Abstract: A cephalosporin derivative of the formula I: ##STR1## in which X is S, O, CH.sub.2 or SO, ##STR2## represents one of the C-7 acyl groups known in the cephalosporin art, R3 is hydrogen or methoxy, R4 is hydrogen, optionally substituted alkyl, allyl, furfuryl or benzyl, and R5 is an aromatic heterocyclic ring system which is linked via carbon, and which contains a quaternized nitrogen atom.

Abstract: Cefadroxil monohydrate is prepared by solubilizing 7-[D-(-)-.alpha.-benzyloxycarbonylamino-.alpha.-(p-hydroxyphenyl)acetamido ]-3-methyl-3-cephem-4-carboxylic acid by silylation or by salification in an organic solvent, subjecting the solubilized acid in the solvent to catalytic hydrogenation, separating the catalyst from the solution, and adding water to the solution at a pH of about 4 to precipitate cefadroxil monohydrate.

Abstract: A process is provided for the preparation of 3-methylene and 3-halomethylene cepham derivatives via 3-phosphoniomethyl-3-cephem derivatives, which in turn can be prepared from 3-halomethyl-3-cephem derivatives. The preparation can be carried out with or without isolating the intermediate phosphonium cephem compounds. The 3-methylene and 3-halomethylene cephem derivatives and in particular the 1-oxo and 1,1-dioxo cephem compounds are also prepared by reducing a 3-halomethyl-3-cephem derivative with activated metal, preferably zinc or magnesium.

Abstract: The present invention relates to an improved process for the preparation of the compounds of formula (I) ##STR1## which involve the direct oxidation without N-protection of the compound of the formula (II) ##STR2##

Abstract: A method for preparing 2-amino-.beta.-lactams which are substituted by readily-removed protecting groups is provided. According to this invention, an acyl-2-amino-.beta.-lactam is further acylated with a different acyl group and is subsequently treated with base to provide a protected 2-amino .beta.-lactam with allyloxycarbonyl, t-butoxycarbonyl, naphthyloxycarbonyl, trichloroethyloxycarbonyl, p-nitrobenzyloxycarbonyl, benzhydryloxycarbonyl, p-methoxybenzyloxycarbonyl, or o-nitrobenzyloxycarbonyl.

Abstract: A method for producing a compound of the formula; ##STR1## wherein R stands for a hydrogen atom, an acyl group or a protective group other than acyl groups, Q stands for a hydrogen atom or an ester residue, Y stands for the residue of a nucleophilic compound and the dotted line shows the double bond at 2- or 3- position of the cephem ring or a salt thereof, characterized by allowing a compound of the formula; ##STR2## [R, Q and the dotted line are of the same meaning as above] or a salt thereof to react with a nucleophilic compound or a salt thereof and a compound of the formula; ##STR3## wherein R.sup.1, R.sup.2, R.sup.3 independently stand for a hydrocarbon group having not more than 8 carbon atoms, or R.sup.1 and R.sup.2, R.sup.1 and R.sup.3 or R.sup.2 and R.sup.

Abstract: This invention provides cephalosporin compounds represented by the following general formula: ##STR1## wherein R.sup.1 and R.sup.2 are same or different hydrogen atom or a lower alkyl group of 1 to 5 carbon atoms; R.sup.3 is a lower alkyl group which may optionally be substituted with a halogen atome (or atoms), an alkenyl group, or a cycloalkylmethyl group of 3 to 6 carbon atoms; and A is hydrogen atom or residue of a nucleophilic compound and pharmacologically acceptable salts thereof. These compounds have broad-spectrum antibacterial activity against Gram-positive and -negative bacteria including Pseudomonas aeruginosa, as well as against a great variety of .beta.-lactamase-producing strains.

Abstract: The invention relates to a novel crystalline cefadroxyl hemihydrate having a K.F. between about 3.5 and 2.0%: such compound is more stable than other cefadroxyl molecules.The novel cefadroxyl is obtained preparing and isolating a novel cefadroxil solvate of dimethylacetamide, or of N-methyl-2-pyrrolidone or of monomethylformamide, slurrying said solvate with a mixture methanol/isopropyl alcohol 30:70 to 50:50 by volume at a temperature of about +45.degree. C. to +55.degree. C. and then filtering the so obtained compound.

Abstract: 3-Exomethylenecepham sulfoxide esters are obtained in improved yields via cyclization of 3-methyl-2-(4-chlorosulfinyl-2-oxo-3-acylamino-1-azetidinyl)-3-butenoic acid esters under anhydrous conditions with stannic chloride in the presence of both an oxo compound, e.g., an ether such as diethyl ether, a ketone such as acetone or methylethyl ketone, and an unsaturated compound, e.g., an alkene such as 1- or 2-hexene, a non-conjugated alkadiene such as 1,4-hexadiene, a cycloalkene such as cyclohexene, an allene, or a non-conjugated cycloalkadiene such as 1,4-cyclohexadiene.

Abstract: A method for the formation of intramolecular amide bonds by the action of cyanogen, under mild reaction conditions, in the preparation of cyclic amides, including lactams, in biologically active compounds. A compound containing at least one carboxylic acid group and at least one primary or secondary amino group is reacted with cyanogen to form an intramolecular amide bond. The method has utility in the synthesis of B-lactam antibiotics, such as penicillins, cephalosporins, and their derivatives, in enzyme modification, in cyclization of peptides, and in covalent cross-linking of proteins.

Abstract: A process for producing a 2-cephem or 3-cephem derivative compound of the formula: ##STR1## wherein R.sub.1 represents a substituted or unsubstituted amino radical and R.sub.4 represents hydrogen or a radical selected from the group consisting of carboxy, protected carboxy, ester, acid amide, acid anhydride, acid halide, acid azide and carboxy salt, and the dotted line indicates the alternate bond structure providing 3-cephem or 2-cephem, which comprises:reacting a halogenated derivative selected from the group consisting of a halogenated penam derivative having the formula: ##STR2## a halogenated cepham derivative of the formula: ##STR3## wherein X represents a halogen atom, R.sub.3 represents a radical selected from the group consisting of carboxy, protected carboxy, ester, acid amide, acid anhydride, acid halide, acid azide and carboxy salt, and R.sub.1 is as defined above, or mixtures thereof with a dehydrohalogenoic acid reagent.

Abstract: Process for the preparation of 7.beta.-amino-3-substituted methyl-3-cephem-4-carboxylic acid derivatives, new intermediates comprising 7.beta.-(cyclo)alkylideneammonio-3-halomethyl-3-cephem-4-carbox ylic acid derivatives and 7.beta.-amino/ammonio-3-bromomethyl-3-cephem-4-carboxylic acid derivatives and the processes for the preparation of these intermediates.

Abstract: A process is described for producing pure crystalline products, in particular penicillin and cephalosporin, wherein the desired product, prepared according to a known method, is treated with ethanol in one or two steps, whereby the crystallization of the pure product and impurity separation are achieved.

Abstract: A method of producing 3-alkanoyloxymethyl-3-cephem-4-carboxylic acids, which are useful as antibiotics or as intermediates in the synthesis of antibiotics, by reacting a 3-hydroxymethyl-3-cephem-4-carboxylic acid with a saturated fatty acid anhydride in an aqueous medium in the presence of an acid-acceptor base and a 4-(tertiary amino)pyridine.

Abstract: The invention relates to a method for producing crystalline cefadroxil hemihydrate. According to the method a cefadroxil solvate is slurried with a mixture methanol:isopropyl alcohol 30:70 to 70:30 by volume containing from 5% to 12% of water, a temperature from +45.degree. C. to +55.degree. C. and then isolating the so obtained crystalline compound.

Abstract: A process for preparing 3-alkoxymethylcephalosporins which are useful as an intermediate for various cephalosporin derivatives having a high antimicrobial activity is disclosed. According to the process of the present invention, the 3-alkoxymethylcephalosporins can be easily obtained in high yield on a commercial scale.

Abstract: The invention relates to a method for preparing crystalline cefadroxil monohydrate.According to such a method a cefadroxil solvate is slurried with isopropyl alcohol containing less 6% to 18% of water at a temperature between +45.degree. to +55.degree. C.: the crystalline cefadroxil monohydrate is isolated by filtration.Some of the cefadroxil solvates which can be used are novel: they are prepared by adding dimethylacetamide, N-methyl-2-pyrrolidone or monomethylformamide to an aqueous solution of cefadroxil at a pH between 5.5 and 6.

Abstract: Diphenylmethyl esters of cephalosporins, and processes for synthesizing such, are described and disclosed.

Abstract: This invention provides azetidinone derivatives represented by the formula ##STR1## and processes for preparing the same. The azetidinone derivatives are used as the intermediates for producing cephalosporin compounds useful as antibiotic agents.

Abstract: There is disclosed a process for the production of certain 2-allyl- and 3-butenyl-3-cephem derivatives by coupling a 3-chloromethyl-3-cephem with a hydrocarbyltributystannane in the presence of bis(dibenzylideneacetonyl)-palladium and a phosphine. The 3-allyl- and 3-butenyl-3-cephem derivatives so-produced are useful as broad-spectrum antibacterial agents.

Abstract: The present invention relates to an improved process for producing cephalosporin derivatives of formula (I), the 3-position of which being substituted by acetoxymethyl or tetrazolylthiomethyl and the 7-acyl group of which being substituted by D-mandelic acid derivatives, which comprises simultaneously reacting the compound of formula (III) with the compound of formula (IV) in the presence of a compound of formula (II) and anamine in high yield, ##STR1## wherein, R.sup.1 is hydrogen or ##STR2## R.sup.

Abstract: The crystalline ethanol or methanol solvates of cephalexin hydrochloride are isolated in high yield from solutions of cephalexin hydrochloride in substantially anhydrous ethanol or methanol, respectively, by adding miscible C.sub.5 -C.sub.6 alkanes after initiating solvate crystallization. Ethanol or methanol solutions of cephalexin hydrochloride can be prepared by adding gaseous HCl to the respective alcohol slurries of cephalexin monohydrate or the novel crystalline ethanolate or desolvated ethanolate. Alternatively, the cephalexin bis-DMF solvate-derived cephalexin hydrochloride isopropanolate can be used to prepare the crystalline hydrochloride monohydrate in accordance with the disclosed improved method.

Abstract: The invention relates to novel intermediates for the preparation of antimicrobial compounds, the intermediate being a compound of the formula: ##STR1## in which R.sup.2 is carboxy or a protected carboxy group,R.sup.8 is 2-hydroxyphenyl andZ is a group of the formula:--CH.dbd.CH.sub.2, --CH.sub.2 --X.sup.2, --CH.sub.2 P.sup.+ (R.sup.7).sub.3.X.sup.3-,--CH.dbd.P(R.sup.7).sub.3 OR--CH.sub.2 OH,wherein X.sup.2 and X.sup.3 are each halogen and R.sup.7 is selected from the group consisting of phenyl, tolyl, xylyl and naphthyl, or a salt thereof.

Abstract: A process for the separation of a mixture of syn and anti oxime isomers one from the other which comprises adsorbing said mixed oxime isomers onto a non-functional macroreticular adsorption resin, and eluting said resin to yield at least one eluate fraction containing one of said isomers while being substantially free of the other of said isomers.The application of this process to the separation of syn and anti isomers of cephalosporin compounds possessing an oxime grouping in a side-chain in the 7.beta.-position, and of acids corresponding to this 7.beta.-side chain, is described.

Abstract: Cephalosporin esters of the formula ##STR1## wherein R.sup.2 is hydrogen or acyl and R.sup.1 is a group which is readily removable by hydrolysis,and pharmaceutically acceptable acid addition salts of basic compounds of formula I in which R.sup.2 is an acyl group, may be prepared by reacting 7-amino-3-methyl-3-cephem-4-carboxylic acid (7-ADCA) in a partially chlorinated lower alkane with a bicyclic amidine of the formula ##STR2## wherein n is the integer 3, 4 or 5, and a halide of the formulaX--R.sup.1 IIIwherein X is halogen and R.sup.1 has the above significance,if desired, treating the resulting compound of formula I in which R.sup.2 is hydrogen with an unprotected or optionally protected acylating agent, cleaving off a protecting group which may be present and, if desired, treating a resulting basic compound of formula I in which R.sup.2 is an acyl group into a pharmaceutically acceptable acid addition salt.

Abstract: A process for the preparation of 7.beta.-acylamino-3-substituted-3-cephem-4-carboxylic acid compounds comprising reacting at -70.degree. C. to 0.degree. C. in an inert organic solvent phosphorus pentachloride with a cephalosporin compound in the presence of an olefinic compound having at least one carbon-carbon double bond having not more than three hydrogen atoms attached thereto capable of removing chlorine at least in part by addition to a carbon-carbon double bond.

Abstract: A compound of the formula: ##STR1## wherein R.sup.1 stands for hydrogen or formylamino, R.sup.2 is a residue of amino acid selected from the group consisting of serine and alanine, or a peptide of at least one of these amino acids, or hydrogen, R.sup.3 stands for --NH--C(.dbd.NH)--NH.sub.2 or --CH.sub.2 NH.sub.2, or its salt, which can be produced by cultivating a microorganism belonging to the genus Xanthomonas, is useful as a therapeutic agent against infectious disease caused by bacteria.

Abstract: 3-[(Z)-1-Propen-1-yl]-7-acylamido cephalosporins in which the 7-acyl group is phenylglycyl or substituted phenylglycyl are orally active antibiotics against Gram+ and Gram- bacteria.

Abstract: An azetidinone compound represented by the formula ##STR1## wherein R.sup.1 represents a substituted or unsubstituted phenyl group, R.sup.2 represents a carboxyl-protecting group, X represents a hydrogen atom or chlorine atom and Y represents --I, --ONO.sub.2, --OH, ##STR2## or --SR.sup.4 in which R.sup.3 is a lower alkyl group or --OR.sup.5 (wherein R.sup.5 is a halogen-containing lower alkyl group) and R.sup.4 is a substituted or unsubstituted, 5-membered aromatic heterocyclic residue containing sulphur and/or nitrogen atom or atoms.

Abstract: There is described a process for preparing a sulphoxide of the formula ##STR1## in which R.sup.1, R.sup.2, R.sup.3 and R.sup.4, taken individually, are alkyl, alkoxy or aryl groups, X is an alkylene group, R.sup.5 is a carboxylic acid protecting group and Y is a linking group through one or two carbon atoms forming a penam or cephem nucleus, which comprises reacting a compound of formula ##STR2## with an oxidizing agent. .alpha.-Sulphoxide compounds of formula (I) are also provided as novel intermediates.

Abstract: A high yield process for preparing beta-lactam antibiotics having a high purity degree, in particular derivatives of the cephalosporanic and penicillanic acids, of the formula: ##STR1## by condensation of the compounds ##STR2## where X.dbd.H --OCH.sub.3 (suitably blocked), with a chloride of the formula ##STR3## wherein R.dbd.H, OH in which said condensation is carried out in the presence of a nicotinic or isonicotinic base.

Abstract: In accordance with this invention, it has been found that the oxygen analog of 7-amino-cephalosporanic acid and biologically active derivatives thereof can be formed from esters of 7-amino-cephalosporanic acid. Esters of 7-oxocephalosporanic acid can be formed by diazotization of an ester or 7-amino-cephalosporanic acid and contact of the diazo compound so formed with a hypohalous acid and a base in a water miscible organic solvent. Oxygen analogs of 7-aminocephalosporins isolated as esters are then formed by reducing the aforesaid ester to the corresponding 7.beta.-hydroxy-cephalosporanate and then forming the desired analog by introduction of a side chain via hydroxyl group modification. Oxygen analogs of 7-amino-cephalosporins are then formed by regeneration of the acid via protective group removal.

Abstract: The novel compound .alpha.-bromodiethylcarbonate, novel methods for the preparation thereof, its use in the preparation of 1-ethoxycarbonyloxyethyl esters of penicillins and cephalosporins, and improvements in the method for preparing such esters.

Abstract: A 2-substituted cephem derivative represented by the formula ##STR1## wherein R.sup.1 represents a substituted or unsubstituted phenyl group, substituted or unsubstituted phenylmethyl group or substituted or unsubstituted phenoxymethyl group, R.sup.2 represents hydrogen atom or protective group for carboxylic acid and Y represents allyloxy group, benzyloxy group, alkylthio group, carboxyalkylthio group or group of the formula ##STR2## wherein R.sup.4 represents hydrogen atom or lower alkyl group, X represents --O--, --S-- or ##STR3## R.sup.5 represents hydrogen atom, a lower alkyl group or phenyl group and R.sup.6 represents hydrogen atom or lower alkyl group, and a process for preparing the derivatives.