Abstract: Intermediates and a process for their preparation are disclosed which are useful for the preparation of a renin inhibiting compound of the formula: ##STR1## wherein R is a nitrogen-containing heterocycle which is bonded via a nitrogen atom to the sulfonyl group, R.sub.6 is hydrogen, alkoxy, halogen or loweralkyl, R.sub.7 is loweralkyl having 2 to 7 carbon atoms, and R.sub.8 is loweralkyl, cycloalkyl, or aryl or a pharmaceutically acceptable acid addition salt thereof.
Type:
Grant
Filed:
February 10, 1993
Date of Patent:
January 4, 1994
Assignee:
Abbott Laboratories
Inventors:
Daniel A. Dickman, Bruce W. Horrom, Chi-Nung W. Hsiao, M. Robert Leanna, Hormoz Mazdiyasni, Howard E. Morton, Thomas M. Zydowsky, William R. Baker, Stephen L. Condon
Abstract: Described is a new process for producing the immunosuppressant, L-683,742, a C-31 demethylated, derivative of L-683,590 (FK-520), produced under fermentation conditions utilizing the new mutant microorganism, Streptomyces hygroscopicus subsp. ascomyceticus (Merck Culture Collection MA 6646) ATCC No. 53855, being a blocked mutant of Streptomyces hygroscopicus subsp. ascomyceticus (MA 6475) ATCC No. 14891. The macrolide immunosuppressant is useful in preventing human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.
Type:
Grant
Filed:
July 23, 1991
Date of Patent:
December 21, 1993
Assignee:
Merck & Co., Inc.
Inventors:
Carolyn L. Ruby, Susan J. Danis, Byron H. Arison
Abstract: Synthesis of semi-synthetic monobactamic or .beta.-Lactamic antibiotics by using derivatives stabilized by various methods of penicillin G acylase from various microbial sources according to a thermodynamically controlled strategy in monophase water/cosolvent organic apolar systems, wherein the concentration of the cosolvent varies between 30% and 90%, the temperature between -10.degree. C. and 50.degree. C., the pH between 4.5 and 8.5, with concentrations of the antibiotic nucleus between 0.5 an 875 mM and acyl donor between 0.2 mM and 1M, with a relationship antibiotic ring/activated or free acyl donor, using a buffer between 0 and 1M. Application to the pharmaceutical industry.
Type:
Grant
Filed:
August 2, 1991
Date of Patent:
December 7, 1993
Assignee:
Cosejo Superior de Invetigaciones Certificas
Inventors:
Jose M. Guisan Seijas, Roberto Fernandez Lafuente, Gregorio Alvaro Campos, Rosa M. Blanco Martin, Cristina Molina Rosell
Abstract: A method of assaying L-carnitine in a specimen comprises reacting a specimen containing L-carnitine with:a) L-carnitine dehydrogenase having coenzymes of the thio-NAD group and of the NAD group, and which catalyzes a reversible reaction forming dehydrocarnitine from a substrate of carnitine,b) A.sub.1 andc) B.sub.1to effect a cycling reaction of the formula ##STR1## wherein A.sub.1 is thio-NAD group or NAD group, A.sub.2 is a reduced form of A.sub.1, when A.sub.1 is thio-NAD group, B.sub.1 is reduced NAD group and when A.sub.1 is NAD group, B.sub.1 is reduced thio-NAD, and wherein B.sub.2 is an oxidized form of B.sub.1 ; and measuring an amount of A.sub.2 or B.sub.1 generated or consumed by the cycling reaction. A composition for performing the assay comprises the above L-carnitine dehydrogenase, as well as the above components A.sub.1 and B.sub.1.
Abstract: A microbiological process for the terminal oxidation of alkyl groups in 5- or 6-ring heterocycles which are substituted with at least one alkyl group with more than 2 carbon atoms to carboxylic acids.
Abstract: A microbiological process for the oxidation of methyl groups in aromatic 5- or 6-member ring heterocycles to the corresponding carboxylic acid. The heterocycle serves as the substrate and exhibits no substituent on the carbon atoms adjacent to the methyl groups to be oxidized. The reaction of the heterocycle takes place by means of microorganisms of the genus Pseudomonas utilizing toluene, xylene, or cymene. The enzymes of the microorganisms been previously induced.
Abstract: Biosynthetic production of 7-[1',2',6',-7',8',8a'(R)-hexahydro-2'(S),6'(R)-dimethyl-8'(S)-hydroxy-1'( S)-naphthyl]-3(R),5(R)-dihydroxyheptanoic acid, "triol acid", is accomplished by enzymatic hydrolysis of lovastatin acid or a salt thereof, by treating it with Clonostachys compactiuscula ATCC 38009 or ATCC 74178, or mutants thereof, or a cell-free extract derived therefrom, or a hydrolase derived therefrom. The triol acid and its lactone form are both inhibitors of HMG-CoA reductase and thus useful as anti-hypercholesterolemic agents, and may also serve as intermediates for preparation of other HMG-CoA reductase inhibitors. Also, in the synthesis of simvastatin by direct methylation of lovastatin, selective hydrolysis of residual lovastatin salt by treatment with Clonostachys compactiuscula ATCC 38009 or ATCC 74178 or mutants thereof or a cell-free extract derived therefrom, or a hydrolase derived therefrom yields the "triol" salt which can be easily separated from simvastatin.
Type:
Grant
Filed:
February 7, 1992
Date of Patent:
June 29, 1993
Assignee:
Merck & Co., Inc.
Inventors:
Michael J. Conder, Steven J. Cianciosi, William H. Cover, Rebecca L. Dabora, Eric T. Pisk, Robert W. Stieber, Bogdan Tehlewitz, Gregory L. Tewalt
Abstract: A process using microorganisms which contain genes, which form an active xylene monooxygenase, which form no effective, chromosomally or plasmid-coded alcohol hydrogenase, and which are, thus, capable of hydroxylating methyl groups on aromatic 5- or 6-atom heterocycles to the corresponding hydroxymethyl derivatives, for the production of hydroxymethylated 5- or 6-atom heterocycles.
Type:
Grant
Filed:
September 23, 1991
Date of Patent:
June 8, 1993
Assignee:
Lonza Ltd.
Inventors:
Thomas Zimmermann, Andreas Kiener, Shigeaki Harayama
Abstract: A microbiological process for oxidation of methyl groups in aromatic 5- or 6-ring heterocycles to the corresponding carboxylic acid. The reaction of the heterocycle takes place by microorganisms of the genus Pseudomonas, which utilize toluene, xylene or cymene. An inducer, the aromatic heterocycle, as the substrate, and a carbon source and energy source are fed in and, after the maximal product concentration is reached, the product is separated.
Abstract: A microorganism for selective production of a specific compound of avermectin having one or more of the following properties:specific accumulation of avermectin compound "a",effective incorporation of isoleucine or its keto acid (3-methyl-2-oxovaleric acid) into avermectin molecule, andmarkedly suppressed incorporation of valine or its keto acid (2-oxoisovaleric acid) into avermectin molecule.
Abstract: A novel pyrimine-producing strain belonging to genus Pseudomonas exhibits the following bacteriological properties: denitrification reaction: negative; assimilation of carbon sources:D-arabinose: positiveL-lysine: negativeand a novel pyrimine-producing strain belonging to genus Pseudomonas exhibits the following bacteriological properties: denitrification reaction: negative, assimilation of carbon sources:D-arabinose: positiveL-lysine: positiveThese novel strains produce pyrimine in high yield and if the strains are cultured in a proper culture medium in the presence of an iron salt, a natural red dye, ferropyrimine, can be easily produced and directly be recovered from the culture medium.
Abstract: The present invention is directed to a process for producing L-aspartyl-L-phenylalanine and/or L-aspartyl-L-phenylalanine diketopiperazine comprising contacting and reacting a culture, cell or a cell-treated product of a microorganism capable of hydrolyzing DKP into AP or capable of performing intramolecular condensation of AP into DKP with DKP and/or AP, in an aqueous medium.
Abstract: In the enzymatic stereoselective ester cleavages of 2-arylpropionate, the reaction rate of the hydrolyzing enzymes can be drastically increased if the vinyl ester of the 2-arylpropionate is employed as the substrate.
Type:
Grant
Filed:
June 8, 1990
Date of Patent:
October 13, 1992
Assignee:
Hoechst Aktiengesellschaft
Inventors:
Gerd Fulling, Merten Schlingmann, Reinhold Keller
Abstract: An improved biological conversion of a nitrile such as acrylonitrile or a cyanopyridine into the corresponding carboxylic acid such as acrylic acid or a nicotinic acid by the action upon the nitrile of a nitrilase enzyme, in which the improvement resides in the use as the source of the enzyme of a microorganism of Rhodococcus, such as Rh. rhodochrous J-1, FERM BP-1478, which is cultured in the presence of a lactam compound.
Abstract: The invention relates to a novel method for preparing pyrocatecholic compounds from monophenolic compounds using catalysis by monophenol monooxygenase in an aqueous solution containing metal ions. The metal ions form complexes with the pyrocatecholic products. This method increases the yield of pyrocatecholic products. In particular, the method of the instant invention can be used to increase the yield of L-DOPA, a drug used in the treatment of Parkinson's disease.
Type:
Grant
Filed:
November 19, 1990
Date of Patent:
June 16, 1992
Assignee:
Industrial Technology Research Institute
Abstract: A novel pyrimine-producing strain belonging to genus Pseudomonas exhibits the following bacteriological properties: denitrification reaction: negative; assimilation of carbon sources:D-arabinose: positiveL-lysine: negativeand a novel pyrimine-producing strain belonging to genus Pseudomonas exhibits the following bacteriological properties: dentrification reaction: negative; assimilation of carbon sources:D-arabinose: positiveL-lysine: positiveThese novel strains produce pyrimine in high yield and if the strains are cultured in a proper culture medium in the presence of an iron salt, a natural red dye, ferropyrimine, can be easily produced and directly be recovered from the culture medium.
Abstract: An enzymatic process for the enantiomer-specific preparation of mercapto alkanoic acids by stereoselective hydrolysis of mercapto or thioester alkanoic acid esters.
Abstract: A microbiological process for the oxidation of methyl groups in aromatic 5- or 6-member ring heterocycles to the corresponding carboxylic acid. The heterocycle serves as the substrate and exhibits no substituent on the carbon atoms adjacent to the methyl groups to be oxidized. The reaction of the heterocycle takes place by means of microorganisms of the genus Pseudomonas utilizing toluene, xylene, or cymene. The enzymes of the microorganisms have been previously induced.
Abstract: The present invention relates to the antitumor antibiotic compound BU-3285T and its preparation. The compound is obtained by culturing a new strain of Chainia rosea and demonstrates both antitumor and antifungal activity. It also relates to the desulfated derivative of BU-3285T which is obtained by treatment of BU-3285T with sulfatase enzyme. BU-3285T desulfate possesses antitumor activity.
Type:
Grant
Filed:
April 11, 1990
Date of Patent:
July 30, 1991
Assignee:
Bristol-Myers Company
Inventors:
Hiroaki Ohkuma, Koji Tomita, Masataka Konishi, Hideo Kamei
Abstract: In a process for the reduction of ketones, the keto compounds are enantioselectively reduced to give secondary alcohols by means of microorganisms. Keto compounds of the formulaR.sup.3 NH--CHR.sup.1 --CO--CH.sub.2 --COOR.sup.2in which R.sup.1, R.sup.2 and R.sup.3 have the meanings defined herein are used as starting compounds.
Type:
Grant
Filed:
July 22, 1988
Date of Patent:
June 25, 1991
Assignee:
Merck Patent Gesellschaft mit beschrankter Haftung
Inventors:
Hans-Eckart Radunz, Harry Schwartz, Martin Heinrich
Abstract: A new antifungal agent which exhibits a moderately broad spectrum of activity towards filamentous fungi and also against Cryptococcus species of the yeast fungi, and which has been isolated from a solid stationary fermentation of an unidentified species of Fusarium is described.
Type:
Grant
Filed:
December 1, 1988
Date of Patent:
April 16, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Louis Chaiet, Sheldon B. Zimmerman, Richard L. Monaghan, George M. Garrity
Abstract: Described is a process for producing a new immunosuppressant, "demethomycin" (L-682,993) a C-31 demethylated analog of L-679,934 under novel fermentation conditions utilizing the microorganism, Actinoplanacete sp., (Merck Culture Collection MA 6559) ATCC No. 53771. The macrolide immunosuppressant is useful in prevent human host rejection of foreign organ transplants, e.g. bone marrow and heart transplants.
Type:
Grant
Filed:
June 29, 1988
Date of Patent:
January 1, 1991
Assignee:
Merck & Co., Inc.
Inventors:
Edward S. Inamine, Byron H. Arison, Shieh-Shung T. Chen, Linda S. Wicker
Abstract: The invention is a gel bead comprising propylene glycol alginate and bone gelatin and is capable of removing metals such as Sr and Cs from solution without adding other adsorbents. The invention could have application to the nuclear industry's waste removal activities.
Type:
Grant
Filed:
April 4, 1989
Date of Patent:
December 18, 1990
Assignee:
United States Department of Energy
Inventors:
Charles D. Scott, Charlene A. Woodward, Charles H. Byers
Abstract: There is disclosed a process for the biotechnological resolution, by enzymatic esterification of the corresponding racemic mixture of the S(+) and R(-) optical isomers of the oxazolidinonic compounds having formula (I): ##STR1## wherein R represents a, linear or branched, C.sub.1 -C.sub.8 alkyl group, which process is characterized in that, the racemic 3-alkyl-5-hydroxymethyl-oxazolidin-2-one derivative of formula (I) is reacted with an esterifying compound, selected from esters having formula (III): ##STR2## wherein R represents a, linear or branched, C.sub.1 -C.sub.10 alkyl or alkenyl group and R" represents a linear or branched, C.sub.1 -C.sub.4 alkyl, alkenyl group, a haloalkyl (chlorine, bromine) group or a diacyl glycerolic group or from acids having formula (IV):R'"--COOH (IV)wherein R'" represents a, linear or branched, C.sub.1 -C.sub.20 alkyl or alkenyl group or from anhydrides having formula (V): ##STR3## wherein R.sup.IV represents a, linear or branched, C.sub.1 -C.sub.
Type:
Grant
Filed:
December 24, 1987
Date of Patent:
June 12, 1990
Assignee:
Montedison S.p.A.
Inventors:
Pietro Cesti, Daniele Bianchi, Franco Francalanci, Walter Cabri
Abstract: The invention relates to a method for microbiologically resolving racemic 2,3-o-substituted glycerol esters to obtain optically activated 2,3-o-substituted glycerol with remaining esters also being optically active.
Type:
Grant
Filed:
September 9, 1985
Date of Patent:
June 5, 1990
Assignee:
The Wisconsin Alumni Research Foundation
Abstract: A method of resolving glycidyl esters to high enantiomeric excess involves fractionation of hydrolytic enzymes (e.g. lipases) to prepare biocatalysts with high enantioselectivity, and using these catalysts to selectively hydrolyze one enantiomer of the glycidyl esters. Also a method for fractionation includes stirring an aqueous solution of the enzyme with a solid inert adsorbent to provide an adsorbed and non-adsorbed enzyme fraction, where the non-adsorbed fraction displays a higher enantioselectivity than the crude non-fractionated enzyme. Also a composition composed of a glycidyl ester is obtained with an enantiomeric excess of greater than or equal to 97%.
Abstract: 3',4'-anhydrovinblastine, a precursor of the anti-tumor alkaloids vincristine and vinblastine, is prepared by the enzymatic coupling of catharanthine and vindoline using an iron-containing compound such as peroxidase optionally in the presence of a peroxide. Substantially enhanced yields are obtained.
Type:
Grant
Filed:
August 4, 1986
Date of Patent:
April 17, 1990
Assignee:
Allelix Biopharmaceuticals Inc.
Inventors:
Anne E. Goodbody, Endo Tsuyoshi, John Vukovic, Masanaru Misawa
Abstract: An exotoxin of the plant pathogen, Pseudomonas syringae pv. tagetis selectively inhibits the development of chloroplasts in growing plant tissue. The exotoxin, known as tagetitoxin, can be produced efficiently from a mutant high-producing line of the bacteria, designated C42mr2+. The tagetitoxin can also be readily purified from the culture medium of the bacteria.
Type:
Grant
Filed:
February 17, 1987
Date of Patent:
October 17, 1989
Assignee:
Wisconsin Alumni Research Foundation
Inventors:
Richard D. Durbin, Jean H. Lukens, Thomas F. Uchytil, Nicholas Rhodehamel
Abstract: A process for producing a sphingophospholipid derivative comprising reacting a sphingophospholipid with a specified compound having an alcoholic hydroxyl group selected from the group consisting of specified primary alcohol compounds, specified secondary alcohol compounds and specified saccharides or their phenol glycosides in the presence of phospholipase DM.
Abstract: The invention relates to a novel microorganism of the genus Rhodococcus, to the use thereof in a process for the microbiological degradation of amino-s-triazines and cyanuric acid in wastewaters, as well as to a process for the microbiological degradation of s-triazine derivatives to biomass or to degradation products such as NH.sup.30.sub.4 and/or chloride, which comprises the combined use of said microorganism with Pseudomonas spp.
Abstract: Process for the production of 6-hydroxynicotinic acid by biotechnological methods. Nicotinic acid is enzymatically hydroxylated in the presence of equivalent quantities of magnesium or barium ions with the help of nicotinic acid-hydroxylating microorganisms. The resultant magnesium or barium salt of the 6-hydroxynicotinic acid is separated from the reaction mixture. Then the 6-hydroxynicotinic acid is freed from the separated salts. Examples of the microorganism are the species Pseudomonas, Bacillus or Achromobacter, for example, Achromobacter xylosoxydans. Preferably the enzymatic hydroxylation is carried out at 20.degree. to 40.degree. C. and a pH of 5.5 to 9.0 under aerobic conditions.
Abstract: A hitherto undescribed microorganism, Streptomyces virginiae NRRL 12525, which upon culturing produces the A41030 antibiotic complex comprising several factors. The A41030 antibiotics produced show antibacterial activity against the gram-positive genera Staphylococcus and Streptococcus which are resistant to penicillin. In addition, these antibiotic act to promote growth and improve feed efficiency in ruminant animals, poultry and swine, and other livestock, and to improve milk production in ruminant animals.
Abstract: Aerocavin, a novel antibiotic substance having the structure ##STR1## and aerocyanidin, a novel antibiotic substance having the structure ##STR2## can be prepared by cultivation of the microorganism Aerocavin caviae SC 14,030 A.T.C.C. No. 53434.
Type:
Grant
Filed:
July 14, 1986
Date of Patent:
August 11, 1987
Assignee:
E. R. Squibb & Sons, Inc.
Inventors:
Wen-Chih Liu, William L. Parker, Pushpa Singh, Richard B. Sykes
Abstract: This invention relates to a process for preparing 7-(S)-acylamino-3-hydroxymethyl-3-cephem-4-carboxylic acid sulfones and the salts and esters thereof. The instant process involves contacting a 7-(S)-acylamino-3-acetoxymethyl cephalosporin sulfone in an aqueous solution buffered from about pH 6 to about pH 8 with citrus acetylesterase, which is immobilized on silica gel. The 3-hydroxymethyl cephalosporin sulfones produced by the process of this invention are intermediates in the synthesis of 1-oxa .beta.-lactam antibiotics.
Abstract: In the enzyme-mediated synthesis of an ester or lactone from at least one carboxylic acid of the formulaR--CH.sub.2 --CH.sub.2 --COOHwhereinR is a hydrogen atom, or a hydrocarbon radical which has 1 to 21 carbon atoms and which can be optionally substituted by hydroxyl groups or alkoxy groups with 1 to 10 carbon atoms,with at least one primary or secondary alcohol having 1 to 15 carbon atoms, the improvement which comprises employing as the enzyme the esterase from Mucor miehei and effecting the synthesis in the absence of water. Advantageously, the synthesis is effected at about room temperature, the mol ratio of carboxylic acid to alcohol is from about 1:1 to 1:1.1, and the enzyme is used in a quantity of about 3 to 20% by weight of the carboxylic acid. The absence of water facilitates recovery, as by distillation.
Abstract: Novel antibiotic U-58,431 producible in a fermentation under controlled conditions using a biologically pure culture of the microorganism Streptomyces helicus Dietz and Li sp. n., NRRL 11461. This antibiotic is active against various Gram-positive bacteria, for example, Staphylococcus aureus, Streptococcus hemolyticus, and Streptococcus faecalis. It is also active against various Gram-negative bacteria, for example, Escherichia coli, Proteus vulgaris, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Salmonella schottmuelleri. It has strong activity against Diplococcus pneumoniae. Thus, antibiotic U-58,431 can be used in various environments to eradicate or control such bacteria.
Abstract: A process for preparing N-carbamoyl-D-(2-thienyl or 3-thienyl)glycine by subjecting 5-(2-thienyl or 3-thienyl)hydantoin to the action of a cultured broth, cells or treated cells of microorganisms having an ability of stereospecifically hydrolyzing the hydantoin ring. N-carbamoyl-D-(2-thienyl or 3-thienyl)glycine is a useful intermediate for the preparation of medicines and can be readily converted into D-(2-thienyl or 3-thienyl)glycine.
Abstract: L-carnitine is obtained by reacting 3-dehydrocarnitine or one of its salts, in aqueous medium, simultaneously with: (a) carnitine dehydrogenase,(b) a coenzyme utilized by carnitine dehydrogenase for reducing dehydrocarnitine, preferably nicotinamide adenine dinucleotide, and(c) a reducing agent for the coenzyme, the coenzyme (b) and carnitine dehydrogenase being preferably used in catalytic amount.
Abstract: A novel antibiotic No. 2-200 represented by the formula ##STR1## which has a broad antimicrobial spectrum and a process for producing the same by cultivating an antibiotic No. 2-200 producing microorganism of the genus Nocardia, and recovering by isolation the antibiotic No. 2-200 accumulated in the culture.
Abstract: Antibiotic A-21978C complexes, in particular the A-21978C complex, comprising microbiologically active, related factors, C.sub.0, C.sub.1, C.sub.2, C.sub.3, C.sub.4, and C.sub.5. A-21978 complex and A-21978C complex are produced by submerged aerobic fermentation of Streptomyces roseosporus NRRL 11379. The individual A-21978C factors are separated and isolated by chromatography. The A-21978 and A-21978C complexes, the A-21978C factors, and pharmaceutically acceptable salts thereof are antibacterial agents and improve growth promotion in poultry.