Resolution Of Optical Isomers Or Purification Of Organic Compounds Or Composition Containing Same Patents (Class 435/280)
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Patent number: 5902736Abstract: In a process for the production of a D-.alpha.-amino acid, in which an N-carbamyl-D-.alpha.-amino acid corresponding to the general formula: ##STR1## wherein R represents phenyl, hydroxy-substituted phenyl, substituted or unsubstituted alkyl, or thienyl, is converted by a microbial enzyme in an aqueous medium to a D-.alpha.-amino acid corresponding to the general formula: ##STR2## wherein R is the same as defined above, decarbamylase produced by a microorganism of the genus Comamonas, Blastobacter, Alcaligenes, Sporosarcina, Rhizobium, Bradyrhizobium or Arthrobacter is used as the enzyme converting the N-carbamyl-D-.alpha.-amino acid to the D-.alpha.-amino acid.The conversion of the N-carbamyl-D-.alpha.-amino acids to the D-.alpha.-amino acids is carried out in a neutral to alkaline pH range.Type: GrantFiled: June 6, 1994Date of Patent: May 11, 1999Assignee: Kanegafuchi Chemical Industry Co., Ltd.Inventors: Hideaki Yamada, Sakayu Shimizu, Yasuhiro Ikenaka, Kazuyoshi Yajima, Yukio Yamada, Hirokazu Nanba, Masayuki Takano, Satomi Takahashi
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Patent number: 5900368Abstract: The present invention is directed to an improved process for making PDE IV inhibitors. In specific, this application describes a process for making and purifying a chiral bisaryl alcohol, an intermediate compound necessary for the preparation of PDE IV inhibitors such as CDP 840, by asymmetric bioreduction of a pro-chiral ketone. Furthermore, the bioprocess provides for production of each enantiomer of a bisaryl alcohol at elevated optical purity.This invention takes advantage of a microorganism's ability to reduce a pro-chiral bisaryl ketone to the chiral bisaryl alcohol. The alcohol is readily isolated from the media by solvent extraction, crystallography, or other purification method known to the skilled artisan. The chiral alcohol can then be converted to a PDE IV inhibitor, such as CDP 840, by methods well known in the art.Type: GrantFiled: September 8, 1997Date of Patent: May 4, 1999Assignee: Merck & Co., Inc.Inventors: Michel M. Chartrain, Hywyn R.O. Churchill, Woo-Baeg Choi, Shigeko Yamazaki
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Patent number: 5891685Abstract: Microbial cells and/or a preparation thereof of a microorganism is allowed to act on ester of .gamma.-halogenated-acetoacetic acid, and its carbonyl group at .beta.-position is stereospecifically reduced to produce ester of (S)-.gamma.-halogenated-.beta.-hydroxybutyric acid in a short period of time at a highly accumulated degree and at a high yield, the microorganism being selected from the group consisting of those belonging to the genera Phoma, Nectria, Pseudonectria, Spondylocladium, Melanospora, Metarhizium, Gliocladium, Pestalotia, Pestalotiopsis, Curvularia, Hormonema, Sydowia, Sarcinomyces, Dothiora, Xanthothecium, Dothidea, Pringsheimia, and Selenophoma.Type: GrantFiled: June 3, 1997Date of Patent: April 6, 1999Assignee: Mitsubishi Chemical CorporationInventors: Masahiro Yamagishi, Yukie Takai, Takashi Mikawa, Mari Hara, Makoto Ueda, Akiko Ohara
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Patent number: 5888804Abstract: The present invention provide processes for producing an optically active quinuclidinol from a quinuclidinone using an asymmetric reduction by a microorganism and enzyme with commercial advantages in simple and easy manner. In the present invention, permit a microorganism or preparation thereof to act on a quinuclidinone (3-quinuclidinone), and recover or harvest an optically active quinuclidinol produced (3-quinuclidinol). The microorganisms capable of producing an (R)-3-quinuclidinol from a 3-quinuclidinone include the genus Nakazawaea, the genus Candida and the genus Proteus. The microorganisms capable of producing an (S)-3-quinuclidinol from a 3-quinuclidinone include the genus Arthrobacter, the genus Pseudomonas and the genus Rhodosporidium.Type: GrantFiled: March 4, 1998Date of Patent: March 30, 1999Assignee: Daicel Chemical Industries, Ltd.Inventors: Akinobu Matsuyama, Takeshi Hamatani
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Patent number: 5885809Abstract: A method for producing (S)-cyanohydrins of general formula ##STR1## in which R and R' independently represent (1) hydrogen; (2) a substituted or unsubstituted saturated alkyl group which may include amine, imine, hydroxy, C.sub.1 -C.sub.8 -alkoxy, halogen, carboxyl, C.sub.3 -C.sub.20 -cycloalkyl groups and/or a N,O,S-heteroatom-substituted aromatic ring as substituent; (3) a substituted or unsubstituted, singly or multiply unsaturated alkenyl- or alkinyl group which may include one or several amine, imine, hydroxy, C.sub.1 -C.sub.8 -alkoxy, halogen, carboxyl, C.sub.3 -C.sub.20 -cycloalkyl groups and/or one optionally N,O,S-heteroatom-substituted aromatic ring as substituents; (4) a substituted or unsubstituted aromatic or heteroaromatic group.Type: GrantFiled: February 7, 1997Date of Patent: March 23, 1999Assignee: Degussa AktiengesellschaftInventors: Franz Effenberger, Harald Wajant, Siegfried Forster, Jurgen Roos
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Patent number: 5885816Abstract: A process for conducting optical resolution of a racemic mixture of an amino acid derivatives and a process for preparing an optically active amino acid using a catalytic antibody enantioselectively hydrolyzing an amino acid ester derivative are provided. The catalytic antibody and hybridoma producing said antibody are also provided. The hybridomas in the present invention are typically produced by stimulation with an antigen comprising as a hapten a compound of the formula: ##STR1## wherein CBZ is N-benzyloxycarbonyl.Type: GrantFiled: November 15, 1996Date of Patent: March 23, 1999Assignee: Protein Engineering Research InstituteInventors: Ikuo Fujii, Fujie Tanaka, Keiko Kinoshita
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Patent number: 5879930Abstract: L-PTC (L-phosphinothricin, L-2-amino-4-methylphosphino-butyric acid) is the active herbicidal component of D,L-PTC and can be obtained according to the invention when D,L-PTC derivatives which are N-acylated and esterified on the phosphinic acid group as well as optionally esterified or amidated on the carboxylic group, are treated with a hydrolytically active enzyme in an aqueous or aqueous-organic medium, in which process the L-PTC derivatives are selectively hydrolyzed on the N-acyl group or the modified carboxyl group, the resulting product mixture is resolved, and the desired L-PTC derivative is hydrolyzed to give the L-PTC and isolated by customary methods.Type: GrantFiled: January 5, 1998Date of Patent: March 9, 1999Assignee: Hoechst AktiengesellschaftInventors: Lothar Willms, Gerd Fulling, Reinhold Keller
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Patent number: 5879929Abstract: Methods for the enzymatic resolution of mixtures of enantiomers, such as .beta.-lactam compounds, which may be employed as intermediates in the preparation of taxanes bearing a C-13 sidechain containing a heterocyclic or cycloalkyl group, the latter useful in the pharmaceutical field.Type: GrantFiled: June 5, 1995Date of Patent: March 9, 1999Assignee: Bristol-Myers Squibb CompanyInventor: Ramesh N. Patel
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Patent number: 5874262Abstract: A microbiological process for the preparation of N,N'-ethylenediaminedisuccinic acid of formula (1), by (a) precultivation of a strain of the genus Amycolatopsis orientalis on a specified nutrient medium (1st preculture), (b) inoculation of a nutrient solution of the same composition as the base of the production fermenter by the 1st preculture (2nd preculture), (c) inoculation of the base nutrient solution in the production fermenter with the 2nd preculture and incubation in accordance with a specified timetable, (d) feeding of the production fermenter in the fed-batch process with a feeding solution under aerobic conditions at a pH of from 2 to 8 and at a temperature of from 15.degree. to 40.degree. C., wherein the base nutrient and feeding solutions are free of zinc-containing compounds, is described. The compound prepared by the process according to the invention is suitable as complexing agent with good biodegradability in detergents.Type: GrantFiled: November 17, 1997Date of Patent: February 23, 1999Assignee: Ciba Specialty Chemicals CorporationInventors: Hans Zahner, Ingeborg Cebulla, Michael Harder
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Patent number: 5869324Abstract: A method of preparing (.+-.)-calanolide A, 1, a potent HIV reverse transcriptase inhibitor, from chromene 4 is provided. Useful intermediates for preparing (.+-.)-calanolide A and its derivatives are also provided. According to the disclosed method, chromene 4 intermediate was reacted with acetaldehyde diethyl acetal or paraldehyde in the presence of an acid catalyst with heating, or a two-step reaction including an aldol reaction with acetaldehyde and cyclization either under acidic conditions or neutral Mitsunobu conditions, to produce chromanone 7. Reduction of chromanone 7 with sodium borohydride, in the presence of cerium trichloride, produced (.+-.)-calanolide A. A method for resolving (.+-.)-calanolide A into its optically active forms by a chiral HPLC system or by enzymatic acylation and hydrolysis is also disclosed. Finally, a method for treating or preventing viral infections using (.+-.)-calanolide A or (-)-calanolide A is provided.Type: GrantFiled: September 8, 1997Date of Patent: February 9, 1999Assignee: Sarawak MediChem Pharmaceuticals, Inc.Inventors: Michael T. Flavin, Ze-Qi Xu, John D. Rizzo, Alla Kucherenko, Albert Khilevich, Abram Kivovich Sheinkman, Vilayphone Vilaychack, Lin Lin, Wei Chen, William A. Boulanger
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Patent number: 5866381Abstract: Described is a microbiological method for producing C.sub.9, C.sub.11 and C.sub.13 alkanols defined according to the structures: ##STR1## wherein R.sub.1 is methyl or n-propyl using ketones defined according to the generic structure: ##STR2## as a substrate and using the microorganism: Pseudomonas cepacia ATCC 55792or mutants thereof.Type: GrantFiled: April 23, 1998Date of Patent: February 2, 1999Assignee: International Flavors & Fragrances Inc.Inventors: Mohamad I. Farbood, Laura E. Kizer, Lynda B. McLean, Mark A. Sprecker
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Patent number: 5861304Abstract: Process for the resolution of rac-2-oxotricyclo?2.2.1.0.sup.3,5 !heptane-7-carboxylic acid esters using lipase from candida.Compounds of the formula I ##STR1## in which R.sup.1 has the meanings mentioned, may be obtained in isomerically pure form from enantiomer mixtures or racemic mixtures by reacting the compound of the formula I in the presence of a lipase or esterase from porcine liver, porcine pancreas, bovine pancreas or from microorganisms such as Candida, Pseudomonas, Mucor, Rhizopus and Aspergillus, or proteases from Bacillus in the presence of water and, if desired, a cosolvent and separating from one another the esters and acids present in the solution obtained.Type: GrantFiled: September 17, 1997Date of Patent: January 19, 1999Assignee: Hoechst AktiengesellschaftInventors: Wolfgang Holla, Gerhard Beck
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Patent number: 5858737Abstract: A process is disclosed that bioconverts indene to (1S)-amino-(2R)-indanol substantially free of any of its stereoisomers, by the action of a strain of P. putida or Rhodococcus sp., followed by various chemical step(s), e.g., chiral specific crystallization, treatment with strong acid in the presence of acetonitrile.Type: GrantFiled: August 14, 1996Date of Patent: January 12, 1999Assignee: Merck & Co., Inc.Inventors: Barry C. Buckland, Neal C. Connors, Michel M. Chartrain, Francis P. Gailliot, Randolph L. Greasham, Barbara Jackey, Brian Heimbuch, Chanyong Lee, Roger C. Olewinski, Jr., F. Edward Roberts, Paul J. Reider, Thomas R. Verhoeven, Chris H. Senanayake
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Patent number: 5854062Abstract: Method of preparing an optically active compound of formula, wherein R and R.sup.1 are independently alkyl, alkenyl, alkynyl, alkoxy, alkoxyalkyl, cycloalkyl, aryl, aralkyl, a heterocyclic group or a C.sub.1 -C.sub.4 alkyl-heterocycle, each being optionally substituted, procided that R and R.sup.1 are not identical and * is an optically active chiral center, from the corresponding racemic ester or diol by treating with a hydrolase enzyme. In particular, racemic 2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazol-1-yl)propan-1,2 diol, an intermediate in fluconazole synthesis, is resolved using porcine pancreatic lipase or lipase from Chromobacterium viscosum.Type: GrantFiled: December 11, 1995Date of Patent: December 29, 1998Assignees: Zeneca Limited, Mochida Pharmaceuticals Co., Ltd.Inventors: Andrew John Blacker, Andrew George Brewster, Robert Jeffrey Copeland, Robert Antony Holt
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Patent number: 5854015Abstract: A method is disclosed for making the 3R-3'R stereoisomer of zeaxanthin as a sole detectable or heavily dominant (more than about 90%) stereoisomer, for human ingestion. Zeaxanthin, a yellowish pigment which is naturally present in macular cells in the center of the human retina, absorbs blue and near-ultraviolet light radiation, thereby protecting the retinal cells against phototoxic damage. Zeaxanthin preparations which contain only the desired R--R isomer can be produced by a strain of Flavobacterium multivorum cells (ATCC accession number 55238). These cells (and other cells transformed with their zeaxanthin-producing genes) do not create any detectable quantities of the undesired S--S or S-R isomers of zeaxanthin, and they do not synthesize significant quantities of other carotenoids which might compete against zeaxanthin for alimentary uptake after oral ingestion.Type: GrantFiled: October 31, 1995Date of Patent: December 29, 1998Assignee: Applied Food Biotechnology, Inc.Inventors: Kevin M. Garnett, Dennis L. Gierhart, Luis H. Guerra-Santos
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Patent number: 5849568Abstract: A process is disclosed that hydrolyzes, by the action of an epoxide hydrolase of Diplodia gossipina (alternatively named Diplodia gossypina) ATCC 16391 or ATCC 10936, the undesired enantiomer of racemic indene oxide, an epoxide of indan.Type: GrantFiled: February 20, 1996Date of Patent: December 15, 1998Assignee: Merck & Co., Inc.Inventors: Michel M. Chartrain, Chris H. Senanayake, John P. N. Rosazza, Jinyou Zhang
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Patent number: 5846792Abstract: Tyrosine decarboxylase, or microorganisms of the genuses Enterococcus, Lactobacillus, Providencia, Fusarium, and Gibberella were reacted with a mixture of the enantiomers of threo-3-phenylserine or its halogen substitution products to produce (R)-2-amino-1-phenylethanol or its halogen substitution products. At the same time, one of the enantiomers of threo-3-phenylserine or its halogen substitution products were selectively left, and optically active threo-3-phenylserine or its halogen substitution products were produced. In addition, a novel material of 3-(3-chlorophenyl)serine, which is a substrate of the reaction in the present invention, was produced. (R)-2-amino-1-phenylethanol or its halogen substitution products, and optically active threo-3-phenylserine or its halogen substitution products can economically be produced on an industrial scale.Type: GrantFiled: April 22, 1997Date of Patent: December 8, 1998Assignee: Daicel Chemical Industries, Ltd.Inventors: Teruyuki Nikaido, Naoki Kawada, Takeshi Hamatani, Yoichiro Ueda
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Patent number: 5843765Abstract: The invention disclosed relates to the biological production of substantially isomerically pure (R)-baclofen and structurally related compounds, from the racemic mixture of (R)- and (S)-isomers thereof, and to the isolation of a Streptomyces microorganism from Nature which is capable of preferentially metabolizing one of the isomers while showing minimal metabolic activity on the other isomer. A fermentation or bioconversion process using this microorganism or the cell-free enzymes derived therefrom for the biological resolution of a racemic mixture of (R)- and (S)-baclofen and structurally related compounds is also disclosed.Type: GrantFiled: January 31, 1997Date of Patent: December 1, 1998Assignee: National Research Council of CanadaInventors: Wayne Levadoux, Denis Groleau, Michael Trani, Robert Lortie
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Patent number: 5837483Abstract: An enzymatic method for producing N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester by a condensation reaction between N-formyl-L-aspartic acid and L-phenylalanine methyl ester or D,L-phenylalanine methyl ester, which comprises: supplying an organic phase comprising a water-immiscible solvent containing N-formyl-L-aspartic acid and L- or D,L-phenylalanine methyl ester onto an aqueous phase comprising a thermolysin-like metalloprotease; proceeding the condensation reaction in the aqueous phase to produce N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester; and extracting the N-formyl-.alpha.-L-aspartyl-L-phenylalanine methyl ester thus produced from the aqueous phase to the organic phase.Type: GrantFiled: September 29, 1997Date of Patent: November 17, 1998Assignee: Holland Sweetener Company V.o.F.Inventor: Akira Hirata
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Patent number: 5834259Abstract: A process and composition for preparing D-aspartic acid and .beta.-alanine from D,L-aspartic acid, wherein a solution of D,L-aspartic acid or a salt thereof is contacted with a composition having an L-aspartate-.alpha.-decarboxylase activity of greater than 100 .mu.mol L-aspartate used per hour per gram of cells, under appropriate conditions to produce D-aspartic acid and .beta.-alanine.Type: GrantFiled: October 28, 1996Date of Patent: November 10, 1998Assignee: Monsanto CompanyInventors: David P. Pantaleone, Ian G. Fotheringham, Jennifer L. Ton
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Patent number: 5834261Abstract: The disclosure describes a method for the preparation of chiral vicinal aminoalcohols in high optical purity. The method combines the stereoselective reduction of the keto group of a .beta.-ketoacid, .beta.-keotester, or derivative with the stereospecific rearrangement of the corresponding amide, hyroxamic acid, or hydrazide to produce chiral vicinal aminoalcohols with control of stereochemistry at both chiral centers.Type: GrantFiled: May 27, 1997Date of Patent: November 10, 1998Assignee: BioCatalytics, Inc.Inventor: J. David Rozzell, Jr.
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Patent number: 5827727Abstract: A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (-)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner. In particular, deaminase, PPL, PLE and subtilisn are used to resolve 1,3-oxathiolane nucleoside enantiomers.Type: GrantFiled: June 7, 1995Date of Patent: October 27, 1998Assignees: Emory University, Yale UniversityInventors: Dennis C. Liotta, Raymond F. Schinazi, Woo-Baeg Choi, Yung-Chi Cheng
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Patent number: 5811293Abstract: An (R)-2-amino-1-phenylethanol derivative shown by the general formula (IIa) ##STR1## wherein R.sup.1 and R.sup.5 represent a hydrogen atom, etc.; R.sup.2, R.sup.3 and R.sup.4 independently represent a halogen atom, etc., or a salt thereof, can readily be produced (1) by permitting a microorganism belonging to the genus Rhodosporidium, the genus Comamonas or the like to act on a mixture of corresponding (R)-form and (S)-form to asymmetrically utilize, or (2) by permitting a microorganism belonging to the genus Lodderomyces, the genus Pilimelia or the like to act on a corresponding aminoketone derivative to asymmetrically reduce. An (R,R)-1-phenyl-2-?(2-phenyl-1-alkylethyl) amino!ethanol derivative having a high optical purity can easily be obtained from the compound of the formula (IIa) or a salt thereof. Said derivative is useful as an intermediate for producing an anti-obesity agent and so on.Type: GrantFiled: October 28, 1996Date of Patent: September 22, 1998Assignee: Daicel Chemical Industries, Ltd.Inventors: Kazuaki Furukawa, Takayuki Abe, Hidekazu Akamatsu, Akinobu Matsuyama, Michio Ito, Noritsugu Yamasaki, Katsuya Miki, Kiyoshi Ikura, Takeshi Ishiguro
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Patent number: 5811292Abstract: Methods for the enzymatic resolution of mixtures of enantiomers, such as .beta.-lactam compounds, which may be employed as intermediates in the preparation of taxanes such as taxol, the latter useful in the pharmaceutical field.Type: GrantFiled: August 1, 1996Date of Patent: September 22, 1998Assignee: E. R. Squibb & Sons, Inc.Inventors: Ramesh N. Patel, Laszlo J. Szarka, Richard A. Partyka
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Patent number: 5811294Abstract: A process for resolution of a mixture of cis-dihydroxydihydroindene enantiomers comprising treating the mixture of enantiomers with a Pseudomonas putida species microorganism.Resolved dihydroxydihydroindenes are valuable intermediates for the synthesis of biologically active compounds such as pharmaceuticals and agrochemicals.Type: GrantFiled: April 4, 1997Date of Patent: September 22, 1998Assignee: Zeneca LimitedInventors: Christopher Curtis Royston Allen, Derek Raymond Boyd, Howard Dalton
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Patent number: 5798234Abstract: Enzymes with modified substrate specificity and methods of obtaining same by the steps of a) determining the structure of two or more enzymes in the same group, b) comparing the structure of the substrate binding sites of the enzymes, and c) modifying selected amino acids by genetic mutation so that the substrate preference of one of the enzymes is altered. The methods are particularly useful for the stereospecific interconversion of oxyacids and aminoacids.Type: GrantFiled: April 1, 1997Date of Patent: August 25, 1998Assignee: Degussa AktiengesellschaftInventors: Paul C. Engel, David Rice
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Patent number: 5783427Abstract: Disclosed is a process for preparing a D-amino acid selected from the group consisting of D-methionine, D-valine, D-leucine, D-isoleucine and D-histidine, which comprises the steps of:making a culture or treated culture of a microorganism having ability to asymmetrically degrade a L-amino acid selected from the group consisting of L-methionine, L-valine, L-leucine, L-isoleucine and L-histidine act on a corresponding racemic amino acid to the L-amino acid; andseparating and collecting the remaining D-amino acid.Type: GrantFiled: March 26, 1996Date of Patent: July 21, 1998Assignee: Tanabe Seiyaku Co., Ltd.Inventors: Masakatsu Furui, Eiji Takahashi, Hiroyasu Seko, Takeji Shibatani
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Patent number: 5776765Abstract: A compound of formula (II), either as a single enantiomer or in an enantiomerically enriched form ##STR1## wherein: ##STR2## and ##STR3## (wherein N in the benzimidazole moiety of Het.sub.2 means that one of the carbon atoms substituted by any one of R.sub.6 to R.sub.9 optionally may be exchanged for an unsubstituted nitrogen atom; R.sub.1, R.sub.2 and R.sub.3 are the same or different and selected from hydrogen, alkyl, alkoxy optionally substituted by fluorine, alkylthio, alkoxyalkoxy, dialkylamino, piperidino, morpholino, halogen, phenylalkyl, phenylakoxy; R.sub.4 and R.sub.4, are the same or different and selected from hydrogen, alkyl, aralkyl; R.sub.5 is hydrogen, halogen, trifluoromethyl, alkyl, alkoxy; R.sub.6 -R.sub.9 are the same or different and selected from hydrogen, alkyl, alkoxy, halogen, haloalkoxy, alkylcarbonyl, alkoxycarbonyl, oxazolyl, trifluoroalkyl or adjacent groups R.sub.6 -R.sub.Type: GrantFiled: December 18, 1995Date of Patent: July 7, 1998Assignee: Astra AktiebolagInventors: Daniel Graham, Robert Holt, Per Lindberg, Stephen Taylor
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Patent number: 5776766Abstract: A novel method for preparing optically active chlorohydrin compound and optically active 1,2-diol compound and/or optically active 3-hydroxy-.gamma.-butyrolactone which are useful as intermediates for preparing medicaments, agricultural chemicals, physiologically active substances and ferroelectric liquid crystals, which comprises treating a racemic chlorohydrin compound having the formula: ##STR1## wherein R.sup.1 is H or lower alkyl group; and R.sup.2 is substituted or unsubstituted lower alkyl group when R.sup.1 is H; or R.sup.2 is H when R.sup.1 is lower alkyl group with a microorganism, whereby selectively degrading only one of optical isomers thereof, and recovering the remaining an other optically active chlorohydrin and isolating optically active 1,2-diol compound and/or optically active 3-hydroxy-.gamma.-butyrolactone converted by the reaction.Type: GrantFiled: May 21, 1996Date of Patent: July 7, 1998Assignee: Daiso Co., Ltd.Inventors: Naoya Kasai, Toshio Suzuki, Hideaki Idogaki
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Patent number: 5773284Abstract: Process for the preparation of a threo-phenylserine amide of the general formula 2 in which glycine amide is contacted with the corresponding substituted benzaldehyde of formula 3 in an excess relative to the amount of glycine amide, this taking place at a pH between 9 and 14 in the presence of a suitable solvent. The resulting phenylserine amide can subsequently be hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently hydrolyzed to a phenylserine amide of the general formula 1, which is subsequently subjected to a stereoselective enzymatic hydrolysis yielding a (2S,3R) phenylserine. The non-hydrolyzed (2R,3S) phenylserine amide can be isolated as a Schiff base and be recirculated and simply racemized. The (2S,3R) phenylserine obtained can be used in the preparation of thiamphenicol or florfenicol. The threo-phenylserine amides of the general formula 1 or 2 are new intermediates in this commercially attractive process for the preparation of thiamphenicol and florfenicol.Type: GrantFiled: June 12, 1996Date of Patent: June 30, 1998Assignee: DSM N.V.Inventor: Bernardus Kaptein
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Patent number: 5773264Abstract: A process for the production of 17.alpha.-hydroxy-3-methoxy-8,14-seco-1,3,5 (10),9(11)estratetraen-14-one by fermentation of 3-methoxy-8,14-seco-1,3,5(10),9(11) -estratetraene-14,17-dione with a live culture of Kloeckera magna is described, which is characterized in that the substrate is reacted in the form of a solventless aqueous suspension with an average grain size of 0.2 to 5 .mu.m.Type: GrantFiled: September 26, 1994Date of Patent: June 30, 1998Assignee: Schering AktiengesellschaftInventors: Alfred Weber, Mario Kennecke, Hans-Jorg Vidic
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Patent number: 5770438Abstract: A process for producing an optically active form of a compound of formula (I) ##STR1## wherein R.sub.1 represents hydrogen or a hydrocarbon group that may be substituted; R.sub.2 and R.sub.3 independently represent hydrogen, a hydrocarbon group that may be substituted, or a heteroaromatic group that may be substituted; X' represents a substituent comprising an esterified carboxyl group or an acylated hydroxyl group; ring A represents a benzene ring that may be substituted or a heteroaromatic ring that may be substituted; ring J' represents a 7- or 8-membered heterocyclic ring containing at most 3 hetero-atoms as ring-constituent members, which may have a further substituent or substituents in addition to R.sub.1, R.sub.2, R.sub.Type: GrantFiled: October 31, 1995Date of Patent: June 23, 1998Assignee: Takeda Chemical Industries, Ltd.Inventors: Kazuo Nakahama, Motowo Izawa, Yoichi Nagano, Naoki Tarui, Kiyoharu Matsumoto, Masakuni Kori, Tsuneo Kanamaru, Toshiaki Nagata
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Patent number: 5766932Abstract: The present invention is related to a novel process for preparing N-acetyl-(L)-4-cyanophenylalanine by resolving the racemic compound N-acetyl-(D,L)-4-cyanophenylalanine ethyl ester, and a novel process to prepare a stereoisomer of Ac-(L)-pAph-Chg-PalMe(3)-NH.sub.2 by using the intermediate N-acetyl-(L)-4-cyanophenylalanine.Type: GrantFiled: December 17, 1996Date of Patent: June 16, 1998Assignee: Hoechst Marion Roussel, Inc.Inventor: Chi-Hsin R. King
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Patent number: 5766918Abstract: The present invention concerns polypeptides that possess an enantioselective amidase activity. It also concerns the genetic material required for the expression of these polypeptides as well as a microbiological procedure for their preparation. Finally, this invention concerns the utilization of these polypeptides and of transformed microorganisms for the enantioselective synthesis of acids from racemic amides, and in particular propionic acids, especially (S)-2-aryl-propionamide.Type: GrantFiled: October 5, 1995Date of Patent: June 16, 1998Assignee: Rhone-Poulenc SanteInventors: Dominique Petre, Edith Cerbelaud, Jean-Fran.cedilla.ois Mayaux, Patrice Yeh
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Patent number: 5756800Abstract: Process for the enzymatic resolution of 2-amino-4-methylphosphinobutyric acid derivatives.L-PTC (L-phosphinothricin, L-2-amino-4-methylphosphinobutyric acid) is the active herbicidal component of D,L-PTC and can be obtained according to the invention when D,L-PTC derivatives which are N-acylated and esterified on the phosphinic acid group as well as optionally esterified or amidated on the carboxylic group, are treated with a hydrolytically active enzyme in an aqueous or aqueous-organic medium, in which process the L-PTC derivatives are selectively hydrolyzed on the N-acyl group or the modified carboxyl group, the resulting product mixture is resolved, and the desired L-PTC derivative is hydrolyzed to give the L-PTC and isolated by customary methods.Type: GrantFiled: May 25, 1995Date of Patent: May 26, 1998Assignee: Hoechst AktiengesellschaftInventors: Lothar Willms, Gerd Fulling, Reinhold Keller
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Patent number: 5756346Abstract: L-PTC (L-phosphinothricin, L-2-amino-4-methylphosphino-butyric acid) is the active herbicidal component of D,L-PTC and can be obtained according to the invention when D,L-PTC derivatives which are N-acylated and esterified on the phosphinic acid group as well as optionally esterified or amidated on the carboxylic group, are treated with a hydrolytically active enzyme in an aqueous or aqueous-organic medium, in which process the L-PTC derivatives are selectively hydrolyzed on the N-acyl group or the modified carboxyl group, the resulting product mixture is resolved, and the desired L-PTC derivative is hydrolyzed to give the L-PTC and isolated by customary methods.Type: GrantFiled: January 23, 1996Date of Patent: May 26, 1998Assignee: Hoechst AktiengesellschaftInventors: Lothar Willms, Gerd Fulling, Reinhold Keller
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Patent number: 5756321Abstract: Methods for the enzyme catalyzed acylation of primary and secondary alcohols using an enol ester as the acyl donor are described. The acylation occurs in organic media, and is enantioselective for racemic or prochiral alcohols. The reaction is irreversible, and produces unreactive by-products.Type: GrantFiled: February 20, 1996Date of Patent: May 26, 1998Assignee: Hoechst AktiengesellschaftInventors: Manfred Schudok, Gerhard Kretzschmar
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Patent number: 5753495Abstract: A process for the preparation of (L)-2-chloropropionic acid and its alkali metal, alkaline earth metal or ammonium salts which comprises hydrolyzing isobutyl L-chloropropionate at a pH of from 4 to 8 in the presence of a lipase from Pseudomonas spec. DSM 8246 and isolating the optically active reaction product from the reaction mixture either directly or after conversion of the salt into the acid in a conventional way, or further reacting it in situ. The optically active products are important intermediates for preparing crop protection agents.Type: GrantFiled: February 15, 1996Date of Patent: May 19, 1998Assignee: BASF AktiengesellschaftInventors: Wolfgang Ladner, Hansjorg Rettenmaier, Bernhard Zipperer, Hanspeter Hansen
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Patent number: 5750382Abstract: A process for efficiently producing (S,S)-2-alkoxycyclohexanols in a single step by using (.+-.)-trans-2-alkoxycyclohexanols which are inexpensive and can be easily obtained. The process comprises treating a (.+-.)-trans-2-alkoxycyclohexanol with a hydrolase originating in a microorganism and being capable of esterifying stereospecifically the R-isomer in the presence of an acyl donor under such conditions that no hydrolysis occurs substantially to thereby give (S,S)-2-alkoxycyclohexanols and (R,R)-2-alkoxycyclohexanol carboxylate and then taking up the (S,S)-2-alkoxycyclohexanols.Type: GrantFiled: June 13, 1997Date of Patent: May 12, 1998Assignee: Kaneka CorporationInventors: Naoaki Taoka, Mizuho Honda, Kenji Inoue, Kazunori Kan
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Patent number: 5736385Abstract: A reaction system, wherein a cyanohydrin is converted into an optically active .alpha.-hydroxy acid or .alpha.-hydroxyamide via a treatment with a microorganism, is provided with an automatic cyanohydrin controller comprising a cyano ion detector, a regulator and a cyanohydrin supplier linked thereto. The reaction is performed while automatically controlling the cyanohydrin concentration.Thus cyanohydrin can be supplied under automatic control at a relatively low and constant concentration on the basis of its consumption ratio. The reaction rate of the catalyst can be continuously regarded as the rate-limiting factor. As a result, a decrease in the enzymatic activity during the reaction can be suppressed and an optically active .alpha.-hydroxy acid or .alpha.-hydroxyamide can be efficiently obtained at a high yield.Type: GrantFiled: November 9, 1995Date of Patent: April 7, 1998Assignee: Nitto Chemical Industry Co., Ltd.Inventor: Koji Tamura
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Patent number: 5733754Abstract: An enzyme is provided which has acylase activity capable of hydrolyzing N-acetyl-(R,S)-pipecolic acid stereoselectively to give (S)-pipecolic acid, wherein this activity is greater than that on N-acetyl-S-proline, at pH 7.5, 25.degree. C., and substrate concentration 20 g/l, in 75 mM Tris buffer. The enzyme is obtainable from the species of Alcaligenes denitrificans deposited as NCIMB 40587. A microorganism having therein the enzyme also is provided, as is a process for preparing (S)-pipecolic acid comprising contacting a mixture of enantiomers of an N-acyl-pipe colic acid with the enzyme or microorganism.Type: GrantFiled: April 8, 1996Date of Patent: March 31, 1998Assignee: Chiroscience LimitedInventors: Richard Anthony Wisdom, Caroline Susan Lee, Paul Maurice Ricaud
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Patent number: 5733749Abstract: A biologically pure enzyme comprising D-.alpha.-glycerophosphatase from Bacillus licheniformis is disclosed. A genetic construction in a heterologous host capable of producing D-.alpha.-glycerophosphate is also disclosed, wherein the construction includes a protein coding sequence for D-.alpha.-glycerophosphatase from Bacillus licheniformis.Type: GrantFiled: August 14, 1995Date of Patent: March 31, 1998Assignee: Wisconsin Alumni Research FoundationInventors: Douglas C. Cameron, Frank A. Skraly
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Patent number: 5733755Abstract: A method for manufacturing S-3-(4'-tert-butyl)-phenyl-2-methyl propylamines having the structure I ##STR1## where NR.sub.1 R.sub.Type: GrantFiled: November 5, 1996Date of Patent: March 31, 1998Assignee: Industrie Chimiche Capparo S.p.A.Inventors: Vitomir Sunjic, Maja Majeric, Zdenko Hamersak, Amir Avdagic
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Patent number: 5731175Abstract: Tyrosine decarboxylase, or microorganisms of the genuses Enterococcus, Lactobacillus, Providencia, Fusarium, and Gibberella were reacted with a mixture of the enantiomers of threo-3-phenylserine or its halogen substitution products to produce (R)-2-amino-1-phenylethanol or its halogen substitution products. At the same time, one of the enantiomers of threo-3-phenylserine or its halogen substitution products were selectively left, and optically active threo-3-phenylserine or its halogen substitution products were produced. In addition, a novel material of 3-(3-chlorophenyl)serine, which is a substrate of the reaction in the present invention, was produced. (R)-2-amino-1-phenylethanol or its halogen substitution products, and optically active threo-3-phenylserine or its halogen substitution products can economically be produced on an industrial scale.Type: GrantFiled: August 29, 1996Date of Patent: March 24, 1998Assignee: Daicel Chemical Industries, Ltd.Inventors: Teruyuki Nikaido, Naoki Kawada, Takeshi Hamatani, Yoichiro Ueda
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Patent number: 5728575Abstract: A process for the resolution of a racemic mixture of nucleoside enantiomers that includes the step of exposing the racemic mixture to an enzyme that preferentially catalyzes a reaction in one of the enantiomers. The nucleoside enantiomer (-)-2-hydroxymethyl-5-(5-fluorocytosin-1-yl)-1,3-oxathiolane is an effective antiviral agent against HIV, HBV, and other viruses replicating in a similar manner.Type: GrantFiled: June 7, 1995Date of Patent: March 17, 1998Assignee: Emory UniversityInventors: Dennis C. Liotta, Woo-Baeg Choi
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Patent number: 5728876Abstract: A process for producing optically active primary and secondary amines from the corresponding racemates is characterised in that (a) a racemic amine is enantioselectively acylated in the presence of a hydrolase with an ester whose acid component bears a fluorine, nitrogen, oxygen or sulphur atom at the proximity of the carbonyl carbon atom; (b) the mixture of optically active amine and optically active acylated amine is separated so that an enantiomer of amine is produced; (c) if desired the other enantiomer of the amine is extracted from the acylated amine by amide cleavage.Type: GrantFiled: March 11, 1996Date of Patent: March 17, 1998Assignee: BASF AktiengesellschaftInventors: Friedhelm Balkenhohl, Bernhard Hauer, Wolfgang Ladner, Uwe Pressler, Christoph Nubling
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Patent number: 5726055Abstract: A process for preparing 5-(4-?2-(N-methyl-N-(2-pyridyl)amino)-ethoxy!-benzyl)-2,4-thiazolidinedion e, by treating 5-(4-?2-(N-methyl-N-(2-pyridyl)amino)-ethoxy!benzylidene)-2,4-thiazolidine dione with a free whole yeast cell culture or immobilized whole yeast cells from Rhodotorula glutinis CBS 4406 or Rhodotorula rubra CBS 6469 as the microbial reductase source and recovering 5-(4-?2-N-methyl-(N-(2-pyridyl)amino)ethoxy!-benzyl)-2,4-thiazolidinedione , or a salt thereof.Type: GrantFiled: May 19, 1994Date of Patent: March 10, 1998Assignee: SmithKline Beecham plcInventors: Richard Mark Hindley, Stefan Roland Woroniecki
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Patent number: 5726047Abstract: A process for producing optically active 1-halo-3-amino-4-phenyl-2-butanol derivatives from optically active 1-halo-3-amino-4-phenyl-2-butanone derivatives stereoselectively in a high yield by bringing the butanone derivatives into contact with microorganisms.Type: GrantFiled: April 4, 1997Date of Patent: March 10, 1998Assignee: Kaneka CorporationInventors: Tadashi Sugawa, Kenji Inoue
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Patent number: 5716841Abstract: A process for the preparation of ethyl 4,4,4-trifluoro-3(R)-hydroxybutanoate, wherein the ester functional group of the (S) enantiomer of ethyl (.+-.)-4,4,4-trifluoro-3-hydroxybutanoate which comprises (R) and (S) is selectively hydrolysed in aqueous medium, by means of a lipase, and the non-hydrolysed (R) enantiomer is then extracted and used in the preparation of 4,4,4-trifluoro-1,3(R)-butanediol.Type: GrantFiled: April 5, 1996Date of Patent: February 10, 1998Assignee: SynthelaboInventors: Arlette Tixidre, Lydia Zard, Guy Rossey, Andre Bourbon
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Patent number: RE36092Abstract: Substituted cyclodextrins of the general formula ##STR1## in which R.sup.2 and R.sup.6 mean straight-chain or branched alkyl or alkenyl groups with 1 to 8 carbon atoms or cycloalkyl groups with 5 to 8 carbon atoms which can be the same or different, andR.sup.3 represents a straight-chain or branched alkyl or alkenyl group, which can be the same or different to the residues R.sup.2 and R.sup.6, with 1 to 8 carbon atoms or a cycloalkyl group with 5 to 8 carbon atoms, oran acyl group with an optionally substituted, saturated or olefinically unsaturated aliphatic or cycloaliphatic or with an aromatic hydrocarbon residue with 1 to 8 carbon atoms, andn=6 or 7,a process for their production, and a process for the separation of chiral organic compounds by chromatographic separation processes in which the substituted cyclodextri are used as stationary phase.Type: GrantFiled: September 5, 1995Date of Patent: February 9, 1999Assignee: Macherey-Nagel & Co.Inventors: Wilfried Konig, Gerhard Wenz, Sabine Lutz, Eva von der Bey