Abstract: Method for treating tuberculosis with 2-(2-substituted-phenyl)-2-oxazolines and related 5-membered heterocycles represented by the formula Y1 is e.g. an ester or amide forming group, and X is O, S, or NH; and pharmaceutically acceptable formulations useful therein are provided. A preferred method comprises administering (S)-benzyl2-[2-(benzyloxy)phenyl]-2-oxazoline-4-carboxylate in a suitable formulation. The compounds of the above formula are prepared by known methods, e.g. the oxazolines are obtained by coupling a substituted benzoic acid with a serine ester or threonine ester and cyclizing the coupled product.

Abstract: Compounds represented by the formula [1] R1 is H or a substituent; R2 and R3 are C1-C3 alkyl; R4 is siderophore group e.g. CH3—(CH2)n—C(O)—N(OH)—(CH2)m— with n=10-22, m=2-6; X is O, S, or NH; X1 is O or NH; Y is H or alkyl; Z is H or substituted amino, e.g., t-BocNH or CbzNH, and r is 2-4; are useful in the method provided for treating tuberculosis. [1] is prepared by coupling [7], wherein HX1 is HO— or H2N—,  with [4] obtained as the free acid after saponification of the methyl ester.

Abstract: Plasticized liquid membranes and processes for separating monosaccharides from disaccharides and from other monosaccharides employing the membranes are provided. Fructose is separated from glucose via the membrane process to provide fructose in concentrations sufficient for HFS (high fructose syrup) and sucrose, glucose and fructose are separated from crude sources such as molasses, sugar cane juice and beet sugar juice. The plasticized membranes are prepared by dissolving a lipophilic polymer such as cellulose triacetate, an organic liquid plasticizer such as a hydrophobic ether compound e.g. 2-nitrophenyloctyl ether and, a carrier compound such as a quaternary ammonium salt or a boronic acid compound with lipophilic substitution in a suitable solvent which upon evaporation provides the plasticized membrane. The membrane produced is homogeneous having all three components equally dispersed in the membrane.

Abstract: 5'-O-Acyl-5-fluorouridines and 5'-O-acyl-5-sluorocytidines are prepared by the direct acylation of the 5'-hydroxyl group with amino acids under Mitsunobu conditions and the amino acyl derivatives are coupled with other amino acids or peptides to provide antibacterial and antifungal derivatives of the nucleosides. For example, 5-fluorouridine is acylated at the 5'-hydroxyl group with an amino protected L-valine and the acylation product is deprotected to provide 5'-O-(L-valinyl)-5-fluorouridine having activity against Gram-positive bacteria including resistant staphylococcus. Preferred peptide derivatives comprise the tripeptides of ornithine and lysine wherein the terminal amino group is substituted by both hydroxy and acetyl. The latter peptides inhibit the growth of C. albicans.

Abstract: Bicyclic .beta.-lactams comprising a 5- or 6-membered lactone or lactam ring are obtained in a process comprising a base induced intramolecular cyclization of a 4-substututed .beta.-lactam having a leaving group in the 1-position. An intramolecular nucleophile transfer reaction is proposed as the operative mechanism and the bicyclic .beta.-lactams are obtained in the required stereochemical form for biological activity. The compounds provided are useful intermediates for the preparation of antibiotics and .beta.-lactamase inhibitors.

Abstract: The present invention, utilizing recombinant DNA technology, provides a novel method for obtaining 20-deoxotylosin from a tylosin producing microorganism. 20-deoxotylosin is useful as an antibiotic with a microbial inhibitory activity similar to tylosin.

Abstract: 1-Carbapenam-2-one-3-carboxylic acid and 1-carba-3-hydroxy-3-cephem-4-carboxylic acid and esters thereof are provided by a process comprising a rhodium C.sub.2 -C.sub.10 carboxylate catalyzed cyclization of an ester of a 4-(1-alkoxy- or 1-substituted alkoxy)-2-oxo-4-azetidinyl)-.beta.-ketobutyric acid and an ester of a 5-(1-alkoxy- or 1-substituted alkoxy-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketovaleric acid respectively. The process is carried out in an inert organic solvent at a temperature between about 15.degree. C. and about 85.degree. C. The 1-carba bicyclic .beta.-lactams are intermediates for preparing antibiotics.

Abstract: DNA probes for DNA fingerprint analysis. The DNA probes are 15 nucleotide sequences wherein 8 nucleotides of each sequence are G, 3 are T, 1 is C, 1 is A and 2 are A, C, G or T (N), except that the nucleotide sequence is not the M13 consensus sequence GAGGGTGGNGGNTCT. In particular, the 15-nucleotide sequence GGTGGNGATGGCTNG or as randomized variant of this sequence which is not the M13 consensus sequence, may be used as probes to detect hypervariable regions in genomic DNA. Methods for the preparation of such probes and for the detection of restriction length fragment polymorphisms using such probes are disclosed. The DNA probes are useful in genetic origin determination of human, animal or plant DNA-containing samples.

Abstract: There is described a process for producing exomethylene cepham intermediates useful in cephalosporin chemistry. The process comprises the preparation of a compound of the formula ##STR1## in which R.sup.1 is an amino group, a protected amino group, an acylamino group or a diacylamino group,R.sup.2 is hydrogen, C.sub.1-4 alkoxy or C.sub.1-4 alkylthio,R.sup.3 is hydrogen, a salt ion or an ester-forming group, andR.sup.4 is hydrogen or C.sub.1-3 alkyl,by reacting a compound of the formula ##STR2## in which Y is a bridging group of the formula ##STR3## Z is chloro, bromo or iodo, and R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the above defined values, with a reagent providing cobalt I, under reducing conditions.

Abstract: 1-Carbapenam-2-one-3-carboxylic acid and 1-carba-3-hydroxy-3-cephem-4-carboxylic acid and esters thereof are provided by a process comprising a rhodium C.sub.2 -C.sub.10 carboxylate catalyzed cyclization of an ester of a 4-(1-alkoxy- or 1-substituted alkxoy)-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketobutyric acid and an ester of a 5-(1-alkoxy- or 1-substituted alkoxy-2-oxo-4-azetidinyl)-.alpha.-diazo-.beta.-ketovaleric acid respectively. The process is carried out in an inert organic solvent at a temperature between about 15.degree. C. and about 85.degree.0 C. The 1-carba bicyclic .beta.-lactams are intermediates for preparing antibiotics.

Abstract: This invention provides an improvement in the large scale processing of vancomycin which comprises the quiescent precipitation of vancomycin base from an aqueous solution of a pH of at least about 7.8.

Abstract: Monocyclic .beta.-lactam compounds represented by the formula ##STR1## wherein R.sub.1 is H, NH.sub.2, acylamino, C.sub.1 -C.sub.4 alkyl, etc.; R.sub.2 is e.g. C.sub.1 -C.sub.4 alkyl, hydroxyalkyl, aminoalkyl, carboxy, esterified carboxy, esterified carboxyalkyl, or carboxyalkyl; and R.sub.3 is hydrogen, benzyl, substituted benzyl, pivaloyl, --SO.sub.3 M, or --P(C.dbd.O)(OM')2; are obtained by the cyclization of an O-substituted hydroxamate of a .beta.-substituted alkylcarboxylic acid. For example, .alpha.-ethylmalic acid monobenzyl ester is reacted with O-benzylhydroxylamine to form the O-benzylhydroxamate of the free carboxy group, and the hydroxamate is cyclized with diethyl diazodicarboxylate and triphenylphosphine to form the .beta.-lactam of the above formula wherein R.sub.1 is ethyl, R.sub.2 is benzyloxycarbonyl and R.sub.3 is benzyl. The .beta.-lactam compounds are useful intermediates for preparing .beta.-lactamase inhibitors and monocyclic .beta.-lactam antibiotics and, when R.sub.3 is --SO.sub.

Abstract: This invention provides a matrix composition for sustained drug delivery which is comprised of an active agent, a hydrophilic polymer and an enteric polymer. The enteric polymer is impermeable to gastric fluids and aids in retarding drug release in regions of low pH, thus allowing lower levels of hydrophilic polymer to be employed. At the pH range of intestinal fluids, this polymer will dissolve and thereby increase the permeability of the dosage form. This approach is useful in sustaining the release of numerous active agents whose solubility declines as the pH is increased, a characteristic of weakly basic drugs. By responding to changes in physiological pH, these sustained release dosage forms have acceptable performance, in spite of variability in the gastrointestinal transit times of the formulation.

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: The invention provides a free radical process for preparing 1-carba(1-dethia)cephalosporin antibiotics represented by the formula ##STR1## wherein R is amino or protected amino, R.sub.1 is H or alkoxy, R.sub.3 is H or alkyl, Z is ##STR2## where R.sub.2 is, e.g., H, halogen, or alkyl, or --CH.sub.2 R.sub.2 ' where R.sub.2 ' is, e.g., hydroxy, methoxy, or heterocyclicthio group, and A is a carboxy-protecting group which comprises heating a 2-substituted-methylcephalosporin 1,1-dioxide of the formula ##STR3## wherein R, R.sub.1, R.sub.3, and A are the same as in the formula above and Y is a free radical precursor group, e.g., C.sub.1 -C.sub.6 --Se--, C.sub.1 -C.sub.6 --S--, or phenyl--Se--; with a free radical initiator, e.g., a trialkyltin hydride, radiation, or a cobalt I salophen. Also provided are free radical compounds formed as intermediates in the process.

Abstract: Epoxyimines, formed from epoxyaldehydes, react via cycloaddition with amino-protected glycyl halides to provide 3-protected-amino-4-(substituted oxiranyl)azetidinones represented by the formula ##STR1## wherein, e.g., R is protected amino; R.sub.1 and R.sub.2 is H, alkyl, phenyl, etc.; and R.sub.3 inter alia a nitrogen-protecting group. Chiral epoxyimines from chiral epoxyaldehydes induce high levels of asymmetric induction during the cycloaddition to provide substantially one diastereomer of the 3,4-disubstituted azetidinone. For example, the epoxyimine formed with (2R,3S)-2-formyl-3-phenyloxirane and 2,4-dimethoxybenzylamine is reacted with phthalimidoacetyl chloride to provide [3R,4R,4(2S,3S]-1-(2,4-dimethoxybenzyl)-3-phthalimido-4-(3-phenyloxiran-2- yl)-2-azetidinone.The epoxy-substituted azetidinones are useful intermediates for .beta.-lactam antibiotic compounds.

Abstract: Bicyclic pyrazolidinones which have antimicrobial and/or herbicidal properties are discussed. The use of these compounds in pharmaceutical compositions, herbicidal compositions, and methods for treating bacterial infections and controlling undesired plants is set forth.

Abstract: 7.beta.-Acylamino-3-alkoxycarbonyl-(and 3-keto)-1-carba(1-dethia)-3-cephem-4-carboxylic acids and derivatives and related 3-substituted compounds are provided as antibiotics useful for treating infections in man and animals. Pharmaceutical formulations comprising the antibiotics and intermediates a process for their preparation are provided. Exemplary compounds provided are 7.beta.-[D-(2-phenyl-2-aminoacetyl)amino]-3-methoxycarbonyl-1-carba(1-deth ia)-3-cephem-carba(1-dethia)-3-cephem-4-carb oxylic acid and 7.beta.-[2-(2-aminothiazol-4-yl)-2-methoxyimino-acetamido]-3-acetyl-1-carb a(1-dethia)-3-cephem-4-carboxylic acid.

Abstract: Gel-free concentrated aqueous formulations of vancomycin hydrochloride are provided which comprise the antibiotic salt at a concentration between about 12% and about 50% w/v and a gel-inhibiting compound, e.g., ethanol, at a concentration between about 1% and about 20% v/v. The gel-free formulations are especially useful in a freeze-drying process for preparing vancomycin hydrochloride as a dry flowable powder in bulk or in unit-dosage form.

Abstract: 7.beta.-Acylamino-1-carba(dethia)-3-cephem-4-carboxylic acids represented by the formula ##STR1## wherein n is 1 or 2; R.sub.1 is C.sub.1 -C.sub.6 alkyl; C.sub.1 -C.sub.6 alkyl substituted by hydroxy, C.sub.1 -C.sub.4 alkoxy, C.sub.1 -C.sub.4 alkylthio, trifluoromethyl, carboxy, carbamoyl, amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4 alkyl)amino, halogen, cyano, phenyl, substituted phenyl as defined above; C.sub.2 -C.sub.6 alkenyl; C.sub.3 -C.sub.7 cycloalkyl; phenyl or substituted phenyl as defined above; or a 5- or 6-membered heterocycle selected from thienyl, furyl, pyrryl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidyl, triazinyl, or pyrazinyl; the benzheterocycles, benzothienyl, benzofuryl, indolyl, benzimidazolyl, or benztriazolyl, and said 5- or 6-membered heterocycle and said benzheterocycle substituted by C.sub.1 -C.sub.4 alkyl, halogen, hydroxy, C.sub.1 -C.sub.