amino group. R^2 represents a hydrogen atom, a substituted or unsubstituted phenyl group, a heterocyclic group, a saturated or unsaturated alkyl group, a cycloalkyl group, an optionally esterified carboxyl group, or a halogen atom. R^3 represents a hydrogen atom or a lower alkyl group. R^4 represents a hydrogen atom or a methoxy group. ] A 3-acylamino-2-azetidinone-1-sulfonic acid derivative or a salt 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 R^1 is an amino group, R^3 is a methyl group, and R^4 is a hydrogen atom. (4) 3-[2-(2-aminothiazol-4-yl)
-2-benzylideneacetamide]-4-methyl-2-
4. The compound according to claim 3, which is azetidinone-1-sulfonic acid or a salt thereof. (5) 3-[2-(2-aminothiazol-4-yl)
4. The compound according to claim 3, which is -2-(2-tenylidene)acetamido]-4-methyl-2-azetidinone-1-sulfonic acid or a salt thereof. (6) 3-[2-(2-aminothiazol-4-yl)
4. The compound according to claim 3, which is -2-(2-furfurylidene)acetamide]-4-methyl-2-azetidinone-1-sulfonic acid or a salt thereof. (7) General formula ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (II) [In the formula, R^3 represents a hydrogen atom or an alkyl group, and R^4 represents a hydrogen atom or a methoxy group. ] 3-amino-2-azetidinone-1-sulfonic acid or reactive derivatives of amino groups or their salts have the general formula ▲ mathematical formulas, chemical formulas, tables, etc. ▼ (III) [In the formula, R^ 1 represents an amino group or a protected amino group. R^2 represents a hydrogen atom, a substituted or unsubstituted phenyl group, a heterocyclic group, a saturated or unsaturated alkyl group, a cycloalkyl group, an optionally esterified carboxyl group, or a halogen atom. ] or reactive derivatives of carboxyl groups or their salts are reacted to form the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ (I) [In the formula, R^1, R^2, R^ 3 and R^4 are the same as above. A method for producing a 3-acylamino-2-azetidinone-1-sulfonic acid derivative, which comprises obtaining a 3-acylamino-2-azetidinone-1-sulfonic acid derivative or a salt thereof. (8) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I a) [In the formula, Ra^1 represents a protected amino group. R^2 is a hydrogen atom, a substituted or unsubstituted phenyl group,
Indicates a heterocyclic group, a saturated or unsaturated alkyl group, a cycloalkyl group, a carboxyl group that may be esterified, or a halogen atom. R^3 represents a hydrogen atom or a lower alkyl group. R^4 represents a hydrogen atom or a methoxy group. ] The 3-acylamino-2-azetidinone-1-sulfonic acid derivative or its salts shown in [ In the formula, R^2, R^3 and R^4 are the same as above. ] 3-acylamino-2-azetidinone-1-sulfonic acid derivatives or salts thereof are obtained.
-A method for producing an acylamino-2-azetidinone-1-sulfonic acid derivative. (9) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (I) [In the formula, R^1 represents an amino group or a protected amino group. R^2 represents a hydrogen atom, a substituted or unsubstituted phenyl group, a heterocyclic group, a saturated or unsaturated alkyl group, a cycloalkyl group, an optionally esterified carboxyl group, or a halogen atom. R^3 represents a hydrogen atom or a lower alkyl group. R^4 represents a hydrogen atom or a methoxy group. A prophylactic or therapeutic agent for bacterial infections, which contains a 3-acylamino-2-azetidinone-1-sulfonic acid derivative or a salt thereof as an active ingredient.