2-OXO-1-(((SUBSTITUTED SULFONYL)AMINO)CARBONYL)AZETIDINES

Abstract: Antibacterial activity is exhibited by β-lactams having a --NH-SO₂R substituent in the 1-position and an acylamino substituent in the 3-position wherein Z is oxygen or sulfur and R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (R c ), phenylalkyl, (substituted-phenyl)alkyl, R c -alkyl or -NR a R b wherein R a and R b are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of R a and R b is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH₂), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylami­ no, alkylamino, dialkylamino, phenylamino, (substituted phenyl- amino, hydroxy, cyano (-C≡N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted pheny­ l)alkoxy, R c as defined, above R c -alkyl, R c -alkoxy, alkylsul­ fonyl, alkylmethyleneamino, (alkyl-CH=N-), pheny­ lmethyleneamino or (substituted phenyl)methyleneamino.

Description: "2-Oxo-1-[[(SUBSTITUTED SULFONYL)AMINO]CARBONYL] AZETIDINES-AND PROCESS FOR THEIR PREPARATION" This invention is directed to a novel family of B-lactam antibiotics, and to the use of such compounds as antibacterial agents. It has been discovered that the B-lactam nucleus can be biologically activated by a substituent having the formula EMI1.1 attached to the nitrogen atom in the nucleus. ss-Lactams having a EMI1.2 substituent in the 1-position and an acylamino substituent in the 3-position (and salts thereof) exhibit activity against a range of gram-negative and gram-positive bacteria. Illustrative members of the novel family of B-lactam antibiotics of this invention are those encompassed by the formula EMI1.3 and salts thereof. In addition to the above described B-lactams having a EMI1.4 substituent in the l-position and an acylamino substituent in the 3-position, this invention also encompasses B-lactams having a EMI1.5 substituent in the l-position and an amino substituent in the 3-position. lllus'trative compounds of this type have the formula EMI2.1 and salts thereof. These compounds are intermediates useful for the preparation of corresponding 3-acylamino compounds. As used.in formulas I and II, and throughout the specification, the symbols are as defined below. R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (Rc), phenylalkyl, (substituted-phenyl)alkyl, Rc-alkyl or -NR R, wherein Ra and Rb are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of Ra and Rb is hydrogen alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino alkanoylamino, arylcarbonylamino, alkoxy caiionylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)- amino, hydroxy, cyano(-C=N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, Rc as defined above, Rc-alkyl, Rc-alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneamino. R1 is acyl; R2 is hydrogen or methoxy; R3 and R4 are the sane or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, -CH2X1 (wherein X1 is azido, amino t-WH2), hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl) methylthio, triphenylmethylthio, cyano or mercapto), -S-X2 or -O-X2 (wherein X2 is alkyl1 phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or EMI3.1 (wherein one of X3 and X4 is hydrogen and the other is hydrogen or alkyl, or X3 and X4,when taken together with the carbon atom to which they are attached form a cycloalkyl groups and X5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl) carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl EMI3.2 (substituted amino)carbonyl, or cyano (-C--N)), and Z is oxyqen or sulfur. Listed below are definitions of various terms used to describe the 6-lactams of this invention. These definitions apply to the terms as they are used throughout the specification (unless they are otherwise limited in specific instances) either individually or as part of a larger group. The terms "alkyl" and "alkoxy" refer to both straight and branched chain groups. Thqse groups having 1 to 10 carbon atoms are preferred The terms "cycloalkyl" and "cy'clo"akenyl" refer to cycloalkyl and cycloalkenyl groups having 3,4,5,6 or 7 carbon atoms. The terms "alkanoyl", "alkenyl", "alkylnyl", "alken-l-yl" and "alkyn-l-yl" refer to both straight and branched chain groups Those groups having 2 to 10 carbon atoms are preferred. The term "halogen" refers to fiuorine, chlorine, bromine and iodine. The term "protected carboxyl refers to a carboxyl group which has been esterified with a conventional acid protecting group. These groups are well -known in the art; see, for example, United States patent 4,144,333, issued March 13, 1979. The preferred protected carboxyl groups are benzyl, benzhydryl, t-butyl, and p-nitrobenzyl esters. The term "substituted phenyl" refers to a phenyl group substituted with 1, 2 or 3 amino(-NH2), halogen, hydroxyl, trifluoromethyl, alkyl (of 1 to 4 carbon atoms), alkoxy (of 1 to 4 carbon atoms) or carboxyl groups. The term "substitued alkyl" refers to alkyl groups substituted with one, or more azido amino (-NH2), alkylamino, dialkylamino, aralkyl amino, halogen, hydroxy, qarboxy, cyano, alkoxy carbonyl, alkanoyloxy, alkoxy, phenyloxy, aminocarbonyl. (substituted phenyl)oxy, heteroaryl)oxy, mercapto, alkylthio, phenylthio, (substituted phenyl)thio, alkylsulfinyl, alkylsulfonyl or the R6 heterocycle group previously defined. The 5,6 or 7-membered heterocycle (Rc) previously referred to can be a heteroaryl, i.e., aromatic, or a fully or partially saturated ring containing one or more nitrogen, oxygen or sulfur atoms. The heterocycle rings can be substituted with one or more halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, Cl-C4alkyl, C1-C4 alkoxy, alkylsulfonyl, phenyl, substituted phenyl, 2-furylimino EMI5.1 benzylimino or substituted C1-C4 alkyl groups. Exemplary heteroaryl groups are substituted and unsubstituted pyridinyl, furanyl, pyrrolyl, thienyl, 1,2,3-triazolyl, l,2,4-triazolyl, imidazolyl, thiazolyl, pyrimidinyl, oxazolyl, 1,3,4-thiazolyl and tetrazolyl. Exemplary of fully or partially saturated heterocyclic groups are substituted and unsubstituted piperidinyl, piperazinyl, l-imidazolidinyl-2-one, and 1piperazinyl-2,3-dione. The term."substituted amino" refers to a group having the formula -NYiY2 wherein Y1 is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl, and Y2 is alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl) alkyl, hydroxy, cyano, alkoxy, phenylalkoxy, or amino (-NH2). The term "acyl" includes all organic radicals derived from an organic acid (i.e., a carboxylic acid) by removal of the hydroxyl group. Certain acyl groups are, of course, preferred but this preference should not be viewed as a limitation of the scope of this invention. Exemplary acyl groups are those acyl groups which have been used in the past to acylate B-lactam antibiotics including 6-ninopenicillanic acid and derivatives and 7-aminocephalosporanic acid and derivatives; see, for example, Cephalosporins and Penicillins, edited by Flynn, Academic Press (1972), German Of fenlegungsschrift 2,716,677, published October 10, 1978, Belgian patent 867,994, published December Il, 1978, United States patent 4,152,432, issued May 1, 1979, United States patent 3,971,778, issued July 27, 1976, United States patent 4,172,199, issued October 23, 1979, and British patent 1,348,894, published March 27, 1974. The portions of these references describing various acyl groups are incorporated herein by reference. The following list of acyl groups is presented to further exemplify the term "acyl"; it should not be regarded as limiting that term. Exemplary acyl groups are: (a) Aliphatic groups having the formula EMI7.1 wherein R5 is alkyl; cycloalkyl; alkoxy; alkenyl; cycloalkenyl; cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, canto, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups. (b) Carbocyclic aromatic groups having the formula EMI8.1 wherein n is 0, 1, 2 or 3; R6, R7, and R8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms or aminomethyl; and Rg is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino, or t (alkylthio) thioxomethyl) thio. Preferred carbocyclic aromatic acyl groups include those having the formula EMI9.1 EMI9.2 (R9 is preferably a carboxyl salt or sulfo salt) and EMI9.3 (R9 is preferably a carboxyl salt or sulfo salt). (c) Heteroaromatic groups having the formula EMI10.1 wherein n is 0, 1, 2 or 3; R9 is as defined above; and R10 is a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, -2, 3 or 4 (preferably. 1 or 2) nitrogen, oxygen and sulfur atoms. Exemplary heterocyclic rings are thienyl, furyl, pyrrolyl, pyridinyl, pyrazolyl, pyrazinyl, thiazolyl, pyrimidinyl and tetrazolyl. Exemplary substituents ri halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 alkoxy of 1 to 4 carbon atoms, or EMI10.2 Preferred heteroaromatic acyl groups include those groups of the above formulas wherein R10 is 2-amino-4-thiazolyl, 2-amino-5-halo-4-thiazolyl, 4-aminopyrimidin-2-yl,' 5-amino-1, 2, 4-thiadiazol-3 -yl, In-thienyl, 2-furanyl, or 6-aminopyridin-2-yl. (d) [[(4-Substituted-2,3-dioxo-1-piperazinyl) carbonyl)amino)arylacetyl groups having the formula EMI11.1 wherein R11 is an aromatic group (including carbocyclic aroma tics such as those of the formula EMI11.2 and heteroaromatics as included within the definition of R,R); and R12 is alkyl, 'substituted alkyl (wherein the alkyl group is substituted with one or more halogen, cyano, nitro, amino or mercapto groups), arylmethyleneamino (i.e., -N=CH-R11 wherein R11 is as defined above), arylcarbonylamino (i.e., EMI11.3 wherein R11 is as defined above) or alkylcarbonylamino. Preferred [[(4-substituted-2,3-dioxo-1piperazinyl)carbonyl]amino]arylacetyl groups include those wherein R12 is ethyl, phenylmethyleneamino or 2-furylmethyleneamino. '(e) (Substituted oxyimino)arylacetyl groups having the form EMI11.4 wherein R11 is as defined above and R13 is hydrogen, alkyl, cycloalkyl, alkylaminocarbonyl, arylamino- carbonyl (i.e., EMI12.1 wherein R11 is as defined above) or substituted alkyl (wherein the alkyl group is substituted with 1 or more halogen, cyano, nitro, amino, mercapto, alkylthio, aromatic group (as defined by 'It11), carboxyl (including salts thereof), amidoi alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy (phenylmethoxyXphosphinyl, or dialkoxyphosphinyl substituents). Preffered (substituted oxyimino)arylacetyl groups include those wherein R11 is 2-amino-4thiazolyl Also preferred are those groups wherein R13 'is methyl, ethyl, carboxymethyl, 1-carboxy-1-methylethyl or 2,2,2-trifluoroethyl. (f) (Acylamino) arylacetyl groups having the formula EMI12.2 when R11 is as defined above and R14 is EMI12.3 amino, alkylamino, (cyanoalkyl) anino, amido, alkylamido, (cyanoalkyl) EMI13.1 Preferred (acylamino)arylacetyl groups of # the above formula include those groups wherein R14 is amino or amido. Also preferred are those groups wherein R11 is phenyl or 2-thienyl. (g) [[[3-Substituted-2-oxo-1-imidazoli dinyl]carbonyllaminoarylacetyl groups having the formula EMI13.2 wherein R11 is as defined above and. R15 is hydrogen, alkylsulfonyl, arymethyleneamino (i.e., -N=CH-R11 is as defined above), EMI13.3 (wherein R16 is hydrogen, alkyl or nalogen substituted alkyl) aromatic group (as defined by R11 above), alkyl or substituted alkyl (wherein the alkyl group is substituted with one or more halogen, cyano, nitro, amino or mercapto groups). Preferred I[3-substituted-2-oxo-l-imidazoli- dinyl]carbonylamino)arylacetyl groups of the above formula include those wherein R11 is phenyl or 2-thienyl. Also preferred are those groups wherein R15 is hydrogen, methylsulfonyl, phenylmethyleneamino or 2-furylmethyleneamino. The compounds of this invention form basic salts with various inorganic and organic bases which are also within the scope of this invention. Such salts include ammonium salts, alkali metal salts, alkaline earth metal salts, salts with organic bases, e.g., dicyclohexylamine, benzathine, N-methyl-D-glucamine, hydrabamine and the like. The pharmaceutically acceptable salts are preferred, although other salts are also useful, e.g., in isolating or purifying the product. Some of the compounds of this invention may be crystallized or recrystallized from solvents containing water. In these cases wate*of hydration may be formed. This invention contemplates stoichiometric hydrates as well as 'a compounds containing variable amounts of water that may be produced by processes such as a lyophilization. B-Lactams having a EMI15.1 substituent in the 1-position and an amino or acylamino substituent in the 3-position contain at least one chiral center - the carbon atom (in the 3-position of the B-lactam nucleus) to which the amino or acylamino substituent is attached. This invention is directed to those 6-lactams which have been described above, wherein the stereochemistry at the chiral center in the 3-position of the B-lactam nucleus is the same as the configuration at the carbon atom in the 6-position of naturally occurring penicillins (e.g., penicillin G) and as the configuration at the. carbon atom in the 7-position of naturally occurring cephamycins (e.q., cephamycin C). With respect to the preferred B-lactams of formulas I and II, the structural formulas have been drawn to show the stereochemistry at the chiral center in the 3-position. Also indluded within the scope of this invention are racemic mixtures which contain the above-described B-lactams. ss-Lactams having a EMI16.1 substituent in the 1-position of the B-lactam nucleus and an acylamino substituent in the 3-position of the B-lactam nucleus, and salts thereof, have activity against arrange of gram-negative and gram-positive organisms. The compounds are highly active against a range of aerobic gram-negative microorganisms including, for example, strains of Escherichia coli, Xlebsiella sp., Proteus sp., Enterobacter. sp., Serratia marcescens and Pseudomonas aeruainosa. The compounds show good stability to B-lactamases, for example, those enzymes produced by aerobic gram-negative organisms and classified into Groups I-V by Richmond & Sykes, "Advances in Microbial Physiology" (Rose et al., eds.), Vol. S1, 31, Academic Press, London & New York. The compounds of this invention can be used as agents to combat bacterial infections (including urinary tract infections and respiratory infections) in mammalian species, such as domesticated animals (e.g., dogs, cats, cows, horses, and the like) and humans. - For combating bacterial infections in mammals a compound of this invention can be administered to a mammal in need thereof in ananount of about 1.4 mg/kg/day to about 350 mg/kg/day, preferably about 14 mg/kg/day to about 100 mg/kg/day. All modes of adminis tration which have been used in the past to deliver penicillins and cephalosporins to the site of the infection are also contemplated for use with the novel family of B-lactams of this invention. Such methods of administration include oral, intravenous, intramuscular, and as a suppository. A EMI17.1 activating group can be introduced onto the nitrogen atom of a a-lactam by conventional methods as by reacting the ss-lactam with the appropriate isowanate having the formula III O=C-N-S92 -R or with the appropriate isothiocyanate having the formula Ilib S=C=N-SO2-R. The reaction is preferably run in an organic solvent, e.g., an inert solvent such as tetrahydrofuran or dimethoxyethane, in the presence of a base such as triethylamine or alkyl lithium. An alternative, and preferred route for introducing a EMI17.2 substituent onto the nitrogen atom of a B-lactam when R is an amino or substituted amino group, comprises first reacting the 8-lactam with an isocyanate having the formula IVa O=C=N-SO -Y 2 Si with the appropriate isothiocyanate having the formula IVb S=C=N-SO2-Y wherein Y is a leaving group, e.g., a halogen such as chlorine. The reaction is preferably run in an inert organic solvent, e.g., a halocarbon such as dichloromethane or in acetonitrile. The resulting intermediate has a EMI18.1 substituent on the nitrogen atom of the B-lactam. Displacement of the leaving group ("Y")-with the desired -NRaRb group can be accomplished with the appropriate nucleophile having the formula HNRaR. Alternatively, the displacement of the leaving group ("Y?) can be accomplished by reaction with a protected form of the compound HNRaRb, such as the appropriate silyl protected compound, followed by hydrolysis of the silyl group or groups. The B-lactams of formula I can be prepared from a 3-protected amino-2azetidinone having the formula EMI18.2 In formula V, and throughout the specification, the symbol "A" refers to an amino protecting group. These groups are well known in the field of B-lactam chemistry, and the particular group chosen is not critical. Benzyloxycarbonyl, trityl, and t-butoxycarbonyl are exemplary protecting groups. The addition of a EMI19.1 activating group to a compound of formula V (using the procedure described above) yields a compound having the formula EMI19.2 Deprotection of a compound of formula VI using conventional techniques yields the corresponding key intermediate having the formula or a EMI19.3 The particular deprotection reaction used will, of course, depend on the protecting group ("A") present. If, for example, A is a t-butoxycarbonyl protecting group, deprotection can be accomplished by treatment of a compound of formula VI with acid (e.g., formic acid or trifluoroacetic acid). If, for example, A is a benzyloxycarbonyl protecting group, deprotection can be accomplished by catalytic hydrogenation of a compound of formula VI. Well known acylation techniques can be used to convert an intermediate of formula VII to a corresponding product of formula I. Exemplary techniques include reaction of a compound of formula VIIwith a carboxylic acid (R1-OH), or corresponding carboxylic acid halide or carboxylic acid anhydride. The reaction with a carboxylic acid proceeds most readily in the presence of a carbodiimide such as d icyclohexylcarbodiimide and a substance capable of forming an active ester in situ such as N-hydroxybenzotriazole. In those instances where the acyl group (R1) contains reactive functionality (such as amino or carboxyl groups) it may be necessary to first protect those functional groups, then carry out the ,acylation reaction, and finally deprotect the resulting product. An alternative procedure 'for preparing the compounds of formula I comprises first acylating (acylation techniques have been described above) a 3-amino-2-azetidinone having the formula EMI20.1 to eld an intermediate having the formula EMI21.1 EMI21.2 A EMI21.3 activating group can be introduced in the l-position of a compound of formula IX (using the proceduresdescribed above) to obtain the corresponding product of- formula I. In those instances wherein the acyl side-chain "R1" contains reactive functionality (such as amino groups), it may be necessary to first protect those functional groups, then carry out the addition of the activating group in the l-position, and finally deprotect the resulting product. Still another synthesis for the preparation of compounds of formula I wherein R2 is hydrogen comprises the use of a 3-azido-2-azetidinone having the formula EMI21.4 EMI21.5 EMI21.6 activating group can be introduced in the l-position of a compound of formula X (using the procedures described above) to obtain the corresponding compound having the formula EMI22.1 The compounds of formula XI are novel intermediates, and as such, they constitute an integral part of this invention. Reduction of an intermediate of formula XI yields the corresponding intermediate having the formula EMI22.2 The reduction can be accomplished by catalytic (, palladium on charcoal or platinum oxide) hydrogenation or with reducing agents such as zinc or triphenylphosphine. As described above, these key intermediates (compounds of formula VII),using conventional acylation techniques, it is possible to prepare all of the products of formula I wherein a2 is hydrogen. Example 1 (S)-[1-[[[(4-Methylphenyl)sulfonyl]amino]carbonyl] 2-oxo-3-a:etidinylj ca'rbamic acid, phenylmethyl ester A) 1-[(1R)-Carboxy-2-methyl(propyl)]-2-oxo-(3S) [[(phenylmethoxy)carbonyl]amino]azetidine A slurry of 6-aminopenicillanic acid (12.98 q) in 140 ml of water containing 5.18 g of sodium bicarbonate (stirred for about 10 minutes without complete solution) is added in one portion to a well-stirred (mechanical stirrer) suspension of Raney nickel (washed with water to pH 8.0, 260 ml of slurry=130 g) in d 7O0C oil bath. After 15 minutes the slurry is cooled, filtered, and the filtrate treated with 5.18 g of sodium bicarbonate and a solution of 11.94 g of benzyl chloroformate in 12 ml of acetone. After 30 minutes, the solution is acidified to pH 2.5 and extracted with methylene chloride. The organic layer is dried, evaporated, and triturated with etherhexane to give a total of 6.83 a of the title compound. B) l-[(Acetyloxy)-t-methyl (propyl)] -2-oxo- (35)- [[(phenylmethoxy)carbonyl]amino]azetidine A solution of 6.83 g of l-[(lR)-carboxy- 2-methyl(propyl)]-2-oxo-(3S)-[[(phenylmethoxy)carbonyl]amino]azetidine in 213 ml of acetonitrileis treated with 1.95 g of cupric acetate monohydrate and 9.5 g of lead tetraacetate. The slurry is immersed in a 650C oil bath and stirred with a stream of nitrogen bubbling through the slurry until the starting material is consumed. The slurry is. filtered and the solids washed with ethyl acetate. The combined filtrate and washings are evaporated in vacuo and the residue taken up in 100 ml each of ethyl acetate and water and adjusted to pH 7. The ethyl acetate layer is separated dried, and evaporated to give 6.235 g of the title compound. (C) (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester A solution of 3.12 g of I-[(acetyloxy)-2- methyl(propyl)]-2-oxo-(3S)-[[(phenylmethoxy)carbonyl]amino]azetdine in 70 ml of methanol and 7 ml of water is cooled to -150C and 1.33 g of potassium carbonate and 349 mg of sodium borohydride are added. The reaction mixture is stirred at -150C - 0 0C. After the reaction is complete (about 2 hours), the mixture is neutralized to pH 7 with 2N HC1 and concentrated zn vacuo. The concentrate is adjusted to pH 5.8, saturated with salt and extracted with ethyl acetate (3 times). The organic layer is dried and evaporated in vacuo. The residue is combined with material from a similar experiment and triturated with ether to give 3.30 g of the title compound. D) (S)-[1-[[[(4-Methylphenyl)sulfonyl]amino]carbonyl]-2-oxo-3-azetidinyl]carbamic acid, phenylmethyl ester1 triethylammonium salt (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (220 mgs) is dissolved in dry tetrahydrofuran (10 ml) and stirred well under nitrogen. Triethylamine (139 l) is added1 followed by p-toluenesulfonyl isocyanate (153 ul, 1 mmol). After 2 to 3 hours of stirring a crystalline material starts to precipitate out. After 2 hours of further stirring, the solid is removed by filtration, washed with a small volume of acetonitrile and dried in vacuo. Yield of the triethylamine salt is 332 mg, melting point 128-130 C. E) (S)- [1-LI [(4-Methylphenyl)sulfonyl]amino- carbonyl]-2-oxo-azetidinyl]carbamoc acid, phenylmethyl ester The triethylamine salt above (345 mg). is dissolved in water (15 ml) and layered with ethyl acetate (15 ml). The mixture is acidified to pH 2.0 and well shaken. The extraction with ethyl acetate is repeated "dried The combined ethyl acetate layers are dried over anhydrous sodium' 263 mg of evaporated to dryness in vacuo to yeld 263 mg of a gum. This is crystallized from dichloromethane/hexane yielding 131 mg of product, melting point 178-180 C. Analysis for C19H19O6N3S: Calc'd: C, 54.67; H, 4.59 N, 10.07; S, 7.68 Found: C, 54.49i H, 4.71; N, 10.05; S, 7.75 Example 2 (S)-[1-[[[(4-Methylphenyl)sulfonyl]amino]carbonyl]2-oxo-3-aminoazetidine, triethylammonium salt (S)-[1-[[[(4-Methylphenyl)sulfonyl]amino]carbonyl]-2-oxo-3-azetinyl]carbamic acid, phenylmethyl ester, triethylammonium salt (150 mg; see example 1) is dissolved in dry methanol (10 ml). 10% Palladium on carbon (75 mg) is added and the mixture is hydrogenated for 30 minutes. The catalyst is removed by filtration and the filtrate is evaporated in vacuo to dryness, yielding 81 mg of the title compound Example 3 (S)-N-[(4-Methylphenyl)sulfonyl]-2-oxo-3 [(phenylacetyl)amino]-1-azetidinecarboxamide (S)-[1-[[[(4-Methylphenyl)sulfonyl]amino]carbonyl]-2-oxo-3-aminoazetidine, triethyl ammonium salt (626 mg, see example 2) is dissolved in dry acetonitrile (25 ml) and stirred under nitrogen in an ice bath. Triethylamine (.57 ml) is added, followed by phenycetyl chloride (.324 ml). After 3 hours an equal volume of water is added, the pH a is adjusted to 7.5, and the acetonitrile is removed in vacuo. The aqueous residue is extracted twice with ethyl acetate to remove neutral material. The aqueous layer is then acidified to pH 2.0 and extracted three times with ethyl acetate. The acidic extract is dried over anhydrous sodium sulfate and evaporated to dryness in vacuo, yielding 544 mg. This crude product, and an additional 481 mg of crude product from two other runs are combined and purified by chromatography on column of SilicAR CC-4 (100 g), using dichloromethane and dichloromethane:methanol, 99:1 as eluants. The amorphous product is crystallized from acetonitrile to give 154 mg of crystalline material, melting point 170-172 0C. Analysis for ClgH19N305S: C, 56.85, HI 4.77; N, 10.47; S, 7.99 Found: C, 56.70; H, 4.91; N, 10.41; S, 8.05 Example 4 [3S(Z)]-3-[[(2-Amino-4-thiazolyl)(methoxyimino) acetyl]amino]-N-[(4-methylphenyl)sulfonyl)-2 oxo-l-azetidinecarboxamide A) (S) -3-Amino-2-azetidinone (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (3 g; see example 1C) is hydrogenated in, 100 ml of methanol in the presence of 1 g of palladium on charcoal catalyst. When the theoretical amount of hydrogen is absorbed, the catalyst is filtered off and the filtrate evaporated to dryness. On standing, 1.1 g of the title compound crystallizes. B) [3S(Z)]-3-[[(2-(Triphenylmethylamino) 4-thiazolyl)[methoxyimino]acetyl]amino]-2 oxoazetidine (Z)-2-(Triphenylmethylamino)-&alpha;- (methoxyimino)-4-thiazoleacetic acid (2.50 g) is dissolved in dry dimethylformamide (.25 ml). l-Hydroxybenzotriazole (863 mg, 5.64 mmol), N, N' -dicyclohexylcarbodiimide (1.164 g) and 3-amino-2-oxoazetidine (485 mg) are added sequentially, and the mixture is stirred at room temperature under dry nitroqen for 5 hours. The reaction mixture is worked up by diluting it with water (250 ml) adjusting to pH 7.5, and extracting (three times) with an equal volume of ethyl acetate. The combined extract is washed with water followed by saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, and evaporated to dryness in vacuo. The crude product is purified by chromatography over SilicAR CC-7 silica gel, to give 2.50 g of solid. This is crystallized from chloroform ahexane to yield 2.31 g of the title compound, melting point 233-2360C. C) [3S(Z)]-3-[[(2-(Triphenylmethylamino)-4 thiazolyl)[methoxyimino]acetyl]amino]-N [(4-methylphenyl)sulfonyl]-2-oxo-1-azetidine carboxamide [3S(Z)]-2-[[(2-(Triphenylmethylamino)-4 thiazolyl] [methoxyimino] acetyl]amino]-2-oxo-l- azetidine (270 mg) is dissolved in dry tetrahydrofuran (5 ml). Triethylamine (66 l) s added followed by -toluenesulfonyl isocyanate (80 l). The mixture is stirred for 16 hours at room temperature. Following removal of the solvent in vacuo the residue is taken up in ethyl acetate/water and adjusted to pH 7.5. The extraction with ethyl acetate is repeated twice. The combined organic extracts are washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness in vacuo to give 263 mg of crude product, which is purified by chromatography on SilicAR CC-4 silica gel (27 gJ, using dichloromethane:ethyl acetate (3:1), to give 123 mg of the title compound. D) [3S(Z)]-3-[[(2-Amino-4-thiazolyl)(methoxy imino)acetyl]amino]-N-[(4-methylphenyl)sulfonyl] 2-oxo-l-azetidinecarboxamide [3S(Z)-3-[[[2-(Triphenylmethylamino)-4 thiazolyl][methoxyimino]acetyl]amino]-N [(4-methylphenyl)sulfonyl]-3-oxo-1-azetidine carboxamide (122 mg). is dissolved in 70% aqueous formic acid (2 ,ml) and stirred under nitrogen at room temperature for 3 hours. After removal the excess acid in vacuo the residue is taken up in ethyl acetate/water at pH 7.5 The organic layer is removed. The aqueous layer is acidified to pH 2.5 and extracted (five times) with ethyl acetate. The extract is dried over anhydrous sodium sulfate and evaporated to dryness in'vacuo. The residue is dissolved in pure dioxane and lyophilized to yield 50 mg of the title compound as a fluffy powder, which is dried in vacuo at 500C for 2 hours, melting'point 1600C dec. Analysis for C17Hl8o6N6S2 Calc'd: C, 43.78; H, 3.89; N, 18.02; S, 13.75 Found: C, 43.38; H, 4.05; N, 15.86; S, 12.75 Example 5 (S)-N-(Methylsulfonyl)-2-oxo-3-[[(phenylmethoxy)carbonylamino]-1-azetidinecarboxamide A stirred suspension of (-S)-(2-oxo-3- azetidinyl)carbamic acid, phenylmethyl ester (2.20 g; see example 1C) in 60 ml of dry tetrahydrofuran under nitrogen is warmed using a water bath at 40 C until solution occurs. The solution is cooled to -75 C, and 7,4 ml of 1.35 M sec-butyl lithium in cyclohexane (10 mmol) is added. After stirring for 2 minutes, (methylsulfonyl) isocyanate (about 1.20 g) is added. This reaction is stirred at -750C for 10 minutes and poured into 100 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate is added, and the pH is adjusted to ;. After several extractions with ethyl acetate1 the aqueous layer is covered with ethyl acetate and adjusted to pH 2. Repeated extraction with ethyl acetate gives an acidic extract, which is dried sodim sulfate) and evaporated to a residue (2.61 g). Chromatography of this residue on 250 g of SilicAR CC-4 using dichloromethane and then 1% methanol in dichloromethane provides 1.82 g of product as a residue. Example 6 (S)-N-(Methylsulfonyl)-2-oxo-3-amino-1-azetidine carboxamide, hydrochloride salt To a solution of 300 mg of (S)-N-(methyl- sulfonyl)-2-oxo-3-##(phenylmethoxy)carbonyl#- amino-l-azetidiaecaXoxalaide (see example 5) inS ml of dry methanolois added 150 mg of 10% palladium on charcoal. The mixture is hydrogenated at room temperature and 1 atmosphere for 30 minutes and then 2 ml of water is added followed by dilute hydrochloric acid to adjust the pH to 1.8. The-catalyst is filtered using water/methanol-. Evaporation of the-filtrate gives 65 mg of crude product. The catalyst is suspended in water, adjusted to pE 1.8 and stirred at room temperature for 15 minutes. Removal of the catalyst and evaporation of the filtrate provides additional crude product (124 mg). Example 7 (S)-N-(Methylsulfonyl)-2-oxo-3-[(phenylacetyl) amino] -l-azetidinecarboxamide (S)-N-(Methylsulfonyl)-2-oxo-3-amino-1 azetidinecarboxamide, hydrochloride salt (189 mg; see example 6) is suspended in 8 ml of dry acetonitrile and 0.54 ml of triethylamine, and stirred at room temperature under nitrogen until solution occurs (about 15 minutes). The solution is cooled to 0 to 50C, and then phenyl acetylchloride (153 p1) is added. The reaction is stirred at room temperature for 3 hours and then poured into 10 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. The pH is adjusted to 7 (dilute potassium hydroxide) and the solution is extracted twice with ethyl acetate. The aqueous layer is covered with fresh ethyl acetate, and the pH is adjusted to 2 (3N hydrochloric acid). Repeated extraction with ethyl acetate gives an acidic ethyl acetate extract, which is dried (sodium sulfate)and evaporated to a residue (196 mg). Chromatography of this material on 20- g of SilicAR CC-4 using ethyl acetate/dichloromethane (1:1) provides 96 mg of crystalline. product after removal of solvent. Recrystallization from ethyl acetate/dichloromethane provides an analytical sample having a melting point 168-170 C, dec. Anal. Calc'd for C13H15N3O5S: C, 48.0Q; H, 4.65; N, 12.92; S, 9.84 Found C, 47.82; Ht 4.74; N, 12.86; S, 9.13 Example 8 (S) -3-Amino-N- (methylsulfonyl)-2-oxo-1-azetidine- carboxamide, inner salt (S)-N-(Methylsulfonyl)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino-1-azetidinecarboxamide (2.20 g; see example 5) is stirred with 90 ml of methanol under nitrogen at 40 to 450C until solution occurs. The solution is quickly cooled to room temperature and hydrogenated at one atmosphere in the presence of 1.1 g of 10% palladium on charcoal for twenty minutes. Water (20 ml) is added, and the pH is adjusted to 2.0 (1N hydrochloric acid). The product, which is absorbed on the catalyst, is collected by filtration, using Whatman t50 paper, and suspended in 25 ml of water. The pll is adjusted to 2.0 (1N hydrochloric acid), and the mixture is stirred for twenty-five minutes and filtered through Whatman SO paper. Evaporation of the filtrate provides 611 mg of crystalline product, melting point 1800C, dec. Example 9 [3S(Z)]-3-[[(2-Amino-4-thiazolyl))methoxyimino)acetyilamino]-N-(methylsulfonyl)-2-oxo-1 ozetidinecarboxamide, potassium salt Triethylamine (0.47 ml) is added to a stirred suspension of (Z)-(2-amino-4-t}liazolnrl)- (methoxyimino)acetic acid (671 mg) and 2 1 of N-methylmorpholine in 5 ml of dry dimethylformamide at room temperature under nitrogen. The mixture is stirred for five minutes and then cooled to -250C. Diphenyl chlorophosphate (0.69 ml) is added, and the mixture is stirred at -250 to -15 C for forty minutes. Using a syringe, this mixture is transferred to a stirred mixture of (S)-3-amino-N-(methylsulfonyl)-2- oxo-l-azetidinecarboxamide, inner salt (608 mg; see example 8), 5 ml of dry dimethylfosmamide and 1.65 ml (11.8 mmol) of triethylamine at -250C under nitrogen. After stirring at -25 to -15 C for three and a half hours, the reaction mixture is poured into 35 ml of 0.5 X, pH 5.5, monobasic potassium phosphate. Water and ethyl acetate are added, and the pH is adjusted to 7.2 using dilute potassium hydroxide. After extracting with ethyl acetate (three times), the aqueous layer is covered with fresh ethyl acetate and adjusted to pH 2.5 (1N hydrochloric acid). Repeated extraction with ethyl acetate gives an acidic ethyl acetate.extract, which is dried (sodium sulfate), and evaporated to a residue (625 mg). This residue is applied to a column of Si@cAR CC-4 (50 g) packed in ethyl acetate/ diçploromethane (1:1). Elution with this' solvent and. then ethyl acetate removes non-polar impurities. Elution with 3-4% methanol in ethyl acetate provides 334 mg of partially purified product (H+ form), which was taken up in 3 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. The pH is adjusted to 6.5 (dilute potassium hydroxide), and the solution is passed, using water, through a column of HP-20 resin (100 ml), which has been prewashed with the monobasic potassium phosphate buffer and then water. A combination of phosphomolybdic acid test (PO4 3) and Rydon's test locates the desired product. Evaporation of appropriate. fractions provides 145 mg of desired potassium, salt as a residue. The aqueous pB 2.5 layer mentioned above, is evaporated to remove water and dimethylformamide. Water and ethyl acetate are added, and after adjusting the pH to 2.5, another acidic ethyl acetate extract is obtained and evaporated to a residue t658 mg). This material is dissolved in 4 ml of 0.5 M monobasic potassium phosphate buffer and adjusted to pH 6.5. Subsequent passage through 100 ml of HP-20 resin using water provides 54 mg of additional potassium salt as a residue. This material is combined with the 145 mg portion above and lyophilized from water to give 199 mg of the title potassium salt as a solid, melting point 2050C, dec. Anal. Calc'd. for C11H13N6O6S2K#2 H,O: C, 28.45; H, 3.69; N, 18.10; S, 13.78 Found: C, 28.15; H, 2.87; N, 18.09; S, 13.64 Example 10 [3S-[3#,4#]]-3-[[(1,1-Dimethylethoxy)carbony1]amino -4-methyl-N- (methylsulfonyl) -2-oxo-l- azetidinecarboxamide A) N-Benzyloxy-t-buttoxycarbonyl-threonine amida A solution of 8.76 q of t-butoxycarbonyl threonine and the free amine from 6.4 g of O-benzylhydroxylamine HC1 (ethyl acetate-sodium bicarbonate liberation) in 100 ml of tetrahydrofuran is treated with 6.12 g of N-hydroxybenzotriazole and 8.24 g of dicyclohexylcarbodiimide in 20 ml of tetrahydrofuran. The mixture is stirred under nitrogen for 26 hours, filtered, and evaporated in vacuo. The residue is chromatographed on a 300 g silica gel column (elution with chloroform and chloroform/ethyl acetate (3:1) yielding 7.2 g of compound. Crystallization from ether-hexane gives 4.18 g of the title compound. B) (3S-trans)-N-Benzyloxy-3-t-butoxycarbonyl amino-4-methylazetidinone A A solution of 12.67 g of N-benzyloxy-t- btoxycarbonyl-threonine amide, .11.5 g of triphenylphosphine, and 6.23 ml of diethylazodicarboxylate in 380 ml of tetrahydrofuran is - stirred under nitrogen for about 16 hours. The solution is evaporated and chromatographed on a 900 gram silica gel column. Elution with chloroform-ethyl acetate (3:1) gives 13.69 g of compound that crystallizes from ether-hexane to yield 9.18 g of the title compound. C) (3S-trans)-3-t-Butoxycarbonylamino-1 hydroxy-4 -methyl azetid inone A solution of 9.18 g of (3S-trans)-N benzyloxy-3-t-butoxycarbonylamino-4-methyl azetidinone in 300 ml of 95% ethanol is stirred in an atmosphere of hydrogen with 1.85 g of 10% palladium on charcoal. After 141 minutes the slurry is filtered and evaporated in vacuo. The residue is recrystallized from ether-hexane to yield 5.12 g of the title compound. D) (3S-trans) -'3-t-Butoxycarbonylamino-4-methyl- azetidinone A solution of 4.98g of (3S-trans)-3-t butoxycarbonylamino-1-hydroxy-4 -methylazetidinone in 200 ml of methanol is treated with 132 ml of 4.5 X ammonium acetate and then 66 ml of 1.5 M titanium trichloride and stirred for 4.5 hours. The aqueous solution is diluted with an equal volume of 8% sodium chloride and extracted with ethyl acetate to give 3.48 g of crude product. Recrystallization from ether-hexane yields 3.3 g of the title compound. E) [3S-[3&alpha;,4ss]]-3-[[(1,1-Dimethylethoxy)carbonyl] amino) -4-methyl-N- (methylsulfonyl) -2-oxo-1- azetidinecarboxamide Sec-Butyl lithium (14.8 ml of 1.35 N solution in cyclohexane) is added to a stirred solution of (3S-trans)-3-t-butoxycarbonylamino4-methylazetidinone (20 mmole) in 150 ml of dry tetrahydrofuran at -75 C under nitrogen. After stirring for 2 minutes methylsulfonyl- isocyanate (2.4 ml) is added, and the solution is stirred for 25 minutes at -750C and poured into 200 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Water and ethyl acetate are added, and the pH is adjusted to 2.5 using 3 N hydrochloric acid. The ethyl acetate layer and subsequent ethyl acetate extract are combined, dried (sodium sulfate)., and evaporated' to a residue (7.15 g), which is chromatographed on 450 g of SilicAR CC-4, using dichloromethane and then 1% methanol in dichloromethane, to give 3.67 a of desired product as a residue. Example 11 [3S-[3&alpha;,4ss]]-3-amino-4-methyl-N-(methylsulfonyl)- 2-oxo-l-azetidinecarboxamide, trifluoroacetic àcid salt [3S-[3a,4$])-3- [ [ (1,1-Dimethylethoxy)- carbony1]amino]-4-methyl-N-(methylsulfonyl)-2oxo-l-azetidinecarboxamide (482 mg; see example 10) is stirred with 4.5 ml of trifluoroacetic acid at 0 to 50C under nitrogen for 30 minutes. The solution is evaporated in vacuo to a residue, which is evaporated from acetonitrile (four times) to give the desired salt as a residue. Example 12 [3S-[3&alpha;(Z),4ss]]-3-[[(2-Amino-4-thiazolyl)(methoxy- imino)acetyl]amino]-4-methyl-N-(methylsulfonyl) 2-oxo-l-azetidinecarboxamide, potassium salt Triethylamine (243 yl) is added to a stirred suspension of (Z)-(2-amino-4-thiazolyl) (methoxyimino)acetic acid (303 mg) in 4.5 ml of dry dimethylformamide at room temperature under nitrogen. After stirring for 2- minutes, ** the mixture is cooled to -250C, and diphenyl chlorophosphate (312 pl) is added. The mixture is stirred for 50 minutes at -250C'and added, via syringe, to a stirred solution of [3S-[3&alpha;,4ss]]- 3-amino-4-methyl-N-(methylsulfonyl)-2-oxo-1 azetidinecarboxamide, trifluoroacetic acid salt and 1.05 ml of triethylamine in dimethylformamide at -250C under nitrogen. The reaction is stirred for 2.5 hours at this temperature and poured into 18 ml of 0.5 M pH 5.5 monobasic potassium ,phosphate buffer. Ethyl acetate and water are "added and the pH is adjusted to 7. The aqueous layer is separated and adjusted to 2.5, using 3N hydrochloric acid, and the solvents are removed in vacuo *^ to give a residue, which is taken up in ethyl acetate and water (pH 2.5). Repeated extraction gives a combined ethyl acetate extract, which is dried (sodium sulfate), and evaporated to a residue. This residue is solubilized by addition of 5 ml of 0.5 M monobasic potassium phosphate buffer and adjusted to pH 6.5 usinq dilute aqueous potassium hydroxide. Chromatography on a column (120 ml) of HP-2Q resin, using water as eluent gives 296 mg of the desired potassium salt. The lyophilized solid has a melting point 201 C,dec. Analy Calc'd for C12H15N6O6K#o.5 H2O: C, 31.92; H, 3.57; N, 18.61; S, 14.20 Found: C, 32.08; H, 3.62; N, 18.51; S, 14.07 Example 13' [3S-[3a(Z),4ss]]-3-[[(2-Amino-4-thiazolyl) [[2-(diphenylmethoxy)-1,1-dimethyl-2-oxoethoxy]imino]acetyl]amino]-4-methyl-N-(methylsulfonyl)2-oxo-l-azetidinecarboxamide [3S-[3&alpha;4ss]]-3-Amino-4-methyl-N-(methylsulfonyl)-2-oxo-l-azetidinecarboxamide, trifluoroacetic acid salt (167 mg; see example 11) is dissolved in dry dimethylformamide (1.5 ml) and dry triethylamine (0,35 ml) and stirred at -25 C under dry nitrogen. To this solution is added, via syringe, a solution of mixed anhydride which is prepared by sequentially adding (Z)-2-amino-&alpha;-[[2-(diphenylmethoxy)-1,1- dimethyl-2-oxoethoxyliminol-4-thiazoleacetic acid (220 mg), dry triethylamine (126 1) ando diphenylchlorophosphate (155 p1, .75 mmol) to dry dimethylformamide (1.5 ml) and stirring for 50 minutes at -25 0C under nitrogen. The resulting mixture is stirred at -250C for 2.5 hours under dry nitrogen. It is then poured into .5 N pH 5.5 monobasic potassium phosphate buffer (6 ml) and evaporated to dryness in vacuo. The residue is taken up in ethyl acetate/water, acidified with dilute hydrochloric acid to pH 2.5 and extracted (three times) with ethyl acetate. The extract is washed with water, dried over anhydrous sodium sulfate, evaporated to dryness, in vacuo, and purified by thin-layer chromatography on silica gel in ethyl acetate: methanol (4:1). The eluted product is taken up in ethyl acetate/water at pH 2.5. The organic layer is washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness in vacuo to give 152 mg of the desired product. Example 14 [3S-[3&alpha;(Z), 4ss]]-3-[[(2-Amino-4-thiazolyl)[(1carboxy-1-methylethoxy) imino]acetyl]amino]-4methyl-N-(methylsulfonyl)-2-oxo-1-azetidinecarboxamide, dipotassium' salt [3S-[3&alpha;(Z), 4ss]]]-3-[[(2-Amino-4-thiazolyl) ) 2-(diphenylmethoxy)-1,1-dimethyl-2-oxoethoxy] - amino]acethyl]amino]-4-methyl-N-(methylsulfonyl) oxo-1-azetidinecarboxamide (152 mg; see example 13) is dissolved in dry dichloromethape. Anisole (135 l) and trifluoroacetic acid (1 ml) are added, and the solution is stirred in an ice bath under dry nitrogen for 1.5 hours. The mixture is then evaporated to dryness in vacuo with the residue being evaporated in vacuo (four times) from dry acetonitrile to remove residual trifluoroacetic acid and anisol. The residue is taken up in ethyl acetate/ water and 0.5 M pH 5.5 monobasic potassium phosphate buffer (2 ml). This is adjusted to pH 6.5 with dilute potassium hydroxide and extracted (two times) with ethyl acetate. The aqueous layer. is evaporated to dryness in vacuo, and the residue is purified by chromatography on HP-20 resin (110ml) using water. The product is lyophilized from water to give 82 mg, melting point 240 C, dec. Anal. for C15HlgN6OgS2K2 H20 Calc'd: C, 30.60; H, 3.77; N, 14.28; S, 10.89 Found: C,-b0.61; H, 3.43; N, 14.23; S, 10.51 Example 15 (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]-N (methylsulfonyl) -2-oxo-l-azetidinecarbothioamide A) (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]2-oxoazetidine (S)-3-Amino-2-azetidinone (21.77 g; see example 4A) and 30 g of triethylamine are dissolved in 200 ml of t-butanol and tetrahydrofuran (9:1). At 0 C a solution of 37 g of bis(t-butyl)pyrocarbonate in 50 ml of tetrahydrofuran is dropped in; stirring for about 16 hours completes the reaction. The solvents are distilled off and the residue is dissolved in ethyl acetate. Extraction with aqueous citric acid and water yields 25.3 g of the title compound from the organic phase. B) (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino] N-(methylsulfonyl)-2-oxo-1-azetidinecarbothioamide Sec-Butyl lithium (9.25 ml of 1.35 fl solution in cyclohexane2 is added to a stirred solution of (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]-2-oxoazetine (2.33 g) in 250 ml of dry tetrahydrofuran at -75 C under nitrogen. After stirring for 2 minutes, (methylsulfonyl) isothiocyanate (1.75 ml) is added, and the 4' solution is stirred for 25 minutes at -75 C and poured into 125 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate and water are added, and the pH is adjusted to2.5 (3 N hydrochloric acid). The ethyl acetate layer is washed with water, dried with sodium sulfate, and evaporated to, a residue (3.69 g), which is recrystallized from ethyl acetate to give 2.04 g of the -title compound. Recrystallization of a portion from ethyl acetate gives crystals, melting point 1810C,dec. Anal. Calc'd for C10H17N3O5S2: C, 37.15; H 5.30; N, 13.00; S, 19.80 Found: C, 37.05; H, 5.34; N, 12.97; S,-19.76 Example 16 (S) -3-Amino-N- (methylsulfonyl) -2-oxo-l-azetidinecarbothioamide, trifluoroacetic acid salt (S)-3-[[(1,1-Dimethylethoxy)carbonylzamino]- N- (methylsulfonyl) -2-oxo-l-azetidinecarbothioamide (323 mg) is stirred with 3 ml of trifluoroacetic acid at 0-5 C under nitrogen for 50 minutes. The solution is evaporated in vacuo to a residue, which is evaporated from acetonitrile (four times) to give the desired salt. Example 17 [3S(Z)]-3-[[(2-Amino-4-thiazolyl) (methoxyimino) acetyll amino] -N- (methylsulfonyl) -2-oxo-I- azetidinecarbothioamide, potassium salt Triethylamine (162 ul) is added to a stirred suspension of (Z)-2-amino-o-(methoxy- imino)-4-thiazole acetic acid (201 mg) in 3 ml of dry dimethylformamide at room temperature under nitrogen. After stirring for 2 minutes, the mixture is cooled to -250C, and diphenyl chlorophosphate (208 l, 1.0 mmol) is adde,d. The mixture is stirred for 1.5 hours at -250C and ititded, using a syringe, to a stirred solution of (-3-amino-N- (methylsulfonyl) -2-oxo-l- azetidinecarbothioamide, trifluoroacetic acid salt (1.0 mmol;.see example 16) and 0.70 ml a of triethylamine in 3 ml of dimethylformamide at -250C under nitrogen. The reaction is stirred for 2.5 hours at this temperature and poured into 12 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. Ethyl acetate and water are added, and the pH is adjusted to 7. The aqueous layer is adjusted to 2.5 t3 N hydrochloric acid), and the solvents are removed in vacuo to give a residue, which is taken up in ethyl acetate and water (pH 2.5). Repeated extraction with ethyl acetate gives a combined ethyl acetate extract, which is dried podium sulfate), and evaporated to a residue. This residue is solubilized by addition of 5 ml of 0.5 M monobasic potassium phosphate buffer. Adjustment of the pH to 6.5, using dilute potassium hydroxide, and chromatography on a column of HP20AG resin (110 ml), using water as eluant, yields 42 mg of the desired potassium salt as a residue. Treatment of a 36 mg portion of this sample with water and a small amount of acetone gives 31 mg of the desired potassium salt as crystals melting point 205 C,dec. Anal. Calc'd for C11H13N6O5S 3K 0.5 H20: C, 29.14; R, 3.11; N, 18.54; S, 21.17 Found: C, 29.40; H, 3.05; N, 18.52; S, 21.13 Example 18 [3S(Z)]-3-[[(2-Amino-4-thiazolyl) (methoxyimino) acetyll aminol -N- (aminosulfonyl) -2-oxo-lazetidinecarboxamide, ammonium salt [3S(Z)]-3-[[[2-(Triphenylmethylamino)-4 thiazolyl][methoxyimino]acethyl]amino]-2-oxoazetidine (0.51 g; see example 4B) is suspended in 10 ml of anhydrous acetonitrile. The mixture is cooled to -300C. A solution of chlorosulfonyl isocyanate (0.18 g) in 5 ml of acetonitrile is added with stirring. The mixture is stirred at -300C for 30 minutes, the cooling bath is removed, and the mixture is stirred for an additional 60 minutes at 0 0C. Ammonium carbonate (0.39 g) is added and'the mixture is stirred at 0 C for 1 hour and at room temperature for an additional 2 hours. The precipitate is filtered, yielding 1.26 g of crude [35(Z)1-3- [[f 2- (trieny1methylamino) -4-thiazolyl] [methoxyinino] acetyl]- amino] -N- (aminosulfonyl) -2-oxo-l-azetidine- carboxamide, ammonium salt contaminated with some ammonium carbonate. The crude product is dissolved at room temperature in 12 my of 70% formic acid and stirred for 90 minutes. - precipitate is filtered, the filtrate evaporated, the residue treated with water and adjusted to pH 6.5 with aqueous ammonia. The solution is filtered and freeze-dried. The freeze-dried product is purified by chromatography on HP-20 resin, eluting with water. The first 100 ml are discarded, 10 ml fractions are collected. Fractions 25-31 contain 60 mg of pure product. From fractions 32-40 additional 30 mq, of slightly less pure product are obtained. Example 19 [3S(Z)]-3-[[(2-Amino-4-thiazolyl) (methoxyimino)acetyl]amino]-N-[[(1-methylethyl)amino]sulfonyl]2-oxo-1-azetidinecarboxamide, sodium salt [3S(Z)]-3-[[[2-(Triphenylmethylamino)-4 thiazolyll(methoxyiminoacetyl]aminol-2- azetidinone (1.02 g; see example 4B) is suspended in 10 ml of acetonitrile; the mixture is cooled to -30 C. A solution of chlorosulfonyl isocyanate (0.35 g) in 10 ml of acetonitrile is added with stirring. The mixture is stirred for 30 minutes at -30 C and for an additional 60 minutesat 0 C. The solution is cooled to -10 C and a solution of isopropylamine (0.5 g) in 5 ml of acetonitrile is added to form a clear solution. The cooling bath is removed and the mixture is stirred at 0 C for 60 minutes. After 'evaporation to dryness, 2.2 g of crude [3S(Z)-3-1[[o-(triphenylmethyl- amino)-4-thiazolyl][methoxyimino]acetyl]amino] N-[[(1-methylethyl)amino]sulfonyl]-2-oxo-1azetidinecarboxamide as the isopropylamine salt is obtained as a light syrup.The syrup is dissolved in 35 ml of 70% formic acid and stirred for 3 hours at room temperature. A precipitate (048 g) is removed by filtration and the filtrate is evaporated to dryness. The residue is treated with water, adjusted to pH 6.5 with 2N sodium hydroxide, and freeze-dried. The crud,e product is subjected to HP20AG chromatography (100-200 mesh) eluting with water (500 ml), then with water/acetone (8:2); 10 ml fractions are taken. The elution is monitored by thin-layer chromatography. Fractions 72-76 contain most of the product and are divided into three parts: fractions 72-74 contain 0.19 g of product, fraction 75 contains 0.36 g of product and fraction 76 contains 0.16 g of product. The product from fractions 72-74 and 76 is slightly less pure than the product from- fraction 75. Example 20 (S)-N-(Aminosulfonyl)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinecarboxamide Method I (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (11 g; see example 1C) is dissolved in a mixture of 200 ml of acetonitrile and 50 ml of dichloromethane. The mixture is cooled to -50 and a solution of chlorosulfonyl isocyanate (9 g) in 25 ml of dichloromethane is added with stirring. .After warming the mixture to -30 C a solution of 6 g of ammonia w 160 ml of acetonitrile is added slowly. The reaction temperature is raised to -10 C and finally to 0-5 C. The reaction time is 3 hours. The ammonium salt of the title a compound precipitates and is filtered by suction (20 g). The crude product is purified by HP-20 chromatography (10Q-200 mesh) eluting with 2000 ml of water and water/acetone (8:2); 20 ml fractions are taken. The elution is monitored by thin-layer chromatography. From fractions 142-154, 9.3 g of product is obtained by evaporation. The ammonium salt of the title compound is dissovled in 100 ml of water, layered with 200 ml of ethyl acetate and acidified. After separation and washing of the aqueous layer twice with ethyl acetate, the organic layer is washed with saturated sodium chloride solution, dried with- anhydrous magnesium sulfate and evaporated to yield 8.1 g-of the title compound-. Method II A mixture of (S)- (.2-oxo-3-azetidinyl) carbamic acid phenylmethyl ester ( g; see example 1C) in 175 ml of dichloromethane is cooled to -30 C. While stirring 7.7 g of chlorosulfonyl isocyanate in 75 ml dichloro methane is added dropwise within 15 minutes. The temperature of the solution is allowed to rise to 0 C over 30 minutes. Subsequently the clear solution is again cooled to -300C and 8.8 g of bis-(trimethylsilyl)amine dissolved in 30 ml of dichloromethane, is dropped in, while passing dry nitrogen through the, flask. After an hour the reaction temperature is allowed to rise to -15 C and is maintained for an additional 3Q minutes. The solvent is distilled off in vacuo, and the residue is triturated with 400 ml of ether to give a solid (16.6 g) which is washed with an additional 20 ml ether. From the ethereal mother liquor there is obtained a second crop of 4.2 g of product. The crude material (18.0 g) along with about 20 g of HP-20 resin is suspended in 30 ml of water and the mixture is chromatographed on an HP-20 column eluted with Åa) 3 L of water; b) 2.5 L of water/acetone (8:2);- c) 4 L of water/acetone (7:3); d) 6 L of water/acetone (6:4). Fraction d yields 6.2 g of the title compound melting point 150-152 C. Example 21 (S)-N- (Aminosulfonyl ) -3- r L(l, 1-dimethylethoxy) - carbonyl]amino]-2-oxo-1-azetidenecarboxamide, ammonium salt (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]2-oxoazetidine (5.1 g; see example 15A) is dissolved in a mixture of 160 ml of acetonitrile and 40 ml of dichloromethane. At -50 C a solution of 5.4 g of chlorosulfonyl isocyanate in 30 ml of dichlgromethane is added dropwise (15 minutes). The mixture is kept at -300C for 30 minutes. Then 4 ml of a solution of ammonia in acetonitrile (containing 2.4 g of ammonia) is added slowly . at -10 to OOC. The title compound precipitates together with inorganic material and is filtered by suction (crude yield 9.8 g). From the filtrate another crop of 2.7 g of crude title compound is obtained. According to thin-layer chromatography both fractions are of similar purity. The combined material is dissolved in 50 ml of water, adjusted to pH 6.5 by the addition of diluted aqueous ammonia and purified by chromatography on HP-20, eluting with water; 20 ml fractions are taken. Fractions 70-130 contain 2.7 g of the title compound. Example 22 S., (S) -3-Amino-N- (aminosulfonyl) 1 carboxamide, inner salt Method I: (S)-N-(Aminosulfonyl)-3-[[(1,1-dimethyl ethoxy)carbonyl]amino]-2-oxo-1-azetidine carboxamide, ammonium salt (2 g; see example 21) is added to 50 ml of trifluoroacetic acid at 0 0C. The solution is stirred at 0 0C for 10 minutes and then for 30 minutes at room temperature, evaporated to dryness and the # residue is treated with ether to yield 2.1 g of the trifluoroacetic acid salt of the title compound, contaminated with ammonium trifluoro acetate. 1.6 g of the trifluoroacetic acid salt of the title compound is suspended in 25 ml of acetonitrile. Addition of 6 ml of bis-trimethyl silylacetamide yields a clear solution from which, on the addition of 5 ml methanol, the title compound (0.58 g) precipitates. Method II: (S)-3-[(1,1-Dimethylethoxy)carbonyl]aminol-2-oxoazetidine (1.87 g; see example 15A) is dissolved in 50 ml of dichloromethane/ acetonitrile (4:1) and cooled to -200C. Chlorosulfonyl isocyanate (1.42 g) in 15 ml of dichloromethane is added dropwise. Stirring is continued for 3 hours and a solution of 1.9 g of N-trimethylsilyl t-butylcarbamate in 20 ml of dichloromethane is added and the mixture is stirred for 10 hours at 0 C. After this time the solvents are distilled off and the residue is treated with ether/petroleum ether (3:1) yielding 2 g of crude (S)-3-[[(1,1- dimethylethoxy),carbonylSaminol-N- I[(l,lQimethyl- ethoxy)carbonyl]amino]-2-oxo-1-azetidinecarboxamide as a crystalline material. This is stirred for 90 minutes in 20 ml trifluoroacetic acid/ anisole (4:1) at -100C. The reaction solution is then poured into 200 ml of ether; 2.3 g of solid is collected and dried. Suspension of this solid in dry acetonitrile and addition of 3 g of monosilyltrifluoroacetamide yields a clear solution'. To this solution 6,ml of methanol is aged. The title compound precipitates from the solution immediately, yielding 0.76 g of product. a Example 23 [3S(Z)]-N-(Aminosulfonyl)-3-[[(2-amino-4thiazolyl)(methoxyimino)acetyl]amino]-2-oxo-1azetidinecarboxamide, sodium salt (S)-3-Amino-N-(aminosulfonyl)-2-oxo-1azetidinecarboxamide (see example 22, or prepared by hydrogenating 4.8 g of' (S) -N- (aminosulfonyl),- 3-[[(phenylmethoxy)carbonyl]amino]-2-oxo-1azetidinecarboxamide using 2.5 g of 10% palladium on charcoal catalyst) is acylated using 4.22 g of (Z)-2-amino-&alpha; ;-(methoxyimino)-4-thiazoleacetic acid in 100 ml of dimethylformamide, 3.46 g of dicyclohexylcarbodiimide -in 30 ml of dimethylformamide and 0.5'g of hydroxybenzotriazole. After 2.5 hours at room temperature the precipitated dicyciohexylurca is removed b filtration and the filtrate evaporated. The residue is triturated with 300 ml ethyl acetate to yield 4.2 g of insoluble material. After evaporation and trituration of the residue with ether ariother 1.6 g of solid are obtained. The combined solid material is suspended in water and the suspension adjusted to pH 6.5 wish 1N sodium hydroxide, filtered and the filtrate subjected to HP-20 chromatography, elyfting with water. The first 700 ml of eluate are discarded. Fractions 85-137 contain 1.04 g of the title compound m.p. 230 C. (dec.). Another 0.3 g of slightly less pure material are obtained from fractions 70-84 and 138-150. Example 24 (S)-N-(Aminosulfonyl)-3-[[(phenylmethyl)carbonyl] amino] -2-oxo-l-a zetidinecarboxamide (S)-3-Amino-N-(aminosulfonyl)-2-oxo-1azetidinecarboxamide (see example 22, or prepared by hydrogenating 140 mg of (S)-N-(aminosulfonyl)3-[[(phenylmethoxy)carbonyl)-2-oxo-1azetidinecarboxamide in dimethylformamide using 50 mg of 5% palladium on charcoal catalyst) is acylated with 100 mg of dicyclohexylcarbodiimide, 20 mg of hydroxybenzotriazole and 55 mg of benzeneacetic acid. The mixture is stirred at 0 C for 6 hours and dicyclohexylurea is filtered off. Dimethylformamide is distilled off, the residue is dissolved in 5 ml of acetone and the solution is, after standinq for about 16 hours, filtered and then evaporated. The crude material is chromatographed on an HP-20 column eluting with water/acetone (6:4) to give 45 mg of the title compound, melting point 137 C. Example 25 (S)-3-[[Phenylmethoxy)carbonyl]amino]-N [[(phenylmethoxy)amino]sulfonyl]-2-oxo-1acetidinecarboxamide, potassium salt (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (5.1 q; see example 1C) is suspended in 80 ml of dry dichloromethane at,-500C. At this temperature 3.9 g chlorosulfonyl isocyanate dissolved in 25 ml or dichloromethane is dropped in with stirring. When the addition is complete, a clear solution is obtained and stirring is continued for 2 hours. Triethylamine (5.6 g) is added and 3.7 g of benzyloxyamine, dissolved in 20 ml of dichloromethane is added dropwise to the solution. The reaction mixture is stirred for about 16 hours at OOC. Tetrabutylammonium- hydrogensulfate (8.5 g) dissolved in 150 ml of ice water is added and the pH is adjusted to 6.7 with 1N potassium hydroxide. The organic layer is separated,' dried with sodium sulfate, and the solvent removed in vacuo. The oily residue is treated with 8.5 g of potassium perfluorobutanesulfonate in 50 ml of acetone. This solution. is slowly poured into 200 ml of ether; crude product precipitates and is filtered off. Purification is achieved by reverse-phase chromatography using HP-20 and water/acetone 6:4 as eluent, yielding 3.2 g of product, melting point 200 C, dec. Example 26 [3S(Z)]-3-[[(2-Amino-4-thiazolyl)(methoxyimino) rbonyl] amino] -N-[l (phenylnethoxy) amino- sulfonyl]-2-oxo-1-azetidinecarboxamide, potassium salt (S)-3-[[Phenylmethosa)carbonyl]amino]-N [[(phenylmethoxy)amino]sulfonyl]-2-oxo-1 azetidinecarboxamide, potassium salt (1.2; see example 25) is dissolved in 80 ml of dry dimethylformamide and hydrogenated in the presence of 0.75 g of palladium on charcoal. After 40 minutes the hydrogenation is complete. The catalyst is filtered off, and 0.55 g of (Z)-2-amino-&alpha;-(methoxyimino)-4-thiazoleacetic acid, 0.17 g of hydroxybenzotriazole and 1.03 g of dicyclohexylcarbodiimide are added. The solution is stirred at ambient temperature for about 16 hours. The precipitated urea is filtered off, the solvent removed in vacuo and the residue is chromatographed using HP-20 and water/acetone 9:1) as eluant. The product is a mixture of 50 mg of the title compound and 200 mg of [3S(Z)]-3-[[(2-amino-4-thiazolyl)- (methoxyimino)carbonyl]amino]-N-(aminosulfonyl) 2-oxo-l-azetidinecarboxamide, potassium salt. Example 27 [3S(Z)]-3-[[(2-Amino-4-thiazolyl)(ethoxyimino) acetyl]amino]-2-oxo-1-azetidinecarboxamide, potassium salt (S)-N-(Aminosulfonyl)-2-oxo-3-[l(phenyl- methoxy)carbonyl]amino]-l-azetidinecarboxamide, potassium salt (0.5 g; see example 20) is hydrogenated for 20 minutes in 70 ml of dry dimethylformamide with 0.2 g of palladium on charcoal. (Z)-2-Amino-a-(ethoxyimino)-4 thiazoleacetic acid (0.36 g), 0.1 g of hydroxybenzotriazole and 0.62 g of dicyclohexyl carbodiimide are added and the solution is stirred for about 16 hours. The precipitated urea is filtered off, the solvent is removed and the residue is suspended in S ml of water. The pH is adjusted to 6.5 with IN potassium hydroxide. This solution is immediately chromatographed using HP-20 and water as eluent, yielding 200 mg of the title compound, melting point 198-2000C, dec. Example 28 [3S(R*)]-N-(Aminosulfonyl)-3-[[[[[3-[(2-furanylmethylene]amino]-2-oxo-1-imidazolidinyl]carbonyl]amino]phenylacetyl]amino]-2-oxo-1-azetidinecarboxamide, potassium salt (S)-N-(Aminosulfonyl)-Z-oxo-3-[[(phenyl methoxy) carbonyl) amino] azetidinecarboxamide (0.8 g; see example 20) is dissolved in 80 ml of dry-dimethylformamide and hydrogenated with 0.4 g of palladium on charcoal. After 20 minutes catalyst is filtered off and 0.92 g of (R)-&alpha;-[[(3-[(2-furanylmethyene)- amino]-2-oxo-1-imidazolidinyl]carbonyl]amino] benzeneacetic acid, 0.16 g of hydroxybenzotriazole and 0,97 g of dicyclohexylcarbodiimide are added and the solution is stirred at ambient temperature for about 16- 'hour. The precipitated urea is filtered off and the solvent is removed inv uo. The residue is chromatographed on HP-20 using water/acetone (7:3) as eluent. ? Freeze-drying of the appropriate fractions yields 200 mg of product. The potassium salt is prepared by dissolving the compound in water/acetone and adjusting the pH to 6.7 with 1N potassium hydroxide. The solution is freeze-dried. Example 29 [3S(R*)]-N-(Aminosulfonyl)-3-[[[[(4-ethyl-2,3dioxo-1-piperazinyl)carbonyl]amino]phenylacetyl] amino]-2-oxo-l-azetidinecrboxamide (S)-N-(Aminosulfonyl)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinecarboxamide (0.8 g; see example 20) is hydrogenated in the presence of Q.4 g of palladium on charc'oal. After 20 minutes the catalyst is filtered off and 0.82 g of (R)-&alpha;-[[(4-ethyl-2,3- dioxo-1-piperazinyl)carbonyl)amino]benzeneacetic acid, 0.16 g of hydroxybenzotriazole and 0.97 g of dicyclohexylcarbodiimide are added. The solution is stirred about 16 hours at ambient temperature. The precipitated urea is filtered off and the solvent is removed in vacuo. The residue is suspended in 10 ml of water/acetone and the pH is adjusted to 6.5 with 1N potassium hydroxide, and then immediately chromatographed (HP-20, water/acetone:9/1) to yield 330 w of prokt, m. p. K+salt 185 C (dec.). Example 30 [3S(Z)]-2-[[[1-(2-Amino-4-thiazolyl)-2 [[1-[[(methylsulfonyl)amino]carbonyl]-2-oxo-3azetidinyl]amino]-2-oxoethylidene]amino]oxy]-2methylpropanoic acid, dipotassium salt A) (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino] N-(methylsulfonyl)-2-oxo-1-azetidinecarboxamide (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino]2-azetidinone (1.12 g) is dissolved in dry tetrahydrofuran (120 ml) and stirred at -75 C under dry nitrogen. sec-Butyl lithium (4.44 ml of a 1.35 M solution in cyclobexane) is added and followed in two minutes by methylsulfonyl isocyanate (0.72 ml). After stirring for 25 minutes at -75 0C, the reaction is quenched by the addition of Q.5 M pH 5.5 monobasic potassium phosphate buffer (60 ml), diluted with ethyl acetate-water, acidified to pH 2.5 with 3N.hydrochloric acid, and (60 ml), diluted with ethyl acetate-water, acidified. to pH 2.5 with 3N hydrochloric acid, and extracted with ethyl acetate (three times, The extract is washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness in vacua to yield the desired product as a foam (1.73 g). B) (S)-3-Amino-N-(methylsulfonyl)-2-oxo-1 azetidinecarboxamide, trifluoroacetic acid salt (S)-3-[[(1,1-Dimethylethoxy)carbonyl] amino] -N- (methylsulfonyl) -2-oxo-l-azetidine carboxamide (612 mg) is stirred with trifluoro acetic acid (6 ml) under nitrogen in an ice bath for 30 minutes The solvent is removed in vacuo, and the residue is evaporated from acetonitrile (four times) to give the desired salt as a foam (638 mg). C) [3S(Z)]-2-[[[1-(2-Amino-4-thiazolyl)2-[[1-[[(methylsulfonyl)amino]carbonyl]-2-oxo3-azetidinyl]amino]-2-oxoethylidene]amino]oxy]2-methylpropanoic acid, diphenylmethyl ester (Z)-(2-Amino-4-thiazolyl)[[2-(diphenylmethoxy)-1,1-dimethyl-2-oxoethoxy]imino]acetic acid (880 mg) in dry dimethylformamide (6 ml) is stirred at -25 0C under nitrogen. Triethylamine (0.48 ml) is added, followed by diphenylchloro- phosphate (0.62 ml), and the mixture is stirred at -25 C for 55 minutes. This mixture is added to a stirred solution of the above mentioned- crude trifluoroacetic acid salt (612 mg). and triethylamine (1.40 ml) in dry dimethylformamide (6 ml) at -250C under nitrogen. The reaction is stirred at 250C for 2.5 hours and quenched with 0.5 M pH 5.5 monobasic potassium'phosphate buffer (24 ml). It is then diluted with ethyl acetate/water,acidified to pH 2.5, and extracted with ethyl acetate (three times). The ethyl acetate extract is washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness in vacuo to yield a yellow solid (1,408 g). After chromatography on silica gel, using ethyl acetate-methanol, the product is taken up in ethyl acetate-water at pH 2.5 and extracted with ethyl acetate (three times). The extract is washed with water, dried over anhydrous sodium sulfate, and evaporated to dryness in vacuo to give the desired product as a solid (360 mg). D) [3S(Z)]-2-[[[1-(2-Amino-4-thiazolyl) 2-[[1-[[(methylsulfonyl)amino]carbonyl]-2-oxo 3-azetidinyl]amino]-2-oxoethylidene]amino]oxy] 2-methylpropanoic acid, dipotassium salt [3S(Z)]-2-[[[1-(2-Amino-4-thiazolyl) 2-[[1-[[(methylsulfonyl)amino]carbonyl]-2-oxo 3-azetidinyljamino]-2-oxoethylidene]aminoloxy] - 2-methylpropanoic acid, diphenylmethyl ester (360 mg) is dissolved in dry dichloromethane (1Q ml) and stirred under dry nitrogen in an ice bath. Anisole (312 iil)'and anhydrous trifluoroacetic acid (2 ml) are added, and the solution is stirred for 2 hours. The solvent is then removed in vacuo, and the residual solid is evaporated (four times) in vacuo from a solution in dry acetonitrile to remove traces of trifluoroacetic acid. The product is taken up in ethyl acetate-water. 0.5 M pH 5.5 monobasic potassium phosphate buffer (2 ml) is added, and the pH is adjusted to 6.5 with dilute potassium hydroxide. The organic layer is removed, and the aqueous layer is evaporated to a residue, which is combined with a similar residue, derived by treating a second portion (176 mg) of diphenyl dimethyl ester with trifluoroacetic acid-anisole. This crude potassium salt mixture is purified, by chromatography on HP20AG, using water, to give the desired dipotassium salt as a powder (221 mg) after lyophilization, melting point 250-255 C, dec. Anaylsis for C14H16O8N6S2#K2#3H2O Calc'd: C,28.37: H, 3.74; N, t4.18; S, 10.82 Found: C, 28.38; H, 3.58; N, 14.05; S, 10.82 Example 31 (S)-N-(1-Imidazolylsulfonyl)-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinecarboxamide, potassium salt (S)-(2-Oxo-3-arzetidinyl)carbamic acid, phenylmethyl ester (3 g) is suspended in 100 ml of dry dichloromethane and cooled to -5 0C. Chlorosulfonyl isocyanate (2.1 g) in 1Q ml of dichloromethane is dropped in with stirring, which is continued for 45 minutes. Triethylamine (3.5 g) and 1.02 g of imidazole are added and the solution is stirred overnight at OOC. After the addition of 4.6 g. of tetrabutylammonium hydrogen sulfate in 200 ml of ice water, the pli is adjusted to 6.5 with 1N potassium hydroxide. The organic layer is separated, dried (sodium sulfate), filtered and evaporated to dryness. The residue is treated with 4.6 g of potassium perfluorobutane sultanate in 50 ml of acetone. This solution is poured into 200 ml of ether and crude product, (4.5 g) is filtered off. Purification is accomplished by chromatography using HP2OAG resin and water/acetone '(8:2) as eluant, yielding 1.7 g of the title compound, melting point 130 C, dec. Example' 32 135(z)]-3-l[(2-Amino-4-thiazolyl) (methoxyimino)- carbonyl]amino]-N-(1-imidazolylsulfonyl)-2 oxo-l-azetidinecarboxamide, potassium salt (S)-N-(1-Imidazolylsulfonyl)-2-oxo-3 [[(phenylmethoxyl)carbonyl]amino]-1-azetidine carboxamide, potassium salt (0.5 g; see example 31) is dissolved in 50 mi of dry dimethyl formamide. After the addition of 0.2 g of 10% palladium on charcoal, hydrogen is bubbled through the mixture for 20 minutes. The catalyst is filtered off and 0.23 g of (z)-2- amino-a- (methoxyimino) -4-thiazoleacetic acid, 0.05 g of hydroxybenzotriazole and 0.5 g of dicyclohexylcarbodiimide are added. The solution is stirred for 12 hours at room temperature. The precipitated urea is filtered off and the solvent is removed in vacuo. The residue is purified by HP20 chromatography using water/ acetone (9:1), yielding 0.3 g of the title ,,,compound, melting point 2100C, dec. Example 33 [3S(Z)]-2-[[[1-(2-Amino-4-thiazolyl)-2 [[1-[[(aminosulfonyl)amino]carbonyl]-2-oxo-3azetidinyl]amino]-2-oxoethylidene]amino]oxy]2-methylpropanoic acid, disodium salt (S)-3-Amino-N-(aminosulfonyl)-2-oxo-1azetidinecarboxamide, inners-alt (see example 22) is reacted with 3.2 g (a 20% excess) of (Z)-(2-amino-4-thiazolyl)[[2-(diphenylmethoxy)1,1-dimethyl-2-oxoethoxy]imino]acetic acid in the presence of 1.5 g of dicyclohexyl- carbodiimide and 0.2 g The mixture is stirred for 5 hours at room temperature, the solution is evaporated and the residue is dissolved in ethyl acetate. The insoluble dicyclohexylurea is filtered off and the filtrate is washed three times with water and once with saturated sodium chloride solution, dried (magnesium sulfate) and evaporated to yield 4g of crude [3S(Z)]-2-[[[1-(2-amino-4-thiazolyl)-2-[[1 [[(aminosulfonyl)amino]carbonyl]-2-oxo-3azetidinyl]amino]-2-oxoethylidene]amino]oxy]2-methylpropanic acid, diphenylmethyl ester. A A portion of the crude is dissolved in 15 ml of anisole, cooled with stirring to -10 C and 40 ml of trifluoroacetic acid is added. The mixture is stirred at -10 C for an additional 30 minutes. Then, at -lO0C, 100 ml of ether and 100 ml of petroleum ether are added to yield a precipitate (2.4 gt. The precipitate is suspended in SO ml of water at 0 C and adjusted to pH 6.5 by the slow addition of 2N sodium hydroxide. Some insoluble material is removed by filtration and the filtrate freeze-dried to yield 2 g of crude product. The crude material is purified by HP2OAG chromatography eluting with water; 10 ml fractions are taken. From fractions 22-26, 0.63 g of pure product are obtained after freeze-drying, m.p. 275 C(dec.) as sodium salt. From fractions 20-21 and 27-29 another 0.39 g of less pure product are obtained. Example 34 [3S(Z)]-3-[[(2-Amino-4-thiazolyl)(methoxyimino) acetyl)amino]-2-oxo-N-[(phenylamino)sulfonyl] l-azetidinecarboxamide, sodium salt [3S(Z)]-3-[[[2-(Triphenylmethylamino)-4 thiazolyl][methoxyimino]acetyl]amino]-2-oxo azetidine (1;02 g; see example 4B) is suspended in a mixture of 13 ml of acetonitrile and 13 ml of dichloromethane. At -50 C a @ solution of chlorosulfonyl isocyanate (0.36 g) in 5 ml of dichloromethane is dropped in with stirring. The temperature is raised to -20 C 'within' 30 minutes. Addition of triethylamine, (0.84 ml) immediately yields a clear solution to which a solution of aniline (0.22 ml) is added. The reaction mixture is stirred at O 0C for 60 minutes and at room temperature for another 60 minutes, then evaporated. The residue is suspended in water and the suspension is adjusted to pH 3.5 by the addition of 2N acetic acid. The insoluble crude [3S(Z)]-3-[[[(triphenyl- methyl)amino]-4-thiazolyld][methoxyimino]acetyl]amino]-2-oxo-N-[(phenylamino)sulfonyl]-1azetidinecarboxamide is isolated -by filtration, yield 1.2.. To remove the trityl group, 1.1 q of [3S(Z)]-3-[[[2-(triphenylmethylamino)-4-thiazolyl] [methoxyimino]acetyl]amino]-2-oxo-N-[(phenylamino)sulfonyl] -1-azetidinecarboxamide is dissolved in 15 ml of tetrahydrofuran and 25 ml of 70% formic acid is added with cooling. After standing for 2 hours at room temperature the mixture is evaporated and the residue is treated with ether to yield 0.59 g of solid material. The solid is dissolved in 10 ml of tetrahydrofuran. Then 10 ml of water is added and the mixture is adjusted to pH 6.5 by the addition of 2N sodium hydroxide-. The tetrahydrofuran is removed by evaporation, the turbid water-phase is extracted once with ethyl acetate and freeze-dried. The crude material thus obtained is purified by HP2OAG chromatography; 10 ml fractions are collected. It is first eluted with water (fractions 1-801, then with water/acetone(95:5). From fractions 98-108, 70 mg of pure product is obtained. Example 35 [3S(Z)]-3-[[[2-Amino-4-thiazolyl)methoxyimino)acetyl]amino]-N-[(dimethylamino)sulfonyl]-2oxo-l-azetidinecarboxamide, sodium salt Following the procedure of example 34, but substituting dimethylamine for aniline, yields the title compound. Example 36 (S)-2-Oxo-3-[[(phenylmethoxy)carbonyl]amino]-N [[(4-pyridy)amino]sulfonyl]-1-azetidinecarboxamide. sodium salt (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester t6.6 g: see example 1C) is suspended in'a mixture of 160 ml of acetonitrile and 40 ml of dichloromethane. To the suspension a solution ofchIorosulfonyl isocyanate- (5.1 g) in 15 ml dichloromethane is added at -500C with stirring. The mixture is stirred for 1 hour at -30eo -250C. A clear solution of (S)-N-[(chlorosulfonyl)amino]-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinecarboxamide forms to which i2;4 ml of triethylamine is added, followed by a suspension of (4-pyridyl)amine (3.4 g) in 40 ml of-a 1:1 mixture of acetonitrile and dichloromethane. The temperature is raised to 0-50C and the mixture is stirred at this temperature for 90 minutes. A clear solution forms, from which crystals precipitate. After stirring for an additional 2 hours at room temperature the precipitate is filtered by suction, suspended in water and the pH of the suspension is adjusted to pH 3.5. After stirring for 30 minutes, the precipitate is filtered, wished with water and dried to yield 8 g of the title compound, m.p. 2120C. From the organic filtrate a second crop of 3.4 g of less pure product is obtained by evaporation, suspension in water, adjustment of the suspension to pH 3.5 and filtration. Example 37 (S)-N-[(Methylamino)sulfonyl]-2-oxo-3-[[(phenylmethoxy)carbonyl]amino]-1-azetidinecarboxamide (S)-(2-Oxo-3-azetidinyl)carbamic acid, phenylmethyl ester (6.6 g; see example 1C) is suspended in a mixture of 160 ml of acetonitrile and 40 ml of dichloromethane. Then, at -SO 0C, chlorosulfonyl isocyanate (5.1 g) dissolved in 15 ml of dichloromethane, is added with stirring. After stirring for 1 hour at -30 C, a solution of 6 g of methylamine in 50 ml of acetonitrile is added so that an excess of amine is avoided (pH Ca. 6.5) t40 ml of the solution is required). After stirring for 90 minutes at -10 C and 90 minutes at 0 C the precipitateis filtered to yield 10.5 g of a solid. Evaporation of the filtrate yields another 5.2 g of a foam. According to the spectra (NMR, IR) both contain the methylammonium salt of the title compound. The combined material is purified by chromatography on HP20AG. ghe methylammonium salt of the title compound is eluted with water/acetone (80:20) to yield 4.6 g of pure material. From the methylammonium salt, the title compound is prepared by dissolving it in water (50 ml), layering with ethyl acetate and acidifying the mixture with cooling and stirring. From the organic layer 3.5 g of the title compound is obtained. Example 38 (S)-3-Amino-N-[(methylamino)sulfonyl]-2-oxo-1 azetidinecarboxamide, inner salt (S)-N-[(Methylamino)sulfonyl]-2-oxo-3 [[(phenylmethoxy)carbonyl]amino]-1-azetidine carboxamide (2.1 g, see example 37) is suspended in 25 ml of acetonitrile and bis(trimethylsilyl)- acetamide (3.3 g) is added. The solution is added to a suspension of 1 g of 10% palladium on charcoal in 25 ml of acetonitrile, through which hydrogen is passed for 30 minutes prior to the addition of the solution of the starting azetidinone. After 15 minutes the catalyst is removed by filtration and 2 ml of methanol is added to the filtrate to precipitate 1.3 g of the title compound. Example 39 (S)-3-Amino-2-oxo-N-[[(4-pyridyl)amino]sulfonyl] l-azetidinecarboxamide (S)-2-Oxo-3-N-[[(phenylmethoxy)carbonyl]amino]-N-[[(4-pyridyl)amino]sulfonyl]-1-azetidine carboxamide (2.1 g; see example 36) is suspended in 25 ml of acetonitrile and 3 g (3.6 ml) of bis(trimethylsilyl)acetamide is added with stirring. After a few minutes a clear solution is formed. This solution is added to a suspensiLon of 1 g of 10% palladium on charcoal in 25 ml of acetonitrile, through which hydrogen is passed for 30 minutes prior to the addition of the solution of the starting azetidinone. ffydrogenation is complete after 70 minutes. The catalyst is removed by filtration. On addition of 1 ml of methanol the title compound crystallizes from the solution; yield 1.0 g. Example 40 [3S(Z)-3-[[(2-Amino-4-thiazolyl)(methoxyimino)acetyl]amino]-2-oxo-N-[[(4-pyrodyl)amino]sulfonyl] --l azetidinecarboxamide (S)-3-Amino-2-oxo-N-[[(4-pyridyl)amino] s'lfonyll -1-azetidinecarboxamide (0.57 g; see example 39) is dissolved in 10 ml of dimethylformamide and added to a mixture of (Z)-2-amino-&alpha;-(methoxyimino)-4-thiazoleacetic acid (0.6 g), dicyclohexylcarbodiimide (0.49 g) and N-hydroxybenzotriazole (60 mg) ih 20 ml of dimethylformamide and stirred at room temperature. After 2 hours the conversion is complete. Dicyclohexylurea is removed by filtration and the filtrate is evaporated and treated with ether to yield 1.3 g of a solid. The solid is dissolved in a mixture of 15 ml of water and 15 ml of acetone and adjusted to pH 6.5 by the addition of a solution of sodium bicarbonate. On removal of the acetone by evaporation, 0.5 g of the title compound precipitates from the aqueous phase. mp. 221 C.(dec.). Example 41 [3S(Z)]-2-Amino-N-[1-[[[(dimethylamino) sulfonyllamino]thioxomethyl]-2-oxo-3-azetidinyl]- &alpha;-(methoxyimino)-4-thiazoleacetamide A) (S)-3-[[(1,1-Dimethylethoxy)carbonyl]amino] N- [[[l-(dimethylamino)sulfonyl]aminolthioxo- methyl]-2-oxoazetidine (S)-3[[(1,1-Dimethyletoxy)carbonyl]amino 2-oxoazetidine (0.93 g, .005 mole) and triethyl amine (1.35 ml, .01 mole) were dissolved in 20 ml of dry acetonitrile at 0 C. [Dimethylamino (sulfonyl)] isothiocyanate (1.09 ml, .01 mole) was added dropwise and the reaction was stirred at 0 C for 3 hrs and at room temperature overnight. The reaction mixture was concentrated in vacuo. To the residue was added 10 ml of 0.5N pH 5.5 KH2PO4 and 5 ml of water The pH was adjusted to 2.8 with dilute acid (1N HC1), and product was extracted with 3 200 ml portions of ethyl acetate. The ethyl acetate was concentrated in vacuo and product was recrystallized from methanol to yield 0.76 g, m.p. dec. 1840C. B) (S)-3-Amino-N-[[[(dimethylamino)sulfonyl] amino] thioxomethyl] -2-oxoazetidine, trifluoroacetic acid salt The above thioxomethyl azetidine (0.352 g, .001 mole) was dissolved in 3 ml of trifluoroacetic acid and stirred at 00 for 2 hrs. The solution was concentrated in vacuo, and the residue was evaporated from acetonitrile (3X) to give the desired product. C) [3S(Z)]-2-Amino-N-[1-[[[(dimethylamino)sulfonyl]amino]thioxomethyl]-2-oxo-3-azetidinyl] &alpha;-(methoxyimino)-4-thiazoleacetamide, potasium salt To a solution of t2-amino-4-thi azolyl)- methoxyimino acetic acid (0.266 g, .001 mole) in 3 ml dry DMF was added triethylamine (.1,53 ml, .0011 mole) under N2. This solution was cooled to -250C and diphenyl chlorophosphate (0.207 ml, .001 mole) was added. The reaction mixture was stirred at -250C for 1 hr. The above crude trifluoroacetic acid salt and triethylamine (0.7 ml) was dissolved in 3 ml of DMF. The above mixed anhydride was added via syringe to this solution at -500C to -250C. After 3 hrs. the solution was poured into 12 ml of 0.5M pH 5.5 KH2PO4 buffer, and the pH,was adjusted to 7.8 with dilute KOH. The DMF and water were evaporated off in vacuo and the pot residue was dissolved in 20 ml of water and washed with ethyl acetate. The aqueous solution was acidified to pH 2.8 and product was extracted with two portions of ethyl acetate. This was dried (Na2SO4), filtered, and concentrated in vacuo. The product was purified by chromatographing twice through two 60 ml portions of HP-20 resin using water as eluant. The aqueous fractions containing product (Rydon positive) were lyophilized to give 109 mg of analytical product, after drying at 450C/lmm for 4 hrs, having m.p. 204-2080dec. Example 42. [3S(R)]-4-Ethyl-N-]2-[[1-[[(methylsulfonyl)- amino]carbonyl]-2-oxo-3-3-azetidinyl]amino]-2oxo-1-phenylethyl]-2,3-dioxo-1-piperazinecarboxamide By substituting (R)-&alpha;-[[(4-ethyl-2,3-dioxo 1-piperazinyl)carbonyl]amino]phenyl acetyl chloride for the phenylacetyl chloride used in Example 7, the titled product is obtained as an amorphous solid, m.p. l81-1S50C as the sodium salt. Example 43 [2S-[2&alpha;,3ss(R)]]-4-Ethyl-N-[2-[[2-methyl-1- [[(methylsulfonyl)amino]carbonyl]-4-oxo-3azetidinyl]amino]-2-oxo-1-phenylethyl]-2,3dioxo-l-piperazinecarboxamide By reacting (R)-&alpha;-[[4-ethyl-2,3-dioxo-1- piperazinyl)carbonyl]amino]phenyl acetic acid and C3S-[3a,481-3-amino-4-methyl-N-(methyl- sulfonyl)-2-oxo-1-azetidinecarboxamide (from Example 11) according to the procedure of example 7, the titled product is obtained as a solid, m.p. 170 C.(d). as the sodium salt. Example 44 [3S(R)-3-[(Aminophenylacetyl)amino]-N-(methylsulfonyl)-2-oxo-1-azetidinecarboxamide By substituting a-amino-phenyl acetic acid for the (2-amino-4-thiazolyl)-(methoxyimino)acetic acid used in Example 12, the titled product is obtained, m.p. 1490C.(d.) as the trifluoroacetic acid salt. Example 45 [35(Z) ]-2-Amino-N-Il-I II (4-aminophenyl)sulfonyl)- amino]carbonyl]-2-oxo-3-azetidinyl]-&alpha;-(methoxy- imino)-4-thiazoleacetamide By substituting (S) -3-amino-N- 1(4-amino- phenyl)sulfonyl]-2-oxo-1-azetidinecarboxamide for the azetidinecarboxamide used in Example 12, the titled product is obtained as a solid potassium salt) m.p. 2200C.(d.). Example 46 [3S(Z)]-2-[[[1-Amino-4-thiazolyl)-2-[[1 [[(1N-imidazol-1-ysulfonyl)amino]carbonyl]-2oxo-3-azetidinyl]amino]-2-oxoethylidene]-amino] oxy] -2-methylpropanoic acid By following the procedure of Example 33, substituting (S) -N- (l-imidazolylsulfonyl) -2-oxo- l-azetidinecarboxamide for the azetidinecarboxamide used therein, the titled product is obtained, m.p. potassium salt 240oC. (d.). Example 47 [3S[R)]-4-Ethyl-N-[2-[[1-[[(1H-imidazol-1-yl sulfonyl)amino]carbonylJ-2-oxo-3-azetidinyllaminol- 2-oxo-1-phenylethyl]-2,3-dioxo-1-piperazinecarboxamide By reacting (S)-N-(1-imidazolylsulfonyl)-2 ox-l-azetidinecarboxamide and (R) -a- [[-4-ethyl- 2,3-dioxo-1-piperazinyl)carbonyl]amino]phenylacetic acid in the presence of dicyclohexylcarbodiimide and N-hydroxybenzotriazole according to the procedure of Example 33, the titled product is obtained, potassium salt m.p. 175 C.(d.). Example 48 [3S(Z)-2-amino-N-[1-[[[thiazol-2-ylamino)sulfonyl] amino]thioxomethyl]-2-oxo-3-azetidinyl]-&alpha;- (methoxyimino)-4-thiazoleacetamide By substituting (S)-3-amino-2-oxo-N-[[(2thiazolinyl)amino]sulfonyl]-1-azetidinecarboxamide for the carboxamide used in Example 40, the titled compound is obtained, m.p. sodium salt, 250 C(d.). Example 49 [3S(Z)-2-amino-N-[1-[[[5-methyl-1,3,4-thiadiazol 2-ylamino]sulfonyl]amino]thioxomethyl]-2-oxo-3- azetidinyl]-a-(methoxyimino)-4-thiazoleacetamide - > By substituting (S)-3-amino-2-N-[[(5-methyl- ' 1,3,4-thiadiazol-2-yl)amino]sulfonyl]-1azetidinecarboxamide for the carboxamide used in Example 40, the titled compound is obtained, m.p. 209-212 C. Example 50 By substituting the carboxylic acids containing the acyl groups shown in the first column of Table I into Example 23 for the acid used therein (2-amino-a-(methoxyimino)-4-thiazoleacetic acid), and in the case of parts (j) through (o), substituting the azetidinecarboxamide containing the R-radical indicated, for the azetidinecarboxamide used in Example 23, the products shown in Table I are obtained. TABLE 1 EMI76.1 EMI76.2 <tb> <SEP> Acyl <SEP> R <SEP> m.p.aC. <tb> <SEP> H25L <SEP> L-CO <SEP> -NH2 <SEP> 20b <SEP> d. <SEP> K <SEP> salt <tb> (a) <tb> <SEP> H2N-C-C <SEP> CtH-CO <SEP> 2 <SEP> 212 <SEP> d. <SEP> K <SEP> salt. <tb> <SEP> (b) <SEP> C6H5 <tb> <SEP> C6U5 <tb> <SEP> *2v-C0-Xl-CH-CCk- <SEP> 2 <SEP> 185 <SEP> d. <SEP> ° <SEP> salt <tb> <SEP> 0 <SEP> 0 <SEP> C6H5 <tb> <SEP> (d) <SEP> : <SEP> 0-105 <tb> <SEP> C,COI <SEP> NHc, <SEP> 100-1050 <tb> <SEP> C1 <tb> <SEP> (e) <SEP> CX-CO- <SEP> NH2 <SEP> 132-135 <SEP> d. <tb> <SEP> 0E <tb> TABLE 1 (cont.) EMI77.1 <tb> <SEP> Acyl <SEP> -R <SEP> mp.'C. <tb> Acyl <SEP> CH-CO- <SEP> -R <SEP> m.p. <SEP> d. <tb> CH-CO- <SEP> NHZ <SEP> 14'O <SEP> d. <tb> <SEP> COOH <tb> (CH-CO- <SEP> NH2 <SEP> 2450d. <SEP> K+salt <tb> <SEP> NHZ <SEP> 2 <tb> <SEP> N <tb> <SEP> 0 <tb> <SEP> !CHnn <tb> (h) <SEP> -C0- <SEP> NH2 <SEP> 216 d. <SEP> CF3COOH <tb> <SEP> 2 <tb> <SEP> c <tb> (i) <SEP> --co- <SEP> -NH2 <SEP> . <SEP> 204 <SEP> ""6 <SEP> d, <tb> '-OC2Hg <tb> <SEP> NH2 <tb> TABLE 1 (cont.) EMI78.1 <tb> <SEP> Acyl <SEP> ' <SEP> R <SEP> m.p.C. <tb> (j) <tb> <SEP> H2NNifli <SEP> C-CO'- <SEP> -NHCH2CH2OC'0CH3 <SEP> 2000d. <SEP> K+salt <tb> <SEP> II <tb> <SEP> N-u <SEP> CH3 <tb> <SEP> N- <SEP> CH3 <tb> (k) <tb> <SEP> H2N <tb> <SEP> C-CO"- <SEP> C-CO-- <SEP> -,NH-(CH2)3-N(CE3)2 <SEP> 1600 <SEP> d. <tb> <SEP> II <tb> <SEP> N-OCH3 <tb> (1) <tb> <SEP> H2 <SEP> -CO- <SEP> -NH-CH2-CO-NH2 <SEP> 211-213 RFsdt <tb> <SEP> |-OCH3 <tb> (m) <SEP> 0 <tb> <SEP> C6H5CH2O-CO- <SEP> -NHNH-COO-tC4H9 <SEP> 130 <SEP> d. <tb> (n) <tb> <SEP> 2 <SEP> -NI1-NHCOCH <SEP> 182-2000d, <SEP> salt <tb> <SEP> -CO <tb> <SEP> II <tb> <SEP> N-O033 <tb> (o) <tb> <SEP> RN <SEP> -NH-NH2 <SEP> 150 <SEP> 0d. <SEP> 'K+ <SEP> salt <tb> <SEP> 2 <SEP> C-CO <tb> <SEP> II <tb> <SEP> N-OCR3 <tb> TABLE 1 (cont.) EMI79.1 <tb> <SEP> Acyl <SEP> R <SEP> m.p. <SEP> C. <tb> (p) <tb> <SEP> HZN'--- <SEP> 0 <tb> <SEP> Sl¯c <SEP> Ii <SEP> -NHCH2CH2-NAN <SEP> 179 184 <SEP> d <SEP> t <tb> <SEP> N-OCE3 <tb> (q) <tb> <SEP> rJ-n <SEP> NHCHZCHZNHCOCH3 <SEP> 152 <SEP> d <SEP> K+ <SEP> salt <tb> <SEP> 3 <tb> <SEP> 'I <tb> Example 51 By substituting the carboxylic acids containing the acyl groups shown in the first column of Table II into Example 23 for the acid used therein, and substituting the azetidinecarboxamide containing the R-radical indicated for the azetidinecarboxamide used in Example 23, the products shown in Table II are obtained. In the general formula Y can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl) alkyl. TABLE II EMI81.1 EMI81.2 <tb> <SEP> Acyl <SEP> R3 <SEP> Y <SEP> m.p.OC. <tb> (a) <tb> <SEP> /S\ <SEP> H <SEP> -C2H'5 <SEP> 2080d. <SEP> K+sa1t <tb> <SEP> N-OC2H5 <tb> <SEP> N¯o¯C2H5 <tb> (b) <tb> <SEP> 2 <SEP> XLc <SEP> co <SEP> H <SEP> -C2H5 <SEP> 2020d. <SEP> K+salt <tb> <SEP> N-OCH3 <tb> (c) <tb> <SEP> CR'n-CO-NH-CR-CO-' <SEP> H <SEP> -C2RS <SEP> 1780 <SEP> d. <SEP> K+salt <tb> <SEP> 25, <SEP> 1 <tb> <SEP> 0 <SEP> 0 <SEP> C6H5 <tb> (d) <tb> <SEP> BZN' <SEP> S\ <tb> <SEP> I <SEP> H <SEP> -C2H5 <SEP> 2200d. <SEP> R <SEP> salt <tb> <SEP> N'Q <SEP> a <tb> <SEP> CH3-C1-CE3 <tb> <SEP> COOS <tb> TABLE II (cont.) EMI82.1 <tb> <SEP> Acyl <SEP> R3 <SEP> Y <SEP> m.p. <SEP> C. <tb> <SEP> (e) <tb> <SEP> 2Nm <SEP> R <SEP> H <SEP> -iC <SEP> 3H7 <SEP> 235-2380 <SEP> K+salt <tb> <SEP> I <SEP> CC-CO- <tb> <SEP> II <tb> <SEP> N-OCR3 <tb> (f) <tb> <SEP> C2R5-CO-NH-CH-C0- <SEP> H <SEP> -iC337 <SEP> 1930d.X+saIt <tb> <SEP> 0 <SEP> 0 <SEP> C6H5 <tb> (g) <tb> <SEP> H2N(%-CO <SEP> H <SEP> -iC3H7 <SEP> 237Qa. <SEP> K <SEP> K+salt <tb> <SEP> N p <tb> <SEP> CR3--CR3 <tb> <SEP> COOH <tb> <SEP> (h) <tb> <SEP> R2 <SEP> XLgcss <SEP> co <SEP> H <SEP> }I <SEP> 201 <SEP> '0d. <SEP> K+salt <tb> <SEP> N-O-iC3H7 <tb> <SEP> (i) <tb> <SEP> (i) <tb> <SEP> 2 < 11 <SEP> fi-CO <SEP> R <SEP> SC2H5 <SEP> 180 d. <SEP> K+salt <tb> <SEP> %-O-CH2CF3 <tb> TABLE II (cont.) EMI83.1 <tb> <SEP> R <SEP> 0 <tb> <SEP> Acyl <SEP> R3 <SEP> Y <SEP> m.p. <SEP> C. <tb> (j) <tb> <SEP> HZN'--'fS\ <tb> <SEP> C-CO <SEP> -CR3 <SEP> -C2H5 <SEP> 2310d. <SEP> K+salt <tb> <SEP> CH3--CR3 <tb> <SEP> COOR <tb> (k) <tb> <SEP> 2 <SEP> t) <SEP> C-CO- <SEP> H <SEP> -C <SEP> 175-1800 <SEP> K+sal: <tb> <SEP> N11 <SEP> -OCR3 <tb> <SEP> ':4 <tb> (1) <tb> <SEP> 2N <SEP> C-CO <SEP> H <SEP> 222-2280K+salt <tb> <SEP> N-p <tb> <SEP> CR3- <SEP> 3 <tb> <SEP> COOH <tb> <SEP> (m) <tb> <SEP> < <SEP> 0-CO <SEP> - <SEP> H <SEP> -C <SEP> d. <SEP> 207d. <SEP> K <SEP> salt <tb> <SEP> 1, <tb> <SEP> -OH <tb> Example 52 By substituting the carboxylic acids containing the acyl groups shown in the first column of Table III into Example 23 for the acid used therein, and substituting the azetidinecarboxamide containing the R-radical indicated for the azetidinecarboxamide used in Example 23, the products shown in Table III are obtained. In the general formula, n can be zero or one and X can be methylene, oxygen or a nitrogen atom which can be substituted with alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)- alkyl, amino, alkylamino, dialkylamino, alkylidenamino, aralkylidenamino, alkylsulfonyl, carboxy, carboxyalkyl and the like. TABLE III EMI85.1 EMI85.2 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p. <SEP> ec. <tb> (a) <SEP> I <tb> C <SEP> 6R5CH2OCO- <SEP> N-H <SEP> 0 <SEP> 158 <SEP> d. <SEP> K+ <SEP> salt <tb> (b) <SEP> I <tb> <SEP> 12 <SEP> N-H <SEP> 0 <SEP> 252 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 2 <SEP> -CO <SEP> N- <SEP> I <tb> <SEP> II <tb> <SEP> N-OCR3 <tb> <SEP> (c) <SEP> I <tb> <SEP> C <SEP> R'n <SEP> -CO-NH-CR-CO- <SEP> Nvil <SEP> 0 <SEP> 187 <SEP> d. <SEP> R+ <SEP> salt <tb> <SEP> 2' <SEP> I <tb> <SEP> O <SEP> 0 <SEP> C6H5 <tb> <SEP> 1 <tb> <SEP> N-H <SEP> 0 <SEP> 230 <tb> <SEP> HzN-rfS\ <tb> <SEP> -CO <tb> <SEP> I <tb> <SEP> CS3T-CH3 <tb> <SEP> COOB <tb> TABLE III (cont.) EMI86.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p. C. <tb> (e) <tb> -CO-- <SEP> CC- <SEP> I <SEP> 0 <SEP> 210 <SEP> d. <SEP> K+ <SEP> salt <tb> N <SEP> 11 <SEP> ICI-CO <SEP> N1- <SEP> 502 <SEP> CR3 <tb> (f) <tb> C2X5N-CO-NEI-CEI-CO- <SEP> ;-So2Cz3 <SEP> <SEP> 187 <SEP> d. <SEP> salt <tb> <SEP> O <SEP> 0 <SEP> C6H5 <tb> (g} <tb> R2N! <SEP> O <SEP> 227 <SEP> I <tb> <SEP> -,-CO--- <SEP> 3 <SEP> L <SEP> rl <tb> <SEP> 1 <tb> <SEP> -- <SEP> S3--CEX3 <tb> <SEP> I <SEP> 3-CH3 <tb> <SEP> COOS <tb> (h) <tb> C2H5NWNCO-NH-CH-CO- <SEP> n-iC3H7 <SEP> 0 <SEP> 183 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 0 <SEP> 0 <SEP> C6R5 <SEP> I <tb> TABLE III (cont.) EMI87.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p.C <tb> (i) <tb> B,N---I <SEP> ---C-COO <tb> N-iC3H7 <SEP> N-iC3 <SEP> 0 <SEP> 252 <SEP> salt <tb> <SEP> I <SEP> I <tb> <SEP> N-Q <tb> <SEP> CR3 <SEP> -CR3 <tb> <SEP> OOH <tb> <SEP> ,\ <tb> (j) <SEP> \ <tb> H,NI;ks-h <SEP> C-CO- <SEP> K+ <SEP> salt <tb> N <SEP> lgg <SEP> co¯ <SEP> B <SEP> 0 <SEP> 253 <SEP> d. <SEP> K+ <SEP> N-N-CR-C65 <tb> <SEP> N-OCH3 <tb> (k) <tb> <SEP> In <SEP> N-N=CH-C <SEP> I <tb> CR <SEP> -CO-NR-CH-CO- <SEP> | <SEP> 6R5 <SEP> 5 <tb> <SEP> 25 <SEP> I <tb> <SEP> O <SEP> O <SEP> C6, <SEP> H5 <tb> (1) <tb> 2 < <SEP> ) <SEP> 1 <SEP> C2S5 <SEP> 183 <SEP> Åa. <SEP> R <SEP> salt <tb> <SEP> co <SEP> I-C2Hs <SEP> 0 <SEP> 183 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N-OCH3 <tb> TABLE III (cont.) EMI88.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p.-C. <tb> <SEP> '(m) <tb> <SEP> rn <SEP> I <tb> CH-CO-NH-CH-CO- <SEP> N-C2H5 <SEP> 0 <SEP> 179 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 25 <SEP> 1 <SEP> I <tb> <SEP> O <SEP> O <SEP> C6H5 <tb> <SEP> t <tb> (n) <SEP> ; <tb> -CO-- <tb> <SEP> II <SEP> "-CO-- <SEP> P <tb> <SEP> I <SEP> N-C2z5 <SEP> <SEP> 232 <SEP> d. <SEP> X <SEP> alt <tb> <SEP> N-Q <tb> <SEP> C83f <SEP> -CH3 <tb> <SEP> COOR <tb> <SEP> (o) <tb> H2 <SEP> - <SEP> I <tb> <SEP> 'C-CO- <SEP> NrC,6R5 <SEP> 0 <SEP> 222 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N-OCR3 <SEP> I <tb> (P) <tb> H <SEP> I <tb> <SEP> 2 <SEP> N-CH2-C6-H5 <SEP> 0 <SEP> 197 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N-CO- <SEP> I <tb> <SEP> N-OCH3 <tb> TABLE III (cont.) EMI89.1 <tb> <SEP> Acyl <SEP> m.p.-C. <tb> (q) <tb> <SEP> ,n <SEP> I <tb> C2R5-CO-NH-CH-CO- <SEP> 'CsHg <SEP> 0 <SEP> 5 <SEP> 186 <SEP> d. <SEP> R+ <SEP> salt <tb> <SEP> O <SEP> <SEP> C6H5 <tb> (r) <tb> <SEP> S <tb> <SEP> H2N <SEP> I <tb> <SEP> N-CO- <SEP> N-C6R5 <SEP> 0 <SEP> 230 <SEP> d. <SEP> K+ <SEP> salt. <tb> <SEP> CI, <SEP> I <tb> <SEP> COOH <tb> <SEP> COOR <tb> <SEP> (s) <tb> <SEP> N-CH2CgHg <SEP> 0 <SEP> 175 <SEP> d. <SEP> K+ <SEP> salt <tb> C2Rs;CO <SEP> I <SEP> 0\-CH2C6 <SEP> H5 <tb> <SEP> . <SEP> ¯ <SEP> ¯ <tb> <SEP> O <SEP> 0 <SEP> t <SEP> b <SEP> C6H5 <tb> <SEP> (t) <tb> <SEP> EN <tb> <SEP> H5 <SEP> 5AN-CO-- <SEP> Y-CH2-C6E5 <SEP> 0 <SEP> 207 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N-9 <SEP> I <tb> <SEP> 3i <SEP> 3 <tb> <SEP> COOH <tb> TABLE III(cont.) EMI90.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p.0C. <tb> (u) <tb> H2 <SEP> I <tb> N-COOtC4H9 <SEP> 0 <SEP> 170-175 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 'C <SEP> -CO- <SEP> I <tb> <SEP> ii <tb> <SEP> N-OCH3 <tb> (v) <tb> H <SEP> {ell <SEP> g-Co <SEP> N-CH2CR2NH2 <SEP> 0 <SEP> 198-203 <SEP> d. <SEP> X <SEP> salt <tb> <SEP> 2 <tb> <SEP> -CO <tb> <SEP> l{-OCH3 <tb> (w) <tb> <SEP> I <tb> C,H! <SEP> -CO-NH-CH-CO- <SEP> ' <SEP> N-CR2CR2NR2 <SEP> 0 <SEP> 188-193 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> O <SEP> <SEP> C6R5 <tb> <SEP> DZ <tb> <SEP> (x) <tb> 2 <SEP> ti <SEP> co- <SEP> . <SEP> 1SCH2CH2NH2 <SEP> Q <SEP> 202-205. <SEP> d. <SEP> Ks <SEP> salt. <tb> HzN <SEP> rl <SEP> 1 <SEP> Fi'CO' <SEP> LLL <tb> <SEP> 3i <SEP> 3 <tb> <SEP> COOR <tb> TABLE III(cont.) EMI91.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> mvp.-C. <tb> (y) <tb> H2N <SEP> zero <SEP> N-NXI <SEP> 0 <SEP> 190-195 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 'OCH3 <SEP> I <tb> <SEP> -OC83 <tb> (z) <tb> <SEP> , <SEP> I <tb> c,a <SEP> -CO-NR-CR-CO- <SEP> N=iC3H7 <SEP> 0 <SEP> 183 <SEP> - <SEP> 188 <SEP> d. <SEP> R+ <SEP> salt <tb> <SEP> 2 <SEP> I <tb> <SEP> O <SEP> <SEP> C6s5 <tb> (aa) <tb> pni5) <SEP> ICg-CO <SEP> H2 <SEP> 2 <SEP> 0 <SEP> 2Q0 <SEP> d. <SEP> R+ <SEP> salt <tb> <SEP> II <tb> <SEP> N-OCB3 <tb> (bb) <tb> <SEP> n <tb> <SEP> -CO-NH-CR-CO- <SEP> CR2 <SEP> 0 <SEP> 187 <SEP> d. <SEP> K+ <SEP> salt <tb> C2H5 <SEP> CO-NH-CH-CO- <SEP> CH2 <SEP> 0 <SEP> 187 <SEP> d. <tb> <SEP> 0 <SEP> <SEP> C6H5 <tb> TABLE III(cont.) EMI92.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p.-C. <tb> Ccc) <tb> BZN'--'rfs <SEP> 0 <SEP> 245 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N <SEP> C-CO- <SEP> I <tb> <SEP> N-? <tb> <SEP> CB-CEI3 <tb> <SEP> (dd) <tb> R2N <SEP> I' <SEP> 0 <SEP> 202 <SEP> K+ <SEP> salt <tb> <SEP> -CO-' <SEP> C1H2 <tb> <SEP> -OR <tb> (ee) <tb> R <SEP> - <SEP> I' <tb> ¯¯¯¯¯ <SEP> CR <SEP> 0 <SEP> 195 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> C <SEP> CC <SEP> j2 <tb> <SEP> U <tb> <SEP> * <SEP> N-OC2H5 <tb> (ff) <tb> Razz <SEP> N/; <SEP> ) <SEP> it <SEP> -CO- <SEP> o <SEP> 184 <SEP> d. <SEP> R+ <SEP> salt <tb> <SEP> h-OCH3 <tb> TABLE III(cont.) EMI93.1 <tb> <SEP> Acyl <SEP> X <SEP> n <SEP> m.p.µC. <tb> <SEP> (gg) <tb> <SEP> C <SEP> H <SEP> -CO-NH-CR-CO- <SEP> 0 <SEP> 0 <SEP> 176 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 25 <SEP> 1 <tb> <SEP> O <SEP> o <SEP> Czars <tb> R <tb> <SEP> (hh) <SEP> + <SEP> "-CO <SEP> I <tb> <SEP> 6 <SEP> 259 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> I <SEP> 0 <tb> <SEP> CR3,3 <tb> <SEP> COOB <tb> (ii) <tb> EI <SEP> <tb> <SEP> 1 <SEP> Ir <SEP> n <tb> <SEP> R--LC-COO <tb> 1 <tb> q <tb> R2 <SEP> I <tb> <SEP> N <SEP> No <SEP> 11 <SEP> NRi <SEP> no <SEP> 1 <SEP> 220 <SEP> d. <SEP> K+ <SEP> 'salt <tb> <SEP> &verbar;-ocE3 <tb> Example 53 By substituting the carboxylic acids containing the acyl groups shown in the first column of Table IV into Example 23 for the acid used therein, and substituting the azetidinecarboxamide containing the R-radical indicated for the azetidine carboxamide used in Example 23, the products shown in Table TV are obtained. In the general formula, W can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl) alkl. TABLE IV EMI95.1 EMI95.2 <tb> Acyl <SEP> W <SEP> m.p.0C. <tb> (a) <tb> C2H5lQN-CO-NXI-CE-CO- <SEP> H <SEP> 221 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> I <tb> <SEP> O <SEP> O <SEP> C6H5 <tb> <SEP> (b) <tb> B2N < ) <tb> <SEP> N <SEP> fi-Co- <SEP> H <SEP> 198 <SEP> d. <SEP> R+ <SEP> salt <tb> <SEP> NS <tb> <SEP> CH3 <SEP> -CR3 <tb> <SEP> COOB <tb> <SEP> (c) <tb> <SEP> 2CS <SEP> 11 <tb> <SEP> -- <SEP> S <SEP> 247 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> 3 <tb> <SEP> sn <tb> <SEP> (d) <tb> <SEP> H,N-' <SEP> /S3r <tb> <SEP> 2 <SEP> C11 <SEP> -CO- <SEP> 3 <SEP> 212 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N-OCS3 <tb> TABLE IV EMI96.1 <tb> Acyl <SEP> W <SEP> m.p.'C. <tb> (e) <tb> C <SEP> 5}v-CO-NH-CH-CO- <SEP> CH3 <SEP> 197 <SEP> d. <SEP> K+ <SEP> salt <tb> 2 <SEP> ""O-rH-CB-CO- <SEP> 3 <tb> <SEP> QO <SEP> C6H5 <tb> <SEP> (f) <tb> <SEP> CH3 <SEP> 235 <SEP> d. <SEP> K+ <SEP> salt <tb> <SEP> N-Q <tb> <SEP> N"p <tb> <SEP> Ca3i-CE13 <tb> <SEP> COOR <tb>

Claims: Claims: d. 2-Oxo-1-[[(substituted sulfonyl)amino]carbonyl]azetidines having a EMI97.1 substituent in the l-position and an amino substituent or acylamino substituent in the 3-position, or a salt thereof; wherein Z is oxygen or sulfur, and R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (roc) . phenylalkyl, (substituted-phenyl)alkyl, Rc-alkyl or NRaRb wherein Ra and % are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl. substituted phenyl, phenylalkyl,' (substituted phenyl)alkyl or one of Ra and Rb is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NR2), alkanoylamino, arylcarbonylamino, alkoxy carbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl) amino, hydroxy, cyano(-C-N), alkoxy, phenyloxy, (substituted phenyl)oxy. phenylalkoxy, (substituted phenyl)alkoxy, Rc as defined above, Rc-alkyl, Rc-alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted 13ghenyl) methyleneamino. 2. A 8-lactam in accordance with claim having a EMI97.2 substituent in the l-position an amino, substituent or acylamino substituent in the 3-position, and a methoxy substituent in the 3-position, or a salt thereof. 3. A B-lactam in accordance with claim 1 wherein Z is oxygen. 4. A.B-lactam in accojnce with claim 1 having a EMI98.1 substituent in the l-pdsition and an amino substituent or acylamino substituent in the 3-position, or a salt thereof. 5. A B-lactam in accordance with claim 1 having the formula EMI98.2 or a salt thereof; wherein R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (Rc), phenylalkyl, (substituted-phenyl)alkyl, Rc-alkyl or -NRaRb wherein Ra and Rb are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of Ra and Rb is hydrogen, alkyl phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NR2) alkanoylamino, arylcarbonylamino, alkoxy carbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl) amino, hydroxy, cyano(-C=N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, Rc as defined above, %-alkyl, Rc -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneaminor R1 isacyl; R2 is hydrogen or methoxy; ; R3 and R4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, -CH2X1 (wherein is azido, amino, hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl)methylthio, triphenylmethylthio, cyano or mercapto), -S-X2 or -O-X2 (wherein X2 is alkyl, phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or EMI99.1 (wherein one of X3 and X4 is hydrogen and the other is hydrogen or alkyl, or e and X4 when taken together with the carbon .atos to which they are attached form a cycloalkyl group, and X5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carbonyl, alkoxycarbonyl, aminocarbonyl, (substituted amino) - carbonyl, or cyano); and Z is oxygen or sulfur. 6. A B-lactam in accordance with claim 5 wherein R2 is hydrogen. 7. A B-lactam in accordance with claim 6 wherein R3 is hydrogen and R4 is hydrogen or methyl. 8. A B-lactam in accordance with claim 7 wherein Z is oxygen. 9. A Blactam in accordance with claim S wherein Z is oxygen. 10. A B-lactam in accordance with claim 5 having the formula EMI100.1 or a salt thereof. 11. A B-lactam in accordance with claim 10 wherein Ra and Rb each is hydrogen. 12. A B-lactam in accordance with,claim 5 wherein R1 is EMI100.2 R11 is 2-amino-4thiazolyl and R13 is alkyl or carboxy substituted alkyl. 13. A B-lactam in accordance with claim 1 having the formula EMI100.3 or a salt thereof; wherein is is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (roc) . phenylalkyl, (substituted-phenyl)alkyl, Rc-alkyl or -NRaRb wherein Ra and % are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of Ra and Rb is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH2), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)- amino, hydroxy, cyano(-C=N), alkoxy, phenyloxy, (substituted phenyl)oxy. phenylalkoxy, (substituted phenyl)alkoxy, Rc as defined above, Rc-alkyl. Rc-alkoxy, alkylsulfonyl, alkylmethyleneamino. (alkyl-CH=N-), phenylmethyleneamino or (substituted phenyl)methyleneamino. R2 is hydrogen or methoxy; R3 and R4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one or R3 and R4 is hydrogen and the other is alkoxycarbonyl, alkan-1-yl, alkyl-1-yl, 2-phenylethenyl, 2-ptenylethynyl, carboxyl, -C112X1 (wherein X1 is azido, amino; ; hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phenyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl)methylthio, triphenylmethylthio, cyano or mercapto), -S-X2 or -O-,X2 (wherein X2 is alkyl, phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or EMI102.1 (wherein one of us and X4 is hydrogen and the other is hydrogen or alkyl, or X3 and X4 when taken together with the carbon atom to which they are attached form a cycloalkyl group, and X5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl) carbonyl, phenylalkylcarbonyl, (substituted phenyl) alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)carbonyl, or cyano); and Z is oxygen or sulfur, and the amino group can be in a protected form. 14. A B-lactam in accordance with claim 13 wherein R2 is hydrogen. 15. The compound in accordance with claim 5, (S)-[1-[[[(4-methylphenyl)sulfonyl]amino]carbonyl] 2-oxo-3-azetidinylacarbamic acid, phenylmethyl ester. -- - 16. The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-N-[(4-methylphenyl)sulfonyl]-2oxo-l-azetidinecarboxamide. 17. The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-N-(methylsulfonyl)-2-oxo-1azetidinecarboxamide, potassium salt. 18. The compound in accordance with claim 5, [3S-[3&alpha;(Z), 4ss]]-3-[[(2-amino-4-thiazolyl)(methoxy- imino) acetyl] amino] -4-methyl-N- (methylsulfonyl) 2-oxo-l-azetidinecarboxamide, potassium salt. 19. The compound in accordance with claim 5, [3S-[3o(Z) ,4s]]-3-[I(2-amino-4-thiazolyl) [(1- carboxy-l-methylethoxy)imino]acetyl]amino]-4- methyl-N-(methylsulfonyl)-2-oxo-1-azetidine carboxamide, dipotassium salt. 20. The compound in accordance with claim 5,' [3S(Z)]-3[[(2-amino-4-thiazolyl)(methoxy imino)acetyl]amino]-N-(methylsulfonyl)-2 oxo-l-azetidinecarbothioamide, potassium salt. 21. The compound in accordance with claim 5, [3S(Z)]-2[[(1-(2-amino-4-thiazolyl)-2 [[1-[[(methylsulfonyl)amino]carbonyl]-2-oxo-3 azetidinyl]aminol-2-oxoethylidene]amino]oxy]-2- methylpropanoic acid, dipotassium salt. 22. The compound in accordance with claim 5 [3S(Z)]-3[[(2-amino-4-thiazolyl)(methoxy imino)acetyl]amino]-N-(aminosulfonyl)-2-oxo-1 azetidinecarboxamide, ammonium salt. 23. The compound in accordance with claim 5, [3S(Z)]-3[[(2-amino-4-thiazolyl)(methoxyimino) acetyl]amino]-N-[[(1-methylethyl)amino]sulfonyl] 2-oxo-1-azetidinecarboxamide, sodium salt. 24. The compound in accordance with claim 5, [3S(Z)]-3-[[(2-amino-4-thiazolyl)(methoxyimino) acetyl]amino]-2-oxo-N-t(phenylamino)sulfonyl]- l-azetidinecarboxamide, sodium salt. 25. The compound in accordance with claim 5, [3S(Z)]-3[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]-N-[(dimethylamino)sulfonyl]-2oxo-l-azetidinecarboxamide, sodium salt. 26. The e compound in accordance with claim 5, [3S(Z)]-2[[[1-(2-amino-4-thiazolyl)-2-[[1 [[(aminosulfonyl)amino]carbonyl]-2-oxo-3azetidinyl]amino]-2-oxoethylidene]amino]oxo]2-methylpropanoic acid, disodium salt. 27. The compound in accordance with claim 13, (S)-N-(methylsulfonyl)-2-oxo-3-amino-l-azetidinecarboxamide, hydrochloride salt. 28. The compound in accordance with claim 13, (S) -3-amino-N- (methylsulfonyl) -2-oxo-l'-azetidine- carboxamide, inner salt. 29. The compound in accordance with. claim 13, [3S-[3&alpha;, 4ss]]-3-amino-4-methyl-N-(methylsulfonyl)- 2-oxo-l-azetidinecarboxamide, trifluoroacetic acid salt. 30. The compound in accordance with claim 13, (S)-3-amino-N- (methylsulfonyl) -2-oxo-l-azetidirie- carbothioamide, trifluoroacetic acid salt. 31. The compound in accordance with claim 13, (S)-3-amino-N-(aminosulfonyl)-2-oxo-1-azetidine car6xamide, inner salt. 32. The compound in accordance with claim 13, (S)-3-amino-N-[(methylamino)sulfonyl)-2-oxo-1azetidinecarboxamide, inner salt. 33. The compound in accordance with claim 13, (S)-3-amino-2-oxo-[[(4-pyridyl)amino]sulfonyl]l-azetidinecarboxamide. 34. The compound in accordance with claim 13, (S)-l-1[[(4-methylphenyl)sulfonyl]aminolcarbonyll- 2-oxo-3-aminoazetidine, triethylammonium salt. 35. A compound according to claim 1 of the formula EMI105.1 wherein Y can be hydrogen, alkyl, substituted'alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl. 36. A compound according to claim 1 of.the formula EMI105.2 wherein n can be zero or one and X can be methylene, oxygen or a nitrogen atom which can be substituted with alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)-alkyl, amino, alkylamino, dialkylamino, alkylidenamino, aralkylidenamino, alkylsulfonyl, carboxy, carboxyalkyl and the like. 37. A compound according to claim l of the formula EMI105.3 wherein W can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl. 38. A process for preparing a S-lactam of any oX the preceding claims having a EMI106.1 substituent in the l-position and an amino substituent or a protected form thereof or an acylamino substituent in the 3-position, or a salt thereof; wherein Z is oxygen or sulfur, and R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a5,6 or 7-membered heterocycle (Rc), phenylalkyl, (substituted-phenyl)alkyl, Rc-alkyl or -NRaRb wherein Ra and Rb are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of Ra and Rb is hydrogen, alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NE2), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dialkylamino, phenylamino, (substituted phenyl)amino, hydroxy, cyano(-C=N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy, (substituted phenyl)alkoxy, Rc as defined above, Rc-alkyl, Rc -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH-N-), phenylmethyleneamino or (substituted phenyl)methyleneamino. 39. A process according to claim 38 wherein said B-lactam which is unsubstituted in the l-position is reacted with a compound of the formula Z=C:N-SO2-R 40. A process according to claim 38 wherein R is an amino or substituted amino group, wherein said B-lactam which is unsubstituted in the l-position is reacted with a compound of the formula XnC=N-S02-Y wherein Y is a leaving group such as a halogen and the intermediate resulting therefrom is then reacted with an amine of the formula HNRa g 41. A process according to claims-38 through 40 wherein the product has an acylamino substituent in the 3-position and said acylamino substitutent is introduced by acylating a product thereof having an amino substituent in the l-position. 42. A process according to claims 38 through 41 wherein Z is oxygen. 43. A process according to claim 42 wherein R is amino. 44 A process according to claims 38 through 43 wherein the product has a methoxy substituent in the 3-position. AS. A process according to claims 38 through 44 wherein the product has the formula EMI107.1 or a salt thereof; wherein R is alkyl, alkenyl, alkynyl, substituted alkyl, phenyl, substituted phenyl, a 5,6 or 7-membered heterocycle (Rc). phenylalkyl, (substituted-phenyl)alkyl, Rc-alkyl or -NRaRb wherein Ra and Rb are the same or different and each is hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)alkyl or one of Ra and Rb is hydrogen, alkyl, phenyl, substituted phenyl',. phenylalkyl or (substituted phenyl)alkyl and the other is amino (-NH2), alkanoylamino, arylcarbonylamino, alkoxycarbonylamino, alkylsulfonylamino, alkylamino, dgalkylamino, phenylamino, Csubtituted phenyl)amino, hydroxy, cyano-(-C-N), alkoxy, phenyloxy, (substituted phenyl)oxy, phenylalkoxy. (substituted phenyl)alkoxy, Rc as defined above, Rc -alkyl, Rc -alkoxy, alkylsulfonyl, alkylmethyleneamino, (alkyl-CH-N-), phenylmethyleneamino or (substituted phenyl)methyleneamino; R1' amino, protected amino or acylamino; R2 is hydrogen or methoxy; ; R3 and R4 are the same or different and each is hydrogen, alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl, 2-phenylethynyl, carboxyl, -CR2X1 (wherein X1 is azido, amino, hydroxy, alkanoylamino, alkylsulfonyloxy, phenylsulfonyloxy, (substituted phnyl)sulfonyloxy, phenyl, substituted phenyl, halogen, benzylthio, (substituted phenyl)methylthio, triphenylmethylthio, cyano or mercapto), -S-X2 or -O-X2 (wherein X2 is alkyl, phenyl, substituted phenyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, or heteroarylcarbonyl), or EMI109.1 (wherein one of X3 and X4 is hydrogen and the other is hydrogen or alkyl, or X3 and X4 when taken together with the carbon atom to which they are attached form a cycloalkyl group, and X5 is formyl, alkanoyl, phenylcarbonyl, (substituted phenyl)carbonyl, phenylalkylcarbonyl, (substituted phenyl)alkylcarbonyl, carboxyl, alkoxycarbonyl, aminocarbonyl, (substituted amino)- . carbonyl, or cyano).; and Z is oxygen or sulfur. 46. A process according to claim 45 wherein R1 is acylamino and said product is obtained by acylating a product wherein R1' is amino. 47. A process in accordance with claims 45 and 46 wherein R2 is hydrogen. 48. A process in accordance with claim 47 wherein R3 is hydrogen and R4 is hydrogen or methyl. 49. A process in accordance with claim 48 wherein Z is oxygen. 50. A process in accordance with claims 45 and. {E Aherein Z is oxygen. 51. A process in accordance with claim 45 and 46 wherein the product has the formula EMI109.2 wherein R1 is acyl br a salt thereof. 52. A process in accordance with claim 51 wherein Ra and Rb each is hydrogen. 53. A process in accordance with claims 45 and 46 wherein R1.1 is acylamino of the formula EMI110.1 R11 is 2-amino-4-thiazolyl and R13 is alkyl or carboxy substituted alkyl. 54. A process in accordance with claim 45 wherein the product is of the formula EMI110.2 or a salt thereof, or a form thereof wherein the anino group is protected. 55-. A process according to claim 38 wherein the product is of the formula EMI110.3 wherein y can be hydrogen , alkyl, substitutd alkyl. phenyl, substituted phenyl, phenylalkyl or Esubstituted phenyl) alkyl. 56. A process according to claim 38 wherein the product is of the formula EMI110.4 wherein n can be zero or one and X can be methylene, oxygen or a nitrogen atom which can be substituted with alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl, (substituted phenyl)-alkyl, amino, alkylamino, dialkylamino, alkylidenamino, aralkylidenamino, alkyl sulfonyl, carboxy, carboxyalkyl and the like. 57. A process according to claim 38 wherein the product is of the formula EMI111.1 wherein W can be hydrogen, alkyl, substituted alkyl, phenyl, substituted phenyl, phenylalkyl or (substituted phenyl) alkyl.

Inventors: BREUER, HERMANN, DENZEL, THEODOR, SLUSARCHIYK, WILLIAM A., TREUNER, UWE D.
Applicants: E.R. SQUIBB & SONS, INC.
Application year: 1982
Main classification: C07D205
IPC codes: C07D403, A61K31, C07D417, C07D205, C07D413, C07D405, C07D401, A61P31, C07D521