Abstract: The present invention relates to a method for producing optically active 2-(N-substituted aminomethyl)-3-hydroxybutyric acid esters wherein a 2-(N-substituted aminomethyl)-3-oxobutyric acid ester is treated with an enzyme source capable of stereoselectively reducing said ester to the corresponding optically active 2-(N-substituted aminomethyl)-3-hydroxybutyric acid ester having the (2S,3R) configuration. The present invention provides an efficient method for industrially producing optically active 2-(N-substituted aminomethyl)-3-hydroxybutyric acid esters, in particular such compounds having the (2S,3R) configuration, which are useful as intermediates for the production of medicinal compounds, among others.

Abstract: The present invention relates to a process for producing an optically active 2-substituent-oxy-3-(4-substituent-oxyphenyl)propionic acid derivative which comprises stereoselectively reducing an 2-oxo-3-(4-substituent-oxyphenyl)propionic acid by an enzyme and subjecting the thus-obtained optically active 2-hydroxy-3-(4-substituent-oxyphenyl)propionic acid to esterification of the carboxyl group according to need, then to alkylation of the hydroxyl group and, if necessary, to deprotection of an ether type protective group. The present invention may make it possible to produce an optically active 2-substituent-oxy-3-(4-substituent-oxyphenyl)propionic acid derivative, which is useful as intermediates for the synthesis of medicinal compounds, efficiently, in a simple and easy manner, and commercially advantageously.

Abstract: The present invention is to provide a process for efficiently producing an optically active alcohol including (R)-3-hydroxy-3-phenylpropanenitrile. One of the features of the present invention is a polypeptide having an activity of asymmetrically reducing 3-oxo-3-phenylpropanenitrile isolated from a microorganism belonging to the genus Candida to produce (R)-3-hydroxy-3-phenylpropanenitrile, DNA encoding the polypeptide and a transformant of producing the polypeptide. Another feature of the present invention is a process for producing an optically active alcohol such as (R)-3-hydroxy-3-phenylpropanenitrile by reducing a carbonyl compound such as 3-oxo-3-phenylpropanenitrile by use of the polypeptide or the transformant.

Abstract: The present invention relates to a polypeptide having an activity to asymmetrically reduce (3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanone to produce (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol isolated from a microorganism belonging to the genus Ogataea, a DNA encoding the polypeptide and a transformant that produces the polypeptide. The present invention moreover relates to a method of producing (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol utilizing the polypeptide or the transformant. Using the polypeptide or transformant of the present invention, optically active alcohols such as (2R,3S)-1-chloro-3-tert-butoxycarbonylamino-4-phenyl-2-butanol and the like can be produced efficiently.

Abstract: The present invention provides a novel polypeptide forming (R)-2-chloro-1-(3?-chlorophenyl)ethanol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on 2-chloro-1-(3?-chlorophenyl)ethanone with NADPH or NADH as a coenzyme, to form (R)-2-chloro-1-(31-chlorophenyl)ethanol; (2) optimum pH for activity: 5.0 to 6.0; (3) optimum temperature for activity: 40° C. to 50° C.; (4) molecular weight: about 40,000 as determined by gel filtration analysis, about 30,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

Abstract: The present invention relates to a method of producing an optically active pyridineethanol derivative. More particularly, it relates to a method of producing an optically active polycyclic pyridineethanol derivative by causing an enzyme or enzyme source to act on polycyclic acetylpyridine derivatives. The present invention also relates to a novel enzyme which can be used in the production method mentioned above, a DNA coding for said enzyme, a recombinant vector having said DNA, and a transformant having said recombinant vector. The invention further relates to a method of producing an optically active polycyclic pyridineethanol derivative by causing the above novel enzyme or the above transformant to act on optically inactive polycyclic pyridineethanol derivatives.

Abstract: The present invention provides a process for producing an optically active 2-allylcarboxylic acid derivative, which is useful as a pharmaceutical intermediate, from readily available and inexpensive starting materials by the process which can be practiced on a commercial scale in a simple and easy manner, and certain 2-allylcarboxamide derivatives, which are novel and important intermediates in that process. An N-allylcarboxamide derivative undergoes rearrangement reaction diastereoselectively in the presence of a base to give a 2-allylcarboxamide derivative, the resulting derivative is subjected to a carbamation reaction and solvolysis to give an optically active 2-allylcarboxylic acid ester, and then the ester obtained is stereoselectively hydrolyzed using an enzyme to produce 2-allylcarboxylic acid having a high optical purity. In addition, the present invention provides a 2-allylcarboxamide derivative compound which is a novel intermediate in the process of the present invention.

Abstract: The present invention provides a novel polypeptide efficiently forming (R)-N-benzyl-3-pyrrolidinol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on N-benzyl-3-pyrrolidinone with NADH or NADPH as a coenzyme, to form (R)-N-benzyl-3-pyrrolidinol; (2) optimum pH for activity: 5.5 to 6.0; (3) optimum temperature for activity: 50° C. to 55° C.; (4) molecular weight: about 55,000 as determined by gel filtration analysis, about 28,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

Abstract: The present invention provides a method for easily producing an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative useful for an intermediate for pharmaceutical products, particularly an inhibitor of a cholesteryl ester transfer protein (CETP) from easily available raw materials. In the present invention, (S)-N-[4-(trifluoromethyl)phenyl]-3-hydroxypentanoic acid amide prepared from easily available raw materials leads a production of (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone to give (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide. Furthermore, (R)-4-ethyl-1-[4-(trifluoromethyl)phenyl]-2-azetidinone is reacted with a carbamic acid ester to give an (R)-3-[4-(trifluoromethyl)phenylamino]-pentanoic acid amide derivative.

Abstract: The present invention provides a novel polypeptide efficiently forming (R)-N-benzyl-3-pyrrolidinol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on N-benzyl-3-pyrrolidinone with NADH or NADPH as a coenzyme, to form (R)-N-benzyl-3-pyrrolidinol; (2) optimum pH for activity: 5.5 to 6.0; (3) optimum temperature for activity: 50° C. to 55° C.; (4) molecular weight: about 55,000 as determined by gel filtration analysis, about 28,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

Abstract: An object of the present invention is to provide a simple and easy process for producing optically active alcohols, specifically, a (R)-3-hydroxypentanenitrile, optically active 3-hydroxybutanoic esters, and optically active 1-phenylethanol derivatives, and to provide a novel enzyme useful for producing the above optically active alcohols, particularly a (R)-3-hydroxypentanenitrile. The present invention provides a novel acetoacetyl-CoA reductase capable of asymmetrically reducing a 3-ketopentanenitrile to produce a (R)-3-hydroxypentanenitrile having an optical purity of 99% e.e. or more; and a process for allowing the novel enzyme or a known acetoacetyl-CoA reductase to act on each of the 3-ketopentanenitrile, an acetoacetic ester, and a 1-phenylethanone derivative to produce a corresponding optically active alcohol.

Abstract: The present invention provides a method for preparing optically active 3-hydroxypentanenitrile with high yield. Optically active 3-hydroxypentanenitrile is prepared by stereoselectively reducing 3-ketopentanenitrile by action of an enzyme, which asymmetrically reduces 3-ketopentanenitrile to optically active 3-hydroxypentanenitrile. Also, alkali metal salt of 3-ketopentanenitrile, which is a stable compound without problems regarding storage, can be efficiently obtained.

Abstract: The present invention provides a process for producing an optically active 2-allylcarboxylic acid derivative, which is useful as a pharmaceutical intermediate, from readily available and inexpensive starting materials by the process which can be practiced on a commercial scale in a simple and easy manner, and certain 2-allylcarboxamide derivatives, which are novel and important intermediates in that process. An N-allylcarboxamide derivative undergoes rearrangement reaction diastereoselectively in the presence of a base to give a 2-allylcarboxamide derivative, the resulting derivative is subjected to a carbamation reaction and solvolysis to give an optically active 2-allylcarboxylic acid ester, and then the ester obtained is stereoselectively hydrolyzed using an enzyme to produce 2-allylcarboxylic acid having a high optical purity. In addition, the present invention provides a 2-allylcarboxamide derivative compound which is a novel intermediate in the process of the present invention.

Abstract: The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1, 3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor. The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-?-hydroxy-?-butyrolactone at a temperature not lower than ?30° C.

Abstract: The present invention provides a novel polypeptide producing (S)-N-benzyl-3-pyrrolidinol, a DNA coding for it and a method of using them. A polypeptide having the following physicochemical properties (1) to (5): (1) Action: It asymmetrically reduces N-benzyl-3-pyrrolidinone to produce (S)-N-benzyl-3-pyrrolidinol with NADPH as a coenzyme; (2) Optimum action pH: 4.5 to 5.5; (3) Optimum action temperature: 40° C. to 45° C.; (4) Molecular weight: About 29,000 as determined by gel filtration analysis, about 35,000 as determined by SDS-polyacrylamide gel electrophoresis analysis; (5) Inhibitor: It is inhibited by the divalent copper ion.

Abstract: The present invention provides a novel polypeptide forming (R)-2-chloro-1-(3?-chlorophenyl)ethanol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on 2-chloro-1-(3?-chlorophenyl)ethanone with NADPH or NADH as a coenzyme, to form (R)-2-chloro-1-(31-chlorophenyl)ethanol; (2) optimum pH for activity: 5.0 to 6.0; (3) optimum temperature for activity: 40° C. to 50° C.; (4) molecular weight: about 40,000 as determined by gel filtration analysis, about 30,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

Abstract: The present invention provides a novel polypeptide efficiently forming (R)-N-benzyl-3-pyrrolidinol, a polynucleotide coding for said polypeptide, and use of the same. The present invention relates to a polypeptide having the following physical and chemical properties (1) to (4): (1) activity: acting on N-benzyl-3-pyrrolidinone with NADH or NADPH as a coenzyme, to form (R)-N-benzyl-3-pyrrolidinol; (2) optimum pH for activity: 5.5 to 6.0; (3) optimum temperature for activity: 50° C. to 55° C.; (4) molecular weight: about 55,000 as determined by gel filtration analysis, about 28,000 as determined by SDS polyacrylamide gel electrophoresis analysis. The present invention also relates to a polypeptide comprising the amino acid sequence shown under SEQ ID NO:1 in the sequence listing, a polynucleotide coding for said polypeptide, and a transformant producing said polypeptide at high levels.

Abstract: The present invention is to efficiently and simply prepare an optically active 7-substituted-2-aminotetralin with industrial advantage. In the process, a 7-substituted-2-tetralone or its bisulfite adduct is reduced with a microorganism to an optically active 7-substituted-2-tetralol. Then, a sulfonyl group is introduced to the hydroxy group to form an optically active 7-substituted-2-sulfonyloxytetralin. Then, with inversion of the configuration, a nitrogen substituent is introduced using a nitrogen nucleophile to form an optically active 2,7-substituted tetralin. Furthermore, if necessary, the nitrogen substituent is converted into a non-substituted amino group. Thus, an optically active 7-substituted-2-aminotetralin or its salt is prepared.

Abstract: This invention provides a process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which are of value as intermediates of drugs, from inexpensive starting materials without using any special equipment such as that required for super-low temperature reactions. A process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives which comprises reacting an acetic acid derivative at a temperature of not less than ?30° C.

Abstract: The present invention is to provide a production technology by which an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative, which are of value as pharmaceutical intermediates, can be produced from inexpensive and readily available starting materials without using any extraordinary equipment such as an ultra-low-temperature reactor. The present invention is a production process of an optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivative which comprises reacting an enolate, prepared by permitting a base or a 0-valent metal to act on an acetic acid ester derivative with (S)-?-hydroxy-?-butyrolactone at a temperature not lower than ?30° C.