BETA-LACTAM ANTIBIOTICS

Abstract: β-Lactams having a suifonic acid substituent in the 1-position and one or two substituents as specified in the 4-position and an amine function in the 3-position and their use as antibiotics.

Description: 8-LACTAM ANTIBIOTICS This invention is directed to a novel family of S-lactam antibiotics, and to the use of such compounds as antibacterial agents. ss-Lactams having a sulfonic acid salt (including "inner salt") substituent in the l-position and an acylamino substituent in the 3-position and having one or two alkyl, cycloalkyl, phenyl or substituted phenyl substituents in the 4-position or a single alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl or 2phenylethynyl substituent in the 4-position exhibit activity against a range of gram-negative and gram-positive bacteria. The preferred members of the novel family of ss-lactam antibiotics of this invention are those encompassed by the formula EMI1.1 In addition to the above described ss-lactams an acylamino substituent in the 3-position, this invention also encompasses counterpart compounds having an amino substituent in the 3-position. The preferred compounds of this type have the formula EMI2.1 These compounds are intermediates useful for the preparation of corresponding 3-acylamino compounds. As used in formulas I and Ia, and throughout the specification, the symbols are as defined below: R1is acyl; R2 is hydrogen or alkoxy of 1 to 4 carbons; R3 and R4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl or 2-phenylethynyl. M is hydrogen or a cation. The terms "alkyl" and "alkoxy" refer to both straight and branched chain groups. Those groups having 1 to 10 carbon atoms are preferred. The terms "cycloalkyl" and "cycloalkenyl" refer to cycloalkyl and cycloalkenyl groups having 3,4,5,6 or 7 carbon atoms. The term "alkenyl" refers to both straight and branched chain groups. Those groups having 2 to 10 carbon atoms are preferred. The term "halogen" refers to fluorine, chlorine, bromine and iodine. The term "substituted phenyl" refers to a phenyl group substituted with 1,2 or 3 amino, halogen, hydroxyl, trifluoromethyl and lower alkyl or alkoxy groups. The term "protected carboxyl" refers to a carboxyl group which has been esterified with a conventional ester 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 carbon groups are benzyl, benzhydryl and t-butyl esters. 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-aminopenicillanic acid and derivatives and 7-aminocephalosporanic acid and derivatives; see, for example, Cephalosporins and Penicillins, edited by Flynn, Academic Press (1972), German Offenlegungsschrift 2,716,677 published October 10, 1978, Belqian patent 867,994, published December 11, 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 EMI4.1 wherein R5 is alkyl; cycloalkyl; alkoxy; alkenyl; cycloalkenyl; cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups. (b) Carbocyclic aromatic groups having the formula EMI4.2 EMI5.1 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 [(alkylthio)thioxomethyllthio. Preferred carbocyclic aromatic acyl groups include those having the formula EMI5.2 EMI6.1 (Rg is preferably a carboxyl salt or sulfo salt) and EMI6.2 (Rg is preferably a carboxyl salt or sulfo salt). (c) Heteroaromatic groups having the formula EMI6.3 wherein n is 0, 1, 2 or 3; Rg is as defined above; and R10is 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, pyrazinyl, thiazolyl, morpholinyl, pyrimidinyl and tetrazolyl. Exemplary substituents are halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, or alkoxy of 1 to 4 carbon atoms. Preferred heteroaromatic acyl groups include those groups of the above formulas wherein R10 is 2-amino-4-thiazolyl, 2-amino-5-halo4-thiazolyl, 4-aminopyrimidin-2-yl, 5-amino-1,2,4thiadiazol-5-yl, 2-thienyl or 2-furanyl. (d) i [(4-Substituted-2,3-dioxo-l-piperazinyl)- carbonyljamino]arylacetyl groups having the formula EMI7.1 wherein RUis an aromatic group (including carbocyclic aromatics such as those of the formula EMI7.2 and heteroaromatics as included within the definition of Rl0); 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., EMI7.3 wherein Rllis as defined above) or alkylcarbonylamino. Preferred [[(4-substituted-2,3-dioxo-l piperazinyl) carbonyl] amino) arylacetyl groups include those wherein R12 is ethyl1 phenylmethyleneamino or 2-furylmethyleneamino. (e) (Substituted oxyimino)arylacetyl groups having the formula EMI8.1 wherein Rllis as defined above-and R13 is hydrogen, alkyl, cycloalkyl, alkylaminocarbonyl, arylaminocarbonyl (i.e., EMI8.2 wherein Rllis 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 R1, carboxyl (including salts thereof), amido, alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy (phenylmethoxy)phosphinyl, or dialkoxyphosphinyl substituents). Preferred (substituted oxyimino)arylacetyl groups include those wherein Rllis 2-amino-4-thiazolyl. Also preferred are those groups wherein R13 is methyl, ethyl, carboxymethyl, or 2-carboxyisopropyl. (f) (Acylamino)arylacetyl groups having the formula EMI8.3 wherein Rllis as defined above and R14 is EMI9.1 amino, alkylamino, (cyanoalkyl)amino, amido, alkylamido, (cyanoalkyl) EMI9.2 Preferred (acylamino) arylacetyl groups of the above formula include those groups wherein R14 is amino, or amido. Also preferred are those groups wherein Rllis phenyl or 2-thienyl. (g) [ [[3-Substituted-2-oxo-l-imidazoli- dinyl]carbonyl]aminoaarylacetyl groups having the formula EMI9.3 wherein R11 is is as defined above and R15 is hydrogen, alkylsulfonyl, arylmethyleneamino (i.e., -N-CH-R11 wherein R11 is as defined above), EMI10.1 (wherein R16 is hydrogen, alkyl orhalogen substituted alkyl), aromatic group (as defined by R11above), alkyl or substituted alkyl (wherein the alkyl group is substituted with one or more halogen,cyano, nitro, amino or mercapto groups). Preferred [[3-substituted-2-oxo-l-imidazoli- dinyl]carbonyl]amino]arylacetyl groups of the above formula include those wherein R11is phenyl or 2-thienyl. Also preferred are those groups wherein R15 is hydrogen, methylsulfonyl, phenyl methyl eneamino or 2-furylmethyleneamino. The term "cation", as used throughout the specification, refers to any positively charged atom or group of atoms. The "-SO3M#" substituent on the nitrogen atom of the B-lactams of this invention encompasses all sulfohic acid salts. Pharmaceutically acceptable salts are, of course, preferred, although other salts are alsb useful in purifying the products of this invention or as intermediates for the preparation of pharmaceutically acceptable salts. The cationic portion of the sulfonic acid salts of this invention can be obtained from either organic or inorganic bases. Such cation portion includes, but is not limited to, the following ions: ammonium; substituted ammonium, such as alkylammonium (e.g., tetra-n-butylammonium, referred to hereinafter as tetrabutylammonium); alkali metal, such as lithium, sodium and potassium; alkaline earth metal, such as calcium and magnesium; pyridinium: dicyclohexylammonium; hydrabaminium benzathinium; N-methyl-D-alucaminium. Some of the compounds of this invention may be crystallized or recrystallized from solvents containing water. In these cases water of hydration may be formed. This invention contemplates stoichiometric hydrates as well as compounds containing variable amounts of water that may be produced by processes such as lyophilization. ss-Lactams having a sulfonic acid salt substituent in the l-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 ss-lactam nucleus) to which the amino or acylamino substituent is attached. This invention is directed to those ss-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.g., cephamycin C). With respect to the preferred B-lactams of formulas I and Ia, the structural formulas have been drawn to show the stereochemistry at the chiral center in the 3-position. Because of the nomenclature convention, those compounds of formulas I and Ia wherein R2 is hydrogen have the S configuration and those compounds of formulas I and Ia wherein R2 is alkoxy have the R configuration. Also included within the scope of this invention are racemic mixtures which contain the above-described B-lactams. The compounds of this invention have activity against a range of gram-negative and gram-positive organisms and 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 an amount of about 1.4 mg/kg/day to about 350 mg/kg/day, perferably about 14 mg/kg/day to about 100 mg/kg/day. All modes of administration 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 ss-lactams of this invention. Such methods of administration include oral, intravenous, intramuscular and as a suppository. The -lactamproducts of this invention are generally prepared by the introduction of a sulfonic acid substituent (a sulfo group -SO3-) onto the nitrogen atom in the l-position of the ss-lactam nucleus. This sulfonation reaction is readily effected by treating the ss-lactam with a sulfur trioxide complex or within equivalent sulfonating reagent such as a chlorosulfonate. The sulfur trioxide complexes most commonly used are pyridine-sulfur trioxide; lutidine-sulfur trioxide; dimethylformamide-sulfur trioxide; and picoline-sulfur trioxide. Instead of using a pre-formed complex, the complex can be formed in situ, e.g., using chlorosulfonyl-trimethylsilyl ester and pyridine as reagents. Alternatively, sulfonation can be effected by way of an intermediate compound as for example first silylating the nitrogen atom of the ss-lactam nucleus and then subjecting the silated compound to a silyl interchange reaction with trimethylsilylchlorosulfonate or a similar reagent. Exemplary silylating agents are monosilyltrifluoroacetamide, trimethylsilylchloride/triethylamine and bis-trimethylsilyl trifluoroacetamide. Generally, the sulfonation reaction is carried out in the presence of an organic solvent such as pyridine or amixture of organic solvents, preferably a mixture of a polar solvent such as dimethylformamide and a halogenated hydrocarbon such as dichloromethane. The product initially formed in the sulfonation reaction is a salt of the sulfonated S-lactam. When pyridine-sulfur trioxide is the sulfonating complex the product initially formed is the B-lactam-sulfonated pyridiniumsalt of the sulfonated ss-lactam wherein M+ in the formula below is the pyridinium ion: EMI13.1 These complexes can be converted to other sulfonic acid salts using conventional techniques (e.g., ionexchange resins, crystallization or ion-pair extraction. These conversion techniques are also useful in purifying the products. Conversion of the pyridine salt to the potassium salt using potassium phosphate or potassium ethyl hexanoate; to the tetrabutylammonium salt using tetrabutyl ammonium hydrogen sulfate; or to a zwitterian (M+ = hydrogen) using formic acid; are particularly useful. It should be appreciated that the sulfonation reaction which introduces the sulfo group onto the nitrogen atom of the ss-lactam nucleus can be effected at various stages of the synthesis, including insertion prior to the formation of a ss-lactam nucleus, where such procedure is followed as outlined below. The sulfonation reaction is effected in the presence of solvents previously described and usually at room temperature, Where the amino function is present it is preferably conducted with the amino function protected. Using a benzyloxycarbonyl protecting group as an example, the sulfonation reaction can be visualized as follows: EMI14.1 Other protecting groups can be used to protect the amine function, for example, a t-butyloxycarbonyl group, a simple acyl group-such as acetyl or benzopl of phenylacetyl, a triphenylmethyl group, or having the amino function in the form of an azide group. The desired acyl group (R1) can then be affixed by a conventional acylation redaction. Exemplary acylation techniques for converting a compound of formula III to a product of formula I include reaction with a carboxylic acid (R1-OH), or corresponding carboxylic acid halide or carboxylic acid anhydride. When R2 is alkoxy, acylcation is best effected by use of an acid chloride or acid bromide. The reaction with a carboxylic acid proceeds most readily in the presence of a carbodiimide such as dicyclohexylcarbodiimide and a substance capable of forming an active ester in situ such as N-hydroxybenzotriazole. In those instances when 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. Alternatively, the sulfonation reaction can be effected with the acyl group already in place, i.e., EMI15.1 In the case where R2 is lower alkoxy, there can be an additional variation in that the R2-lower alkoxy group can be inserted after the sulfonation as well as before the sulfonation using the conventional procedure of chlorinating the acylated nitrogen atom in the 3position followed by reaction with a lower alkoxide EMI16.1 The acyl groups in the above reactionalsoincludeeasily removable groups which function as a protecting group and which can be removed after the reaction to afford the "deacylated" product (-NH2). In addition, the ss-lactam ring can be formed via a cyclization reaction and the sulfonation reaction can be effected prior to cyclization as well as subsequent thereto, i.e., EMI16.2 The acyl group in this reaction can also be an easily removable group which functions as a protecting group and which on removal affords the -NH2 product. The azetidinone starting materials wherein R2 is hydrogen and one of R3 and R4 is hydrogen can also be prepared from amino acids having the formula EMI17.1 (one of R3 and R4 is hydrogen). The amino group is first protected with a classical protecting group, e.g., t-butoxycarbonyl (referred to hereinafter as "Boc"). The carboxyl group of the protected amino acid is then reacted with an amine salt having the formula + XIII Y-O-NH3C1 wherein Y is alkyl or benzyl, in the presence of a carbodiimide to yield a compound having the formula EMI17.2 ( one of R3 and R4 is hydrogen). The hydroxyl group of a compound of formula XIV is converted to a leaving group (V) with a classical reagent, e.g., methanesulfonyl chloride (methanesulfonyl is referred to hereinafter as "Ms"). Other leaving groups (V) which can be utilized are benzenesulfonyl, toluenesulfonyl, chloro, bromo and iodo. The fully protected compound having the formula EMI18.1 (one of R3 and R4 is hydrogen) is cyclized by treatment with base, e.g., potassium carbonate. The reaction is preferably carried out in an organic solvent such as acetone, under reflux conditions, and yields a compound having the formula EMI18.2 (one of R3 and Rd is hydrogen). Alternatively, cyclization of a compound of formula XIV can be accomplished without first converting the hydroxyi group to a leaving group. Treatment of a compound of formula XIV with triphenylphosphine and diethylazodicarboxylate, yields a compound of formula XVI wherein one of R3 and R4 is hydrogen. Removal of the protecting group from the 1position of an azetidinone of formula XVI can be accomplished via sodium reduction when Y is alkyl, and yields an intermediate having the formula EMI19.1 (one of R3 and R4 is hydrogen). If Y is benzyl, catalytic (e.g., palladium on charcoal) hydrogenation will initially yield the corresponding N-hydroxy compound, which upon treatment with titanium trichloride yields an intermediate of formula XVII wherein one of R3 and R is hydrogen. Synthesis involving ring closure of the type described above results in inversion of the stereochemical configuration of the R3 and R4 substituents. As previously mentioned, the above azetidinone can be sulfonated to form a compound havina the formula EMI19.2 (one of R3 and R4 is hydrogen). An alternative procedure for preparing a compound of formula I wherein R2 is hydrogen and one of R3 and R4 is hydrogen, utilizes as a starting material an amino acid amide having the formula EMI19.3 (ene of R3 and R4 is hydrogen). Protection of the amino group with a classical protecting group, e.g., benzyloxycarbonyl (reffered to hereinafter as Z) or Boc, and conversion of the hydroxyl group to a leaving group (V) such as Ms yields a compound having the formula EMI20.1 (one of R3 and P4 is hydrogen), wherein A is a protecting group. Sulfonation of a compound of formula XX yields a compound having the formula EMI20.2 (one of R3 and R4 is hydrogen). Cyclization of a compound of formula XXI is accomplished with base, e.g., potassium carbonate. The reaction is preferably carried out in a mixture of water and an organic solvent (e.g., a halogenated hydrocarbon such as l,2-dichloroethane) under reflux conditions and yields a compound having the formula EMI20.3 (one of R3 and R4 is hydrogen, Deprotection of a sulfonated azetidinone of formula XXII, wherein A is a protecting group, as well as the counterpart compounds previously described having an R2alkoxygroup by catalytic hydrogenation yields a compound having the formula EMI21.1 (one of R3 and R4 is hydrogen), wherein R2 is hydrogen or alkoxy which can be converted to the corresponding zwitterion having the formula EMI21.2 (one of R3 and R4 is hydrogen) by treatment with an acid such as formic acid. Deprotection of a sulfonated azetidinone of formula XXII wherein A is a Boc protecting group using acidic conditions (e.g., using formic acid) yields the corresponding zwitterion of formula XIX. A 3-azido-2-azetidinone starting material can be prepared by first reacting an oleo in having the formula EMI22.1 with a halosulfonylisocyanate (preferably chloro sulfonylisocyanate) having the formula XXVI O=C=N- SO2 -halogen to yield an azetidinone having the formula EMI22.2 Reductive hydrolysis of an azetidinone of formula XXVII yields an N-unsubstituted i-lactam having the formula EMI22.3 For a more detailed description of the above described reaction sequence reference can be made to the literature; see, for example, Chem. Soc. Rev., 5, 181 (1976) and J. Org. Chem., 35, 2043 (1970). An azido group can be introduced in the 3position of an azetidinone of formula XXVIII (or the sulfonated counterpart) by reaction of the compound with an arylsulfonyl azide (such as toluenesulfonyl azide) to obtain a starting azetidinone having the formula EMI23.1 The reaction proceeds best by first protecting the azetidinone nitrogen with a silyl residue (e.g., t-butyldimethylsilyl, or t-butyldiphenylsilyl), then generating the anion at the 3-position of the nucleus with a strong organic base (e.g., lithium diisopropylamine) at a low temperature, and then treating the anion with toluenesulfonyl azide. The resulting intermediate is quenched with trimethylsilyl chloride, and subsequent acid hydrolysis or fluoride solvolysis of the N-protecting group yields the compound of formula XXIX. Alternatively, the compound of Formula XXXI can be obtained by first reacting a primary amine having the formula EMI23.2 with an aldehyde of the formula R3CH=O to yield the corresponding Schiff base. A[2+2]cycloaddition with an activated form of azido acetic acid yields a 3azido-2-azetidinone having the formula EMI23.3 wherein Q is EMI24.1 Oxidative removal of the Q-substituent yields the compound of formula XXIX. The 3-acylamino-2-azetidinones can be obtained by first reducing a 3-azido-2-azetidinone of formula XXX. to obtain the corresponding 3-amino-2-azetidinone and then acylating the 3-amino-2-azetidinone. As previously mentioned in the case where R2 is lower alkoxy, the product can be prepared from the counterpart product wherein R;2 is hydrogen. Clorination of the amide nitrogen of a nonalkoxylated compound yields an intermediate having the formula EMI24.2 Reagents and procedures for N-chlorinating amides are known in the art. Exemplary reagents are tert.-butyl hypochlorite, sodium hypochlorite, and chlorine. The reaction can be run in an organic solvent (e.g., à lower alkanol such as methanol) or in a two phase solvent system (e.g., water/methylene chloride) in the presence of a base such as sodium borate decahydrate. The reaction is preferably run at a reduced temperature. Reaction of an intermediate of formula XXIX with an alkoxylating agent, e.g., an alkali metal alkoxide yields a product of formula I wherein R2 is alkoxy, in combination with its enantiomer. The reaction can be run in an inorganic solvent, e.g., a polar organic solvent such as dimethylformamide, at a reduced temperature. An alternative synthesis for preparing the compounds of formula I wherein R2 is alkoxy comprises first alkoxylating an intermediate of formula VI wherein R1NH is a carbamate (e.g., R1 is benzyloxycarbonyl) and R2 is hydrogen and then introducing a sulfo group in the l-position of the resulting compound. Chlorination of a compound of formula VI using the procedure described above (for chlorination of a non-alkoxylated compound of formula I to yield a compound of formula XXX yields an intermediate having the formula EMI25.1 Using the alkoxylation procedure described above -(for converting a compound of formula XXX to a product of formula I), and subsequently adding a reducing agent such as trimethylphosphite, the compound of formula XXX can be converted to an intermediate having the formula EMI25.2 in a combination with its enantiomer. The above procedures yield those products of formula I wherein R2 is alkoxy as a racemic mixture. If desired the enantiomer having the R configuration can be isolated from the racemic mixture using conventional techniques such as fractional crystallization of a suitable salt with an optically active organic amine or by ion-paired chromatography utilizing an optically active cation. Example 1 (#-cis)-4-Methyl-2-oxo-3-[[(phenylmethoxy)carbonyl]- amino)-l-azetidinesulfonic acid, potassium salt A) N-Benzyloxy-t-boc*-allothreonine emide A solution of 6.9 g of d,l-t-boc-allothreonine and the free amine from 5.3 g of o-benzylhydroxyl- amine. HC1 Cr"O.033 mole, ethyl acetate-sodium bicarbonate liberation) in 80 ml of tetrahydrofuran is treated with 4.82 g of N-hydroxybenzotriazole and 6.5 g of dicyclohexylcarbodiimide in 20 ml of tetrahydrofuran. After stirring for about 16 hours at room temperature the slurry is filtered, concentrated in vacuo and chromatographed on a 400 ml of silica gel column. Elution with 5-10% ethyl acetate in chloroform gives 6.8 g of the title compound in fractions (200 ml each) 7-22. B) (#-cis)-N-Benzyloxy-3-t-butoxycarbonylamino-4- methylazetidinone A solution of 6.8 g of N-benzyloxy-tboc-allothreonine amide in 200 ml of tetrahydrofuran is stirred for about 16 hours with 5.24 g of triphenylphosphine and 3.2 ml of diethylazodicarboxylate. The solvents are evaporated in vacuo and the residue is chromatographed on a 500 ml silica gel column. Elution with methylene chloride followed by crystallization from ether gives a total of 2.65 g of azetidinone. Rechromatography of the mother liquors and mixed fractions give an * "boc" is used to describe butoxycarbonyl additional 0.6 g. Crystallization of a portion twice from ether C-200C) gives the analytical sample of the title compound melting point 140-142 C. C) (#-cis)-3-t-Butoxyca rbonylamino-1-hydroxy-4- methylazetidinone A solution of 3.2 g of cis-N-benzyloxy 3-t-butoxycarbonylamino-4-methylazetidinone in 200 ml of 95% ethanol is stirred in an atmosphere of hydrogen with 0.7 g of 10% palladium on charcoal. After 4Q minutes the slurry is filtered uptake 249 mll and the filtrate is evaporated and triturated with ether to give, in two crops, 2.05 g of solid, melting point 134-1360C. D) (+ -cis - 3-t-Butoxycarbonyl amino- 4-methyl azetidinone A solution of 2.05 g of -cis-3-t-butyloxy- carbonylamino-l-hydroxy-4 -methylazetidinone in 60 ml of methanol is treated with a total of 90 ml of 4.5 M ammonium acetate (40, 20 and 30 ml portions) and 45 ml of 1.5 M titanium trichloride (20, 1D and 5 ml portions) the second and third additions are made after 15 and 120 minutes, respectively. After 135 minutes the solution is diluted with an equal volume of 8% sodium chloride and extracted with three 300 ml portions of ethyl acetate. The combined organic layer is washed with a mixture of 100 ml each of 5% sodium bicarbonate and saturated salt, dried, and evaporated. Trituration with ether gives, in two crops, 1.65 g of solid. A portion of the first crop is recrystallized from ether to give the analytical sample, melting point 176-178.5 C. E) (#-cis)-3-Benzyloxycarbonylamino-4-methylazetidinone A solution of 1.55 g of cis-3-t-butoxycarbonylamino-4-methylazetidinone in 4 ml each of methylene chloride and anisole is cooled to OOC and 50 ml of cold trifluoroacetic acid is added. After 90 minutes the solvents are evaporated in vacuo (benzene added and evaporated three timesl. The residue is dissolved in 25 ml of acetone, the initial pH C2.5) is raised to 7 with 5% sodium bicarbonate, and 2 ml of benzylchloroformate is added. The solution is kept at o C and pR 7 for 4 hours and the acetone is removed in vacuo to give a slurry that is filtered. The filtrate is saturated with salt and extracted with methylene chloride. The solid is dissolved in methylene chloride and dried. The organic layers are combined, concentrated, and the residue chromatographed on a 200 ml silica gel column. Elution with 3:1 chloroform, ethyl acetate gives 850 mg of the title compound in fractions (100 ml each) 4-li. Crystallization of a small sample from ether gives the analytical sample, melting point 165-166 C. F) (#-cis)-4-Methyl-2-oxo-3-[[(phenylmethoxy)- carbnyl]amino]-1-azetidinesulfonic acid, potassium salt To a suspension of cis-3-benzyloxycarbonyl- amino-4-methylazetidinone (0.75 g) in 7 ml each of dimethylformamide (dried with 4A sieves activated at 3200C for 15 hours under argon flow) and methylene chloride (dried through basic A12O3) is added 1.66 g of pyridine-sulfur trioxide complex. After 3 hours stirring at room temperature under nitrogen, an additional amount of pyridine-sulfur trioxide complex (1.66 g) is added. The reaction mixture is then stirred at room temperature under nitrogen for about 16 hours. The dimethylformamide is removed lin vacuo to give 4.6 g of residue which is dissolved in 300 ml of Q*5 M monobasic potassium phosphate solution (40 C for 10-15 minutes). The solution is cooled, passed through a column of HP-20 resin (3 cm x 60 cm) with 400 ml of 0.5 M monobasic potassium phosphate 1 L of distilled water and C14:1) water:acetone to give 280 mg of product in fractions 13 to 26 (100 ml each). Crystallization from MeO: petroleum ether gives 757.5 mg of an analytical sample, melting point 214-215.5 C, dec. Analysis calc'd for C12H13N2SO6K C, 40.90; H, 3.72 N, 7.95; S, 9.10; K, 11.10 Found: C, 40.43; H, 3.60; N, 7.89; S, 8.69; K, 10.82 Example 2 (3S-trans)-4-Methyl-2-oxo-3-[(phenylmethoxy)carbonyl] amino3-1-azetidinesulfonic acid, potassium salt Following the procedure of Example 1, but substituting l-t-boc-threonine for d,1-t-boc- allothreonine, yields the title compound, melting point 133-1350C. Analysis calc'd for C12H13N2O6SK: C, 40.90; H, 3.72; N, 7.95; S, 9.10; K, 11.10 Found: C, 40.72; H, 3.60; N, 7.99; S, 8.80; K, 10.82 Example 3 (3S-trans)-4-Methyl-2-oxo-3-[phenylacetyl)amino]l-azetidinesulfonic acid, potassium salt A) (3S)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid, tetrabutylammonium salt (4S-trans)-4-methyl-2-oxo-3[[(phenylmethoxy)carboyl]amino]-1-azetidinesulfonic acid, potassium salt (352.4 mg; see Example 9g) is dissolved in 20 ml of distilled water and treated with 373.5 mg (1 mmole) of tetrabutyl ammonium hydrogen sulfate. After 10 minutes stirring at room temperature, the solution is extracted three times with. 10 ml portions of methylene chloride after saturation with sodium chloride. The methylene chloride is dried over sodium sulfate and evaporated in vacuo to give 536 mg of the tetrabutylammonium salt which is hydrogenated with 270 mg 6f 10% palladium on charcoal in 25 ml of dimethylformamide. The mixture is filtered through Celite and washed twice with 2.5 ml portions of dimethylfonnamide to yield the title compound in solution. B) (3S-trans)-4-Methyl-2-oxo-3-[(phenylacetyl) aminol-l-azetidinesulfonic acid, potassium salt The crude (3S) -3-amino-4-methyl-2-oxo-lazetidinesulfonic acid, tetrabutylammonium salt from part A (the combined filtrate and washings) are treated at 0 0C with 206 mg of dicyclohexylcarbodiimide, 153 mg of N-hydroxybenzotriazole, and 138 mg of phenylacetic acid. The reaction mixture is stirred at QOC for 1 hour and then at room temperature for 2 hours. The resulting precipitate is filtered1 the filtrate is evaporated in vacuo, the residue is dissolved in 10 ml of acetone and filtered. The filtrate is treated with 25 ml of acetone saturated with potassium iodide and then 200 ml of ether. The Tesulting solid (752.7 mg) is a mixture of the potassium and tetrabutylammonium salts of the title compound. The solid is dissolved in 5Q ml of 0.5 monobasic potassium phosphate and applied to an HP-20 column. Elution with water and then water-acetone gives several fractions that are combined and evaporated to give the purified tetrabutylammonium salt. An aqueous solution of this material is passed through Dowex 50W-X2 (K+form) to give the title potassium salt (121.4 mg). Trituration with. acetone-hexane yields 104.6 mg of the title compound, melting point 211-2130C. Analysis calc'd from C12H13N2O5SK.1/2 H2O: C, 41.72; H, 4.09; N, 8.11; S, 9.28; K, 11.32 Found: C, 41.70; H, 4.01; N, 8.07; S, 9.01; K, 11.02 Example 4 (cis)-4-Methyl-2-oxo-3-I (phenylacetyl) amino]-1azetidinesulfonic acid, potassium salt A solution of 320 mg of (t-cis)-4-methyl- 2-oxo-3- [[(phenylmethoxy) carbonyl]amino]-1-azetidinesulfonic acid, potassium salt (see example 98) is prepared in 20 ml of water containing 483 mg of tetrabutylammonium hydrogen sulfate and adjusted to pH 5.5. Extraction with six 25 ml portions of methylene chloride gives 517.3 mg of oil. A solution of this material in 15 ml of dimethylformamide is stirred with 400 mg of 108 palladium on charcoal in an atmosphere of hydrogen for 90 minutes. The catalyst is filtered and the filtrate stirred with 150 mg of phenylacetic acid, 169 mg of N-hydroxybenzotriazole and 247 mg of dicyclohexylcarbodiimide for 7.5 hours. The solvent is removed in vacuo and the residue is dissolved in 2Q ml of acetone and filtered. The filtrate is treated with 25 ml of t.Q44 M potassium iodide in acetone. Dilution with an equal volume of ether gives a solid (330 mgl which is applied to a 50 ml HP-20 column in 20 ml of 0.05 Monobasic potassium phosphate. Elution with 200 ml of water followed by 5:9 acetone-water gives Rydon positive material in fractions (50 ml) 6-10. Evaporation of fractions 7-9 gives 81 mg of solid. Recrystallization from acetonitrile-water gives 46 mg of the title comound, which decomposes at > 205 C. A second crop (6 mg) is obtained from the filtrate. A further 5 mg is obtained from fractions 6 and 10 by evaporation and recrystallization. Analysis calc'd for C12Hl3N2O5SK: C, 42.84; H, 3.89 N, 8.33; S, 9.53; K, 11.62 Found: C, 42.75; H, 3.82; N, 8.32; S, 9.26 K, 11.63 Example 5 [3S-[3&alpha; (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) (methoxyimino)acetyllamino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt A) (3S-trans)-4-Msthyl-2-oxo-3-II (phenylmethoxy)carbonyl]amino]-1-azetidinesulfonic acid, tetrabutylammonium salt (3S-trans) -4-Nethyl-2-oxo-3- I I (phenylmethoxy) carbonyl] amino]-1-azetidinesulfonic acid, potassium salt (352.4 mg; see Example 99) is dissolved in 20 ml of water and tetrabutylammonium hydrogen sulfate (373.5 mg) is added. The aqueous solution is extracted three times with methylene chloride and the combined extracts are dried over sodium sulfate. After removal of the solvent, 534.6 mg of the title compound is obtained. B) [3S-[3&alpha; (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) (methoxy imino) acetyl) amino) -4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt A solution of 534.6 mg of (3S-trans)-4-methyl- 2-oxo-3-[[(phanylmethoxy) carbonyl]amino]-1-azetidine sulfonic acid, tetrabutylammonium salt in 20 ml of dimethylformamide is hydrogenated with 220 mg of 10$ palladium on charcoal at atmospheric pressure for 2.75 hours; the uptake of hydrogen is 26.3 ml. The mixture is filtered and washed twice with 2.5 ml of dimethylformamide. The filtrate and washings (total ca. 25 ml) are stirred under nitrogen with 161 mg of (Z)-&alpha;-(metoxyimino)-2-amino-4-thiazole- acetic acid, 136 mg of N-hydroxybenzotriazole and 164.8 mg of dicyclohexylcarbodimide. The mixture is stirred under nitrogen for about 16 hours. The dimethylformamide is removed in vacuo and the gummy residue is dissolved in acetone and filtered to remove urea. To the filtrate is added a solution containing 272 mg (0.8 mole) of perfluorobutanesulfonic acid, potassium salt in Q.8 ml of acetone. The slurry is diluted with an equal volume of ether and filtered to give 325.5 mg of crude product which is purified through chromatography on 75 ml of HP-20AG. Elution with 400 ml of water and 400 ml of (9:11 water: acetone mixture (50 ml fractions) gives 335 mg in fractions 3 to 10. After trituration with acetone-hexane, 97.3 mg of an analytical sample is obtained from fractions 3-5. Similar trituration of fractions 6-1Q gives an additional 90.4 mg of product as a solid. Analysis calc'd for C10H12N506S 2K: C, 29.92; H, 3.01; N, 17.45; S, 15.97; K, 9.74 Found: C, 30.32; H, 3.49; N, 15.82; S, 13.95; K, 10.45 NMR(D20) 1.57 (3H, d,j=7), 3.97 (3H,S), 4.30(lH, d of q, =7.3), 4.70(1H, d. )=7), 6.95ppm(lH,S). Example 6 [3S-[3&alpha; (Z), 4ss]]-3-II(2-Amino-4-thiazolyl)[(1-carboxy- 1-methylethoxy) imino] acetyl]amino]-4-methyl-2-oxol-azetidinesulfonic acid, dipotassium salt A) N-Ben zyloxy-t-boc- threonine amide A solution of 8.76 g of t-boc-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 2Q 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 chloroformethyl acetate (3:1}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-butoxycarbonylamino4-methylazetidinone A solution of 12.67 g of N-benzyloxy-t-bocthreonine 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-meihylazetidinone A solution of 9.18 g of (3 S-trans)-N-benzyloxy- 3-t-butoxycarbonylamino-4-methylazetidinone in 300 ml of 95% ethanol is stirred in an atmosphere of hydrogen with 1.85 g of 109s 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) (35-trans) -3-t-Butoxycarbonylamino-4-inethyl- azetidinone A solution of 4.98 of (3S-trans)-3-t-butoxy cabonylamino-l-hydroxy-4-methylazetidinone in 20Q ml of methanol is treated with 132 ml of 4.5 M 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-trans)-3-Benzyloxycarbonylamino-4-methylazetidinone A solution of 3.3 g of (3S-trans)-3-t-butoxy- carbonylamino-4-methyla2etidinone in 10. ml each of dichloromethane and anisole is cooled to 0 0C and 112 ml of trifluoroacetic acid is added. The solution is stirred for 90 minutes and evaporated in vacuo (benzene added and evaporated three times) The residue is dissolved in 70 ml of acetone and the solution is adjusted to pH 7 with 5% sodium bicarbonate solution. A total of 5.33 g of benzyl chloroformate is added over 1 hour at pII 6.5-7.5. The mixture is stirred for 30 minutes at pH 7, diluted with 100 .ml of saturated salt, and extracted with ethyl acetate (three 400 ml portions). The residue obtained by evaporation is chromatographed on a 1 liter silica gel column. Elution with chloroform-ethyl acetate (4:1) gives 2.19 g of compound. Crystallization from ether-hexane yields 1.125 g of the title compound. Fl (3S-trans]-4-Methyl-2-oxo-3-[[(phenylmethoxylcarbonyl]amino]-1-azetidinesulfonic acid, tetrabutylammonium salt A solution of 600 mg of (3S-trans)-3benzyloxycarbonylamino-4-methylazetidinone in 2 ml of dimethylformamide is cooled to 0 C and 4 ml of 0.8 M sulfur trioxide in dimethylformamide is added. The solution is stirred at room temperature under nitrogen for 1 hour and poured into 80 ml of cold 0.5 N monobasic potassium phosphate (adjusted to pH 5.51. The solution is extracted with three 50 ml portions of methylene chloride (discarded) and 868 mg of tetrabutylammonium bisulfate is added. The resulting solution is extracted with four 75 ml portions of methylene chloride. The combined organic layer is washed with 8% aqueous sodium chloride, dried, and evaporated in vacuo yielding 1.54 g of the title compound. Gl [3S-[3&alpha; (Z), 4ss]]-3-II(-Amino-4-thiazolyl) [(-diphenylmethoxycarbnyl-1-methylethoxy) imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt A solution of 1.54 g of (3S-trans)-4-methyl2-oxo-3-II(phenylmethoxy) carbonyl] amino]-1-azetidinesulfonic acid, tetrabutylammonium salt in 45 ml of dimethylformamide is stirred in an atmosphere of hydrogen with 800 mg of 10% palladium on charcoal for 2 hours. The catalyst is filtered and the filtrate stirred for about 16 hours with 1.24 g of (Z)-2-amino-&alpha;-I(1-diphenylmethyoxycarbonyl-1 methylethoxy)imino]-4-thiazoleacetic acid, 0.4 g of N-hydroxybenzotriazole, and 580 mg of dicyclohexylcarbodiimide. The slurry is evaporated in vacuo and the residue is triturated with 20 ml of acetone and filtered. The filtrate (plus 2 ml of washings) is treated with 868 mg of potassium perfluorobutanesulfonate in 3 ml of acetone. Dilution with 75 ml of ether gives a solid thatis isolated by decantation of the mother liquor, trituration with ether, and filtration to give 0.91 g of the title compounds The mother liquor is diluted with a further lQ0 ml of ether to give a second crop, 0.45 g, of the title compound. H) [3S-[3&alpha; (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) I(1carboxy-1-methylethoxy)imino]-acetyl] aminol-4 methyl-2-oxo-l-azetidinesulfonic acid, dipotassium salt A slurry of 140 mg of [3S-[3&alpha; (Z), 4ss]]-3- If (2-amino-4-thiazolyl) [(l-diphenylmethoxycarbonyl- 1-methylethoxy)imino] acetyl] amino]-4-methyl-2oxo-l-azetidinesulfonic acid, potassium salt (first crop) in 0.5 ml of anisole is stirred at -120C under nitrogen and 2.5 ml of cold (-10 C) trifluoroacetic acid is added. After 10 minutes, 10 ml of ether and 5 ml of hexane are added and the resulting slurry is stirred for 5 minutes at -12 C, and allowed to warm to room temperature. The solid is isolated by centrifugation and washed twice with ether. A solution of this solid in 5 ml of cold water is immediately adjusted to pH 5.5 with 0.4 N potassium hydroxide and then applied to an 80 ml HP-20AG column. Elution with water gives 72 mg of the title compound in fractions (10 ml) 7-11 after evaporation (acetonitrile added and evaporated three times] and trituration with ether, m.p. # 250 (dec.). Analysis calc'd for C13H15N5O8S2K2: C, 30.51; H, 2.95; N, 13.69; S, 12.53; K, 15.28 Found: C, 29.63; H, 3.20; N, 12.96; S, 11.94; K, 12.78 NMR (D20) 1.46 (S, 6H), 1.58(1H, d, j=7) 4.28 (1H, d of q, @=7, 2.5), 4.67 (1H, d, @=2), 6.95ppm(S, 1H). The remaining 1.22 g of [3S-[3&alpha;(Z), 4ss]]-3- [[(2-amino-4-thiazolyl) [(1-diphenylmethoxycarbonyl1-methylethoxy) imino] acetyl]amino-4-methyl-2oxo-l-azetidinesulfonic acid, potassium salt (crops 1 and 2) are treated as above (4.2 ml anisole, 16 ml of trifluoroacetic acid, 13 minutes at -15 0C). Chromatography on a 300 ml HP-20AG column gives 694 mg of the title compound in fractions (60 ml) 6-9 after treatment as above. Example 7 (3&alpha; (Z), 4&alpha;]-3-[[(2-Amino-4-thiazolyl) (methoxy- imino) acetyl] amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt A solution of 51.8 mg of (cis)-4-methyl2-oxo-3-[[(phenylmethoxy) carbonyl] amino]-1azetidinesulfonic acid, potassium salt and 51 mg of tetra-n-butyl-ammonium bisulfate in 5 ml of water is extracted with methylene chloride (four 10 ml portions) to give 81 mg of oil. This is stirred in an atmosphere of hydrogen for 2 hours with 40 mg of 10% palladium on charcoal in 4 ml of dimethylformamide. The catalyst is filtered and washed with 1 ml of dimethylformamide. The filtrate and washings are combined and stirred for about 16 hours with 31 mg of (Z)-2-amino-a-(methoxyimino)-4- thiazoleacetic acid, 27 mg of N-hydroxybenzotriazole, and 31.5 mg of dicyclohexylcarbodiimide. The solution is evaporated in vacuo and the residue triturated with 3 ml of acetone. The resulting slurry is centrifuged and the liquid treated with 51 mg of potassium perfluorobutanesulfonate. Dilution with 5 ml df ether and filtration gives a solid. Chromatography on HP-20 AG (40 ml) gives Rydon positive material in fractions (20 ml) 3-5 (elution with water). Evaporation and ether trituration gives 23 mg of product, as a hygrosoopic solid. Analysis calc'd for C10H12N5O6S2K: c,29.91; H, 3. 01; N, 17. 44 Found: C,29.30; H,3.31; H,16.66 NMR (D20) 1.40 (3H, d, j=7), 3.97 (3H,S), 4.46 (1H, apparent pentet, j=7), 5.37 (1H, d, #=7, 6.97 ppm(lH,S). Example 8 (3S-cis) -3-Amino-4-methyl-2-oxo-l-.azetidinesulfonic acid A) t-Boc-l-allothreonine A suspension of 6,72 g of l-allothreonine in 70 ml of 50% aqueous dioxane is treated with 9.45 ml of triethylamine and 18.1 g of t-butylpyrocarbonate. The resulting mixture is stirred at room temperature for 4 hours, and then diluted with 70 ml of water and 140 ml of ethyl acetate. After thorough shaking, the layers are separated and the organic layer is washed with 30 ml of 2:1 water:brine. Combined aqueous layers are then back-extracted with 70 ml of ethyl acetate. The aqueous layer is cooled in an ice bath and 10% potassium bisulfite solution is added to pH 2.3. The acidified solution is extracted with ethyl acetate (four 150 ml portions). Combined organic layers are dried over anhydrous sodium sulfate and stripped of solvent to give 9.13 g of the title .compound. B) N-Methoxy-t-boc-i-al lothreonine amide t-Boc-l-allothreonine (9.13 g) is dissolved in 85 ml of water and 41 ml of 1N potassium hydroxide solution. Methoxyamine hydrochloride (5.22 g) and 8.67 g of l-ethyl-3,3-(dimethyl- aminopropyl)carbodiimide HCl are added. The mixture is stirred at room temperature for 4 hours and then saturated with sodium potassium tartarate. The resulting mixture is extracted with. ethyl acetate (four 150 ml portions) and the organic layer is dried over anhydrous sodium sulfate and stripped of solvent to give 7.38 g of the title compound as a solid. C) O-Methanesulfonyl-N-methoxy-t-boc-1-allothreonine amide N-Nethoxy-t-boc-l-allothreonine amide t7.32 g) is dissolved in 40 ml of pyridine and cooled to -20 C under nitrogen. Methanesulfonyl chloride (3 m is added dropwise by syringe over a 5-minute period. The resulting mixture is slowly warmed to 0 C and stirred at that temperature for 3 hours. Ethyl acetate (500 ml) is added and the solution washed with 250 ml of ice-cold 3N HC1 solution, then 100 ml of 5% NaHC03 solution. The ethyl acetate layer was dried over anhydrous sodium sulfate and stripped of solvent to give 8.64 g of the title compound as a white solid. D) (3S-cis)-3-t-Butoxycarbonylamino-1-methoxy4-methylazetidinone O-methanesulfonyl-N-methoxy-t-boc-1-allothreonine amide t8.64 g) is dissolved in 530 ml of acetone and 11 g of solid potassium carbonate is added. The mixture is slowly heated to 65 0C under nitrogen and stirred at this temperature for one hour. The reaction mixture is then filtered through Celite and the filter cake is washed with ethyl acetate. The filtrate is concentrated and the residue is taken up in 250 ml of ethyl acetate. The ethyl acetate solution is washed with 100 ml of 1N hydrochloric acid solution and 100 ml of 5% sodium bicarbonate solution. The ethyl acetate layer is dried over anhydrous sodium sulfate and stripped of solvent to give 6.63 g of crude product. E) (3S-cis]-3-t-Butoxycarbonylamino-4-methylazetidinone Sodium (1.35 gl is dissolved in about 30G ni of liquid ammonia at -500C and 5.87- g of BS-cis)- 3-t-Butoxycarboflyl amino-l-methoxy-4-methyl azetidinone in 35 ml tetrahydrofuran is added dropwise via syringe. An additional 10 ml of tetrahydrofuran is used for rinsing. Near the end of the addition about 100 mg of additional sodium is added. The mixture is stirred for five more minutes, then quenched by adding 3.35 g of solid ammonium chloride in one portion. Ammonia is blown off with a nitrogen stream and 250 ml of ethyl acetate is added to the residue. After filtration and washing the solid with ethyl acetate, the combined filtrate is stripped of solvent to give 4.82 g of the title compound. F) (3S-cis)-3-t-Butoxycarbonylamino-4-methyl 2-oxo-1-azetidinesulfonic acid, tetrabutyl ammonium salt [3S, 4R]-3-T-Butoxycarbonylamino-4-methylazetidinone (4.98 g) is dissolved in 30 ml of dimethylformamide. Pyridine-sulfur trioxide complex 11.9 g is added and the mixture is stirred at room temperature under nitrogen. After 14 hours stirring, an additional 1.8 g of pyridine-sulfur trioxide complex is added and stirring is continued for 8Q hours. The reaction mixture is poured into 70Q ml of 0.5 M monobasic potassium phosphate solution and washed with methylene chloride (three 300 ml portions). tetra-n-Butylammonium bisulfate (8.45 g) is added to the aqueous solution and the mixture is extracted with methylene chloride (four 300 ml portions). The combined methylene chloride layers are dried over anhydrous sodium sulfate and stripped of solvent to give 10.76 g of the title compound as a gum. G) (3S-cis)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid (3S-cis)-3-t-Butoxycarbonylamino-4-methy 2-oxo-l-azetidinesulfonic acid, tetrabutyl ammonium salt (10.76 g) is dissolved in 50 ml of 95-978 formic acid and stirred for 4 hours under nitrogen. A small amount of product from a previous reaction is added as seed and the mixture is stirred for-onemore hour. The mixture is stored in the freezer for about 16 hours and the frozen mixture is warmed to room temperature and stirred for an additional hour. The solid formed is filtered and washed with methylene chloride to yield 982 mg of the title compound. The filtrate is diluted with 1 liter of methylene chloride and kept at -200C for 4 hours. The precipitate that forms is recrystallized from water-methanol-acetone to give an additional 167 mg of title compound. NMR(D20) 1.63 (3H, d, v=6.5 cps), lR(nujol)1775 cm 1. Example 9 [3S-[3&alpha; (Z), 4&alpha;]]-3-]]2-Amino-4-thiazolyl)- methoxyimino) acetyl] amino-4-methyl-2-oxo-1azetidinesulfonic acid, potassium salt A solution of 201 mg of (Z)-2-amino-- Cmethoxyimino)-4-thiazoleacetic acid and 153 mg of N-hydroxy-benzotriazole monohydrate in 3 ml of dimethylformamide is treated with 206 mg of dicyclohexylcarbodiimide. The mixture is stirred at room temperature for 20 minutes under nitrogen and a solution of 180 mg of (3S-cis)3-amino-4-methyl-2-oxo-1-azetidinesulfonic acid and 0.14 ml of triethylamine in 2 ml of dimethylformamide is added (an additional 1 ml of dimethylformamide is used for rinsing) and the mixture is stirred for about 16 hours. The slurry is evaporated in vacuo, triturated with 12 ml of acetone, centrifuged and the liquid treated with 338 mg of potassium perfluorobutanesulfonate. Dilution with 10 ml of ether and filtration gives a solid product which is chromatographed on 200 ml of HP-20 resin eluting with water. Fractions (20 ml each) 18-30 are combined and lyophilized to give 274 mg of the title compound as a hygroscopic solid. Anal. calc'd. for C10H12N5O6S2K: C,29.91; H, 3.01; N,17.44 Found: C,30.03; H,3.21; N,17.06 NMR(D20) 1.40 (3H, d, @=6.5), 3.98(3H,S), 4.48 1H, d of t, j=6.4, 5.5), 5.36(1H, d, J=5.S) 6.97 (lH,S). Example 10 (3S-trans) -3-Amino-4-methyl-2-oxo-l-azetidine-sulfonic acid A) Threonine, methyl ester, hydrochloride Under an atmosphere of nitrogen, a flask containing 500 ml of methanol is cooled to -50C (ice/brine) and 130 ml (excess) of thionyl chloride is added at such a rate as to maintain the reaction temperature between 0 and 100C. After recooling to -50C, 59.5 g of 1threonine is added and the mixture is allowed to reach room temperature and stirred for 16 hours. The mixture is concentrated and evacuated at 10-1 torr for 2 hours to yield a viscous oil. This material is used directly in the following step. B) Threonine amide The crude product from part A is dissolved in 2.5 1 of methanol and cooled to -5 C (ice/brine). The solution is saturated with ammonia gas, the cooling bath is removed and the sealed vessel is allowed to stand for 3 days. After removing the bulk of the unreacted ammonia via aspirator, 100 g of sodium bicarbonate and 50 ml of water is added and the mixture is stripped to a viscous oil. Cl Benzykloxycarbonylthreonine amide The crude product from part B (already containing the requisite amount of sodium bicarbonate is diluted to a volume of 1 liter with water. To this rapidly stirring solution, 94 g 588 ml of 90% pure material) of benzyloxycarbonyl chloride is added as a solution in 80 ml of tetrahydrofuran over a 1 hour period. The reaction mixture is then stirred for an additional 16 hours and extracted with ethyl acetate (one 500 ml portion, two 250 ml portions). The combined extracts are dried over magnesium sulfate and concentrated. The crystalline residue is then dissolved in 250 ml of hot ethyl acetate and 300 ml of hexane is added followed by boiling until a clear solution is reached. Cooling and filtration of the crystalline mass give, after drying, 104 g of the title compound. D) 3enzyloxycarbonylthreonine amide, O-mesylate Under an atmosphere of argon, 100 g of benzyloxycarbonylthreonne amide is dissolved in 400 ml of anhydrous pyridine and cooled in an ice/salt bath. To this stirring solution, 36.8 ml (54.5 g) of methanesulfonyl chloride is added over a 15 minute period. After 2 hours of stirring an additional 0.3 equivalents of methanesulfonyl chloride is added. The reaction is then stirred for 1 hour and poured into a mixture of 1.5 1 of ice and 2 1 of water. The resulting slurry is stirred for about 3Q minutes and filtered. Drying of the crude product at 600C for about 16 hours in a vacuum oven gives 109 g of the title compound. E) N-Sulfonyl benzyloxycarbonylthreonine amide, O-mesylate, tetrabutylammonium salt A solution of 2-picoline (17.8 ml) in 90 ml of methylene chloride is cooled to -50C (ice-brine) and chlorosulfonic acid 5.97 ml is added at such a rate as to maintain the internal-reaction temperature below 50C. The resulting solution is added via canula, to a suspension.of 7.56 g of benzyloxycarbonylthreonine amide, O-mesylate in 120 ml of methylene chloride. The resulting heterogeneous mixture is refluxed for about 16 hours yielding a clear solution. The solution is poured into 500 ml of pH 4.5 phosphate buffer (0.5 M) and further diluted with 120 ml of methylene chloride. The separated organic layer is then washed once with 10Q ml of buffer solution and the combined aqueous phases are treated with 10.2 g of tetra-n-butylammonium hydrogensulfate and extracted with methylene chloride (one 30Q ml portion and two 150 ml portions). After drying the combined organic extracts over sodium sulfate, the solution is concentrated to yield 12.7 g of a foam. F) (3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid A mixture consisting of 5.52 g of potassium carbonate in 20 ml of water and 160 ml of 1,2dichloroethane is brought to reflux and 15.5 mmole of N-sulfonyl benzyloxycarbonyl threonine amide, O-mesylate, tetrabutylaznmonium salt is added in 20 ml of 1,2-dichloroethane (20 ml used as a rinse). After refluxing for 30 minutes, the mixture is poured into a separatory funnel, diluted with 50 ml of water and 100 ml of methylene chloride and the phases split. The resulting organic phase is dried over sodium sulfate and concentrated to yield crude L3S-trans)- 3-benzyloxycarbonylamino-4 -methyl-2-oxo-l-azetidine- sulfonic acid, tetrabutylammonium salt. The crude azetidinone is treated in 250 ml of ethanol with 0.8 g of 5% palladium on charcoal catalyst and hydrogen is bubbled through the solution. After 90 minutes the mixture is-filtered through Celite with 50 ml of ethanol used as a rinse. The addition of 1.2 ml of formic acid to this solution causes an immediate precipitation of the title zwitterion which is filtered after stirring for 1 hour to yield, after drying at }0 1 torr for 1 hour, 1.1 g of product. A second crop of product is obtained upon concentration of the filtrate and addition of more formic acid to give 1.3 g of the title zwitterion. m.p. A218 dec., [a]D = -41.1(C=1, H2O). NMR(D20) 1.58 (3H, d )=7), 4.80(2H,M). Examples .11-14 Following the procedure of Example 9, but substituting (3S-trans)-3-amino-4-methyl-2-oxol-azetidinesulfonic acid for (3S-cis)-3-amino-4methyl-2-oxo-l-azetidinesulfonic acid and the acid listed in column I for (Z)-2-amino-&alpha;-(methoxyimino)- 4-thiazoleacetic acid, yields the compound listed in column II. 11. (R)-&alpha;-[[[3-[(2-furanylmethylene)amino]- [3S-[3&alpha;(R#),4ss]]-3-[[[[[3-[(2-furanyl2-oxo-1-imidazolidinyl]-carbonyl]amino]- methylene)amino]-2-oxo-1-imidazolidinyl]benzeneacetic acid carbonyl] amino]phenylacetyl]amino]-4-methyl2-oxo-1-azetidinesulfonic acid, potassium salt; melting point 213 C, dec. 12. (R)-&alpha;-[[(4-ethyl-2,3-dioxo-1-piperazinyl)- [3S-[3&alpha;(R#),4ss]]-3-[[[[(4-ethyl-2,3-dioxocarbonyl] amino] benzeneacetic acid 1-piperazinyl)carbonyl] amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt; melting point 177 C, dec. 13. (Z)-2-amino-&alpha;-(hydroxyimino)-4-thiazole- [3S-[3&alpha;(Z),4ss]]-3-[[(2-amino-4-thiazolyl)acetic acid (hydroxyimino)acetyl]amino]-4-methyl-2-oxo1-azetidinesulfonic acid, potassium salt; melting point 230 C. 14. (#)-&alpha;-[(aminooxoacetyl)amino]-2-thio- [3S-[3&alpha;(#),4ss]]-3-[[[(aminooxoacetyl)amino]-2pheneacetic acid thienylacetyl]amino]-4-methyl-2-oxo-1-azetidine .sulfonic acid, potassium salt; melting point 135 C, dec. Example 15 [3S-[3&alpha; (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) [[1,1dimethyl-2-[(4-nitrophenyl)methyoxy]-2-oxoethoxy]imino] acetyl] amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt To a slurry of (3S-trans)-3-amino-4-methyl2-oxo-1-azetidinesulfonic acid (0.36 g; see example 139) in dry dimethylformamide (30 ml) under nitrogen at 260C is added triethylamine (309 1). After about S minutes a clear solution is obtained and (Z)-2-amino-&alpha;-[I1,1- dimethyl-2-I(4-nitrophenyl)methy]-2-oxoethoxy] imino)-4-thiazoleacetic-acid (0.816. g) is added followed by N-hydroxybenzotriazole (0.334 g) and dicyclohexylcarbodiimide (0.453 g). The mixture is stirred for twelve hours at 260C, whereupon the solvent is removed in vacuo, and the residue is triturated with acetone (30 ml). After stirring five minutes, the solids are removed and the filtrate is treated with potassium perfluorobutane sulfonate (3.680 g) in acetone, (5 ml). Addition of ether (approximately 40 ml) affords a precipitate which is collected and dried in vacuo (1.073 g; second crop 0.066 g; total of 1.14 g). Anal. calc'd. for C20H21N6O10S2K.1 H2O: C, 38.33; H, 3.70; N, 13.41; S, 10.23; K, 6.24 Found: C, 38.30; H, 3.63; N, 13.41; S, 9.88; K, 5.98 Example 16 [3&alpha;(Z), 4&alpha;]-3-[[(2-Amino-4-thiazolyl) [(1-carboxy- 1-methylethoxy) imino]acetyl]amino]-4-methyl-2oxo-l-azetidinesulfonic acid, potassium salt (1:2) A) [3&alpha; (Z), 4&alpha;]-3-[[2-Amino-4-thiazolyl) [(1- diphenylmethoxycarbohyl-l-methylethoxy) imino] - acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt A solution of (cis)-4-methyl-2-oxo-3-l[(phenyl- methoxy) carbonyl] amino]-1-azetidinesulfonic acid, tetrabutylammonium salt (201 mg.; prepared from the corresponding potassium salt of example 98 as described in example 136) in 5 ml of dimethylformamide is stirred with 90 mg of 10% palladium on calcium carbonate in an atmosphere of hydrogen for 2 hours. The slurry is filtered and the filtrate is stirred for about 16 hours with 146 mg of (Z)-2-amino-&alpha;-[1-diphenylmethoxycarbonyl-1-methylethoxy) imino]4-thiazoleacetic acid, 73 mg of dicyclchexylcazbcdiimide and S1 mg of N-hydroxybenzotriazole under nitrogen. The slurry is evaporated in vacuo and triturated with 4 ml of acetone. The slurry is filtered and the solid washed twice with 2 ml portions acetone. The filtrate and washings are combined and treated with 113 mg of potassium perfluorobutanesulfonate. Dilution with 24 ml of ether gives a solid that is isolated by centrifugation and washed three times with ether yielding 186 mg of the title compound. B) [3&alpha; (Z), 4&alpha;-3-[[(2-Amino-4-thiazolyl) [1-carboxy1-methylethoxy] imino] acetyl] amino]-2-methyl-4-oxo l-azetidinesulfonic acid, potassium salt (1:2) A slurry of 186 mg of [3&alpha; (Z), 4&alpha;]-3-[[2-amino- 4-thiazolyl) [(1-diphenylmethoxycarbonyl-1methylethoxy) imino] acetyl]amino]-4-methyl-2-oxol-azetidinesulfonic acid, potassium salt in 0.6 ml of distilled anisole is cooled to -12 C and 3.0 ml of distilled trifluoroacetic acid (at -10 0C) is added. The solution is stirred for 10 minutes and 12 ml of ether followed by 6 ml of hexane are added. After 5 minutes at -100C and stirring for 15 minutes at ambient temperature, the solid is isolated by centrifugation and washed four times with ether to give 141 mg of material. This is dried in vacuo, powdered, dissolved in 5 ml of cold water and immediately adjusted to pH 5.6 with 0.4 N potassium hydroxide. The solution is applied to a 100 ml HP-20AG column and eluted with water. Fractions (10 ml) 8-12 are combined and evaporated in vacuo (acetonitrile is added three times and evaporated. The residue is triturated with ether to give 101.7 mg of product, as a hygroscopic solid. Anal. Calc'd for C13N15N5O8B22K: C, 30.51; H, 2.95; N, 13.69; S, 12.53; K, 15.28 Found: C, 30.11; H,- 3.26; N, 13.35; S, 12.12; K, 15.02 Example 17 [3S-[3&alpha;(Z), 4ss]]-3-[[(2-Amino-4-thiazolyl)-[(1- carboxy-1-methylethoxy) imino]acetyl]amino]-4methyl-2-oxo-l-azetidinesulfonic acid [3S-[3&alpha; (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl)- [(1-carboxy-1-methylethoxy) iminolacetylamino] 4-methyl-2-oxo-1-azetidinesulfonia acid, dipotassium salt (87.3 mg; see example 103) is dissolved in 1.38 ml of water, cooled to OOC, treated with, 0.34 ml of 1N hydrochloric acid and the resulting crystals separated by centrifugation. The wet solid is dissolved in methanol, filtered, concentrated to about 0.5 ml and mixed with 1 ml of water, giving 55.9 mg of the title compound. Example 18 [3S-[3&alpha;(Z), 4ss]-3-[[(2-Amino-4-thiazolyl) [(1- carboxy-1-methylethoxy)imino]-4-methyl-2-oxo-1azetidinesulfonic acid, sodium salt A 99.7 mg sample of [3S-[3&alpha; (Z), 4ss]]-3- [[(2-amino-4-thiazolyl) [(1-carboxy-1-methylethoxy) imino]acetyl]amino]-4-methyl-2-oxo-Iazetidinesulfonic acid is mixed with 0.207 ml of IN sodium hydroxide and the resulting mixture is gently warmed to dissolve the remaining solid. Water is removed azeotropically with acetonitrile and the residue is crystallized from a mixture of 0.5 ml of methanol (to dissolve the residue) and 1 ml of acetonitrile, giving 81.8 mg of solid. A second recrystallization from 0.8 ml of methanol gives 47.9 mg, a third from 0.24 ml of methanol and 0.24 ml of absolute ethanol gives 44.8 mg, and a fourth from 0.225 ml of methanol and 0.225 ml of absolute ethanol gives 38.8 mg. The solid is dried at 200C and 0.01 mm of Hg for 18 hours and then equilibrated with atmospheric moisture for 24 hours, giving 40.9 mg of the title compound. Example 19 [3S-[3&alpha; (Z), 4ss]]-3-[[2-Amino-4-thiazolyl) [(1- carboxy-1-methylethoxy) imino]-4-methyl-2-oxo-1azetidinesulfonic acid, disodium salt A 3.00 g sample of I3S-[3a(Z),4)]-3- [[(2-Amino-4-thiazolyl)-[(1-carboxy-1-methylethoxy)imino]acetyl]amino]-4-methyl-2-oxo-1azetidinesulfonic acid, (see example 146), is suspended in 30 ml of water and titrated with 1N sodium hydroxide requiring 12.0 ml to give the title disodium salt. The pH is reduced to 6.5 by the addition of a little Dowex 50W-X2 (H+). The mixture is filtered and the filtrate diluted to 66.3 g with water. A 6.63-g portion is removed for other purposes. The remaining filtrate is lyophilized, giving 2.38 g of solid. Partial equilibration (24 hours) with atmosphereic moisture gives 2.54 g of the title compound. Examples 20-22 Following the procedure of Example 9, but substituting the compound listed in column I for (Z)-2-amino-&alpha;-(methoxyimino)-4-thiazoleacetic acid, yields the compound listed in column II. Column I Column II 20. (R)-&alpha;-[[[2,3-dioxo-4-[[(phenylmethoxy)- [3S-[3&alpha;(R#),4&alpha;]]-[4-[[[2-[(4-methyl-2-oxo-1carbonyl]amino]-1-piperazinyl]carbonyl]- sulfo-3-azetidinyl)amino]-2-oxo-1amino]benzeneacetic acid phenylethyl]amino]carbonyl]-2,3-dioxo1-piperazinyl]carbamic acid, phenylmethyl ester, potassium salt, melting point 191 C,dec. 21. (R)-&alpha;-[[[[(2-furanylmethylene)amino]-2-oxo- [3S-[3&alpha;(R#),4&alpha;]]-3-[[[[[3-[(2-furanylmethylene)imidazolidinyl]carbonyl]amino]benzeneacetic amino]-2-oxo-1-imidazolidinyl]carbonyl]acid amino]phenylacetyl]amino]-4-methyl-2-oxo1-azetidinesulfonic acid, potassium salt 22. (R)-&alpha;-[[(4-ethyl-2,3-dioxo-1-piperazinyl)- [3S-[3&alpha;(R#),4&alpha;]]-3-[[[[(4-ethyl-2,3-dioxocarbonyl]amino]benzeneacetic acid 1-piperazinyl)carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt Example 23 [3S-[3&alpha; (Z), 4&alpha;]]-3-[[(2-Amino-4-thiazolyl) I(1carboxy-i-methylethoxY)LminoZacetyl]amino]-4-methyl- 2-oxo-l-azetidinesulfonic acid, potassium salt (1:2) A) [3S-[3&alpha; (Z), 4&alpha;]]-3-[[(2-Amino-4-thiazolyl)- [(1-diphenylmethoxycarbonyl-1-methylethoxy) imino]acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt A solution of 440 mg of (Z)-2-amino-a l(l-carboxy-l-methylethoxy)imino]-4-thiazoleacetic acid and 153 mg of N-hydroxybenzotriazole monohydrate in 3 ml of dimethylformamide is treated with 206 mg of dicyclohexylcarbodiimide. The mixture is stirred at room temperature for 30 minutes under nitrogen and a solution of 180 mg of (3S-cis)-3-amino-4-methyl-2-oxo-1-azetidinesulfonic acid, (see example 137) and 0.14 ml of triethylamine in 2 ml of dimethylformamide is added (an additional 1 ml of dimethylformamide is-used for rinsing) and the mixture is stirred for about 16 hours. The slurry is evaporated in vacuo and triturated with 12 ml of acetone. The slurry is filtered and the solid washed with acetone (two 3 ml portions). The combined -filtrate and washings are treated with 338 mg of potassium perfluorobutanesulfonate. Dilution with 30 ml of ether gives a gummy solid, which slowly solidifies. The solid is filtered and washed with ether to give 656 mg of the title compound. B) [3S-[3&alpha; (Z), 4&alpha;]]-3-[[(2-Amino-4-thiazolyl)- [(1-carboxy-1-methylethoxy) imino]acetyl]amino]-4methyl-2-oxo-1-azetidinesulfonic acid, potassium salt (1:2) A slurry of 656 mg of [3S-[3&alpha;(Z), 4&alpha;]]-3- [[(2-Amino-4-thiazolyl) [(1-diphenylmethoxycarbonyl1-methylethoxy) imino]acetyl]amino]-4-methyl-2oxo-l-azetidinesulfonic acid, potassium salt in 2.3 ml of distilled anisole is cooled to -120C and 11.5 ml of trifluoroacetic acid (precooled to -100C) is added. The solution is stirred for 15 minutes and 46 ml of ether followed by 23 ml of hexane are added. After 5 minutes at -100C and stirring for 15 minutes at room temperature, the solid is filtered and washed with ether to give 457 mg of a very hydroscopic gum. This is dissolved in 6 ml of cold water and immediately adjusted to pH 5.6 with 0.4N potassium hydroxide solution. The solution is applied to -a 200 ml HP-20 resin and eluted with water. Fractions (50 ml each) 7-11 are combined and lyophilized to give 239 mg of the title compound as a solid. Anal. Calc'd. for C13H15O8N5S2K2.1/2 H2O: C, 29. 99 ; H, 3.10; N, 13.45; S, 12.32 Found: C, 29.94; H, 3.30; N, 13.30; S, 11.93 NMR(D20) 1.44 (3H d, j=75), 1.46(6H,S), 4.48(lH,d of t J=75, 5.5), 5.34(1H, d, v=5.5) 6.96ppm(lH,S). Example 24 (j) -3-Amino-4 , 4-dimethyl-2-oxo-l-azetidinesulfonic acid A) (@)-4,4-Dimethyl-2-oxo-1-azetidine-tertbutyl- diphenylsilane A solution of 40.5 ml of t-butylchlorodiphenylsilane in 112 ml of dimethylformamide is cooled to 0 C. To this is added 22 ml of triethylamine. A solution of 12.87 g of 4,4-dimethyl-2-azetidinone in 25 ml of dimethylformamide is added dropwise over 10 minutes to the cooled triethylaine solution. The resulting cloudy soution is stirred for 18 hours at 5 C under argon. This mixture is poured into 400 ml of ice water and extracted with three 150 ml portions of 2:1 ether:ethyl acetate. The combined extracts are washed with four 100 ml portions of 0.5M monobasic potassium phosphate buffer, one 150 ml portion of sodium bicarbonate solution, two 150 ml portions of water and one 150 ml portion of saturated sodium chloride solution. The solution is dried over sodium sulfate and concentrated in vacuo to yield 33.03 g of the title compound as a solid. B) (#)-3-azido-4,4-dimethyl-2-oxo-1-azetidine- tertbutyldiphenylsilane A solution of 4.25 ml of 1.6M (in hexane) n-butyllithium and llml of dry tetrahydrofuran is prepared at -500C under argon in a 100 ml three-necked flask. A solution of 0.083 g of triphenylmethane in 1 ml of tetrahydrofuran is added. The resulting solution is cooled to -60 0C, and 1.0 ml of diisopropylamine is added dropwise by syringe. This is stirred for 15 minutes and then cooled to -780C. A solution of 2.3 g of (-+) -4, 4-dimethyl-2-oxo-l-azetidine-tertbutyl- diphenylsilane in 8 ml of tetrahydrofuran is added slowly by syringe. The resulting solution is stirred for 20 minutes at -780C, during which time heavy precipitation occurs and uniform stirring becomes difficult. A solution of 1.33 g of p-toluenesulfonyl azide in 5 ml of tetrahydrofuran is added dropwise. The resulting mixture is allowed to stir at -780C for 20 minutes, and 2 ml of trimethylsilyl chloride is added dropwise. The reaction mixture is warmed to ambient temperature and stirred for 1 hour. Then the mixture is cooled to OOC- and poured into 150 ml of 0 0C ethyl acetate. Enough 0.5 M monobasic potassium phosphate buffer is added to make both the aqueous and organic layers clear. The two layers are separated and the organic layer is washed with three 150 ml portions of 0.5 M monobasic potassium phosphate solution, one 150 ml portion of sodium chloride solution, one 150 ml portion pf saturated sodium chloride solution and dried over sodium sulfate. The solution is concentrated in vacuo to 2.83 g of oil, which upon trituration with hexane yields 1.67 g of the title compound as a solid. C) (+)-3-Azido-4,4-dimethyl-2-oxo-1-azetidine In a 50 ml three-necked flask, 1.52 g of (+)-3-azido-4,4-dimethyl-2-oxo-1-azetidine- tertbutyldiphenylsilane is dissolved in 25 ml of acetonitrile. To this stirred solution is added 0.25 ml of 48% hydrofluoric acid. This is stirred at ambient temperature, and 0.5 ml portions of 48% hydrofluoric acid are added every 60 minutes until, after 6.5 hours, a total of 3.25 ml of 48% hydrofluoric acid has been added. The reaction mixture is then cooled to 0 C, neutralized with saturated sodium bicarbonate, and extracted with 120 ml of ethyl acetate. The organic layer is then washed with 100 ml of water, 100 ml of saturated sodium chloride solution, and dried over sodium sulfate. The dry solution is concentrated in vacuo to yield 1.34 g of oil. This impure oil is chromatographed on 27 g of silica gel with hexane, followed by 33% ethyl acetate in hexane, to yield 0.358 g of the title compound as a solid. D) (+-) -3-Azido-4, 4-dimethyl-2-oxo-l-azetidine- sulfonic acid, tetrabutylammonium salt To 0.100 g of (#)-3-azido-4,4-dimethyl-2- oxo-1-azetidine at 0 C is added under argon 2.8 ml of 0.5M dimethylformamide-sulfur trioxide complex. This mixture is allowed to warm to ambient temperature and stir for 45 minutes. The solution is then poured into 20 ml of 0.5 M pH 5.5 monobasic potassium phosphate buffer. This is washed with three 20 ml portions of methylene chloride (discarded) and Q.237 g of tetrabutylammonium hydrogen sulfate is added to the aqueous solution. This was extracted with four 20 ml portions of methylene chloride and the combined organic extracts are washed with 20 ml of 88 sodium chloride solution. The methylene chloride solution is dried Csodium sulfate) and concentrated in vacuo to yield a .31 g of oil, which appeared by nmr to be 50% dimethylformamide and 50% of the title compound. E) (#)-3-Amino-4,4-dimethyl-2-oxo-1-azetidine- sulfonic acid A solution of 0.155 g of (+}-3-azido-4,4dimethyl-2-oxo-1-azetidinesulfonic acid, tetrabutylammonium in 0.6 m 1 of methanol is hydrogenated over 10% palladium on charcoal for 20 minutes at 1 atmosphere. The catalyst s filtered off and rinsed with methylene chloride which is combined with the methanol solution. This clear solution is treated with 0.123 ml, 97% formic acid. Upon addition of the acid the solution immediately becomes cloudy. After standing for 1 hour at 50C, the solid is filtered off to yield 0.0664 g of the title compound, m.p. 200-2020C(dec.). NMR(D20) 1.64(3H,S), 1.68(3H,S), 4.42(lH,S), - IR (KBr) 1765cm-1. Example 25 [3#(Z)]-3-[[(2-Amino-4-thiazolyl) (methoxyimino)acetylZamino]-4,4-dimethZl-2-oxo-1-azetidinesulfonic acid, potassium salt A solution of N-hydroxybenzotriazole hydrate (50 mg) and (Z)-2-amino-&alpha;-(methoxyimino)-4- thiazoleacetic acid (0.323 mmole) in 0.5 ml of dimethylformamide is treated with 67 mg of dicyclohexylcarbodiimide under argon at ambient temperature. The resulting mixture is stirred for 1 hour at which time (t) -3-amino-4 , 4-dimethyl- 2-oxo-1-a zetidinesulfonic acid (57 mg; see example 153) is added as a solid followed by triethylamine dropwise (0.05 ml). The reaction is stirred at ambient temperature for 16 hours. The dimethylformamide is removed under high vacuum at 30 C, and the residue is slurried in 4 ml of acetone and filtered. The filter cake is washed with an additional 4 ml of acetone, and potassium perfluorobutanesulfonate' (85 mg) is added to the filtrate, followed by ether. Trituration of the resulting gum with ether gives 40 mg of a tan solid which is chromatographed on a 70 ml HP-20AG column. Elution with water gives 20 mg of the title compound in fractions (5 ml) 16-40 after evaporation, trituration with 1:1 acetone-hexane and drying. m.p. '2250(dec). Anal. Calc'd. for C11H14N5O6S2 K: C, 31.80; H, 3.40; N, 16.86; S, 15.43 Found: C, 29.47; H, 3.48: N. 14.98: S, 1.5 Example 26 (#)-4,4-Dimethyl-2-oxo-3-[(phenylacetyl) amino]- l-azetidinesulfonic acid, potassium salt A solution of N-hydroxybenzotriazole hydrate (45 mg) and phenylacetic acid (40 mg) in 0.5 ml of dimethylformamide is treated with dicyclohexylcarbodiimide (61 mg) under argon at ambient temperature. The resulting mixture is stirred for 1 hour and (#)-3-amino-4,4-dimethyl-2-oxo- l-azetidinesulfonic acid, (52 mg; see example 153) is added as a solid, followed by triethylamine dropwise (0.04 ml). The reaction is stirred at ambient temperature for 24 hours. The dimethylformamide is removed under high vacuum at 30 0C and the residue is slurried in acetone and filtered. Potassium perfluorobutanesulfonate is added to the filtrate, ethers is added and the mixture is cooled. The resulting solid is washed with acetone, hexane, and dried yielding the title compound as a powder. Anal. calc'd. for C13H15N205SK: C, 44.55; H, 4.32; N, 8.00; S, 9.15; K, 11.16 Found: C, 43.83; H, '4.16; N, 7.96; S, 8.76; K, 11.43 NMR(D20) 1.33(S,3H), 1.58(S,3H), 3.68(S,3H), 4.70 (S,1H), 7.56ppm (broad S, 5H). Example 27 (3S-trans)-3-[[(2-Amino-4-thiazoyl)oxoacctyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid, potassium salt To a solution of diphenylphosphinyl chloride (1.85 g) in dry dimethylformamide (15 ml) cooled in an ice-methanol bath (-15 to -200C) is added (2-amino-4-thiazolyl)glyoxylic acid, triethylamine salt (2.14 g). After stirring for 0.5 hour a solution of (35-trans) -3-amino-4-methyl-2-oxo- l-azetidinesulfonic acid (1.08 g; see example 139) and triethylamine (1.92 ml) in dry dimethylformamide (5 ml) is added to the. cold mixed anhydride solution and the reaction mixture is stirred at 50C for 24 hours. Solvent is removed in vacuo, the residual dark oil is dissolved in water, and chromatographed on Dowex 50 X 2-400resin (K# form; 200 ml). Upon elution with water (15 ml fractions) the crude product is collected in fractions 13-27 (3.37 g). Chromatography on HP-20 resin (200 ml), eluting with water (15 ml fractions), gives the desired product in fractions 18-26. Removal of water in vacuo gives the title compound as an amorphous powder. Anal. Calc'd for C9H9N406S2K (372.42): C, 29.02; H, 2.44; N, 15.04; S, 17.22; K, 10.50 Pound: C, 28.87; H, 2.62, N, 14.85; S, 15.09; K, 10.81 Example 28 (#S-trans)-3-Methoxy-4-methyl-2-oxo-3-[[(phenyl- methoxy) carbonyl]amino]-1-azetidinesulfonic acid, potassium salt A) (3Strans)-4-Methyl--metfroxy-2-oxo-4- [[(phenylmethoxy) carbonyl]amino]azetidine A solution of 2.5 g (0.0106 mole) of (3R-trans)-4-methyl-2-oxo-3[[(phenylmethoxy) carbonyl]amino] azetidine (prepared from dthreonine in 12.6% yield essentially as described for the racemic cis isomer in Example 98C) in 112 ml of 4% borax in methanol is cooled to nO and 3.5 ml of t-butyl hypochlorite is added. After 20 minutes the solution is poured into 1 liter of cold water and extracted with two 750 ml portions of cold ethyl acetate. The organic layer is washed with cold water (two 750 ml portions), saturated salt, dried and evaporated to give 3.05 g of crude N-,N'-dichloroamide. A solution of 426 mg of lithium methoxide in 20 ml of dry methanol is cooled to -78 0C and diluted with 40 ml of dry tetrahydrofuran. Over 30 seconds a solution of the above chloroamide in 20 ml of tetrahydrofuran (-78 C) are added via syringe. After 20 minutes at -780C, 2 ml each of acetic acid and trimethyl phosphite are added. After 40 minutes at room temperature the solution is poured into 500 ml of water and extracted with ethyl acetate (two 300 ml portions). The organic layer is washed with water, dried, and evaporated to give an oil. Chromatography on a 200 ml silica gel column eluting with 3:1 chloroform-ethyl acetate gives a total of 1.25 g of the title compound. B) (3S-trans)-3-Methoxy-4-methyl-2-oxo-3 [[(phenylmethoxy) carbonyl]amino-1-azetidinesulfonic acid, potassium salt A solution of 800 mg (0.00303 mole) of (3S-trans) -4-methyl-3-methoxy-2-oxo-4- 1± (phenyl- methoxy) carbonyl]amino]azetidine in 2 ml of dimethylformamide is cooled to 0 C and 4 ml of dimethyl formamide-sulfur trioxide complex is added. After 1 hour at 0 C and 4 hours at room temperature the solution is poured into 80 ml of 0.5 M monobasic potassium phosphate (adjusted to pH 5.5) and extracted with methylene chloride (two 50 ml portions, discard). The e aqueous layer is treated with 1.04 g of tetrabutyl ammonium sulfate and extracted with dichloromethane to give 1.42 g of oil. This is dissolved in acetone and treated with 1.04 g of potassium perfluorobutanesulfonate in 10 ml of acetone. Dilution with 250 ml of ether and extensive trituration of the oily solid gives 584 mg of crude product. Chromatography on RP-20 AG (200 ml) gives 418 mg of purified product in fractions (1@0 ml) 13-16 (elution with 1 liter of water and then 9:1 water-acetone). Trituration of 114 mg of this material with ether gives 104 mg of an analytical sample. Analysis calc'd for C13H14N207SKH2O: C, 39.06; H, 4.04; N, 7.01; S, 8.03; K, 9.78 Found: C, 38.91; H, 3.62; N, 6.91; S, 8.06; K, 9.51 NMR(D20) l.33(3H, d, j=7), 3.46(3H,S), 4.22(2H, d of d, ) @6), 5.18 (2H,S), 7.43 ppm (5H,S). Example 29 (3S-trans) -3-Methoxy-4-raethyl-2-oxo-3-I (,phenylacetyl) - amino] -1-a zetidinesulfonic acid, potassium salt (3S-trans)-3-amino-3-Methoxy-4-methyl-2-oxo-1 azetidinesulfonic acid, tetrabutylammonium salt is prepared by the catalytic hydrogenation of (3S-trans)-3-methoxy-4-methyl-2-oxo-3-[[(phenylmethoxy) carbonyl] amino]-1-azetidinesulfonic acid, potassium salt Csee example 158) after conversion -to the tetrabutylammonium salt. Following the procedure of example 88, but utilizing (3S-trans)-3-amino-3-methoxy 4-methyl-2-oxo-1-azetidinesulfonic acid, tetrabutylammonium salt and phenylacetyl chloride yields the title compound. Anal. calc'd for C13H15N2O6SK: C,42.61; H,4.31; N,7.65 Found: C, 39.67; H, 4.08; N, 7.30 NMR (D20) 1.29(BH, d, J=7) 3.45(3H,S), 3.73(2H,S), 4.36 (2H, d of d, j=6), 7.38ppm (5H,S). Example 30 [3S-[3&alpha;(Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) [[2- (diphenylmethoxy)-2-oxoethoxy]imino]acetyl] amino]-2-methyl-4-oxo-1-azetidinesulfonic acid, potassium salt Following the procedure of example 9, but substituting (Z)-2-amino--jj2-(diphenylmethoxy)- 2-oxoethoxy]imino]-4-thiazoleacetic acid for (Z)-2-amino-&alpha;-(methoxyimino)-4-thiazoleacetic acid and first treating the (3S-cis)-3-amino- 4-methyl-2-oxo-l-azetidinesulfonic acid, with triethylamine, yields the title compound, meltin point 155-160 C, dec. Example 31 [3S-[3&alpha; (Z), 4ss]]-3-[[[(Carboxymethoxy)imino] (2-amino4-thiazolyl)acetyl]amino]-4-methyl-2-oxo-1azetidinesulfonic acid, dipotassium salt The deprotection of 13S-13a (Z), 4ss]]-3-]](2- amino-4-thiazolyl) I 12- (diphenylinethoxy) -2-oxoethoxy] - imino] acetyl]amino]-2-methyl-4-oxo-1-azetidinesulfonic acid, potassium salt (see example 160) using trifluoroacetic acid and anisole yields the title compound, which decomposes at > 250 C. Example 32 [3S (R*)]-3-[[[[(4-Amino-2,3-dioxo-1-iperazinyl)carbonyl]amino] phenylacetyl)amino)-4-methyl-2oxo-l-azetidinesulfonic acid, potassium salt [3S (R*)]-[4-[[[2-[(4-methyl-2-oxo-1-sulfo3-azetidinyl)amino]-2-oxo-1-phenylethyl]amino]carbonyl]-2,3-dioxo-1-piperazinyl]carbamic acid, phenylmethyl ester, potassium salt (see example 149) is hydrogenated using gaseous hydrogen and 10% palladium on charcoal as catalyst, yielding the title compound, melting point 1650C, dec. Example 33 (trans)-3-Amino-4-ethyl-2-oxo-1-azetidinesulfonic acid A) t-Boc-N-methoxy-ss-threoethylserinamide threo-D,t-j3-'Ethylserine (1.33 g) is dissolved in 10 ml of 2N potassium hydroxide and S ml of t-butanol. After the addition of 2.46 g of di-t-butylpyrocarbonate the two-phase mixture is stirred for 4 hours at ambient temperature. O-Methylhydroxylaitiiaonium chloride (1.25 g) is added and the pH is adjusted to 4 with 1N hydrochloric acid. 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide, hydrochloride (1.92 g) is added and the pH is again adjusted to 4. After stirring for 1 hour the reaction mixture is saturated with sodium chloride and extracted with four 50 ml portions of ethyl acetate. The ethyl acetate extracts are combined and dried over MgSO4. Removal of the solvent in vacuo yields 1 g of the title compound. B) t-Boc-O-methanesulfonyl-N-methoxy-ss-threopropionamide t-BOC-N-methoxy-ss-threoethylserinamide (10.5 g) is dissolved in 65 ml of pyridine. Methanesulfonyl chloride (4.65 ml) is added dropwise at OOC. After stirring for 3 hours at ambient temperature, the reaction mixture is poured into 200 g of ice and 300 ml of 1N hydrochloric acid. The pH is adjusted to 4 with concentrated hydrochloric acid. After extraction with three 85 ml portions of ethyl acetate the combined extracts are dried over MgSO and concentrated in vacuo. The residue is treated with carbon tetrachloride and concentrated again. Stirring with ether followed by filtration yields 6.9 g of the title compound. C) (trans) -3 -t-Butoxycarbonylamino-4-ethyl -1- methoxy-2-azetidinone Anhydrous potassium carbonate (4.15 g) and 125 ml of dry acetone are brought to reflux and 3.4 g of t-Boc -Ome thanesulf onyl -N-methoxy- B-threo-propionamide in 25 ml of acetone is added. After 1 hour the reaction mixture is cooled and filtered, and the filtrate is concentrated in vacuo. The oily residue is stirred with hexane to yield 2.2 g of the title compound. D) (trans)-3-t-Butoxyzarbonylamino-4-ethyl-2- azetidinone (trans)-3-t-Butoxycarfbnylamino-4-ethyl-l- methoxy-2-azetidinone (3 g) is added to 170 ml of liquid ammonia at -78 0C under nitrogen and 1.68 g of sodium is added in 5 portions with stirring over a 5 minute period. Stirring is continued for 30 minutes. Ammonium chloride is the added slowly until the blue color of the reaction mixture disappears. After removal of the ammonia under nitrogen the solid is extracted with two 100 ml portions of ethyl acetate. Removal of the solvent followed by drying in vacuo yields 2.7 g of the title compound. E) (trans)-3-t-Butoxycarbonylamino-4-ethyl-2 oxo-1-azetidinesulfonic acid, tetrabutylammonium salt To a 2 ml of absolute pyridine in 20 ml of dry dichloromethane is added trimethylsilylsulfonyl chloride (3.7 ml in 5 ml of dry dichloromethane. The addition is accomplished at -300C, under nitrogen, over a 10 minute period. After stirring at ambient temperature for 30 minutes, the flask is evacuated to yield a pyridine-sulfur trioxide complex. (trans) -3- t-Butoxycarbonyl amino-4 -ethyl-2-azetidinone (2.67 g) and 20 ml of dry pyridine are added to the flask which is then placed in an oil bath preheated to 90 C. After 15 minutes a clear solution is obtained and poured into 200 ml of a -lM solution of dibasic potassium phosphate. After the addition of 27 g of dibasic potassium phosphate and 100 ml of water a clear solutionis obtained. The solution is extracted with two 60 ml portions of ethyl acetate. Tetrabutylammonium hydrogensulf ate is added to the aqueous layer, and the aqueous solution is extracted with three 100 ml portions of dichloromethane and the combined organic layers are dried over MgSO4. Concentration in vacuo yields 6.9 g of the title compound. F) (trans)-3-Amino-4-ethyl-2-oxo-1-azetidinesulfonic acid (trans)-3-t-Butoxycarbonylamino-4-ethyl-2oxo-l-azetidinesulfonic acid, tetrabutylammonium salt (6.75 g) in 40 ml of 98% formic acid is stirred for 3 hours at ambient temperature. Dichloromethane (60 ml) is added and the mixture is refrigerated for about 16 hours. The resulting precipitate is separated by filtration and then dried in vacuo to yield Q.85 g of the title compound, melting point 1850C, dec. Example 34 (trans, Z)-3-[[(2-Amino-4-thiazolyl) [(1-carboxy1-methylethoxy) imino] acetyl]amino]-4-ethyl-2oxo-l-azetidinesulfonic acid, dipotassium salt A) (trans, Z)-3-[[(2-Amino-4-thiazolyl) [(1diphenylmethoxycarbonyl-1-methylethoxy)imino]acetyl]amino]-4-ethyl-2-oxo-1-azetidinesulfonic acid, dipotassium salt (trans)-3-Amino-4-ethyl-2-oxo-1-azetidinesulfonic acid CO .55 g) and 335 mg of triethylamine are dissolved in 50 ml of dry dimethylformamide. (Z)-2-Amino-&alpha;-[(1-diphenylmethoxycarbonyl-1- methylethoxy)imino]-4-thiazoleacetic acid (1.14 g) is added with stirring at 0 C followed by 450 mg of hydroxybenzotriazole and then 0.69 g of dicyclohexylcarbodiimide. After stirring for about 16 hours at 0 0C the flask is evacuated. Dry acetone (25 ml) is added to the solid with stirring. The mixture is filtered and Q.94 g of potassium perfluorobutanesulfonate is added to the filtrate followed by 100 ml of ether. After standing for 1 hour at 0 C the solid is filtered, washed with ether and dried in vacuo yielding 1.58 g of the title compound. B) (trans, Z) r (2-Amino-4-thiazoiyl')-I (1-carboxy- 1=methylethoxy) imino]acetyl]amino]-4-ethyl-2oxo-1-azetidinesulfonic acid, dipotassium salt To a suspension of 1.31 g of (transl, Z)-3- I I (2-amino-4 -thiazolyl)] (l-diphenylmethoxycarbonyl1-methylethoxylimino]acetyl]amino]-4-ethyl-2oxo-l-azetidinesulfonic acid, dipotassium salt in 10 ml of anisole is added 5 ml of trifluoroacetic acid over a 10 minute period at -15 C. After stirring for 2 hours at -100C a clear solution is obtained. At -300C 80 ml of dry ether is added and the resulting precipitate is filtered and then treated with S ml of water. The pH is adjusted to 5.5 with 1N potassium hydroxide at 0 0C, and the mixture is filtered to remove unconverted starting material. The filtrate is chromatographed on EP-20 with water as eluent. Lyophilization yields 185 mg of the title compound, melting point 160 0C, dec. Example 35 (3S-trans)-&alpha;-[[(4-Methyl-2-oxo-1-sulfo-3-azetidinyl)- aminoAcarbonylAbenzeneacetic acid, dipotassium salt (3S-trans)-3-Amino-4-methyl-2-oxo-1-azetidinesulfonic acid (see example 139) is coupled with a-(carboxyl).benzeneacetyl chloride and treated with triethylamine and potassium perfluorobutanesulfonate to yield the title compound, melting point 147 C, dec. Example 36 [3S-trans]-3-Amino-4-cyclohexyl-2-oxo-1-azetidinesulfonic acid A] &alpha;-(t-Butoxycarboylamino)-ss-cyclohexyl-ss- hydroxy-threo-propionic acid B-Cyclohexyl-&alpha;-amino-ss-hydroxy-thre-propionic acid (15 g) is suspended in 150 ml of acetonitrile and 70 ml of water. Triethylamine (17.8 g) is added and the mixture is heated with stirring to 60 C. At this temperature a clear solution is obtained and 21.0 g of di-t-butylpyrocarbonate is added and stirring at 60 0C is continued for 1.5 hours. The solvent is removed in vacuo and 50 ml of water is added. The aqueous layer -s extracted with ethyl acetate at a pH of 2, which is adjusted by addition of 3N HC1. The organic layer is separated, dried over Na2SO4 and evaporated to dryness. The remaining crystalline material is filtered with petrol ether, yielding 20.4 g of the title compound, melting point 113-1150C. B) &alpha;-(t-Batoxycarbonylamino)-ss-cyclohexyl-ss- hydroxy-N-methoxy-threo-propionamide &alpha;-(t-Butoxycarbonylamino)-ss-cyclohexyl-ss- hydroxy-threo-propionic acid (20.2 g) and 7.6 g of O-methylhydroxylamine hydrochloride are suspended in 350 ml of water and 175 ml of t-butanol. The pH of the mixture is adjusted with potassium carbonate to 4.1-Ethyl-3-(3-dimethyl- aminopropyl)carbodiimide (16.4 g) is added and the pH is maintained at 4 with stirring for 1.5 hours. t-Butanol is removed in vacuo and the remaining aqueous solution is saturated with sodium chloride and extracted twice with 100 ml portions of ethyl acetate. The organic layers are combined, dried with Na2SO4and evaporated to dryness. The remaining crystals are filtered off with petrol ether yielding 18.6 g of the title compound, melting point 125-127 C. C) &alpha;-(t-Butoxycarbonylamino)-ss-cyclohexyl-ss- (methanesulfonyloxy) -N-methoxy-threo-propionamide &alpha;-(t-Butoxycarbonylamino)-ss-cyclohexyl-ss- hydroxy-N-me thoxy-threo-propionamide (18.3 g) is dissolved with'stirring'in'lO0 ml of dry pyridine. The solution is cooled with stirring to 0 C and 9.3 g of methanesulfonyl chloride is dropped in. After one hour at 0 C an additional 3.3 g of methanesulfonyl chloride is added and stirring is continued for one more hour. The solution is poured into 300 ml of ice water, 200 ml of ethyl acetate is added and the pH is adjusted to 3 with dilute sulfuric acid. The organic layer is separated, dried with Na 2504 and the solvent is removed in vacua. The remaining solid is collected with petrol ether yielding 19.0 g of the title compound, melting point 150-152 0C. D) [3S-trans]-3-[t-Butoxycarbonylamino)-4cyclohexyl-1-methoxy-2-azetidinone &alpha;-(t-Butoxycarbonylamino)-ss-cyclchexyl-ss- (méthanesulfonyloxy)-N-methoxy-threo-propionamide (18.7 g) is dissolved in 500 ml of dry acetone. Potassium carbonate (9.8 g) is added and the suspension is heated to reflux temperature with stirring for 5 hours. The insoluble inorganic material is filtered off and the solvent removed in vacuo and the remaining oil is dissolved in 30 ml of ethyl acetate. Upon the addition of petrdl ether, the title compound precipitates and is filtered off (12.9 g), melting point 110-112 C. E) [3S-trans]-3-(t-Butoxycarbonylamino)-4 cyclohexyl-2 -azetid inone [3S-trans]-3-(t-Butoxycarbonylamino)-4- cyclohexyl-l-methoxy-2-azetidinone (1 g) is added to 50 ml of liquid ammonia with stirring. Sodium (0.154 g) is added in 5 to 6 portions within 5 minutes. After this time an additional amount of 0.a25 g sodium is added and stirring is continued for 5 minutes. Ammonium chloride (0.89 g) is added and the ammonia is removed. The residue is extracted with warm ethyl acetate. The organic extract is evaporated to dryness and the remaining crystals of the title compound are filtered with petrol ether, yielding 0,5 g, melting point 130-132 C. F) [3S-trans]-3-(t-Butoxycarbonylamino]-4cyclohexyl-2-oxo-1-azetidinesulfonic acid, pyridine salt [3S-trans]-3-(t-Butoxycarbonylamino)-4cyclohexyl-2-azetidinone (5.3) is dissolved in20 ml of methylene chloride and 80 ml of dimethylformamide. After the addition of 60 mmole of pyridine-sulfur trioxide complex the solution is stirred for f hours at room temperature. Removal of the solvent in vacuo yield 11.3 g of the title compound as an oil. G) (3 S-trans] -3- (t-Butoxy'carbonylamino 1-4- cyclohexyl-2-oxo-1-azetidinesulfonic acid, tetrabutylammonium salt [3S-trans]-3-(t-Butoxycarbonylamino)-4cyclohexyl-2-oxo-l-azetidinesulfonic acid, pyridine salt (11.3 g) is dissolved in 250 ml of water. Tetrabutylammonium hydrogensulfate (9.0 g) is added with stirring and the pH is adjusted to 6.5 with 1N potassium hydroxide. The aqueous solution is extracted twice with 200 ml portions of methylene chloride. The organic portions are dried with Na2SO4, filtered and the solvent is distilled off, y, yielding 8 g of the title compound, melting point 135-138 C. H) [3S-trans]-3-amino-4-cyclohexyl-2-oxo-1 azetidinesulfonic ¯acid [3S-trans]-3-(t-Butoxycarbonylamino)-4 cyclohexyl-2-oxo-l-azetidinesulfonic acid, tetrabutylammonium salt (3.8 g) is stirred in 20 ml of formic acid for 3 hours, followed by the addition of 20 ml of methylene chloride. The precipitated title compound (1.0 g) is filtered off, melting point 2l7-2190C. Example 37 [3S-[3&alpha;(Z), 4ss]]-3-[[(2-Amino-4-thiazolyl)- (methoxyimino) acetyl]amino]-4-cyclohexyl-2oxo-l-azetidinesulfonic acid, potassium salt [3S-trans]-3-Amino-4-cyclohexyl-2-oxol-azetidinesulfonic acid (0.25 g) is dissolved in 30 ml of dry dimethylormamide and 0.12 g of triethylamine with stirring. When a clear solution is obtained, (Z) -2-amino-a- (methoxy- imino)-4-thiazoleacetic acid (0.2 g), 0.16 g of hydroxybenzotriazole and 0.42 g of dicyclohexylcarbodiimide are added. Stirring is continued for 48 hours at ambient temperature. The precipitated urea is filtered off and the solvent is removed in vacuo. The residue is dissolved in 10 ml of acetone and 0.41 g of Potassium perfluorobutanesulfonate is added. After the addition of 50 ml of ether, the title compound precipitates and is filtered. Column chromatography- using HP-20 and water/ acetone (9:1) as eluent, yields 0.36 g of product, melting point 200-205 C Cafter lyophilization). Example- 38 [3S-[3&alpha;(Z), 4ss]]-3-[[(2-Amino-4-thiazolyl)[(1- carboxy-1-methylethoxy) imino] acetyl]amino]-4 cyclohexyl-2-oxo-1-azetidinesulfonic acid, dipotassium salt A) [3S-[3&alpha; (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) [(1- diphenylemthoxycarbonyl-1-methylethoxy) imino] acetyl]aminol-4 cyclohexyl-2-oxo-1-azetidinesulfonic acid, potassium salt [3S-trans]-3-Amino-4-cyclchexyl-2-oxo-1 azetidinesulfonic acid (0.2 g; see example 175) is dissolved in 30 ml of dimethylformamide and O.09 g of triethylamine with stirring. Hydroxy benzotriazole (0.12 g), Q.30 g of (Z)-2-amino-a I (l-diphenylmethoxycarbonyl-l-methylethoxy) imino J - 4-thiazoleacetic acid and 0.33 g of dicyclohexylcarbodiimide are added and stirring at ambient temperature is continued for 12 hours. The precipitated urea is filtered off and the mother liquor is evaporated to dryness. The remaining oil is dissolved in 5 ml acetone, treated with 0.3 g of potassium perfluorobutanesulfonate and poured into 100 ml of ether with stirring. [3S-[3&alpha; (2), 4ss]]-3-[[(2-Amino-4-thiazolyl)- [(1-dihenylmethoxycarbonyl-1-methylethoxy)imino]acetyl]amino]-4-cyclohexyl-2-oxo-1-azetidinesulfonic acid, potassium salt C0.61 g} precipitates and is filtered off. B) [3S-[3a (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) [(1carboxyl-1-methylethoxyl imino] acetyl] amino]-4cyclohexyl-2-oxo-1-azetidinesulfonic acid, dipotassium salt [3S-[3a (Z), 4ss]]-3-[[(2-Amino-4-thiazolyl) [(1-diphenylmethoxycarbonyl-1-methylethoxy) imino] acetyl) amino) -4-cyclohexyl-2-oxo-l-azetidinesulfonic acid, potassium salt (0.61 g) is suspended in 6 ml of anisole, cooled to -150C and 5 ml of trifluoroacetic acid is dropped in with stirring. The temperature is maintained for one hour and then lowered to - 30 C. About 100 ml of dry ether is added at such a rate, that the temperature does not exceed -100C. The precipitated compound is filtered off and chromatographed using HP-20 resin and water/acetone (9:1) as eluent, yielding 0.3 g of the title compound, melting point ll-1200C, dec. (after lyophilization). Example 39 [3S-[3&alpha;, 4ss]-4-Cyclohexyl-3-[[[[[3-[(2-furanyl- methylene) amino]-2-oxo-1-imidazolidinyl]carbonyl]aminolphenylacetyl]amino-2-oxo-1-azetidinesulfonic acid, potassium salt [3S-trans]-3-Amino-4-cyclohexyl-2-oxo-1azetidinesulfonic acid (o.1 g; see example 175) is dissolved in a mixture of 30 ml of dry dimethylformamide and 0.05 g of triethylamine with stirring. [[[[(2-Furanylmethylene) amino]2-oxo-1-imidazolidinyl]carbonyl] amino]phenylacetic acid (P.14 g), 0.06 g hydroxybenzotriazole and 0.17 g of dicyclohexylcarbodiimide are added and the solution is stirred for 5 days at room temperature. The solvent is removed in vacuo, the residue is dissolved in 10 ml of acetone and the precipitated urea is filtered off. The mother liquor is agitated with 0.15 g of potassium perfluorobutanesulfonate and diluted with 50 ml of ether. The precipitate is filtered, and chromatographed with HP-20 resin using water/acetone (9:1) as eluent yielding 0.14 g of product, melting point 195-202 C, dec. (after lyophiliaztion). Example 40 I3S- 13a (R*) 34]] -4-Cycloh.exyl-3-'LI3--(4-ethyl.-2 ,-3- dioxo-1-piperazinyl)-1.3-dioxo-2-phenylpropyl] amino]-2-oxo-1-azetidinesuifon-ic acid, potassium salt [3S-trans]-3-Amino-4-cyclohexyl-2-oxo-1azetidinesulfonic acid (0.1 g; see example 175) is dissolved in 30 ml of dimethylformamide and 0.5 g of triethylamine with stirring. [R]-&alpha;- [[(4-ethyl-2,3-dioxo-1-piperazinyl)carbonyl] amino]benzeneacetic acid, 0.06 g of hydroxybenzotriazole and Q.17 g of dicyclohexylcarbodiimide are added, and the mixture is stirred for about. 16 hours at room temperature. The solvent is distilled off in vacuo and the remaining oil is dissolved in 10 ml of acetone. The precipitated urea is filtered off and the mother liquor is agitated with 0.15 g of potassium perfluorobutanesulfonate and diluted with 50 ml of ether. The precipitate is filtered off and chromatographed with HP-20 resin, using water/acetone (9:1) as eluent, yielding 0.15 g of the title compound, melting point 175-180 C (after lyophilization). Example 41 (trans, Z)-3-[[(2-Amino-4-thiazolyl) (methoxyimino)acetyl]amino2-4-ethyl-2-oxo-1-azetidinesulfonic acid, potassium salt Following the procedure of example 170, part A, but substituting (Z)-2-amino-a-(methoxyimino)-4-thiazoleacetic acid for (Z)-2-amino-a [(1-diphenylmethoxycarbonyl-1-methylethoxy) imino]4-thiazoleacetic acid, yields the title compound, melting point 190 C, dec. Example 42 (#)-(trans)-3-Amino-2-oxo-4-phenyl-1-azetidine- sulfonic acid A) (#)-trans)-2-oxo-4-henyl-1-azetidine-tert- butyldiphenylsilane A solution of tert-butylchlorodiphenylsilane (20.56 gl in dimethylformamide (45 ml) is cooled to 0 C under argon and treated with triethylamine (10.4 ml and then (#)-2-oxo-4-phenyl-1-azetidine. After several hours at 0 0C, the resulting mixture is treated with additional triethylamine (1 ml) and tert-butylchlorodiphenylsilane (2. 11 g), and allowed to stir for 65 hours at 5 C. The reaction mixture is poured into ice water (300 ml) and extracted with 3:1 ether-ethyl acetate (three 125 ml portions). The organic extracts are washed with pH 4.5 phosphate buffer (three 50 ml portions), saturated sodium bicarbonate solution (50 ml), water (two 50 ml portions) saturated sodium chloride solution and dried (Na2SO4). Filtration, and concentration in vacuo yields a solid which is washed with hexane to give after drying (high vacuum) 15 g of the title compound as a solid. 'B) d-) - (trans) -3-azido-2-oxo-4-phenyl-l-a-zetidine- tert-butyldiphenylsilane A 50 ml flask equipped with stirring bar, gas inlet, and septum is flame dried under argon and charged with n-butyl lithium (0.65 ml of a 1.6 M solution in hexane) which is cooled to -40 C and dissolved in tetrahydrofuran (2 ml). Diisopropylamine t0.16 ml} is added dropwise, the resulting mixture is stirred for 30 minutes and cooled to -780C. A solution of C+l-(trans)- 2-oxo-4-phenyl-l-azetidine-tert-butyldiphenylsilane (40Q mg) in tetrahydrofuran .5 ml) is added dropwise over about 5 minutes. After stirring an additional 20 minutes the solution is treated with p-toluenesulfonyl azide (204 mg) in tetrahydrofuran (0.5 ml). The resulting mixture is stirred 10 minutes at -78 0C and treated dropwise with chlorotrimethylsilane (0.4 ml). After an additional 10 minutes of stirring, the cooling bath is removed and the reaction mixture is stirred at ambient temperature for 2.5 hours. Then, while cooling at 0 C, ethyl acetate (20 ml) is added followed by pH 4.5 phosphate buffer (8 ml). The organic layer is washed with additional buffer (two 8 ml portions), 5% sodium bicarbonate solution (three 10 ml portions), 50% sodium chloride solution (10 ml), saturated sodium chloride solution (10 ml) and dried (Na2SO4). Filtration and concentration in vacuo yields 500 mg of oil which is flash. chromatographed with 5% ethyl acetate-hexane, yielding the title compound (253 mg). C) (#)-(trans)-3-zaido-2-oxo-4-phenyl-1-azetidine A solution of 17 g of crude C+)-(trans)-3- azido-2-oxo-4-phenyl-l-azetidine-tert butyldiphenylsilane is dissolved in methanol (240 ml) and treated dropwise at C with concentrated EC1 (35 mll. The cooling bath is removed, the reaction stirred at ambient temperature for 1 hour, and recooled to 0 C whereupon saturated sodium bicarbonate solution is added to neutrality. The resulting mixture is extracted with ethyl acetate (one 300 ml portion and four 100 ml portions) and the organic extracts are washed with 1:1 5% sodium bicarbonate 50% sodium chloride solution, saturated sodium chloride solution, and dried (Na2SO4). Filtration and concentration in vacuo yields 15 g of a heavy oil which is chromatographed on 100 g of silica gel with 20% ethyl acetate-hexane, yielding 460 mg of the title compound. D) (#)-(trans)-3-azido-4-phenyl-1-azetidine- sulfonic acid, tetrabutylammonium salt A solution of (t)-(trans)-3-azido-2-oxo- 4-phenyl-1-azetidine (300 mg) in dimethylformamide (3 ml) is cooled to 0 C under argon and treated dropwise with a complex of dimethylformamide and sulfur trioxide (4.78 ml of a 0.5 M solution in dimethylformamide). The cooling bath is removed, the reaction mixture - is stirred-at ambient temperature for 2 hours and poured into 80 ml of O.S M monobasic potassium phosphate (pH 5,5). The solution is extracted with dichloromethane (discarded) and 541 mg of tetrabutylammonium bisulfate is added. The resulting mixture is extracted with dichloromethane and the organic extracts are washed with 10% sodium chloride solution and dried (Na2SO4). Filtration and concentration in vacuo affords 800 mg of oil; approximately 40% the desired product, the remainder dimethylformamide. This mixture is used without purification in the next step. E) (t) - (trans) -3-amino-4-phenyl-l-azetidine- sulfonic acid A solution of (+)-(trans)-3-amino-4-phenyl- l-azetidinesulfonic acid, tetrabutylammonium salt in 4 ml of methanol is hydrogenated over 30 mg of platinum oxide at 1 atmosphere and room temperature. After 15 minutes, the system is evacuated and fresh hydrogen is introduced. After an additional 45 minutes the reaction is complete, and the system is flashed with nitrogen. After several days at room temperature in dichloromethane-methanol (4:1, 200 ml) catalyst aggregation is complete and filtration i accomplished. The filtrate is concentrated in vacuo to 18 ml and 0.2 ml of 97% formic acid is added. After cooling at 5 C for several hours the resulting solid. is filtered and washed with dichloromethane to afford, after drying, 150 mq of the title compound as a solid. Analysis calc'd for C9H1gN204S: C, 44.62; H, 4.17; N, 11.57; S, 13.23 Found: C, 43.36; H, 4.31; N, 11.09; S, 13.02 Example 43 (#)-(trans)-2-Oxo-4-phenyl-3-I-(phenylacetyl)amino]- 1-azetidinesulfonic acid, potassium salt A) (#)-trans-2-oxo-4-phenyl-3-I(phenylacetyl)amino]- 1-azetidinesulfonic acid tetrabutylammonium salt A solution of N-hydroxybenzotriazole monohydrate (52 mg) and phenylacetic acid C46 mg) in dimethylformamide (0.3 ml) is treated with solid dicyclohexylcarbodiimide (70 mg) under argon at OOC. The cooling bath is removed and the resulting mixture stirred at ambient temperature for 1 hour. After dilution with additional dimethylformamide (0.3 ml), (+)-(trans)-3-amino-2-oxo-4- phenyl-l-azetidinesulfonic acid is added as a solid (75 mg, see example 181) followed by triethylamine (0.05 ml) dropwise. The reaction is stirred at ambient temperature for 23 hours, filtered and the filter cake washed with dimethylformamide. The filtrate was added to 20 ml 0.5 monobasic potassium phosphate (pH 4.5), the mixture washed with three 8 ml portions of ethyl acetate (discard), and 105 mg of tetrabutylammonium bisulfate (0.31 mmole) is added. The resulting mixture is extracted with dichloromethane (three 15 ml portions). The extracts are washed with 10% sodium chloride solution (two 15 ml portions), saturated sodium chloride solution (10 ml) and dried (Na2SO4). Filtration and concentration in vacuo yields (after heating at 320C under high vacuum) 165 mg of oil; approximately 40% is the desired compound, and 608 dimethylformamide. B) (#)-trans-2-oxo-4-phenyl-3-[(phenylacetyl)- amino) -l-azetidinesuifonic acid, potassium salt A solution of L+)-trans-2-oxo-4-phenyl-3- [(phenylacetyl)amino]-1-azetidinesulfonic acid tetrabutylammonium salt in 1.5 ml acetone is treated with 41 mg (Q.121 mmole2 of potassium perfluorobutanesulfonate. Dilution with 12 ml of ether affords a glass, which upon trituration with ether affords 43 mg of solid which contains about 20% of an impurity containing a tetrabutylammonium moiety. The solid is dissolved in 50% aqueous acetone and passed through a Dowex 50W-X2 K# ion-exchange resin (1 ml). Removal of solvent yields a solid which is washed with acetone, hexane and dried (600C, high vacuum). The yield of the title compound is ]5 mg. Analysis calc2d for Cl7H15N205S*K: C, 51.23; H, 3.80; N, 7.03; S, 8.05; K, 9.81 Found: C, 50.44; H, 4.20; N, 7.01; S, 7.59; K, 9.40 Example 44 (#)-(trans,Z)-3-[[2-Amino-4-thiazolyl) (methoxyimino)- acetyl]amino]-2-oxo-4-phenyl-1-azetidinesulfonic acid, potassium salt A solution of N-hydroxybenzotriazole hydrate (52 mg) and (Z)-2-amino-a-(methoxyimino)-4thiazoleacetic acid (69 mg) in dimethylfurmamide (0.3 ml) is treated with solid dicyclohexylcarbodiimide (7Q mg) under argon, at ambient temperature. The resulting mixture is stirred for 1 hour, (3)-(trans)-3-amino-2-oxo-4-phenyl- l-azetidinesulfonic acid (75 mg; see example 181) is added as a solid, followed by triethylamine dropwise (0.05 ml). The reaction is stirred at ambient temperature for 23 hours. The dimethylformamide is removed under high vacuum at 30 C, and the residue triturated with 2'ml of acetone and filtered. The filter cake is washed with additional acetone (two 3 ml portions and potassium perfluorobutanesulfonate (86 mg) is added to the filtrate. Dilution with 10 ml of ether produces a gummy solid which is triturated, washed with acetone and hexane to yield, after drying, 82 mg of the title compound as a solid. Analysis for C15H14NSO6S2.K Calc'd: C, 40.26; H, 3.16; N, 15.65; S, 14.33; K, 8.74 Found: C, 38.60; H, 3.19; N, 15.07; S, 13.87; K, 7.5 Example 45 (cis) -2-Oxo-4-phenyl-3- I (phenylacetyl) amino] -1azetidinesulfonic acid, potassium salt A) N-Benzylidene-2,4-dimethoxybenzylamine 12.0 g of 2,4-dimethoxybenzylamine hydrochloride is added to 100 ml of 1N sodium hydroxide solution and the mixture is extracted with 125 ml of ethyl acetate. The organic layer is dried over anhydrous sodium sulfate and stripped of solvent to give 10.2 g of 2,4-dimethxybenzylamine as an oil. This amine is dissolved in 150 ml of Benzene; 6.47 g of benzaldehyde and 0.6 g of p-toluenesulfonic acid monohydrate are added. The mixture is heated under reflux removing water with a Dean-Stark separator and in two hours the calculated amount of water Cl.l ml) separates out. The mixture is cooled to room temperature. Upon further cooling the benzene solution deposits some precipitate. Benzene is removed under reduced pressure and 60 ml of petroleum ether is added to the residue. An oily- layer separates out with more precipitate. Benzene (10 ml) is added to make the layers homogeneous and the remaining precipitate is filtered. The filtrate is stripped of solvent to give 14.2 g of the title compound as an oil. B) (+)-(cis)-4-Phenyl-l-(2,4-dimethoxybenzyl)- 2-oxo-3-azidoazetidine v-Azidoacetic acid (1.62 g) is dissolved in 25 ml of methylene chloride under nitrogen. To this solution are added 3.24 g of triethylamine and 1.02 g.(4.0 mmole) of the imine N-benzylidene-2,4-dimethoxybenzylamine dissolved in 10 ml of methylene chloride. The mixture is cooled in an ice-bath and 3.36 g of trifluoroacetic anhydride is added slowly; the solution becomes dark colored. After stirring for 1 hour in an ice-bath, the mixture is warmed to room temperature and stirred an additional 15 minutes. The solution is then washed with water 0 ml), 5% NaHC03 solution (two 50 ml portions2, and 1N EC1 solution (60 ml). The organic layer is dried over anhydrous sodium sulfate and stripped of solvent to give 1.72 g of crude product as dark gum. The gum is treated with charcoal several times and the resulting brown mixture is chromatographed on 40 g silica gel eluting with 1:1 petroleum ether:ethyl acetate. The combined fractions yield crystal upon quick-freezing in a dry ice-acetone bath. Using this as a seed the product is recrystallized from petroleum ether-ethyl acetate to give 817 mg of the title compound as needles which melt upon warming to room temperature. C) (#)-(cis)-4-Phenyl-2-oxo-3-azidoazetidine (#)-[cis)-4-Phenyl-1-(2,4-dimethoxybenzyl)- 2-oxo-3-azidoazetidine (737 mg) is dissolved in 25 ml of acetonitrile and heated to 800-830C under nitrogen. To the resulting solution are added over a 1 hour period 943 mg of potassium persulfate and 570 mg of potassium monohydrogen phosphate, both dissolved in 25 ml of water. After the addition, the mixture is further heated at 800-830C for 7 hours. The mixutre is cooled and the pH is adjusted to 6-7 by adding solid potassium monohydrogen phosphate. Most of the acetonitrile is removed under reduced pressure and the resulting mixture is extracted with 60 ml of chloroform. The chloroform layer is washed with water (60 ml), dried over anhydrous sodium sulfate and stripped of solvent to give a crude product as an oil. The crude product is chromatogrpahed on 40 g of silica gel eluting with 1:1 petroleum ether-ethyl acetate. The combined fractions yield crystals and the product is recrystallized from petroleum etherethyl acetate to give 267 mg of the title compound. D) (#)-(cis)-4-Phenyl-2-oxo-3-azido-1-azetidine- sulfonic acid, tetrabutyl animoflium' salt (#)-(cis)-4-Phenyl-2-oxo-3-azidoazetidine (162 mg) is cooled to 0 C under nitrogen and 3.5 ml of ca . SM dimethylformamide-sulfur trioxide complex solution in dimethylformamide is added dropwise via syringe. The resulting clear solution is stirred at 0 C for 15 minutes. The mixture is then poured into 50 ml of 0.5M monobasic potassium phosphate solution and washed with methylene chloride (three 50 ml portions). tetra-n-Butylammonium bisulfate t292 mg) is added to the aqueous solution and the mixture is' extracted with methylene chloride (six 50 ml portions). The combined methylene chloride layers are dried over anhydrous sodium sulfate and stripped of solvent to give 272 mg of the title compound as a gum. E) (+)-(cis)-2-Oxo-4-phXenyl-3-I Whenylacetyl)amino]- l-azetidinesulfonic acid, 'potassium salt (#)-(cis)-4-Phenyl-2-oxo-3-azido-1-azetidine- sulfonic acid, tetrabutyl ammonium salt t293 mg) is dissolved in 4 ml of ethanol and hydrogenated with 8Q mg of platinum oxide catalyst at one atmosphere. After 1 hour stirring the catalyst is filtered through a Millipore filter with Celite; some catalyst particles pass through the filter to give a black filtrate. Ethanol is removed under reduced pressure and the residue is dissolved in 4 ml of dimethylformamide. N-Hydroxybenzotriazole "monohydrate (81 mg), 78 mg of phenylacetic acid, and 117 mg of dicyclohexylcarbodiimide are added and the mixture is stirred for about 16 hours under nitrogen. The slurry is evaporated in vacuo and triturated with 10 ml of acetone. The resulting slurry is filtered through a Millipore filter with a Celite top and the brown filtrate is treated with 193 mg of potassium perfluorobutane sulfonate. Upon adding 20 ml of ether a gum separates out. Liquid is removed and the gum is washed with ether. The gum is dissolved. in 10 ml of methanol. Upon adding ether, a small amount of precipitate is formed. The mixture is filtered and the colored filtrate -' is treated with more ether. The precipitate formed is filtered and recrystallized twice from ether-methanol to give 26 mg of the title compound. Analysis calc1d for C17H15O5N2SK2H2O: C, 46.99; H, 4.41, N, 6.45 Found: C, 47.24; H, 4.19; N, 6.34 Example 46 (cis, Z) -3-11 (2-Amino-4-thiazolyl) (methoxyimino)- acetyollamino]-2-oxo-4-phenyl-1-azetidinesulfonic acid, potassium salt (cis)-2-Oxo-4-phenyl-3-I(phenylacetyl)amino]l-azetidinesulfonic acid, potassium salt (56Q mg; see example 184, part Dl is dissolved in 5 ml of ethanol and hydrogenated with 110. mg of platinum oxide catalyst at one atmosphere. After one hour stirring the catalyst is filtered through a Nillipore filter with Celite; catalyst particles pass through the filter to give a black filtrate. Ethanol is removed under reduced pressure and the residue is dissolved in 4 ml of dimethylformamide. N-Hydroxybenzotriazole monohydrate (168 mg), 221 mg of the (Z)-2-amino-a-(methoxyimino)4-thiazoleacetic acid and 227 mg of dicyclohexylcarbodiimide are added and the mixture is stirred for about 16 hours under nitrogen. The slurry is evaporated in vacuo and triturated with 15-ml of acetone. The resulting slurry is filtered through a Millipore with Celite and the filtrate is treated with 372 mg of potassium perfluorobutane sulfonate. Upon adding 15 ml of ether a gum separates out. Liquid is removed and the gum is washed with ether. The gum is dissolved in 5 ml of water and applied on 150 ml of HP-20 resin eluting with water. Fractions (30 ml each) 16-34 are combined and lyophilized to give 201 mg of the title compound as a solid. Analysis calc'd for C15H14O6N5S2Kl1/2 H2O: C, 36.73; H, 3.49; N, 14.28; S, 13.07; K, 7.97 Found: C, 36.65; H, 3.00; N, 13.99; S, 13.48; K, 8.30 Example 47 (cis)-3-Amino-2-oxo-4-(2-phenylethenyl)-1azetidinesulfonic acid A) N-(3-phenyl-2-propenylidene)-4-methoxyaniline p-Anisidine c12.32 g) is dissolved in 160 ml of methylene chloride and 20 g of anhydrous magnesium sulfate is added. The mixture is cooled in an ice bath and 13.22 g of -transcinnamaldehyde is added. The mixture is stirred under nitrogen for 2 hours and then filtered. The filtrate is evaporated to give a solid. The crude product is recrystallized from methylene chloride-petroleum ether to give 20.96 y of the title compound as a solid. B) (#)-(cis)-3-Azido-1-(4-Methoxyphenyl)-2-oxo- 4- (2-phenylethenyl ) azetidine 2-Azidoacetic acid (24.26 g) is dissolved. in 100 ml of methylene chloride and cooled in an ice bath. To this solution is added 48.57 g of triethylamine and 14.24 g of N- (.'3-phenyl-2- propenylidene)-4-methoxyaniline dissolved in 250 ml of methylene chloride. To the resulting solution is added 50.41 g of trifluoroacetic anhydride dropwise over a one hour period. After stirring for one hour in an ice bath, the mixture is warmed to room temperature and stirred for about 16 hours. The mixture is then diluted with 250 ml of methylene chloride and washed with water (750 ml),, 5% sodium bicarbonate solution (two 750 ml portions), and 1N HC1 solution (75Q ml]. The organic layer is dried over anhydrous sodium sulfate and stripped of solvent to give a solid. The crude product is recrystallized from ethyl acetate to give 11.39 g of the title compound as a solid. Cl (#)-(cis)-3-Azido-2-oxo-4-(2-phenylethenyl) azetidine To a solution of 10.22 g of ceric ammonium nitrate in 13 ml of water at 0 C is added 1.99 g of (#)-(cis)-3-azido-1-(4-methoxyphenyl)-2-oxo- 4-(2-phenylethenyl)azetidine is dissolved in 65 ml of acetonitrile during a 15 minute period (additional 10 ml of acetonitrile is used for rinse). The mixture is stirred for an additional 15 minutes at O C, diluted with 750 ml of ethyl acetate, washed with water (six 600 ml portions), dried over anhydrous sodium sulfate, and stripped of solvent to give an oil. The crude product is chromatographed on 90 g of silica gel, eluting first with 250 ml of 30% ethyl acetate/petroleum ether, then 50% ethyl acetate/petroleum ether. Fractions (50 ml each) 11-16 are combined and evaporated to give 802 mg of the title compound as an oil. D) (#)-(cis)-3-Azido-2-oxo-4-(2-phenylethenyl)-1- azetidinesulfonic acid, tetra-n-butylammonium salt (#)-(cis)-3-Azido-2-oxo-4-(2-phenylethenyl)- azetidine (334 mgl is dissolved in 3 ml of dimethylformamide and 868 mg of pyridine-sulfur trioxide is added. The mixture is stirred at room temperature for 40 hours under nitrogen and then poured into 20Q ml of 0. .5 M monobasic potassium phosphate solution and washed with 30 ml of methylene chloride. tetra-n-Butyl ammonium bisulfate (530 mg) is added to the aqueous solution and the mixture is extracted with methylene chloride (four 50 ml portions). The combined organic layers are back-washed with water (two 100 ml portions), dried over anhydrous magnesium sulfate and stripped of solvent to give 824 ing of the title compound as a gum. E) (#)-(cis)-3-Azido-2-oxo-4-(2-phenylethenyl)-1- azetidinesulfonic acid (#)-(cis)-3-Azido-2-oxo-4-(2-phenylethenyl)- l-azetidinesulfonic acid, tetra-n-butylammonium salt (300 mg) is dissolved in 4 ml of tetrahydrofuran and stirred rapidly. To the mixture is added 600 mg of zinc dust followed by 0.8 ml of 1N monobasic potassium phosphate solution. The mixture is heated to 450C and stirred at this temperature for 3 hours. The mixture is then filtered and the filtrate is taken in 40 ml of methylene chloride and 10 ml of water. The aqueous layer is further extracted with methylene chloride (three 40 ml portions) and the cqmbined methylene chloride layers are stripped of solvent to give 256 mg of a foam. This crude product is dissolved in a small amount of ca. 30 acetone/water and applied on 7.5 ml of Dowex (K+) resin (0.7 meq./vnl) eluting with 4Q ml of water. The eluent is evaporated to give 151 mg of foam, which is dissolved in 2 ml of water and acidified to pH 2 with 1N EC1 solution. A small amount of acetonitrile is added to dissolve the precipitate and the resulting solution is applied on 15 ml of HP-20 resin, eluting with 150 ml of water, then 108 acetone/water. Fractions (15 ml each) 2-13 are combined and evaporated to give 101 mg of the title compound as a foam. Example 48 (#)-(cis, Z)-3-[[(2-Amino-4-thiazolyl) (methoxyimino)acetyljamino]-2-oxo-4-(2-phenylethenyl)-1-azetidine- sulfonic acid, potassium salt A solution of 68 mg of (Z)-2-amino-a (methoxyiinino)-4-thiazoleacetic acid and 51 mg of N-hydroxybenzotriazole.monohydrate in 2 ml of dimethylformamide is treated with 69 mg of dicyclohexylcarbodiimide. The mixture is stirred at room temperature for 30 minutes under nitrogen. [cis)-3-Amino-2-oxo-4-(2-phenylethenyl)-1azetidinesulfonic acid (90 mg; see example 186) and 34 mg of triethylamine are added and the mixture is stirred for 20 hours under nitrogen. The slurry is evaporated in vacuo and triturated with 10 ml of acetone. The slurry is filtered and the filtrate is treated with 113 mg of potassium perfluorobutanesulfonate. Dilution with 30 ml of ether and filtration gives 169 mg of a solid product, which is dissolved in a small amount of ca. 10% acetonitrile/water and applied on 34 ml of HP-20 resin, eluting with 150 ml of water, then 10% acetone/water. Fractions (15 ml each) 16-19 are combined and stripped of solvent to give 11Q mg of the title compound as a solid. Analysis calc'd for C17H16O6N5S2KH2O: C, 40.23; H, 3.57; N, 13.80; S, 12.63; K, 7.70 Found: C, 40.03; H, 3.05; N, 13.61; S, 12.31; K, 7.56 Example 49 (cis ) -3-Ami no-4 -(methoxycqrbonyl ) -2 -oxo-l- azetidinesulfonic acid A) I(4-Methoxyphenyl.) imir;olacetic acid, methyl ester A dry 3-necked, 1 liter flask equipped with a nitrogen inlet and stirring bar is charged with 56.88 g of MgSO4 followed by a solution of recrystallized anisidine (19.43 g) in dichloromethane (250 ml). After cboling to 0 C a solution of methyl glyoxylate hemiacetal (19.92 g) in dichloromethane (250 ml) is added over 1.5 hours. After stirring an additional 20 minutes at 0 0C, the reaction mixture is suction filtered, dried over sodium sulfate, filtered and concentrated in vacuo to one-quarter volume. Hexane C300 ml) is added, and the solution is concentrated to an oil which semi-solidifies on standing under high vacuum at 50C. B) (cis)-3-(1,3-Dihydro-1,3-dioxo-2H-isoindol2-yl)-4-methoxycarbonyl-2-oxo-1-(4-methoxyphenyl) azetidine A dry 3-necked 500 ml flask equipped with stirring bar, addition funnel, septum and nitrogen inlet is charged with a solution of l(4-Methowy- phenyl)imino3acetic acid, methyl ester (21.09 g) in dichloromethane (150 ml) and cooled to OOC. Triethylamine (19.2 ml) 0.14 mole is added dropwise followed by a solution of (N-phthalimido)acetyl acid chloride (28.4 g) in dichloromethane (150 ml) over 1 hour. The resulting mixture is stirred for 1.5 hours at OOC, and diluted with 2.5 1 of dichloromethane. The organic solution is washed with pH 4.5 monobasic potassium phosphate (two 500 ml portions), 5% sodium bicarbonate (two 500 ml port' ions) , saturated sodium chloride solution (500 ml), and dried over sodium sulfate. Filtration and concentration in vacuo yields a solid which is washed with ethyl acetate, cold acetone and hexane to yield 18.65 g of product. C) (cis)-4-(metoxycarbonyl)-1-(4-methoxyphenyl)2-oxo-3-[[(phenylmethoxy) carbonyl]amino]azetidine A dry 500 ml flask equipped with nitrogen inlet, stirring bar, and septum was charged with 18.65 g of (cisr-3-(1,3-dioxo-2H-isoindol-2-yl)- 4-methOxycarbonyl-2-oxo-1-(4-methoxyphenyl)azetidine and 325 ml of dichloromethane. The resulting suspension is cooled to -30 C, and methyl hydrazine C3.52 mlI is added dropwise. The reaction is, warmed to a c and stirred for 1 hour. An additional 0.4 ml of methyl hydrazine is added and the mixture is stirred for 10 minutes. This sequence is repeated with a total of 2.9 equivalents of methyl hydrazine (7.7 ml) has been added. The solvent was removed in vacuo; 200 ml of fresh dichloromethane is added, and the mixture is again concentrated. This sequence was repeated two additional times, the resulting foam was dried under high volume for 20 minutes, redissolved in 225 ml dichloromethane, and allowed to stand at ambient temperature for about 16 hours during which time a considerable amount of solid precipitates. The mixture is filtered under nitrogen, the filtrate cooled to 0 0C (nitrogen atmosphere) and treated with di is opropyl ethyl amine (17 ml) followed by benzyl chloroformate (7 ml) dropwise. The reaction is stirred at 0 C for 30 minutes, then at ambient temperature for 1.5 hours. The mixture is washed with two 300 ml portions of pH 4.5 monobasic potassium phosphate buffer, 5% sodium bicarbonate (two 300 ml portions), saturated sodium chloride (300 ml), dried (sodium sulfate), and filtered. Concentration in vacuo, yields a foam which on trituration with ether yields 9..9 g of the title compound as a solid. D) (cis) -4- (Methoxycarbonyl ) -2-oxo-'3-i .ph.enyl- methoxy)carbonyl]amino]-1-azetidine A solution of ceric ammonium nitrate (8.59 g) in 60 ml of 1:1 acetonitrile-water is treated with a slurry of 2 g (cisl-4- (methoxycarbonyl }- -l - (4-me thoxyph enyl)-2 -oxo -3 - [[(phenylmethoxy)carbonyl]amino]azetidine in 50 ml acetonitrile over' 10 minutes. The reaction mixture is stirred an additional 10 minutes at ambient temperature and diluted with ethyl acetate (100 ml). The e separated aqueous layer is washed with ethyl acetate (three 40 ml portions) and the combined organic extracts are washed with 50% sodium bicarbonate (three 70 ml portions). The basic washings are back-washed with ethyl acetate (50 ml) and the combined organic extracts are washed with aqueous sodium sulfite, 5% aqueous sodium carbonate (100 ml), 5% sodium chloride solution (two 100 ml portions), saturated sodium chloride (two 50 ml portions), and stirred clear Darco G-60 charcoal for 30 minutes. Sodium sulfate is added, and the mixture is filtered and concentrated in vacuo to yield an oil which on trituration with ether yields 685 mg of the title compound as a solid. E) (cis)-4-(methoxycarbonyl)-2-oxo-3-[[(phenylmethoxy) carbonyl]amino]-1-azetidinesulfonic acid, tetrabutylammonium salt A mixture of (cis)-4-(methoxycarbonyl)-2- oxo-3- r r (phenylmethoxy) carbonyl] amino] -1-azetidine (100 mg) and 172 mg of a pyridine-sulfur trioxide complex in 1 ml of pyridine is stirred under argon for 3 hours at 80 C. The reaction mixture is poured into 70 ml of Q.5 M monobasic potassium phosphate (pH .5.5) and extracted with four 30 ml portions of dichloromethane (discard). Tetrabutylammonium hydrogen sulfate n22 mg) is added to the aqueous layer which is then extracted with dichloromethane (four 30 ml portions). The organic extracts are washed with 8% sodium chloride solution, dried over sodium sulfate and filtered,. Concentration in vacuo yields 186 mg of the title compound as a viscous oil. F) (cis)-3-Amino-4-(methoxycarbonyl)-2-oxo-1azetidinesulfonic acid A solution of 186 mg of (cis)-4-(methoxy carbonyl)-2-oxo-3- I r (phenylmethoxyXcarbonyl]amino]- l-azetidinesulfonic acid, tetrabutylammonium salt in 2 ml of methanol is hydrogenated over 10% palladium on charcoal (95 m) for 1.5 hours at 1 atmosphere. The catalyst is filtered off and rinsed with dichloromethane and the filtrate is treated with 97% formic acid and cooled to -500C (the presence of a seed crystal at this stage is necessary to induce crystallization). After crystallization commences, the mixture is allowed to stand for about 16 hours at 10 0C. The resulting solid is washed with dichloromethane, hexane, and dried in,vacuo, yielding 50 mg of the title compound. Example 50 (cis) -3- I I2-Amino-4-thiazo-lyl') [[1- (diphenyl- methoxycarbonyl)-1-methylethoxy] iminolacetyl]amino]-4-(methoxycarbonyl)-Z-oxo-1-azetidinesulfonic acid, potassium salt A solution of N-hydroxybenzotriazole hydrate (34 mg) and 101 mg of 2-amino-a-III-(diphenyl- methoxycarbonyl-l-methylethoxy7iminol-4 thiazoleacetic acid in 0.5 ml of dimethylformamide is treated with solid dicyclohexylcarbodiimide (45 mg) and the mixture is'stirred under argon for 45 minutes (ambient temperature). (cis)-3 Amino-4- (methoxycarbonyl) -2-oxo-l-azetidinesulfonic acid (45 mg; see example 188) is then added as a solid followed by triethylamine (0.03 m).) dropwise. The reaction is stirred at ambient temperature for about 16 hours. The dimethylformamide is removed under high vacuum at 30 0C and the residue is triturated with acetone. The supernatant is treated with potassium perfluorobutanesulfonate (67 mg). Dilution with ether produces a solid which is washed with ether and dried in vacuo to yield 93 mg of the title compound. Example 51 (cis)-3-[[(2-Amino-4-thiazolyl)](1-carboxy-1methylethoxylimino] acetyl] amino]-4-(methoxy carbonyl)-2-oxo-l-azetidinesulfonic acid, dipotassium salt A slurry of (isr-3-IZ2-Amino-4-"Jriazolyl)- [[1-(diphenylmethoxycarbonyl)-1-methylethoxylimino] acetyl] amino]-4-(methoxycarbonyl)-2-oxo-1azetidinesulfonic acid, potassium salt in Q.4 ml of anisole is stirred at -120C under argon, and 0.9 ml of cold (-10 C) trifluoroacetic acid is added. After 1.5 hours, 4 ml of ether and 2 ml of hexane are added and the resulting slurry is stirred for 15 minutes at -100C, then 15 minutes at ambient temperature. The solid is isolated by centrifugation and washed with ether. The pH of a suspension of this material in O.5 ml of cold water is adjusted to 6 with 1N potassium hydroxide and then applied to a 30 ml HP-2OAG column. Elution with water yields 30 mg of the title compound after evaporation (acetonitrile added and evaporated twice). Analysis calc'd for C14H15X2N509S2: C, 31.15, H, 2.81; N, 12.98 Found: C, 29.08; H, 3.03; N, 12.19 Example 52 [3S]-3-[3,6-dichlorophenylthioacetylamino]-2-oxo-1azetidinesulfonic acid, potassium salt Following the procedure, of example 4, utilizing 3,6-dichlorophenylthioacetic acid instead of the acid used therein yields the titled compound. Example 53 (cis)-4-methyl-2-oxo-3-[(3,6-dichlorophenylthioacetyl) amino1-l-azetidinesulfonic acid, potassium salt Following the procedure of example 4, utilizing 3,6-dichlorophenylthioacetic acid instead of the acid used therein yields the titled compound. Example 54 (cis)-4-methyl-2-oxo-3-[(N,N'-diisopropylisothiouronium- acetyl) amino]-1-azetidinesulfonic acid, potassium salt Following the procedure of example 4, utilizing N,N'-diisopropyl-isothiouronium-acetic acid instead of the acid used therein yields the titled compound. Biological Activity The following methodology is used to determine the minimum inhibitory concentration (hereinafter referred to. as MIC) of the B-lactams of this invention. The test organisms are grown in approximately 15-20 ml of Antibiotic Assay broth (Difco) by inoculating (in tubes) the broth with a loopful of the organism from a BHI (Difco) agar slant. The inoculated tubes are incubated at 37 0C for 18 to 20 hours. These cultures are assumed to contain 109 colony forming units (hereinafter CFU) per milliliter. The cultures are diluted 1:100 to give a final inoculum level of 104 CFU; dilutions are made with K-10 broth*. The compounds are dissolved in the appropriate diluent at a concentration of 1000 ug/ml. Twofold dilutions are made in K-10 broth resulting in a range from 1000 g/ml to 0.5 vg/ml. 1.5 ml of each dilution is placed into individual square petri dishes to which 13.5 tal of K-10 agar** is added. The final drug concentration in the agar ranges from 100-g/ml to 0.05 pg/ml. Organism growth control plates containing agar only are prepared and inoculated before and after the test plates. The organisms are applied to the agar surface of each plate with the Denley Multipoint Indculator (which delivers approximately 0.001 ml of each organism) resulting in a final inoculum level of 104 CFU U on the agar surface. The plates are incubated at 370C for 18 hours and the MIC's are determined. The MICis the lowest concentration of compound inhibiting growth of the organism. *,K-l0 broth is a yeast beef broth containing: # Beef extract 1.5 g -Yeast extract 3.0 g Peptone 6.0 g Dextrose 1.0 g Distilled water q.s. 1 liter **K-l0 agar Beef extract 1.5 g Yeast extract 3.0 g Peptone 6.0 g Dextrose 1.0 g Agar 15.0 g Distilled water q.s. 1 liter The tables that follow are tabulated results obtained when the B-lactams of this invention are tested against various organisms. The number following each organism refers to the number of the organism in the collection of E. R. Squibb & BR< Sons, Inc., Princeton, New Jersey. A dash (-) in the tables means that the compound tested did not show activity against the particular organism at 100 g/ml. The symbol "N.T." means not tested. M.I.C. ( g/ml) Product of Example EMI112.1 Organism <tb> 1 <SEP> 2 <SEP> 3 <SEP> 4 <SEP> 5 <SEP> 6 <SEP> 7 <tb> Staphylococcus <SEP> aureus, <SEP> 1276 <SEP> 100 <SEP> 100 <SEP> 50 <SEP> 25 <SEP> 100 <SEP> - <SEP> 100 <tb> Staphylococcus <SEP> aureus, <SEP> 2399 <SEP> 50 <SEP> 100 <SEP> 50 <SEP> 25 <SEP> 100 <SEP> - <SEP> 100 <tb> Staphylococcus <SEP> aureus, <SEP> 2400 <SEP> 50 <SEP> 100 <SEP> 50 <SEP> 50 <SEP> 50 <SEP> - <SEP> 50 <tb> Staphylococcus <SEP> aureus, <SEP> 10165 <SEP> 100 <SEP> - <SEP> 100 <SEP> 100 <SEP> - <SEP> - <SEP> Streptococcus <SEP> faecalis, <SEP> 9011 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> Streptococcus <SEP> agalactiae, <SEP> 9287 <SEP> 100 <SEP> 100 <SEP> 25 <SEP> 12.5 <SEP> 3.1 <SEP> 50 <SEP> 3.1 <tb> Micrococcus <SEP> luteus, <SEP> 2495 <SEP> - <SEP> 100 <SEP> 25 <SEP> 50 <SEP> 3.1 <SEP> 12.5 <SEP> 6.3 <tb> Escherichia <SEP> coli, <SEP> 8294 <SEP> - <SEP> - <SEP> 100 <SEP> 100 <SEP> 0.1 <SEP> 0.4 <SEP> 0.2 <tb> Escherichia <SEP> coli, <SEP> 10857 <SEP> - <SEP> - <SEP> 50 <SEP> 50 <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <tb> Escherichia <SEP> coli, <SEP> 10896 <SEP> - <SEP> - <SEP> 50 <SEP> 100 <SEP> 0.1 <SEP> 0.2 <SEP> 0.2 <tb> Escherichia <SEP> coli, <SEP> 10909 <SEP> - <SEP> - <SEP> 25 <SEP> 50 <SEP> < 0.05 <SEP> < 0.05 <SEP> 0.1 <tb> Klebsiella <SEP> aerogenes, <SEP> 10440 <SEP> - <SEP> - <SEP> 100 <SEP> - <SEP> 0.2 <SEP> 0.4 <SEP> 0.4 <tb> Klebsiella <SEP> pneumoniae, <SEP> 9527 <SEP> - <SEP> - <SEP> 100 <SEP> 100 <SEP> 0.1 <SEP> < 0.05 <SEP> 0.1 <tb> Proteus <SEP> mirabilis, <SEP> 3855 <SEP> - <SEP> - <SEP> 100 <SEP> - <SEP> 0.1 <SEP> < 0.05 <SEP> < 0.05 <tb> Proteus <SEP> rettgeri, <SEP> 8479 <SEP> - <SEP> - <SEP> 50 <SEP> 100 <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <tb> Proteus <SEP> vulgaris, <SEP> 9416 <SEP> - <SEP> - <SEP> 100 <SEP> - <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <tb> Salmonella <SEP> typhosa, <SEP> 1195 <SEP> - <SEP> - <SEP> 50 <SEP> 100 <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <tb> Shigella <SEP> sonnei, <SEP> 8449 <SEP> - <SEP> - <SEP> 50 <SEP> 100 <SEP> 0.1 <SEP> 0.2 <SEP> 0.2 <tb> Enterobacter <SEP> cloacae, <SEP> 8236 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> 0.2 <SEP> 0.4 <SEP> 0.2 <tb> Enterobacter <SEP> aerogenes, <SEP> 10078 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> 0.4 <SEP> 0.4 <SEP> 0.4 <tb> Citrobacter <SEP> freundii, <SEP> 9518 <SEP> - <SEP> - <SEP> 100 <SEP> - <SEP> 0.1 <SEP> 0.4 <SEP> 0.2 <tb> Serratia <SEP> marcescens, <SEP> 9783 <SEP> - <SEP> - <SEP> 50 <SEP> - <SEP> 0.8 <SEP> 0.2 <SEP> 0.4 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 9545 <SEP> - <SEP> - <SEP> 50 <SEP> - <SEP> 0.8 <SEP> 0.8 <SEP> 0.8 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 8329 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> 100 <SEP> 3.1 <SEP> Acinetobacter <SEP> calcoaceticus, <SEP> 8333 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> 12.5 <SEP> 100 <SEP> 50 <tb> M.I.C. ( g/ml) Product of Example EMI113.1 Organism <tb> 9 <SEP> 11 <SEP> 12 <SEP> 13 <SEP> 14 <SEP> 15 <SEP> 16 <tb> Staphylococcus <SEP> aureus, <SEP> 1276 <SEP> 100 <SEP> 25 <SEP> 25 <SEP> 25 <SEP> 50 <SEP> 6.3 <SEP> Staphylococcus <SEP> aureus, <SEP> 2399 <SEP> 50 <SEP> 25 <SEP> 50 <SEP> N.T. <SEP> 50 <SEP> 6.3 <SEP> Staphylococcus <SEP> aureus, <SEP> 2400 <SEP> 50 <SEP> 25 <SEP> 50 <SEP> 12.5 <SEP> 100 <SEP> 12.5 <SEP> Stophylococcus <SEP> aureus, <SEP> 10165 <SEP> - <SEP> - <SEP> - <SEP> 25 <SEP> - <SEP> 50 <SEP> Streptococcus <SEP> faecalis, <SEP> 9011 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> Streptococcus <SEP> agalactiae, <SEP> 9287 <SEP> 1.6 <SEP> 0.4 <SEP> 6.3 <SEP> 25 <SEP> 3.1 <SEP> 0.8 <SEP> 50 <tb> Micrococcus <SEP> luteus, <SEP> 2495 <SEP> 6.3 <SEP> 6.3 <SEP> 6.3 <SEP> 3.1 <SEP> 12.5 <SEP> 1.6 <SEP> 25 <tb> Escherichia <SEP> coli, <SEP> 8294 <SEP> 0.1 <SEP> 1.6 <SEP> 1.6 <SEP> 1.6 <SEP> 1.6 <SEP> 50 <SEP> 0.4 <tb> Escherichia <SEP> coli, <SEP> 10857 <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <SEP> 1.6 <SEP> 0.4 <SEP> 0.4 <SEP> 0.2 <tb> Escherichia <SEP> coli, <SEP> 10896 <SEP> 0.1 <SEP> 0.4 <SEP> 1.6 <SEP> 1.6 <SEP> 1.6 <SEP> 6.3 <SEP> 0.2 <tb> Escherichia <SEP> coli, <SEP> 10909 <SEP> < 0.05 <SEP> 0.1 <SEP> 0.1 <SEP> 0.8 <SEP> 0.8 <SEP> 6.3 <SEP> < 0.05 <tb> Klebsiella <SEP> aerogenes, <SEP> 10440 <SEP> 0.2 <SEP> 0.8 <SEP> 1.6 <SEP> 1.6 <SEP> 3.1 <SEP> - <SEP> 0.8 <tb> Klebsiella <SEP> pneumoniae, <SEP> 9527 <SEP> < 0.05 <SEP> 0.1 <SEP> 0.1 <SEP> 1.6 <SEP> 1.6 <SEP> 12.5 <SEP> 0.1 <tb> Proteus <SEP> mirabilis, <SEP> 3855 <SEP> < 0.05 <SEP> 0.4 <SEP> 0.4 <SEP> 1.6 <SEP> 0.8 <SEP> 6.3 <SEP> < 0.05 <tb> Proteus <SEP> rettgeri, <SEP> 8479 <SEP> < 0.05 <SEP> 0.4 <SEP> 0.4 <SEP> 0.1 <SEP> 0.8 <SEP> 1.6 <SEP> < 0.05 <tb> Proteus <SEP> vulgaris, <SEP> 9416 <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <SEP> 0.8 <SEP> 0.8 <SEP> 1.6 <SEP> < 0.05 <tb> Salmonella <SEP> typhosa, <SEP> 1195 <SEP> < 0.05 <SEP> 0.2 <SEP> 0.2 <SEP> 0.8 <SEP> 0.8 <SEP> 6.3 <SEP> < 0.05 <tb> Shigella <SEP> sonnei, <SEP> 8449 <SEP> 0.1 <SEP> 0.4 <SEP> 0.8 <SEP> 1.6 <SEP> 0.8 <SEP> 25 <SEP> 0.4 <tb> Enterobacter <SEP> cloacae, <SEP> 8236 <SEP> 0.1 <SEP> 0.8 <SEP> 1.6 <SEP> 1.6 <SEP> 3.1 <SEP> 25 <SEP> 0.8 <tb> Enterobacter <SEP> aerogenes, <SEP> 10078 <SEP> 0.2 <SEP> 1.6 <SEP> 3.1 <SEP> 3.1 <SEP> 3.1 <SEP> 100 <SEP> 0.8 <tb> Citrobacter <SEP> freundii, <SEP> 9518 <SEP> 0.1 <SEP> 0.8 <SEP> 1.6 <SEP> 0.8 <SEP> 1.6 <SEP> 25 <SEP> 0.8 <tb> Serratia <SEP> marcescens, <SEP> 9783 <SEP> 0.2 <SEP> 0.8 <SEP> 1.6 <SEP> 0.8 <SEP> 3.1 <SEP> 50 <SEP> 0.4 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 9545 <SEP> 0.4 <SEP> 1.6 <SEP> 0.8 <SEP> 6.3 <SEP> 3.1 <SEP> 12.5 <SEP> 0.8 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 8329 <SEP> 100 <SEP> 12.5 <SEP> 12.5 <SEP> - <SEP> 100 <SEP> - <SEP> 3.1 <tb> Acinetobacter <SEP> calcoaceticus, <SEP> 8333 <SEP> 25 <SEP> 12.5 <SEP> 12.5 <SEP> 12.5 <SEP> 100 <SEP> - <SEP> 50 <tb> M.I.C. ( g/ml) Product of Example Organism EMI114.1 20 <SEP> 21 <SEP> 22 <SEP> 23 <SEP> 25 <SEP> 26 <SEP> 27 <tb> Staphylococcus <SEP> aureus, <SEP> 1276 <SEP> 6.3 <SEP> 3.1 <SEP> 6.3 <SEP> - <SEP> - <SEP> - <SEP> Staphylococcus <SEP> aureus, <SEP> 2399 <SEP> 6.3 <SEP> 3.1 <SEP> 6.3 <SEP> - <SEP> - <SEP> - <SEP> Staphylococcus <SEP> aureus, <SEP> 2400 <SEP> 25 <SEP> 6.3 <SEP> 25 <SEP> - <SEP> - <SEP> - <SEP> Staphylococcus <SEP> aureus, <SEP> 10165 <SEP> - <SEP> 100 <SEP> 100 <SEP> - <SEP> - <SEP> - <SEP> Streptococcus <SEP> faecalis, <SEP> 9011 <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> - <SEP> Streptococcus <SEP> agalactiae, <SEP> 9287 <SEP> 3.1 <SEP> 0.4 <SEP> 6.3 <SEP> 12.5 <SEP> - <SEP> - <SEP> 12.5 <tb> Micrococcus <SEP> luteus, <SEP> 2495 <SEP> 3.1 <SEP> 3.1 <SEP> 6.3 <SEP> 12.5 <SEP> - <SEP> - <SEP> 100 <tb> Escherichia <SEP> coli, <SEP> 8294 <SEP> 3.1 <SEP> 1.6 <SEP> 3.1 <SEP> 0.2 <SEP> 50 <SEP> - <SEP> 6.3 <tb> Escherichia <SEP> coli, <SEP> 10857 <SEP> < 0.05 <SEP> < 0.05 <SEP> 0.1 <SEP> 0.1 <SEP> 6.3 <SEP> 50 <SEP> 3.1 <tb> Escherichia <SEP> coli, <SEP> 10896 <SEP> 0.8 <SEP> 0.4 <SEP> 1.6 <SEP> 0.2 <SEP> 25 <SEP> - <SEP> 3.1 <tb> Escherichia <SEP> coli, <SEP> 10909 <SEP> 0.4 <SEP> 0.2 <SEP> 0.4 <SEP> N.T. <SEP> 25 <SEP> - <SEP> 1.6 <tb> Klebsiella <SEP> aerogenes, <SEP> 10440 <SEP> 12.5 <SEP> 1.6 <SEP> 12.5 <SEP> 0.4 <SEP> 100 <SEP> - <SEP> 6.3 <tb> Klebsiella <SEP> pneumoniae, <SEP> 9527 <SEP> 0.4 <SEP> 0.2 <SEP> 0.1 <SEP> 0.05 <SEP> 6.3 <SEP> - <SEP> 6.3 <tb> Proteus <SEP> mirabilis, <SEP> 3855 <SEP> 1.6 <SEP> 0.8 <SEP> 0.4 <SEP> 0.05 <SEP> 12.5 <SEP> - <SEP> 3.1 <tb> Proteus <SEP> rettgeri, <SEP> 8479 <SEP> 1.6 <SEP> 1.6 <SEP> 0.2 <SEP> 0.05 <SEP> 0.8 <SEP> 100 <SEP> 0.4 <tb> Proteus <SEP> vulgaris, <SEP> 9416 <SEP> < 0.05 <SEP> < 0.05 <SEP> < 0.05 <SEP> 0.05 <SEP> 12.5 <SEP> 100 <SEP> 6.3 <tb> Salmonella <SEP> typhosa, <SEP> 1195 <SEP> 1.6 <SEP> 0.4 <SEP> 0.4 <SEP> 0.05 <SEP> 12.5 <SEP> - <SEP> 3.1 <tb> Shigella <SEP> sonnei, <SEP> 8449 <SEP> 1.6 <SEP> 0.8 <SEP> 1.6 <SEP> 0.1 <SEP> 25 <SEP> - <SEP> 3.1 <tb> Enterobacter <SEP> cloacae, <SEP> 8236 <SEP> 1.6 <SEP> 1.6 <SEP> 0.8 <SEP> 0.1 <SEP> 100 <SEP> - <SEP> 3.1 <tb> Enterobacter <SEP> aerogenes, <SEP> 10078 <SEP> 6.3 <SEP> 3.1 <SEP> 6.3 <SEP> 0.8 <SEP> 100 <SEP> - <SEP> 6.3 <tb> Citrobacter <SEP> freundii, <SEP> 9518 <SEP> 3.1 <SEP> 1.6 <SEP> 3.1 <SEP> 0.4 <SEP> 25 <SEP> - <SEP> 3.1 <tb> Serratia <SEP> marcescens, <SEP> 9783 <SEP> 3.1 <SEP> 3.1 <SEP> 6.3 <SEP> 0.2 <SEP> 100 <SEP> - <SEP> 3.1 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 9545 <SEP> 3.1 <SEP> 12.5 <SEP> 6.3 <SEP> 0.4 <SEP> - <SEP> - <SEP> 50 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 8329 <SEP> 100 <SEP> 12.5 <SEP> 12.5 <SEP> 1.6 <SEP> - <SEP> - <SEP> Acinetobacter <SEP> calcoaceticus, <SEP> 8333 <SEP> 50 <SEP> 50 <SEP> 12.5 <SEP> 25 <SEP> - <SEP> - <SEP> M.I.C. ( g/ml) Product of Example Organism EMI115.1 29 <SEP> 31 <SEP> 32 <tb> Staphylococcus <SEP> aureus, <SEP> 1276 <SEP> - <SEP> - <SEP> 25 <tb> Staphylococcus <SEP> aureus, <SEP> 2399 <SEP> - <SEP> - <SEP> 12.5 <tb> Staphylococcus <SEP> aureus, <SEP> 2400 <SEP> - <SEP> - <SEP> 25 <tb> Staphylococcus <SEP> aureus, <SEP> 10165 <SEP> - <SEP> - <SEP> Streptococcus <SEP> faecalis, <SEP> 9011 <SEP> - <SEP> - <SEP> Streptococcus <SEP> agalactiae, <SEP> 9287 <SEP> - <SEP> 100 <SEP> 6.3 <tb> Micrococcus <SEP> luteus, <SEP> 2495 <SEP> - <SEP> - <SEP> 6.3 <tb> Escherichia <SEP> coli, <SEP> 8294 <SEP> - <SEP> 0.4 <SEP> 3.1 <tb> Escherichia <SEP> coli, <SEP> 10857 <SEP> - <SEP> 0.2 <SEP> 0.4 <tb> Escherichia <SEP> coli, <SEP> 10896 <SEP> 100 <SEP> 0.1 <SEP> 12.5 <tb> Escherichia <SEP> coli, <SEP> 10909 <SEP> 100 <SEP> 0.1 <SEP> 0.8 <tb> Klebsiella <SEP> aerogenes, <SEP> 10440 <SEP> - <SEP> 0.8 <SEP> 1.6 <tb> Klebsiella <SEP> pneumoniae, <SEP> 9527 <SEP> 100 <SEP> 0.2 <SEP> 0.2 <tb> Proteus <SEP> mirabilis, <SEP> 3855 <SEP> - <SEP> 0.2 <SEP> 0.4 <tb> Proteus <SEP> rettgeri, <SEP> 8479 <SEP> - <SEP> 0.05 <SEP> 0.4 <tb> Proteus <SEP> vulgaris, <SEP> 9416 <SEP> - <SEP> 0.2 <SEP> 0.2 <tb> Salmonella <SEP> typhosa, <SEP> 1195 <SEP> - <SEP> 0.2 <SEP> 0.2 <tb> Shigella <SEP> sonnei, <SEP> 8449 <SEP> - <SEP> 0.4 <SEP> 6.3 <tb> Enterobacter <SEP> cloacae, <SEP> 8236 <SEP> - <SEP> 0.2 <SEP> 6.3 <tb> Enterobacter <SEP> aerogenes, <SEP> 10078 <SEP> - <SEP> 0.4 <SEP> 6.3 <tb> Citrobacter <SEP> freundii, <SEP> 9518 <SEP> - <SEP> 0.2 <SEP> 3.1 <tb> Serratia <SEP> marcescens, <SEP> 9783 <SEP> - <SEP> 0.4 <SEP> 3.1 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 9545 <SEP> - <SEP> 0.8 <SEP> 6.3 <tb> Pseudomonas <SEP> aeruginosa, <SEP> 8329 <SEP> - <SEP> 12.5 <SEP> 50 <tb> Acinetobacter <SEP> calcoaceticus, <SEP> 8333 <SEP> - <SEP> 100 <SEP> 50 <tb>

Claims: What is claimed is: 1. A ss-lactam having sulfonic acid salt substituent -SO3#M# wherein M is hydrogen or a cation in the 1-position and having one or two alkyl, cycloalkyl, phenyl or substituted phenyl substituents in the 4-position or a single alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2phenylethenyl or 2-phenylethynyl substituent in the 4-position and an amino substituent -NH2 or a protected form thereof in the 3-position. 2. A ss-lactam in accordance with claim 1 having a sulfonic acid salt substituent -SO3#m wherein M# is hydrogen or a cation in the 1position, an amino substituent -NH2 -in the 3-position and an alkyl substituent in the 4-position. 3. A S-lactam in accordance with claim 2 having a sulfonic acid salt substituent 3. wherein M is hydrogen or a cation in the 1position, an amino substituent -NH2 in the 3-position and a methyl substituent in the 4-position. 4. A ss-lactam in accordance with claim 1 having the formula EMI116.1 wherein R2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R3 and R4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl ; and M# is hydrogen or a cation. 5. A ss-lactam in accordance with claim 4 wherein R2 is hydrogen. 6. A ss-lactam in accordance with claim 5 wherein R3 and R4 are methyl. 7. A ss-lactam in accordance with claim 5 wherein one of R3 and R4 is hydrogen. 8. A ss-lactam in accordance with claim 5 wherein R3 is hydrogen and R4 is methyl. 9. A ss-lactam in accordance with claim 5 wherein R3 is methyl and R4 is hydrogen. 10. A ss-lactam in accordance with claims 4 through 9 wherein the amino substituent (NH2-) in the 3-position is protected. 11. A ss-lactam in accordance with claim 10 wherein the amino substituent is in the form of an azido group. 12. A ss-lactam in accordance with claim 11 having the formula EMI117.1 wherein one of R3 and R4 is hydrogen and the other is alkyl and M# is hydrogen or a cation. 13. A. ss-lactam according to claim 12 wherein one of R3 and R4 is hydrogen and the other is methyl. 14. A ss-lactam having a sulfonic acid salt substituent -S03M wherein M is hydrogen or a cation in the 1-position and an acylamino substituent in the 3-position. 15. A ss-lactam in accordance with claim 14 having a sulfonic acid salt substituent -SO3#M# wherein My is hydrogen or a cation in the 1position, an acylamino substituent in the 3position and an alkyl substituent in the 4position. 16. A ss-lactam in accordance with claim 14 having a sulfonic acid salt substituent -SO3#M# wherein M is hydrogen or a cation in the 1position, an acylamino substituent in the 3-position and a methyl substituent in the 4-position. 17. A ss-lactam in accordance with claim 14 having the formula EMI118.1 wherein R1 is acyl; R2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R3 and R4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl or 2-phenylethynyl; and M is hydrogen or a cation. 18. A ss-lactam in accqrdance with claim 17 wherein R2 is hydrogen. 19. A ss-lactam in accordance with claim i8 wherein R3 and R4 are methyl. 20. A ss-lactam in accordance with claim 18 wherein one of R3 and R4 are hydrogen. 21. A ss-lactam in accordance with claim 18 wherein R3 is hydrogen and R4 is methyl. 22. A ss-lactam in accordance with claim 18 wherein R3 is methyl and R4 is hydrogen. 23. A ss-lactam in accordance with claims 17 through 22 wherein R1 is an aliphatic group having the formula EMI119.1 wherein R5 is alkyl; cycloalkyl; alkoxy; alkenyl; cycloalkenyl; cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups. 24. A ss-lactam in accordance with claims 17 through 22 wherein R1 is a carbocyclic aromatic group having the formula EMI120.1 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 carbons atoms, alkoxy of 1 to 4 carbon atoms or aminomethyl; and R9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrozino, alkylhydrazino, phenylhydrazino, or [(alkylthio)thioxomethyl]thio. 25. A ss-lactam in accordance with claims 17 through 22 wherein R1 is a heteroaromatic group having the formula EMI121.1 wherein n is 0, 1, 2 or 3; R9 is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino or l(alkylthio)- thioxomethyl]thio; and R10 is a substituted or unsubstituted 5-,6- or 7-membered heterocyclic aromatic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms. 26. A S-lactam in accordance with claims 17 through 22 wherein R1 is a group having the formula EMI122.1 wherein R11 is (i) a group having the formula EMI122.2 wherein 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, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R12 is -N=CH-R11, EMI122.3 alkylcarbonylamino, alkyl or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups. 27. A 6-lactam in accordance with claims 17 through 22 wherein R1 is a group having the formula EMI122.4 wherein R11 is (i) a group having the formula EMI122.5 wherein R6, R7 and R8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy or 1 to 4 carbon"-' atoms or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R13 is hydrogen, alkyl, cycloalkyl, alkylamino- . carbonyl, EMI123.1 or alkyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, Rill, carboxyl, carboxyl salt, amido, alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy(phenyimethoxy)phosphinyl or dialkoxyphosphinyl substituents. 28. A 8-lactam in accordance with claims 17 through 22 wherein R1 is a group having the formula EMI123.2 wherein R11 is (i) a group having the formula EMI123.3 wherein R6, R7 and R8 each is independently hydrogen, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl or 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R14 is EMI123.4 wherein n is O, 1, 2 or 3, amino, alkylamino, (cyanoalkyl ) amino, amido, alkylamido, (cyanoalkyl) -amido EMI124.1 29. A ss-lactam in accordance with claims 17 through 22 wherein R1 is a group having the formula EMI124.2 wherein R11 is (i) a group having the formula EMI124.3 wherein 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, or Cii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R15 is hydrogen, alkylsul-fonyl, -N-CH-R11, EMI125.1 wherein R16 is hydrogen, alkyl, or halogen substituted alkyl, R11, alkyl, or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups. 30. A ss-lactam in accordance with claim 27 wherein R11 is 2-amino-4-thiazolyl. 31. A 6-lactam in accordance with claim 30 a salt of [3S-[3&alpha;(Z),4ss]]-3-[[(2-amino-4-thiazolyl)- (methoxyimino) acetyl]amino]-4-methyl-2-oxo-1 azetidinesulfonic acid. 32. A 6-lactam in accordance with claim 30 a salt of [3S-[3c(Z), ss]]-3-[[[(2-amino-4-thiazolyl)- (2 -amino-4 -thiazolyl acetyl] amino) -4-methyl - 2-oxo-l-azetidinesulfonic acid. 33. A B-lactam in accordance with claim 30 a salt of imino] [(1-carboxy-1-methylethoxy) iminolacetyl]amino] 4 -methyl-2-oxo-1-azetidinesulfonic acid. 34. A ss-lactam in accordance with claim 30 [3S-[3&alpha;(Z), 4ss]]-3-[[(2-amino-4-thiazolyl)[(1-carboxy- 1-methylethoxy) imino]acetyl]amino]-4-methyl-2 oxo-l-azetidinesulfonic acid, dipotassium salt. 35. A ss-lactam in accordance with claim 30 a salt of [3S-[3&alpha;(Z),4&alpha;]]-3-[[2-amino-4-thiazolyl)- methoxyimino) acetyl ] amino]-4-methyl-2-oxo-1- azetidinesulfonic acid. 36. A ss-lactam in accordance with claim 30 a salt of [3S-[3&alpha;(Z),4&alpha;]]-3-[[(2-amino-4-thiazolyl)- [(1-carboxy-1-methylethoxy) imino]acetyl]amino]-4 methyl-2-oxo-1-azetidinesulfonic acid. 37. A B-lactam in accordance with claim 29 wherein R1 is a group having the formula EMI126.1 38. A ss-lactam in accordance with claim 37 wherein R1 is a group having the formula EMI126.2 39. A ss-lactam in accordance with claim 37 a salt of [3S-[3&alpha;(R#),4ss]]-3-[[[[[3-[(2-furanyl- methylene) amino] -2-oxo-l-imidazolidinyl ] carboxyl amino] phenylacetyl] amino]-4-methyl-2-oxo-1azetidinesulfonic acid. 40. A ss-lactam in accordance with claim 37 a salt of [3S-[3&alpha;(R#),4&alpha;]]-3-[[[[[3-[(2-furanyl- methylene)amino]-2-oxo-1-imidazolidinyl]carbonyl]amino]phenylacetyl]amino]-4-methyl-2-oxo-1azetidinesulfonic acid. 41. A B-lactam in accordance with claim 26 wherein R1 is a group having the formula EMI127.1 42. A ss-lactam in accordance with claim 4i a salt of [3S-[3&alpha;(R*), 4ss]]-3-[[[[(4-ethyl-2,3- dioxo-1-piperazinyl) carbonyl] amino] phenylacetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid. 43. A ss-lactam in accordance with claim 41 a salt of [3S-[3&alpha;(R*), 4&alpha;]]-3-[[[[(4-ethyl-2,3- dioxo-l-piperazinyl) carbonyl) amino) phenylacetyl) - amino]-4-methyl-2-oxo-1-azetidinesulfonic acid. 44. A. compound according to claims 1 to 3 wherein the amino group is in the protected form of an azide (-N3). 45. A Flactam in accordance with claim 44 having a sulfonic' acid salt substituent -SO0M wherein M is hydrogen or a cation in the l-position, an azido substituent -N3 in the 3-position and an alkyl substituent in the 4-position. 46. A ss-lactam in accordance with claim 44 having a sulfonic acid salt substituent -SO3#M# wherein M# is hydrogen or a cation in the 1-position, an azido substituent -N3 in the 3-position and a cycloalkyl, phenyl or substituted phenyl substituent in the 4-position. 47. A 6-lactam in accordance with claim 44 having a sulfonic acid salt substituent -SOo wherein My is hydrogen or a cation in the l-position, an azido substituent -N3 in the 3-position and an alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl or 2-phenylethynyl substituent in the 4-position. 48. A ss-lactam in accordance with claim 45 having the formula EMI128.1 wherein R2 is hydrogen or alkoxy of 1 to 4 carbon atoms; R3 and R4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one of R3 and R4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-1-yl, alkyn-1-yl, 2-phenylethenyl or 2-phenylethynyl; and M# is hydrogen or a cation. 49. A compound of the formula EMI128.2 wherein R1, R3, R4 and M are as defined in claim 4, and V is a leaving group such as methanesulfonyl, benzenesulfonyl, toluenesulfonyl, chloro, bromo or iodo. 50. A compound of the formula EMI128.3 wherein R2, R3 and R4 are as defined in claim 4. 51. A compound of the formula EMI128.4 wherein R1, R3, R4 and M are as defined in claim 4. 52. A process for preparing a compound of the formula EMI129.1 wherein A is a protecting group and V, R3 and R4 and M are as defined in claim 49 which comprises sulfonating a compound of the formula EMI129.2 wherein the symbols are as defined above. 53. A compound of the formula EMI129.3 wherein the symbols are as defined in claim 52. 54. A compound of the formula EMI129.4 wherein R2, R3, R4 and M are as defined in claim 4. 55. A ss-lactam in accordance with claim 1 as named in any of the Examples. 56. A process for preparing a ss-lactam having a sulfonic acid salt substituent -SO wherein M is hydrogen or a cation, in the 1- position and an amino substituent -NH2 or a protected form thereof in the 3-position and having one or two alkyl, cycloalkyl, phenyl or substituted nenyl substituents in the 4-position or a single alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl or 2-phenylethynyl substituent in the 4-position by sulfonating a corresponding ss- lactam having a hydrogen substituent in the 1position and a protected amino substituent in the 3-position and removing said amino protecting group. 57. A process according to claim 56 wherein the amino substituent in the 3-position is acylated, said acyl group containing a basic function when M+is hydrogen and said acylation is effected either before or after the sulfonation reaction. 58. A process according to claims 56 and 57 wherein the product contains an alkyl substituent in the 4position. 59. A process according to claims 56 through 58 wherein the product is of the formula EMI130.1 wherein R1 is hydrogen or acyl or the group R1-NH- is protected amino R2 is hydrogen or C1-C4 alkoxy; R3 and R4 are the same or different and each is alkyl, cycloalkyl, phenyl or substituted phenyl, or one or R3 and R4 is hydrogen and the other is alkyl, cycloalkyl, phenyl, substituted phenyl, alkoxycarbonyl, alken-l-yl, alkyn-l-yl, 2-phenylethenyl or 2-phenylethynyl; and M+ is hydrogen or a cation and said sulfonation is effected on a compound of the formula EMI131.1 or a precursor compound of the formula EMI131.2 which is cyclized, said sulfonation reaction being effected either before or after said cyclization, R1:NH- in the reactants being a protected amino group or R1 being acyl; V being a leaving group such as methanesulfonyl, benzenesulfonyl, toluenesulfonyl, chloro, bromo or iodo; and R2, R3 and R-4 being as previously defined. 60. A process according to claim 59 wherein R1 is hydrogen or the group R1-NH- is a protected amino group. 61. A process according to claim 59wherein R1 is acyl. 62. A process according to claim wherein the acyl group is selected from the group consisting of (a) an aliphatic group having the formula EMI131.3 wherein R5 is alkyl; cycloalkyl; alkoxy, alkenyl; cycloalkenyl, cyclohexadienyl; or alkyl or alkenyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, or cyanomethylthio groups; (b) a carbocyclic aromatic group having the formula EMI132.1 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 [(alkylthio) thioxomethyl] thio; (c) a heteroaromatic group having the formula EMI133.1 wherein n is 0, 1 2 or 3; Rg is amino, hydroxyl, a carboxyl salt, protected carboxyl, formyloxy, a sulfo salt, a sulfoamino salt, azido, halogen, hydrazino, alkylhydrazino, phenylhydrazino or [(alkylthio) thioxomethyl] thio; and R10 is a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic aromatic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; (d) a group having the formula EMI133.2 wherein R11 is (i) a group having the formula EMI133.3 wherein R6, R7 and R8 each is independently hydrogen, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl or 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitr ogen, oxygen and sulfur atoms; and R12 is -N=CH-R11, EMI133.4 alkylcarbonylamino, alkyl or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto group (e) a group having the formula EMI134.1 wherein R11 is (i) a group having the formula EMI134.2 wherein 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, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and Rt is hvdroa en, alkyl, cycloalkyl, alkylaminocarbonyl, EMI134.3 or alkyl substituted with one or more halogen, cyano, nitro, amino, mercapto, alkylthio, Rill, carboxyl, carboxyl salt, amido, alkoxycarbonyl, phenylmethoxycarbonyl, diphenylmethoxycarbonyl, hydroxyalkoxyphosphinyl, dihydroxyphosphinyl, hydroxy (phenylmethoxy) phosphinyl or dialkoxyphosphinyl substituents; ; (f) a group having the formula EMI134.4 wherein R11 is (i) a group having the formula EMI134.5 wherein R6, R7 and R8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoromethyl, alkyl of 1 to 4 carbon atoms, alkoxy of i to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atoms; and R,14 is EMI135.1 wherein n is 0, 1,2 or 3, amino, alkylamino, (cyanoalkyl)amino, amido, alkylamido,, (cyanoalkyl)amido, EMI135.2 (g) a group hav EMI135.3 wherein the R11 EMI136.1 p having the formula wherein R6, R7 and R8 each is independently hydrogen, halogen, hydroxyl, nitro, amino, cyano, trifluoro methyl, alkyl of 1 to 4 carbon atoms, alkoxy of 1 to 4 carbon atoms, or aminomethyl, or (ii) a substituted or unsubstituted 5-, 6- or 7-membered heterocyclic ring containing 1, 2, 3 or 4 nitrogen, oxygen and sulfur atom ST and R15 is hydrogen, alkylsulfonyl, -N=CH-R11, EMI136.2 wherein R16 is hydrogen, alkyl, or halogen substituted alkyl, Rill, alkyl, or alkyl substituted with one or more halogen, cyano, nitro, amino or mercapto groups. 63. A process in accordance with claim 62 wherein Rli is 2-amino-4-thiazolyl. 64. A process in accordance with, claim 63 wherein the product is a salt of [3S-[3&alpha; (Z), 4ss]]-3-[[(2-amino- 4-thiazolyl) -methoxyimino) acetyl) amino] -4-methyl-2-oxo- l-azetidinesulfonic acid. 65. A process in accordance with claim 63 wherein the product is a salt of [3S-t 3a(Z), 4ss[[-3-[[[carboxy- methOxy)-imino](2-amino-4-thiazolyl)acetyl]amino]-4- methyl-2-oxo-l-azetidinesulfonic acid. 66. A process in accordance with claim 63 wherein the product is a salt of {3S-5a(Z), 4ss]]-3-[[ 4-thiazolyl)-[(1-carboxy-1-methylethoxy) imino] acetyl]amino]-4-methyl-2-oxo-1-azetidinesulfonic acid. 67. A process in accordance with claim 66 wherein the product is [3S-[3a(Z) ,4ss]]-3-[[(2-amino-4-thiazoXyl)- [(1-carboxy-1-methylethoxy) imino] acetyl] amino]-4-methyl2-oxo-l-azetidinesulfonic acid, dipotassium salt. 68. A process in accordance with claim 63 wherein the product is a salt of [3S- [3&alpha;(Z), 4&alpha;]-3-[[2-amino- 4-thiazolyl)-methoxyimino) acetyl] amino]-4-methyl-2-oxo l-azetidinesulfonic acid. 69. A process in accordance with claim 63 wherein the product is a salt of [3S-[3a(Z),4ct]]-3-[[(2-amino- 4-thiazolyl)-[(1-carboxy-1-methylethoxy) imino] acetyl] amino] -4-methyl-2-oxo-l-azetidinesulfonic acid. '70. A process in accordance with claim 62 wherein the product is a salt of [3S-[3&alpha;(R*) 4ss]]-3-[[[[[3-[(2- furanylmethylene) amino]-2-oxo-1-imidazolidinyl] carbonyl] amino] phenylacetyl] amino] -4-methyl-2-oxo-l-azetidine- sulfonic acid. 71. A process in accordance with -claim 62 wherein the product is a salt of [3S-[3ct(R*),4]-3-[[[[[3-[(2- furanylmethylene)amino]-2-oxo-1-imidazolidinyl]carbonyl] amino] -henylacetyl] amino] -4-methyl-2-oxo-l-azetidine- sulfonic acid. 72. A proc-ess in accordance with claim 62 wherein the product is a salt of [3S-[3a(R*) ,4ss] ] -3-[ [ [ [ (4-ethyl- 2,3-dioxo-1-piperazinyl) ca rbonyl] amino] phenylacetyl] amino]4-methyl-2-oxo-l-azetidinesulfonic acid. 73. A process in accordance with claim 62 wherein the product is a salt of [3S-[3a(R*),4a]]-3-[[[[(4- ethyl-2,3-dioxo-1-piperazinyl)carbonyl]amino]phenyl- acetyl] amino]-4-methyl-2-oxo-1-azetidinesulfonic acid. 74. A process according to the preceding claims wherein the sulfonation is effected by treatment with a sulfur trioxide complex or an equivalent sulfonating reagent. 75. A process according to claim 74 wherein the sulfonating complex is pyridine sulfur trioxide complex. 76. A process according to claim 19 wherein the sulfonating complex is dimethylformamide-sulfur trioxide complex. 77. A process according to claim 1 wherein the amino substituent in the 3-position is in the protected form of an azide. 78. A process according to claim 4 wherein the group R1-NH is an amino group in the protected form of an azide. 79. A process according to claims 22 and 23 wherein the azide protecting group is reduced to form the amino substituent (-NH2). 80. A process according to claims 56 and 59 wherein the amino protecting group is benzyloxycarbonyl or butyloxycarbonyl.' 81. A process according to claims 56, 58 and 59 wherein the product is of the formula EMI138.1 'wherein the various groups are as defined in claim 59 and the amino group can be in a protected form. 82. A process according to claim 59 wherein R2 is hydrogen and one of R3 and R4 is hydrogen and the other is alkyl. 83. A process according to claim 77 wherein the alkyl group is methyl. 84. A process according to the preceding claims wherein the cation M is a pyridinium ion or a tetrabutylammonium ion or a potassium ion.

Inventors: CIMARUSTI, CHRISTOPHER MICHAEL, FLOYD, DAVID MACK, FRITZ, ALAN WILLIAM, KOSTER, WILLIAM HENRY, PARKER, WILLIAM LAWRENCE, SLUSARCHYK, WILLIAM ALLEN, SYKES, RICHARD BROOK
Applicants: E.R. SQUIBB & SONS, INC.
Application year: 1981
Main classification: C07D205
IPC codes: C07F9, C07D205, C07F7, C12P17