公开(公告)号：US06642387B2

公开(公告)日：2003-11-04

申请号：US10305105

申请日：2002-11-27

申请人： Susumu Amano ,  Naoaki Taoka ,  Masaru Mitsuda ,  Kenji Inoue

发明人： Susumu Amano ,  Naoaki Taoka ,  Masaru Mitsuda ,  Kenji Inoue

IPC分类号： C07D21346

CPC分类号： C07D213/30 ,  C07D213/50 ,  C07D213/74 ,  C07D213/75 ,  C07D405/04

摘要： It is an objective to produce intermediates of optically active beta-3 adrenaline receptor agonists from readily available raw materials in a safe, efficient and industrially advantageous manner. A substituted acetylpyridine derivative represented by the general formula (9) is reduced by enantioselective reduction to produce an optically active hydroxyethylpyridine derivative represented by the general formula (10) (wherein * represents an asymmetric carbon atom), and it is further derivatized to an intermediate of an optically active beta-3 adrenaline receptor agonist, such as an optically active dihydroxyethylpyridine derivative represented by the general formula (14) or an optically active oxirane derivative represented by the general formula (16)

摘要翻译： 目的是以安全，有效和工业上有利的方式从容易获得的原料生产光学活性β-3肾上腺素受体激动剂的中间体。 由通式（9）表示的取代的乙酰基吡啶衍生物通过对映选择性还原反应来制备由通式（10）表示的光学活性羟乙基吡啶衍生物（其中*表示不对称碳原子），并进一步衍生为中间体 的光学活性β-3肾上腺素受体激动剂，例如由通式（14）表示的光学活性二羟基乙基吡啶衍生物或由通式（16）表示的光学活性环氧乙烷衍生物，

公开(公告)号：US06515134B1

公开(公告)日：2003-02-04

申请号：US09926021

申请日：2001-11-07

申请人： Susumu Amano ,  Naoaki Taoka ,  Masaru Mitsuda ,  Kenji Inoue

发明人： Susumu Amano ,  Naoaki Taoka ,  Masaru Mitsuda ,  Kenji Inoue

IPC分类号： C07D21326

CPC分类号： C07D213/30 ,  C07D213/50 ,  C07D213/74 ,  C07D213/75 ,  C07D405/04

摘要： It is an objective to produce intermediates of optically active beta-3 adrenaline receptor agonists from readily available raw materials in a safe, efficient and industrially advantageous manner. A substituted acetylpyridine derivative represented by the general formula (9) is reduced by enantioselective reduction to produce an optically active hydroxyethyl derivative represented by the general formula (10) (wherein * represents an asymmetric carbon atom), and it is further derivatized to an intermediate of an optically active beta-3 adrenaline receptor agonist, such as an optically active dihydroxyethylpyridine derivative represented by the general formula (14) or an optically active oxirane derivative represented by the general formula (16).

摘要翻译： 目的是以安全，有效和工业上有利的方式从容易获得的原料生产光学活性β-3肾上腺素受体激动剂的中间体。 由通式（9）表示的取代的乙酰基吡啶衍生物通过对映选择性还原而被还原，以制备由通式（10）表示的光学活性羟乙基衍生物（其中*表示不对称碳原子），并进一步衍生为中间体 的光学活性β-3肾上腺素受体激动剂，例如由通式（14）表示的光学活性二羟基乙基吡啶衍生物或由通式（16）表示的光学活性环氧乙烷衍生物。

公开(公告)号：US07094926B2

公开(公告)日：2006-08-22

申请号：US10182260

申请日：2001-01-25

申请人： Susumu Amano ,  Masaru Mitsuda ,  Kenji Inoue ,  Koichi Kinoshita ,  Koki Yamashita ,  Yasuyoshi Ueda

发明人： Susumu Amano ,  Masaru Mitsuda ,  Kenji Inoue ,  Koichi Kinoshita ,  Koki Yamashita ,  Yasuyoshi Ueda

IPC分类号： C07C51/58

CPC分类号： C07C327/32 ,  C07C51/04 ,  C07C51/367 ,  C07C51/60 ,  C07C59/48 ,  C07C57/58 ,  C07C57/76

摘要： A nitrous acid salt is added at a temperature of 10 to 80° C. to an aqueous solution which contains an optically active 2-aminocarboxylic acid (4) and a protonic acid, the amount of the latter acid being 1 to 3 equivalents to the former, and which has a proton concentration of 0.5 to 2 mol/kg to conduct a reaction to thereby produce an optically active 2-hydroxycarboxylic acid (1). Thionyl chloride and a basic compound are caused to act on the compound (1) to chlorinate it and simultaneously invert the configuration in the 2-position. Thus, an optically active 2-chlorocarboxylic acid chloride (5) is induced. The compound (5) is hydrolyzed to induce an optically active 2-chlorocarboxylic acid (2). The compound (2) is reacted with a thioacetic acid salt to incorporate an acetylthio group thereinto and simultaneously invert the configuration in the 2-position to thereby produce an optically active 2-acetylthiocarboxylic acid (3).

公开(公告)号：US20060247470A1

公开(公告)日：2006-11-02

申请号：US11477626

申请日：2006-06-30

申请人： Susumu Amano ,  Masaru Mitsuda ,  Kenji Inoue ,  Koichi Kinoshita ,  Koki Yamashita ,  Yasuyoshi Ueda

发明人： Susumu Amano ,  Masaru Mitsuda ,  Kenji Inoue ,  Koichi Kinoshita ,  Koki Yamashita ,  Yasuyoshi Ueda

IPC分类号： C07C53/15 ,  C07C53/16

CPC分类号： C07C327/32 ,  C07C51/04 ,  C07C51/367 ,  C07C51/60 ,  C07C59/48 ,  C07C57/58 ,  C07C57/76

摘要： A nitrous acid salt is added at a temperature of 10 to 80° C. to an aqueous solution which contains an optically active 2-aminocarboxylic acid (4) and a protonic acid, the amount of the latter acid being 1 to 3 equivalents to the former, and which has a proton concentration of 0.5 to 2 mol/kg to conduct a reaction to thereby produce an optically active 2-hydroxycarboxylic acid (1). Thionyl chloride and a basic compound are caused to act on the compound (1) to chlorinate it and simultaneously invert the configuration in the 2-position. Thus, an optically active 2-chlorocarboxylic acid chloride (5) is induced. The compound (5) is hydrolyzed to induce an optically active 2-chlorocarboxylic acid (2). The compound (2) is reacted with a thioacetic acid salt to incorporate an acetylthio group thereinto and simultaneously invert the configuration in the 2-position to thereby produce an optically active 2-acetylthiocarboxylic acid (3).

摘要翻译： 在10〜80℃的温度下，向含有光学活性的2-氨基羧酸（4）和质子酸的水溶液中加入亚硝酸盐，后者的酸的量为1〜3当量 前者，其质子浓度为0.5〜2mol / kg进行反应，由此制造光学活性的2-羟基羧酸（1）。 使亚硫酰氯和碱性化合物作用于化合物（1）以使其氯化，同时反转2-位的构型。 因此，引入光学活性的2-氯羧酰氯（5）。 将化合物（5）水解以诱导光学活性的2-氯羧酸（2）。 使化合物（2）与硫代乙酸盐反应以引入乙酰硫基，同时反转2-位的构型，从而产生光学活性的2-乙酰基硫代羧酸（3）。

公开(公告)号：US08058471B2

公开(公告)日：2011-11-15

申请号：US12376803

申请日：2007-08-08

申请人： Susumu Amano ,  Akio Fujii ,  Shohei Yamamoto ,  Masaru Mitsuda

发明人： Susumu Amano ,  Akio Fujii ,  Shohei Yamamoto ,  Masaru Mitsuda

IPC分类号： C07C59/00 ,  C07C65/21

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C51/00 ,  C07C51/367 ,  C07C201/12 ,  C07C59/48 ,  C07C205/56

摘要： The present invention has its object to provide a method for producing an optically active hydroxycarboxylic acid derivative which is an intermediate important for production of medicines, agrochemicals, chemical products, and so on. The production method of the present invention comprises: carrying out a hydrogen-transfer reduction of a ketocarboxylic acid or a salt thereof by the reaction of an optically active diamine complex to produce an optically active hydroxycarboxylic acid derivative. According to the present invention, it is possible to safely and efficiently produce an industrially-useful optically active hydroxycarboxylic acid derivative.

摘要翻译： 本发明的目的在于提供一种光学活性羟基羧酸衍生物的制造方法，该方法是制备药物，农药，化学品等的重要中间体。 本发明的制造方法包括：通过光学活性二胺配合物的反应进行酮羧酸或其盐的氢转移还原反应，生成光学活性羟基羧酸衍生物。 根据本发明，可以安全有效地制备工业上有用的光学活性羟基羧酸衍生物。

公开(公告)号：US20060223152A1

公开(公告)日：2006-10-05

申请号：US10553394

申请日：2004-04-16

申请人： Kazumi Okuro ,  Susumu Amano ,  Noriyuki Kizaki ,  Teruaki Takesue ,  Masaru Mitsuda ,  Noriyuki Ito ,  Yoshihiko Yasohara

发明人： Kazumi Okuro ,  Susumu Amano ,  Noriyuki Kizaki ,  Teruaki Takesue ,  Masaru Mitsuda ,  Noriyuki Ito ,  Yoshihiko Yasohara

IPC分类号： C12P13/00 ,  C07F3/02

CPC分类号： C07C233/18 ,  C07B2200/07 ,  C07C51/06 ,  C07C67/20 ,  C07C233/05 ,  C07C271/64 ,  C12P7/40 ,  C12P41/005 ,  C07C57/03 ,  C07C69/533

摘要： 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.

摘要翻译： 本发明提供了一种用于制备可用作药物中间体的光学活性2-烯丙基羧酸衍生物的方法，其由易于获得且廉价的原料通过可以简单和容易的方式在商业规模上实施的方法制备， 和某些2-烯丙基羧酰胺衍生物，它们是该方法中新颖且重要的中间体。 N-烯丙基甲酰胺衍生物在碱存在下非对映选择性地进行重排反应，得到2-烯丙基甲酰胺衍生物，所得衍生物进行氨基甲酰化反应和溶剂解，得到光学活性2-烯丙基羧酸酯，然后得到所述酯 使用酶进行立体选择性水解以产生具有高光学纯度的2-烯丙基羧酸。 此外，本发明提供了在本发明的方法中是新型中间体的2-烯丙基甲酰胺衍生物化合物。

公开(公告)号：US07282605B2

公开(公告)日：2007-10-16

申请号：US10553394

申请日：2004-04-16

申请人： Kazumi Okuro ,  Susumu Amano ,  Noriyuki Kizaki ,  Teruaki Takesue ,  Masaru Mitsuda ,  Noriyuki Ito ,  Yoshihiko Yasohara

发明人： Kazumi Okuro ,  Susumu Amano ,  Noriyuki Kizaki ,  Teruaki Takesue ,  Masaru Mitsuda ,  Noriyuki Ito ,  Yoshihiko Yasohara

IPC分类号： C07C291/00 ,  C07C237/16 ,  C07C237/18 ,  C07C237/20

CPC分类号： C07C233/18 ,  C07B2200/07 ,  C07C51/06 ,  C07C67/20 ,  C07C233/05 ,  C07C271/64 ,  C12P7/40 ,  C12P41/005 ,  C07C57/03 ,  C07C69/533

摘要： 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.

摘要翻译： 本发明提供了一种用于制备可用作药物中间体的光学活性2-烯丙基羧酸衍生物的方法，其由易于获得且廉价的原料通过可以简单和容易的方式在商业规模上实施的方法制备， 和某些2-烯丙基羧酰胺衍生物，它们是该方法中新颖且重要的中间体。 N-烯丙基甲酰胺衍生物在碱存在下非对映选择性地进行重排反应，得到2-烯丙基甲酰胺衍生物，所得衍生物进行氨基甲酰化反应和溶剂解，得到光学活性2-烯丙基羧酸酯，然后得到所述酯 使用酶进行立体选择性水解以产生具有高光学纯度的2-烯丙基羧酸。 此外，本发明提供了在本发明的方法中是新型中间体的2-烯丙基甲酰胺衍生物化合物。

公开(公告)号：US20100191011A1

公开(公告)日：2010-07-29

申请号：US12376803

申请日：2007-08-08

申请人： Susumu Amano ,  Akio Fujii ,  Shohei Yamamoto ,  Masaru Mitsuda

发明人： Susumu Amano ,  Akio Fujii ,  Shohei Yamamoto ,  Masaru Mitsuda

IPC分类号： C07C51/347

CPC分类号： C07B53/00 ,  C07B2200/07 ,  C07C51/00 ,  C07C51/367 ,  C07C201/12 ,  C07C59/48 ,  C07C205/56

摘要： The present invention has its object to provide a method for producing an optically active hydroxycarboxylic acid derivative which is an intermediate important for production of medicines, agrochemicals, chemical products, and so on. The production method of the present invention comprises: carrying out a hydrogen-transfer reduction of a ketocarboxylic acid or a salt thereof by the reaction of an optically active diamine complex to produce an optically active hydroxycarboxylic acid derivative. According to the present invention, it is possible to safely and efficiently produce an industrially-useful optically active hydroxycarboxylic acid derivative.

摘要翻译： 本发明的目的在于提供一种光学活性羟基羧酸衍生物的制造方法，该方法是制备药物，农药，化学品等的重要中间体。 本发明的制造方法包括：通过光学活性二胺配合物的反应进行酮羧酸或其盐的氢转移还原反应，生成光学活性羟基羧酸衍生物。 根据本发明，可以安全有效地制备工业上有用的光学活性羟基羧酸衍生物。

公开(公告)号：US07582781B2

公开(公告)日：2009-09-01

申请号：US10563635

申请日：2004-07-05

申请人： Kazumi Okuro ,  Tatsuyoshi Tanaka ,  Masaru Mitsuda ,  Kenji Inoue

发明人： Kazumi Okuro ,  Tatsuyoshi Tanaka ,  Masaru Mitsuda ,  Kenji Inoue

IPC分类号： C07D301/24 ,  C07D301/26 ,  C07D405/06 ,  C07C33/26 ,  C07C69/353 ,  C07F7/04

CPC分类号： C07C67/29 ,  C07B2200/07 ,  C07C29/10 ,  C07D301/24 ,  C07C33/46

摘要： The present invention provides an industrially safe, easily operable process for producing an optically active epoxy alcohol derivative useful as an intermediate for pharmaceuticals from inexpensively available materials, and also provides a novel halohydrin derivative serving as an important intermediate for the epoxy alcohol derivative. Furthermore, the present invention provides a process for producing an intermediate for a triazole antifungal agent by allowing a halohydrin to react with a triazole sulfonamide, the process including a small number of steps. A process for producing an optically active epoxy alcohol derivative includes allowing an optically active α-substituted propionate derivative to react with a haloacetic acid derivative in the presence of a base to prepare an optically active haloketone derivative, allowing the resulting haloketone derivative to react with an aryl metal compound to stereoselectively prepare a halohydrin derivative, eliminating a substituent for the hydroxy group of the halohydrin derivative, and performing epoxidation with a base. Furthermore, a process for producing an intermediate for a triazole antifungal agent includes allowing a halohydrin derivative to react with a triazole sulfonamide, the process including a small number of steps.

摘要翻译： 本发明提供了一种工业上安全，易于操作的方法，用于制备用作药物的廉价可得材料的中间体的光学活性环氧醇衍生物，并且还提供了作为环氧醇衍生物的重要中间体的新型卤代醇衍生物。 此外，本发明提供了通过使卤代醇与三唑磺酰胺反应来制备三唑抗真菌剂的中间体的方法，该方法包括少量的步骤。 制备光学活性环氧醇衍生物的方法包括使光学活性的α-取代的丙酸酯衍生物与卤代乙酸衍生物在碱的存在下反应以制备光学活性的卤代酮衍生物，使所得到的卤代酮衍生物与 芳基金属化合物立体选择性地制备卤代醇衍生物，除去卤代醇衍生物的羟基的取代基，并用碱进行环氧化。 此外，制备三唑抗真菌剂中间体的方法包括使卤代醇衍生物与三唑磺酰胺反应，该方法包括少量步骤。

公开(公告)号：US06903225B2

公开(公告)日：2005-06-07

申请号：US10242453

申请日：2002-09-13

申请人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

发明人： Noriyuki Kizaki ,  Yukio Yamada ,  Yoshihiko Yasohara ,  Akira Nishiyama ,  Makoto Miyazaki ,  Masaru Mitsuda ,  Takeshi Kondo ,  Noboru Ueyama ,  Kenji Inoue

IPC分类号： C07C67/343 ,  C07C253/30 ,  C07C255/21 ,  C07D319/06 ,  C12P7/62 ,  C12P1/04 ,  C12P17/06

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

摘要： 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. with an enolate prepared by permitting either a base or a metal having a valency of 0 to act on the derivative to produce a hydroxyoxohexanoic acid derivative, reducing this compound with the aid of a strain of microorganism to provide a halomethyldioxanylacetic acid derivative, treating this compound with an acetalizing agent in the presence of an acid catalyst to provide a halomethyl-dioxanylacetic acid derivative, reacted with an acyloxylating agent to provide a acyloxymethyldioxanylacetic acid derivative, and subjecting this compound to solvolysis in the presence of a base.

摘要翻译： 本发明提供了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的2- [6-（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 例如超低温反应所需的。 一种制备光学活性的2- [6-（羟基甲基）-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 通过使碱金属或0价金属作用于衍生物以制备羟基己酸衍生物而制备，借助于微生物菌株还原该化合物以提供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，提供卤代甲基 - 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。