公开(公告)号：EP1024139A4

公开(公告)日：2002-04-17

申请号：EP99935066

申请日：1999-08-05

申请人： KANEKA CORP

发明人： KIZAKI NORIYUKI ,  YAMADA YUKIO ,  YASOHARA YOSHIHIKO ,  NISHIYAMA AKIRA ,  MIYAZAKI MAKOTO ,  MITSUDA MASARU ,  KONDO TAKESHI ,  UEYAMA NOBORU ,  INOUE KENJI

IPC分类号： C07C67/343 ,  C07C253/30 ,  C07C255/21 ,  C07D319/06 ,  C12P7/62 ,  C07C67/31

CPC分类号： C07D319/06 ,  C07B2200/07 ,  C07C67/343 ,  C07C253/30 ,  C12P7/62 ,  C07C69/716 ,  C07C255/21

摘要： A process for the preparation of optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which comprises subjecting an enolate prepared by reacting an acetate ester derivative with either a base or a zero-valent metal to reaction with a hydroxybutyric acid derivative at -30 °C or above to thereby obtain a hydroxyoxohexanoic acid derivative, reducing this hydroxyoxohexanoic acid derivative with a microorganism into a dihydroxyhexanoic acid derivative, treating this dihydroxyhexanoic acid derivative with an acetal-forming reactant in the presence of an acid to thereby obtain a halomethyldioxanylacetic acid derivative, acyloxylating this halomethyldioxanylacetic acid derivative with an acyloxylating agent into an acyloxymethyldioxanylacetic acid derivative, and subjecting this acyloxymethyldioxanylacetic acid derivative to solvolysis in the presence of a base.

摘要翻译： 本发明提供了一种从廉价起始原料生产具有价值作为药物中间体的光学活性2-Ä6-（羟甲基）-1,3-二恶烷-4-基乙酸衍生物的方法，而不使用任何特殊设备，例如 超低温反应需要。 制备光学活性2-δ-（羟甲基）-1,3-二恶烷-4-基乙酸衍生物的方法，其包括使不饱和-30℃的乙酸衍生物与烯醇化物反应 通过使碱价或0价金属作用于衍生物以制备羟基己酸衍生物而制备，借助于微生物菌株将该化合物还原，得到卤代甲基二恶烷基乙酸衍生物，用缩醛化处理该化合物 在酸催化剂存在下反应，得到卤代甲基二恶烷基乙酸衍生物，与酰氧基化剂反应，得到酰氧基甲基二恶烷基乙酸衍生物，并在碱的存在下使其溶解。

公开(公告)号：EP0897911A4

公开(公告)日：2001-03-21

申请号：EP98900354

申请日：1998-01-14

申请人： KANEKA CORP

发明人： KONDO TAKESHI ,  NISHIYAMA AKIRA ,  UEYAMA NOBORU ,  MURAO HIROSHI ,  MANABE HAJIME ,  UEDA YASUYOSHI

IPC分类号： C07C319/14 ,  C07C323/58 ,  C07C323/59 ,  B01J31/02

CPC分类号： C07C319/14 ,  C07B2200/07 ,  Y02P20/55 ,  C07C323/58 ,  C07C323/59

摘要： A process for producing cysteine derivatives having especially high optical purities economically advantageously at a high production efficiency even on an industrial scale. The process for producing cysteine derivatives represented by general formula (III) (wherein R0 represents hydrogen or an amino-protecting group like R1; R1 represents an amino-protecting group; R2 represents a carboxyl-protecting group; and R3 represents C¿1-7? alkyl, C6-10 aryl, or C7-10 aralkyl) is one which comprises reacting an amino acid derivative represented by general formula (I) (wherein R?1, R0, and R2¿ are each as defined above; and X represents a leaving group) with a thiol compound represented by general formula (II) (wherein R3 is as defined above), wherein the reaction is conducted in an organic raction medium in the presence of a base and water.

公开(公告)号：EP1415985A4

公开(公告)日：2005-04-20

申请号：EP02758805

申请日：2002-08-08

申请人： KANEKA CORP

发明人： KONDO TAKESHI ,  UEYAMA NOBORU

IPC分类号： C07C227/32 ,  C07D205/04 ,  C07D209/48 ,  C07C227/18 ,  C07C229/08

CPC分类号： C07D209/48 ,  C07C227/32 ,  C07D205/04 ,  Y02P20/55

摘要： A process for efficiently, easily, and industrially advantageously producing an optically active azetidine-2- carboxylic acid which is important as a material for medicines. The process comprises halogenating an optically active N-protected 4-amino-2-hydroxybutyric acid while inverting the configuration to form an optically active N-protected 4-amino-2-halogenobutyryl halide, subsequently subjecting the halide to hydrolysis and elimination of the amino-protecting group to form an optically active 4-amino-2-halogenobutyric acid, and then subjecting the resultant acid to cyclization and amino group protection in an alkaline aqueous solution to produce an optically active N-protected azetidine-2-carboxylic acid. Also provided is an optically active N-protected 4-amino-2-halogenobutyryl halide represented by the following formula (2), which is useful for producing an optically active azetidine-2-carboxylic acid. (2) (In the formula, P represents a group protecting the primary amino group; * indicates that the carbon atom is asymmetric; and X and Y each independently represents halogeno.)

公开(公告)号：EP1054000A4

公开(公告)日：2003-07-23

申请号：EP99900288

申请日：1999-01-13

申请人： KANEKA CORP

发明人： UEDA YASUYOSHI ,  MURAO HIROSHI ,  KONDO TAKESHI ,  UEYAMA NOBORU ,  MANABE HAJIME ,  YONEDA KENJI ,  NISHIYAMA AKIRA

IPC分类号： C07C319/20 ,  C07C319/28 ,  C07C323/59 ,  C07B53/00 ,  C07B57/00

CPC分类号： C07C319/28 ,  C07B2200/07 ,  C07C319/20 ,  Y02P20/55 ,  C07C323/59

摘要： A process whereby optically active cysteine derivatives having a high optical purity and excellent qualities can be economically advantageously produced at a high efficiently even on an industrial scale. This process comprises reacting an optically active amino acid derivative in the D- or L-form represented by general formula (1): (wherein R1 represents an amino-protective group of the urethane or acyl type; R0 represents hydrogen or R?0 and R1¿ together form an amino-protective group; R2 represents alkyl, aryl or aralkyl; and * represents the location of an asymmetric carbon atom) with an alcohol represented by general formula (3): R3-OH (wherein R3 represents a monovalent organic group), a strong acid and/or a thionyl halide to thereby synthesize an optically active cysteine derivative in the D- or L-form represented by general formula (2), and then recovering the cysteine derivative from the liquid reaction mixture, wherein the successive procedures from the reaction to the recovery are effected under such conditions that n a medium being in contact with the cysteine derivative is an acidic to weakly basic one, thereby recovering the optically active cysteine derivative from the liquid reaction mixture while inhibiting the degradation and racemization of the derivative.