Abstract: The present invention provides a method for preparing (S)-4-halo-3-hydroxybutyric acid ester comprises asymmetric reduction of 4-halo-acetoacetic acid ester using ?-ketoacyl-acylcarrier protein reductase constituting Type II fatty acid synthase or acetoacetyl-CoA reductase constituting the poly-?-hydroxy fatty acid synthesis system. ?-ketoacyl-acyl carrier protein reductase constituting Type II fatty acid synthase or acetoacetyl-CoA reductase constituting the poly-?-hydroxy fatty acid synthesis system has a extremely high reducing activity as well as stereoseletivity for (S)-4-chloro-3-hydroxybutyric acid ester. In addition, the enzyme exhibits almost no oxidizing activity toward either configuration of ethyl 4-chloro-3-hydroxybutyrate, performing only the reducing reaction of ethyl, 4-chloroacetoacetate. Therefore, this enzyme can be used to efficiently produce (S)-4-halo-3-hydroxybutyric acid ester.

Abstract: The present invention provides a process for easily preparing a (S)-&agr;-halomethylpyridine-methanol derivative, which is useful as an intermediate of pharmaceutical products, from inexpensive raw materials. The (S)-&agr;-halomethylpyridine-methanol derivative is prepared by (S)-selectively reducing a 2-haloacetylpyridine derivative using an enzyme source having ability to (S)-selectively reduce a carbonyl group of the 2-haloacetylpyridine derivative, which can be obtained inexpensively. Also, a hydrohalic acid salt of (S)-&agr;-halomethyl-3-pyridine-methanol derivative is isolated and purified as crystal from a (S)-&agr;-halomethyl-3-pyridine-methanol derivative containing impurities using hydrohalic acid and an organic solvent.

Abstract: A process for producing an optical active &bgr;-amino alcohol, the method comprising the step of allowing at least one microorganism selected from the group consisting of microorganisms belonging to the genus Morganella and others, to act on an enantiomeric mixture of an &agr;-aminoketone or a salt thereof having the general formula (I): to produce an optical active &bgr;-amino alcohol with the desired optical activity having the general formula (II) described below in a high yield as well as in a highly selective manner:

Abstract: A description is given of epoxide hydrolases from bacteria of the genus Streptomyces, a novel process for the enzymatic separation of epoxide enantiomeric mixtures, of a novel detection method for epoxide hydrolase activity, a screening method for detecting epoxide hydrolase activity and the use of bacteria of the genus Streptomyces and of the resultant epoxide hydrolases for enantioselective epoxide hydrolysis.

Abstract: The present invention relates to a method for determining the enantioselectivity of kinetic resolution processes and of asymmetrically proceeding reactions of prochiral compounds bearing enantiotopic groups by using isotope-labeled substrates so that the reaction products can be quantitatively determined with an isotope-specific detection system, e.g., an ESI mass spectrometer. In connection with automated sample charging, the method can be employed for high throughput screening. The relevant enantioselective conversions can be induced by chiral homogeneous or heterogeneous catalysts, biocatalysts or stoichiometric amounts of optically active agents.

Abstract: The present invention discloses a process for efficiently producing, on an industrial scale, optically active (R)-2-chloro-1-(3′-chlorophenyl)ethanol which is useful as a raw material for the synthesis of medicines, agricultural chemicals, etc.

Abstract: The present invention relates to a novel D-hydantoinase from Ochrobactrum anthropi that enantio-selectively hydrolyzes D-hydantoins to their corresponding D-N-carbamoyl-amino acids; nucleic acids that encode for the enzyme; expression vectors including the nucleic acids; and host cells capable of expressing the enzyme.

Abstract: The present invention is directed to novel stereoselective processes for the preparation of (S)-1-arylethanols by the reduction of the corresponding keto group containing compounds by microorganisms. (S)-1-arylethanols are useful as intermediates in the synthesis of compounds that are inhibitors of &ggr;-secretase useful in the treatment of Alzheimer's disease.

Abstract: A biotechnological method is described for preparing compounds of the general formulas wherein R1 is acyl or acyloxy and R2 is a hydrogen atom or C1-10 alkyl, comprising the conversion of a lactam of the general formula by means of a hydrolase in the presence of a nucleophile and in the presence of a base in a constant pH range.

Abstract: A method for producing from one of the optical isomers (optical isomer I) of an amino acid represented by Formula (1):R—CH(NH2)—COOH (1), wherein R is defined in the specification, the other of the optical isomers (optical isomer II), said method comprising reacting a biological material which has an ability of converting said one of the optical isomers (optical isomer I) to said the other of the optical isomers (optical isomer II), the isomerism being on the basis of an assymetric carbon atom to which both of an amino group and a carboxyl group are bound and said ability being not inhibited seriously by an amino acid transferase inhibitor &bgr;-chloro-D-alanine, &bgr;-chloro-L-alanine or gabaculine, with said one of the optical isomers (optical isomer I).

Abstract: The present invention provides a process for preparation of optically active azabicyclo heptanone derivates using lactamases that will react with racemic lactam of formula (I) to give a single enanotiomer of lactam (III) and the corresponding ring opened compound of formula (IV) in an enantiomerically pure form.

Abstract: The present invention provides a method for enzymatically producing optically active mandelic acid derivatives. An optically active mandelic acid derivative (shown as Formula II) is produced by reacting a culture or cell body of a microorganism, or processed products thereof, with a phenylglyoxylic acid derivative, and then recovering the obtained optically active mandelic acid derivative, wherein the microorganism has the ability to stereo-selectively reduce the phenylglyoxylic acid derivative. An optically active mandelic acid obtained according to the present invention is useful as an intermediate for the synthesis of pharmaceuticals and agricultural chemicals.

Abstract: The invention relates to the use of the N-acetyl amino acid racemase from Amycolatopsis orientalis subspecies lurida for the racemiszation of N-carbamoyl amino acids. This use permits the 100% preparation of optically pure amino acids starting from racemic hydantoins in an enzymatic overall process.

Abstract: The invention is a process for stereoselectively producing a dioxolane nucleoside analogue from an anomeric mixture of &bgr; and &agr; anomers represented by the following formula A or formula B: wherein R is selected from the group consisting of C1-6 alkyl and C6-15 aryl and Bz is benzoyl. The process comprises hydrolyzing said mixture with an enzyme selected from the group consisting of Protease N, Alcalase, Savinase, ChiroCLEC-BL, PS-30, and ChiroCLEC-PC to stereoselectively hydrolyze predominantly one anomer to form a product wherein R1 is replaced with H. The process also includes the step of separating the product from unhydrolyzed starting material. Additionally, the functional group at the C4 position is stereoselectively replaced with a purinyl or pyrimidinyl or derivative thereof.

Abstract: The present invention has for its object to provide a practical method for the purification and isolation on a commercial scale of said compound (1) or compound (2) in good yield and with high quality. The present invention provides a purification/isolation method of a (2S,3S)-1-halo-2-hydroxy-3-N-(tert-butoxycarbonyl)amino-4-phenylbutane (1) or a (2R,3S)-1-halo-2-hydroxy-3-N-(tert-butoxycarbonyl)amino-4-phenylbutane (2) which comprises, for the purpose of removing contaminant impurity from a mixture containing at least one of said compounds (1) and (2), causing the objective compound (1) or compound (2) to be crystallized in the presence of a solvent comprised of a hydrocarbon solvent and then collecting the obtained crystals.

Abstract: A process for preparation of (R)-1,2-propanediol which comprises cultivating a microorganism belonging to genus Pseudomonas or genus Alcaligenes which has ability to assimilate (S)-1,2-propanediol as a single carbon source, in a culture medium containing racemic 1,2-propanediol as a single carbon source and then isolating the remaining (R)-1,2-propanediol from the culture broth.

Abstract: The present invention relates to a process for the stereoselective enzymatic reduction of 1-halo-2-oxo-3-(protected)amino-4-substituted-butanes utilizing certain species of Rhodococcus and Brevibacterium. The product 1-halo-2-hydroxy-3-(protected)amino-4-substituted-butanes, which are useful as intermediates in the synthesis of compounds that are inhibitors of ACE, renin and HIV proteases, are obtained in high yield and, particularly, in very high diastereomeric purity. The process is advantageously highly selective for the 1S,2S enantiomer of the product.

Abstract: The present invention relates to a method for synthesizing optically active cyanohydrin. An immobilized enzyme is used in the invention, in which (S)-hydroxynitrile lyase is immobilized in a carrier comprising a porous inorganic material.

Abstract: An economical and expedient method is disclosed for the preparation of &agr;-hydroxy-carboxylic acids or salts thereof in very high enantiomeric purity which comprises oxidizing a corresponding &agr;-amino-carboxylic acid or salt thereof using an amino acid deaminase followed by reducing the corresponding &agr;-keto-carboxylic acid or salt produced using a D- or L-lactate dehydrogenase in the combination with an electron donor and an enzyme/substrate system for recycling the electron donor. The resulting &agr;-hydroxy-carboxylic acids, hydrates, and salts thereof are valuable components and intermediates in the preparation of chiral compounds, especially pharmaceuticals. This invention also relates to the use of &agr;-amino-carboxylic acids, hydrates, and salts thereof and a coupled enzyme system in the production of &agr;-hydroxy-carboxylic acids, hydrates, and salts thereof.

Abstract: The present invention relates to a process for the preparation of compounds of formula (1), wherein R1 is unsubstituted or substituted C1-C8alkyl or a radical of formula —COOR3, wherein R3 is hydrogen or unsubstituted or substituted C1-C8alkyl, R2 is hydrogen or unsubstituted or substituted C1-C8alkyl, X is the radical —O— or —NH—, Y is hydrogen or an acyl or silyl radical, n is the number 0, 1 or 2, and the chiral carbon atom denoted by the symbol* in the compound of formula (1) is predominantly in pure form in either the R or S configuration, in which process a compound of formula (2) is converted by enantioselective hydrogenation and, where approriate, introduction of the radical Y to form an enantiomeric mixture, enriched with one of the enantiomers (R or S configuration), of the compound of formula (3), and the enantiomeric mixture is separated by enzymatic stereoselective hydrolysis, alcoholysis, aminolysis or ammonolysis, and in the case of the preparation of compounds of

Abstract: The present invention relates to a process for the systhesis of optically enriched dextro- and laevo-rotatory isomers of rose oxide from racemic citronellol. The invention particularly relates to the preparation of optically enriched (−)-(2 S, 4 R)-rose oxide and its isomer (+)-(2 R, 4 S)-rose oxide torn racemic citronellol.

Abstract: Optically active 2-substituted tetrahydropyran-4-ols or esters thereof may be prepared using esterases or hydrolases from the corresponding racemic mixtures of esters or alcohols. This provides a route to the corresponding optically active ketones. The racemic mixtures are preferably in the cis-form. such mixtures may be produced by reacting but-3-ene-1-ol with an aldehyde in the presence of an acid.

Abstract: A method for separation of enantiomers of a lactam represented by formula (I): where n and m are each, independently, 0, 1, 2, or 3; P is H or an N-protecting group; and the dotted line represents an optional double bond, by liquid chromatographing the mixture on a chiral stationary phase, where said stationary phase is derivitized with at least one sugar derivative, with an eluent which comprises acetonitrile.

Abstract: L(−)-carnitine is synthesized from crotonobetaine, crotonobetaine salts or derivatives in an ecologically advantageous manner by immobilizing cells of Escherichia coli 044 K74 on ceramics, glass beads or polyurethane disks in a two stage continuously operating cell recycle reactor containing a reaction medium. The medium preferably contains between 25 mM and 1 M crotonobetaine and at least 50 mM fumarate. Growing or resting cells of E. coli are retained in the reactor by micro or ultrafiltration membranes which are arranged as a flat membrane module or hollow fiber module. A first stage contains a reactor tank and a second stage contains an external recirculation loop connected to the tank for feeding the reaction medium through a filter unit. L-carnitine is synthesized under anaerobic conditions to produce a reaction medium containing L-carnitine and unreacted crotonobetaine.

Abstract: A process for preparation of an optically active 1,2-diol compound of the following formula: wherein R is alkyl group, hydroxy substituted alkyl group, or alkenyl group, which comprises reacting a corresponding racemic 1,2-diol compound with a strain belonging to the genus Alcaligenes which is being cultivated under aeration.

Abstract: A method of separating enantiomeric lactam esters. The lactam esters are contacted with a biocatalyst, such as an enzyme or a microorganism, in a solution wherein only one enantiomer is selectively hydrolyzed to give the optically active isomer of the corresponding acid. The hydrolysis product is then separated from the unreacted lactam esters. The enzyme is then recycled for reuse in the next enzymatic resolution. The undesired isomer is also racemized and reused in the next enzymatic resolution.

Abstract: A process for producing pyrrole-2-carboxylic acid which comprises the steps of: allowing a microorganism that is derived from the genus Serratia, is capable of catalyzing decarboxylation of pyrrole-2-carboxylic acid, and is capable of catalyzing the synthesis of pyrrole-2-carboxylic acid from pyrrole in the presence of carbonate ion, or the microorganism optionally processed, to act on pyrrole; and recovering the pyrrole-2-carboxylic acid generated.

Abstract: A process for the resolution of an enantiomeric mixture of &bgr;-lactams containing an ester, the process comprising selectively hydrolyzing the ester of one of the enantiomers by combining the mixture with homogenized liver.

Abstract: A chemoenzymatic method is disclosed for preparing N-[N-(3,3-dimethylbutyl)-L-&agr;-aspartyl]-L-phenylalanine 1-methyl ester via the enzymatic regioselective hydrolysis of neotame esters using lipases or esterases.

Abstract: Intermediate compounds, including 2-(t-butyldimethylsilyloxymethyl)-3,4-[(dimethylmethylene)dioxy]-5-hydroxy-tricyclo[5.2.1.02,6dec-8-ene, which are useful for the synthesis of neplanocin A having strong antitumor activity. Improved processes for the preparation of neplanocin A, starting from optically active 2-hydroxymethyl-5-hydroxy-tricyclo[5.2.1.02,6]deca-3,8-diene and via a key step comprising a retro-Diels-Alder reaction of the above intermediate.

Abstract: The present invention relates to a novel protein having amidase activity that stereoselectively hydrolyzes &agr;-amino acid amides and &agr;-hydroxy acid amides, and a gene encoding said protein.

Abstract: Intermediate compounds, including 2-(t-butyldimethylsilyloxymethyl)-3,4-[(dimethylmethylene)dioxy]-5-hydroxy-tricyclo[5.2.1.02,6]dec-8-ene, which are useful for the synthesis of neplanocin A having strong antitumor activity. Improved processes for the preparation of neplanocin A, starting from optically active 2-hydroxymethyl-5-hydroxy-tricyclo[5.2.1.02,6]deca-3,8-diene and via a key step comprising a retro-Diels-Alder reaction of the above intermediate.

Abstract: Intermediate compounds, including 2-(t-butyldimethylsilyloxymethyl)-3,4-[(dimethylmethylene)dioxy]-5-hydroxy-tricyclo[5.2.1.02,6]dec-8-ene, which are useful for the synthesis of neplanocin A having strong antitumor activity. Improved processes for the preparation of neplanocin A, starting from optically active 2-hydroxymethyl-5-hydroxy-tricyclo[5.2.1.02,6]deca-3,8-diene and via a key step comprising a retro-Diels-Alder reaction of the above intermediate.

Abstract: Intermediate compounds, including 2-(t-butyldimethylsilyloxymethyl)-3,4-[(dimethylmethylene)dioxy]-5-hydroxy-tricyclo[5.2.1.02,6]dec-8-ene, which are useful for the synthesis of neplanocin A having strong antitumor activity. Improved processes for the preparation of neplanocin A, starting from optically active 2-hydroxymethyl-5-hydroxy-tricyclo[5.2.1.02,6]deca-3,8-diene and via a key step comprising a retro-Diels-Alder reaction of the above intermediate.

Abstract: The invention relates to a novel method for the preparation of optically active 3,3,3-trifluoromethyl-2-alkyl propionic acid derivatives of the general formulae (I) and (II), in which R is ethyl or methyl and X is OH or NH2, provided that if R is methyl X≠—OH. The method comprises the reaction of a racemic propionic acid amide of the general formula (III) either by means of microorganisms which are able to use the propionic acid amide in the form of the racemate or one of its optically active isomers as the only nitrogen source or by means of a polypeptide with amidohydrolase activity which is able to hydrolyze the propionic acid amide. The invention also relates to new optically active representatives of this category of compounds.

Abstract: Immobilized lipase is prepared by adsorbing lipase from a crude lipase solution onto polyolefin particles such as polypropylene particles which are nonpolar. The crude solution may be a cell-free culture broth. Lipase sources include Pseudomonas burkholderia and Pseudomonas aeruginosa. Uses of the immobilized lipase include enantioselective conversion of substrates such as enantioselective acylating or hydrolyzing.

Abstract: The present invention relates to a process for the preparation of intermediates useful in the synthesis of epothilone analogs by initially enzymatically degrading certain epothilone compounds to form ring-open structures containing a carboxyl group which is esterified, the hydroxyl groups on the moiety protected and the resulting compound oxidized by, e.g. ozone, to form a first intermediate. The first intermediate can be reacted with a triphenylphosphine adduct to yield a compound containing an ester group at position 1 which is subsequently hydrolyzed to form a second intermediate.

Abstract: The present invention relates to processes for carrying out the following stereoselective microbial reduction of a racemic tetralone: which comprises: contacting a compound of formula (I) with a microorganism, or an enzyme reduction system capable of accomplishing the subject reduction comprising an enzyme derived from said microorganism and a co-factor for said enzyme, and incubating the resulting mixture under conditions sufficient to yield the (4R) tetralol of formula (II) and to leave substantially unreacted the (4S) tetralone of formula (V) or “chiral tetralone.” The chiral tetralone can be used in the synthesis of sertraline. The subject process further optionally comprises the separation of the (4S) tetralone of formula (V) from the (4R) tetralol of formula (II). The (4R) tetralol can be recycled to produce the compound of formula (I) and the subject process repeated to result in even more of the desired (4S) tetralone of formula (V).

Abstract: The present invention provides a method for enzymatically producing optically active mandelic acid derivatives. An optically active mandelic acid derivative (shown as Formula II) is produced by reacting a culture or cell body of a microorganism, or processed products thereof, with a phenylglyoxylic acid derivative, and then recovering the obtained optically active mandelic acid derivative, wherein the microorganism has the ability to stereo-selectively reduce the phenylglyoxylic acid derivative. An optically active mandelic acid obtained according to the present invention is useful as an intermediate for the synthesis of pharmaceuticals and agricultural chemicals.

Abstract: A process for the preparation of an enantiomerically pure tertiary &bgr;-hydroxycarboxylic acid or its ester, wherein an enantiomer mixture of compounds is brought into contact with an enzyme, which is capable of the hydrolytic cleavage of an ester bond, in an aqueous medium such that one enantiomer of the enantiomer mixture is hydrolyzed.

Abstract: The present invention relates to a process for producing optically active diols represented by the general formula (II): wherein R1 represents (CH2)n, CH═CH, O, S or NH whereupon n is an integer of 1 to 4, and R2 represents hydrogen, C1-6 alkyl, C1-6 alkoxy, (C1-6 alkoxy)-carbonyl, hydroxy, carboxy, halogen, nitro or amino, which comprises treating compounds represented by the general formula (I): wherein R1 and R2 have the same meanings as defined above, with a culture of a microorganism belonging to the genus Rhodococcus, Bacillus, Brevibacterium or Gordona and being capable of stereoselectively diolating a double bond in ring A, or with a culture of Mortierella vinacea, or with said microorganism itself, or with a treated material from said microorganism.

Abstract: Enzyme-containing polymers are prepared by an anhydrous process of direct reaction of an enzyme in organic solution with crosslinking organic compounds having terminal reactive groups. In a first step, the enzyme is reacted in an organic solvent with a bifunctional monomer such as p-phenylene diisocyanate, 4-methyl-m-phenylene diisocyanate or 4,4′-methylenebisphenyl diisocyanate, and in a second step a bifunctional amine such as N-phenylethylenediamine, 1,6-diaminohexane, N,N′-diethyl-ethylenediamine or 1,4-diaminobutane is added. The enzyme-containing polymers are used as catalysts in chemical reactions such as acylation or enantioselective acylation of alcohols.

Abstract: The invention concerns a method for preparing &agr;-phenylalanine ester with substantially enantiomeric purity of formulae (I) and (II) wherein Alk represents a linear or branched C1-C6 alkyl radical, characterized in that it consists in contacting a mixture of &agr;-phenylalanine ester enantiomers with a lipase, a protease or an esterase.

Abstract: A process for the resolution of an enantiomeric mixture of &bgr;-lactams containing an ester, the process comprising selectively hydrolyzing the ester of one of the enantiomers by combining the mixture with homogenized liver.

Abstract: The present invention is directed to novel stereoselective processes for the preparation of (S)-1-arylethanols by the reduction of the corresponding keto group containing compounds by microorganisms. (S)-1-arylethanols are useful as intermediates in the synthesis of compounds that are inhibitors of &ggr;-secretase useful in the treatment of Alzheimer's disease.

Abstract: The invention is a process for stereoselectively producing a dioxolane nucleoside analogue from an anomeric mixture of &bgr; and &agr; anomers represented by the following formula A or formula B: wherein R is selected from the group consisting of C1-6 alkyl and C6-15 aryl and Bz is benzoyl. The process comprises hydrolyzing said mixture with an enzyme selected from the group consisting of Protease N, Alcalase, Savinase, ChiroCLEC-BL, PS-30, and ChiroCLEC-PC to stereoselectively hydrolyze predominantly one anomer to form a product wherein R1 is replaced with H. The process also includes the step of separating the product from unhydrolyzed starting material. Additionally, the functional group at the C4 position is stereoselectively replaced with a purinyl or pyrimidinyl or derivative thereof.

Abstract: Methods for the enzymatic resolution of mixtures of enantiomers, such as &bgr;-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.

Abstract: The invention discloses a new method for producing enantiomer-enriched 1-amino-4-(hydroxymethyl)-cyclopent-2-ene derivatives of the general formulae (I) and (II) in which R1 is hydrogen or a possibly substituted C1-8 alkyl radical, aryl radical or cycloalkyl radical and R2 is acyl.

Abstract: This invention relates to a method for the production of (2R,3S)-3-(4-methoxyphenyl)glycidic acids and esters thereof, which are synthetic intermediates for the production of the calcium antagonist diltiazem. The method involves the stereoselective enzymatic ester hydrolysis of racemic trans-3-(4-methoxyphenyl)glycidic acid ester to yield the resolved (2R,3S) compound as the ester. Membrane reactor methods and apparatus for the conduct of this enzymatic resolution process are also disclosed herein, as is the use of bisulfite anion in the aqueous reaction phase as a means of minimizing the inhibitory effect of an aldehyde reaction by-product on the reaction's progress. The benefits of selected solvent systems from which may be obtained highly resolved ester product are also disclosed. These enriched organic solutions may be used in subsequent transformations. Alternatively, optically pure product may be obtained directly therefrom.

Abstract: An isolated esterase gene coding for an esterase capable of causing asymmetric hydrolysis of an organic carboxylic acid ester of a cyclopentenolone of formula I: wherein R1 is C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl or C1-C4 haloalky, to produce the cyclopentenolone of formula I in (S)-form, and hybridizing to the base sequence of SEQ ID NO:1, is useful for the industrially favorable production of optically active cyclopentenolones of formula I which serve as the intermediates of drugs, agricultural chemicals or other active products.