公开(公告)号：EP1600438A4

公开(公告)日：2007-05-02

申请号：EP04714501

申请日：2004-02-25

Applicant: KANEKA CORP

Inventor： YAMAMOTO SHOGO ,  TAKEDA TOSHIHIRO ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07C319/14 ,  C07B53/00 ,  C07B55/00 ,  C07C51/363 ,  C07C51/43 ,  C07C57/58 ,  C07C319/28 ,  C07C323/56

CPC classification number: C07B53/00 ,  C07B2200/07 ,  C07C51/363 ,  C07C319/14 ,  C07C57/58 ,  C07C323/56

Abstract: Optically active compounds having thio groups at the 2-position which are important to the production of drugs and so on can be produced with minimized racemization in high yield and at a low cost by chlorinating an optically active compound having a hydroxyl group at the 2-position with the inversion of configuration at the 2-position to form an optically active compound having a chlorine atom at the 2-position, and reacting the optically active compound having a chlorine atom at the 2-position with a metal thiolate to introduce a thio group to the compound with the invention of configuration at the 2-position. Further, optically active compounds having thio groups at the 2-position can be produced at higher optical purities and in higher yields by conducting the reaction of an optically active compound having a chlorine atom at the 2-position with a metal thiolate in the presence of water. Additionally, optically active carboxylic acids having thio groups at the 2-position can be efficiently rid of coexistent impurities such as optical isomers by crystallization in the presence of an aliphatic hydrocarbon solvent and/or a sulfur-containing solvent, whereby optically active carboxylic acids having thio groups at the 2-position can be obtained as crystalline substances at further enhanced purities.

公开(公告)号：EP1088820A4

公开(公告)日：2001-08-16

申请号：EP00915524

申请日：2000-04-14

Applicant: KANEKA CORP

Inventor： KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  NAGASHIMA NOBUO ,  SAKA YASUHIRO ,  HONDA TATSUYA ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07C29/147 ,  C07C31/42 ,  C07D307/20

CPC classification number: C07C29/147 ,  C07B2200/07 ,  C07D307/20 ,  Y02P20/55 ,  C07C31/42

Abstract: An industrially advantageous process for preparing high-purity 3-hydroxytetrahydrofuran easily and simply, which comprises converting a 4-halo-3-hydroxybutyric acid ester into a 4-halo-1,3-butanediol by reducing the ester with a boron hydride compound and/or an aluminum hydride compound in an organic solvent incompatible with water and treating the obtained reaction mixture with an acid and water, recovering an aqueous solution containing the diol, conducting the cyclization of the diol in this aqueous solution, extracting the resulting solution with an organic solvent incompatible with water, and isolating 3-hydroxytetrahydrofuran from the extract through concentration and/or distillation.

公开(公告)号：EP0995745A4

公开(公告)日：2002-11-06

申请号：EP98929672

申请日：1998-06-25

Applicant: KANEKA CORP

Inventor： YOKOTA SHIN-ICHI ,  YAMAMOTO KOZO ,  MORIKAWA SOUICHI ,  FUSE YOSHIHIDE ,  KITAHARA MIKIO

IPC: C07D405/06 ,  A61K31/40 ,  A61K31/445

CPC classification number: C07D405/06

Abstract: Remedies for diseases which function by regulating the expression of a protein induced by a heat shock factor (HSF). Specifically, HSF activity inhibitors or agents inhibiting the induction of the production of a protein regulated by HSF, wherein novel benzo-1,3-dioxole compounds represented by general formula (I) inhibit the transcription of a structural gene having a heat shock element sequence, which is a transcriptional regulatory factor, in a gene region participating in the transcription into RNA, thus inhibit the translation of this gene into a protein and, in its turn, suppress the induction of the production of the RNA, protein, etc. encoded by the gene; and remedies and preventives usable in thermotherapy for cancer and remedies and preventives for stress-induced diseases such as depression. Compounds represented by general formula (I): wherein X is -CH2- and R1 represents C¿1-2? alkyl, formyl or halogeno; or X is -(CH2)2- and R?1¿ represents C¿1-3? alkyl, formyl, acetyl, hydrogen or halogeno.

公开(公告)号：EP1179530A4

公开(公告)日：2005-07-27

申请号：EP01904517

申请日：2001-02-16

Applicant: KANEKA CORP

Inventor： SUGAWARA MASANOBU ,  FUJII AKIO ,  OKURO KAZUMI ,  SAKA YASUHIRO ,  NAGASHIMA NOBUO ,  INOUE KENJI ,  TAKEDA TOSHIHIRO ,  KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07C227/10 ,  C07C227/32 ,  C07C227/42 ,  C07C229/26 ,  C07C229/30 ,  C07C303/36 ,  C07C311/19 ,  C07D203/08 ,  C07D203/20 ,  C07D203/24 ,  C07B53/00 ,  C07C227/04

CPC classification number: C07D203/08 ,  C07B2200/07 ,  C07C227/10 ,  C07C227/32 ,  C07C227/42 ,  C07C229/30 ,  C07C303/36 ,  C07D203/20 ,  C07D203/24 ,  C07C311/19 ,  C07C229/26

Abstract: An optically active amino acid derivative is prepared either by subjecting an optically active 3-haloalanine derivative (1) to N-protection followed by cyclization or cyclization followed by N-protection to prepare an optically active aziridinecarboxylic acid derivative (3) whose imino group is protected with 2- and/or 4-nitrated benzenesulfonyl and treating this derivative (3) with an organometallic reagent or by subjecting an optically active 3-haloalanine derivative to N-protection to obtain an optically active 3-haloalanine derivative (4) whose amino group is protected with 2- and/or 4-nitrated benzenesulfonyl and treating this derivative (4) with an organometallic reagent. According to such processes, natural and nonnatural optically active amino acids can be prepared from inexpensive raw materials through simple and easy operation. In said derivatives, X is halogen; R?1 and R2¿ are each hydrogen or the like; * represents an asymmetric carbon atom; and P1 is 2- and/ or 4- nitrated benzenesulfonyl.

公开(公告)号：ES2277446T3

公开(公告)日：2007-07-01

申请号：ES99944783

申请日：1999-09-22

Applicant: KANEKA CORP

Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02 ,  C07K5/06

Abstract: Un proceso para producir N2-(1(S)-carboxi-3-fenilpropil)-L-silil-L-prolina de la fórmula (2): a partir de una N2-(1(S)-alcoxicarbonil-3-fenilpropil)-N6-trifluoroacetil-L-lisil-L-prolina de la fórmula general (1): en la cual R representa un grupo alquilo, que comprende: el primer paso: someter la N2-(1(S)-alcoxicarbonil-3-fenilpropil)-N6-trifluoroacetil-L-lisil-L-prolina (1) a hidrólisis alcalina en un sistema disolvente que se selecciona de entre una solución mixta compuesta de agua y un disolvente orgánico hidrófilo, y agua utilizando una base inorgánica en una cantidad de n equivalentes molares (n > 3) por mol del compuesto (1) anterior, el segundo paso: neutralizar el producto de hidrólisis utilizando un ácido inorgánico en una cantidad de (n-1) a n equivalentes molares (n > 3) y separar y retirar la sal inorgánica formada a partir de la base inorgánica y el ácido inorgánico anteriores en la mezcla de reacción haciendo que la misma se separe precipitada de un sistema disolvente adecuadopara reducir la solubilidad de la sal inorgánica, seleccionándose dicho sistema disolvente de un disolvente orgánico hidrófilo, un disolvente mixto compuesto de agua y un disolvente orgánico hidrófilo, y agua, y el tercer paso: hacer que la N2-(1(S)-carboxi-3-fenilpropil)-L-silil-L-prolina (2) existente en la mezcla después de la eliminación de la sal inorgánica se separe cristalizada de un sistema disolvente en el punto iso-eléctrico del mismo, seleccionándose dicho sistema disolvente de un disolvente orgánico hidrófilo, un disolvente mixto compuesto de agua y un disolvente orgánico hidrófilo, y agua, y recuperar con ello la N2-(1(S)-carboxi-3-fenilprop-il)-L-silil-L-prolina (2) en forma de cristales en tanto que se retienen las sales que comprenden principalmente la sal de ácido orgánico derivada del ácido trifluoroacético en un estado disuelto en las aguas madres.

公开(公告)号：DE69934084D1

公开(公告)日：2007-01-04

申请号：DE69934084

申请日：1999-09-22

Applicant: KANEKA CORP

Inventor： MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07K5/068 ,  A61K38/05 ,  A61P9/12 ,  C07K5/02 ,  C07K5/06

Abstract: The process for producing N -(1(S)-carboxy-3-phenylpropyl)-L-lysyl-L-proline in a simple, efficient and industrially advantageous manner, which comprises: the first step of subjecting the N -(1(S)-alkoxycarbonyl-3-phenylpropyl)-N -trifluoroacetyl-L-lysyl -L-proline (1) to alkali hydrolysis in a mixed solution composed of water and a hydrophilic organic solvent using an inorganic base in an amount of n molar equivalents (n >/= 3) per mole of the above compound (1), the second step of neutralizing the hydrolysis product using an inorganic acid in an amount of (n - 1) to n molar equivalents (n >/= 3) and removing the inorganic salt formed by causing the same to precipitate out from a solvent system suited for decreasing the solubility of the inorganic salt, and the third step of causing the compound (2) existing in the mixture after removal of the inorganic salt to crystallize out at the isoelectric point thereof and thereby recovering the compound (2) in the form of crystals while retaining the salts comprising the trifluoroacetic acid-derived organic acid salt in a state dissolved in the mother liquor.

公开(公告)号：AT296311T

公开(公告)日：2005-06-15

申请号：AT98932585

申请日：1998-07-21

Applicant: KANEKA CORP

Inventor： UEDA YASUYOSHI ,  KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE

IPC: A61P9/12 ,  C07K1/02 ,  C07K1/08 ,  C07K5/02 ,  C07K5/06 ,  C07K5/062

Abstract: Preparation of salts of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl amino acid derivatives of formula (R1)NH-CH(R2)-CO2H (I) comprises: (a) condensing an amino acid with N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanine N-carboxyanhydride of formula (II), under basic conditions; (b) decarboxylating the condensate under neutral to acidic conditions to give (I); and (c) and converting (I) to its salt. Steps (a), (b) and optionally (c) are carried out in aqueous liquid to inhibit the formation of by-products of formula (III): -N(R1)CH(R2)-C(O)- = e.g. group of formula (i).

公开(公告)号：AU2003289020A1

公开(公告)日：2004-07-29

申请号：AU2003289020

申请日：2003-12-10

Applicant: KANEKA CORP

Inventor： OHISHI TAKAHIRO ,  MORI KOHEI ,  KINOSHITA KOICHI ,  MAEHARA KATSUJI ,  KAWASAKI HIROAKI ,  NAGASHIMA NOBUO ,  FUSE YOSHIHIDE

IPC: C07C319/14 ,  C07C323/56 ,  C07D407/06 ,  C07D317/60 ,  C07D305/12

Abstract: The present invention provides a process for simply producing an optically active 2-thiomethyl-3-phenylpropionic acid derivative useful as an intermediate for medicines from inexpensive raw materials. An optically active 2-hydroxymethyl-3-phenylpropionic acid ester derivative which can be relatively easily obtained by asymmetric reduction reaction with an enzyme is cyclized to an optically active P-lactone derivative which is then reacted with a sulfur compound to produce an optically active 2-thiomethyl-3-phenylpropionic acid derivative in high yield.

公开(公告)号：AT259794T

公开(公告)日：2004-03-15

申请号：AT00915524

申请日：2000-04-14

Applicant: KANEKA CORP

Inventor： KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  NAGASHIMA NOBUO ,  SAKA YASUHIRO ,  HONDA TATSUYA ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: C07C29/147 ,  C07C31/42 ,  C07D307/20

Abstract: The application is concerned with a process for producing a 3-hydroxytetrahydrofuran of the formula (3): by cyclizing a 4-halo-1,3-butanediol of the general formula (2): wherein X represents a halogen atom in an aqueous solution, which comprises carrying out the cyclization reaction under weakly acidic to neutral conditions. Furthermore several methods are disclosed for the isolution of highly pure 3-hydroxytetrahydrofuran.

公开(公告)号：CZ293008B6

公开(公告)日：2004-01-14

申请号：CZ20001004

申请日：1999-07-19

Applicant: KANEKA CORP

Inventor： KINOSHITA KOICHI ,  MOROSHIMA TADASHI ,  YANAGIDA YOSHIFUMI ,  FUSE YOSHIHIDE ,  UEDA YASUYOSHI

IPC: A61P9/00 ,  C07K1/00 ,  C07K5/06 ,  C07K5/062 ,  C07K1/30 ,  C07B57/00

Abstract: The present invention relates to a method for crystallizing the maleic acid salt of N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline (Enalapril) from an aqueous liquid with ease in good yield, which comprises mixing an aqueous liquid containing N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline, maleic acid and a base with an acid in an amount of the acid sufficient to convert the base to a neutral salt, to thereby crystallize N-(1(S)-ethoxycarbonyl-3-phenylpropyl)-L-alanyl-L-proline in the form of a maleic acid salt.