Abstract: 7.beta.-Heterocyclicacetylamino-(and 7.beta.-heterocyclicthioacetamido)-3-chloro-3-cephem-4-carboxylic acids and pharmaceutically acceptable salts thereof, e.g., 7.beta.-[2-(2-aminothiazol-4-yl)acetamido]-3-chloro-3-cephem-4-carboxylic acid and salts thereof, exhibit surprising peroral bioavailability and are useful in a method for treating infections in man and animals and in formulations for oral administration.

Abstract: 7.beta.-[2-Amino-2-(benzothien-4,5,6, and 7-yl)acetylamino]-3-substituted-3-cepham-4-carboxylic acids and 7.beta.-[2-amino-2-(2,3-dihydrobenzothien-4,5,6, and 7 yl)acetylamino]-3H- or 3-substituted-3-cephem-4-carboxylic acids (1), e.g. 7.beta.-[2-amino-2-(benzothien-4-yl)acetylamino]-3-methyl-3-cephem-4-carbo xylic acid, are orally effective antibiotics. Also provided are benzothienyl oximino compounds, the corresponding 2,3-dihydro compounds (2) useful as intermediates to (1) and as antibiotics, as well as 7.beta.-(2,2-dialkyl-5-oxo-4-benzothienyl-1-imidazolidinyl)-3H-(3-substitu ted)-3-cephem-4-carboxylic acids and the corresponding 2,3-dihydro compounds (3) useful as antibiotics, and prepared with (1) by condensation with ketones. Pharmaceutical formulations of antibiotic compounds (1), (2), and (3) are provided.

Abstract: 7-(3-Benzothienyl)glycylamido cephalosporins have good gram positive activity and favorable pharmacokinetics and are orally effective.

Abstract: 7-Epi-3-exomethylenecephams are useful intermediates for synthesis of antibiotics.

Abstract: Aryl 4R[1-(2-N-3-methyl-4-al-Z-but-2-ene-oate)-2-oxo-3s-acylamino azetidinone]disulfides are prepared by reacting the corresponding 7.alpha.-acylamino-2.alpha.-alkoxy-3-methyl-3-cephem-4-carboxylates first with either phenylsulfenyl chloride or a monosubstituted-phenylsulfenyl chloride where the substituent is either chloro, methoxy, methyl or acetoxy. The disulfide compounds produced in this invention are intermediates in the synthesis of the 7.beta.-acylamino-7.alpha.-alkoxy-3-methyl 1-oxa .beta.-lactam acids, a class of antibiotic compounds.

Abstract: 4R, 4'R bis [1-(2-N-3-methyl-4-al-Z-but-2-ene-oate)-2-oxo-3S-acylamino azetidine]disulfide compounds are prepared by reacting the corresponding 7.alpha.-acylamino-2.alpha.-alkoxy-3-methyl-3-cephem-4-carboxylates first with an N-chloro halogenating agent, e.g., N-chlorosuccinimide, then with an aqueous suspension of mercury dichloride and cadmium carbonate. The disulfide compounds produced in this invention are intermediates in the synthesis of the biologically active 7.beta.-acyl-amino-7.alpha.-alkoxy-3-methyl 1-oxa .beta.-lactam antibiotic compounds.

Abstract: Process for 4-halo azetidinones of the formula ##STR1## wherein R.sub.1 is acylamino or diacylamino, X is chloro, bromo or iodo, and R is a carboxy-protecting group which comprises treating a 4-sulfinoazetidinone of the formula ##STR2## with positive halogen reagent, eg. N-chlorosuccinimide, N-bromosuccinimide, N-iodosuccinimide, hypohalite. The 4-haloazetidinones are useful intermediate for .beta.-lactam antibiotics.

Abstract: Novel beta-lactam compounds of the formula ##STR1## and process for their preparation in which a penicillin ester is reacted with a source of positive halogen to selectively open the thiazolidine nucleus of the penicillin.

Abstract: Azetidinone alcohol disulfides are synthesized by reduction of the corresponding aldehydes. The azetidinone alcohol disulfides are the substrates for a process which cyclizes these compounds to 1-oxa .beta.-lactam compounds, employing a cyclizing reagent chosen from the class consisting of divalent mercury salts or tri-valent phosphine compounds. The 1-oxa .beta.-lactam compounds produced by this process are intermediates in the synthesis of 1-oxa .beta.-lactam antibiotics.

Abstract: Aryl 4R[1-(2-N-3-methyl-4-al-Z-but-2-ene-oate)-2-oxo-3S-acylamino azetidinone]disulfides are prepared by reacting the corresponding 7.alpha.-acylamino-2.alpha.-alkoxy-3-methyl-3-cephem-4-carboxylates first with either phenylsulfenyl chloride or a monosubstituted-phenylsulfenyl chloride where the substituent is either chloro, methoxy, methyl or acetoxy. The disulfide compounds produced in this invention are intermediates in the synthesis of the 7.beta.-acylamino-7.alpha.-alkoxy-3-methyl 1-oxa .beta.-lactam acids, a class of antibiotic compounds.

Abstract: Azetidinone alcohol disulfides are synthesized by reduction of the corresponding aldehydes. The azetidinone alcohol disulfides are the substrates for a process which cyclizes these compounds to 1-oxa .beta.-lactam compounds, employing a cyclizing reagent chosen from the class consisting of divalent mercury salts or trivalent phosphine compounds. The 1-oxa .beta.-lactam compounds produced by this process are intermediates in the synthesis of 1-oxa .beta.-lactam antibiotics.

Abstract: 4R,4'R bis[1-(2-N-3-methyl-4-al-Z-but-2-ene-oate)-2-oxo-3S-acylamino azetidine]disulfide compounds are prepared by reacting the corresponding 7.alpha.-acylamino-2.alpha.-alkoxy-3-methyl-3-cephem-4-carboxylates first with an N-chloro halogenating agent, e.g., N-chlorosuccinimide, then with an aqueous suspension of mercury dichloride and cadmium carbonate. The disulfide compounds produced in this invention are intermediates in the synthesis of the biologically active 7.beta.-acylamino-7.alpha.-alkoxy-3-methyl 1-oxa .beta.-lactam antibiotic compounds.

Abstract: A penicillin sulfoxide ester is reacted with an N-chloro halogenating agent at a temperature of from about 75.degree. C. to about 135.degree. C. to produce a novel 2-chlorosulfinylazetidin-4-one intermediate. The intermediate can be treated with stannic chloride to produce a 3-exomethylenecepham sulfoxide.

Abstract: Penicillin sulfoxide derived azetidinone sulfinyl chlorides and related sulfinic acid derivatives are cyclized to 3-methylenecephams by reaction with Friedel-Crafts catalysts or metathetic cation forming agents.

Abstract: 7-Acylamido-3-hydroxy-3-cephem-4-carboxylic acid ester sulfoxides are chlorinated and reduced in a single step process with phosphorus trichloride in dimethylformamide to provide 7-acylamido-3-chloro-3-cephem-4-carboxylic acid ester sulfides.

Abstract: A novel 4-(2'-benzothiazolyldithio)-3-imidoazetidin-2-one of the formula ##STR1## in which X is chloro or bromo and R.sub.2 is methylene or oxygen is ring-closed to the corresponding 3-exomethylenecepham or 3-"oxo" cepham by treatment with sodium or potassium iodide at a temperature of from about 40.degree. C. to about 80.degree. C.

Abstract: A penicillin sulfoxide ester is reacted with an N-chloro halogenating agent at a temperature of from about 75.degree. C. to about 135.degree. C. to produce a novel 2-chlorosulfinylazetidin-4-one intermediate. The intermediate can be treated with stannic chloride to produce a 3-exomethylenecepham sulfoxide.

Abstract: Penicillin sulfoxide derived azetidinone sulfinyl chlorides and related sulfinic acid derivatives are cyclized to 3-methylenecephams by reaction with Friedel-Crafts catalysts or metathetic cation forming agents.

Abstract: 3-Hydroxycephalosporins are prepared by treating a 3-hydroxy-4-bromo-2-(2-formylthio-4-oxo-3-amido or imido-1-azetidinyl)-2-butenoate ester with 1,5-diazabicyclo[3.4.0]non-5-ene (DBN) or 1,5-diazabicyclo[5.4.0]undec-5-ene (DBU) at a temperature of from about 0.degree. C. to about 25.degree. C.

Abstract: 7-Acylamido-3-exomethylenecepham ester sulfoxides are reacted with ozone to provide the corresponding 3-hydroxy-3-cephem ester sulfoxides, intermediates for 3-methoxy and 3-halo substituted cephalosporin antibiotics; e.g., p-nitrobenzyl 7-phenoxyacetamido-3-exomethylenecepham-4-carboxylate-1-oxide provides the corresponding 3-hydroxy-3-cephem ester sulfoxide.