公开(公告)号：US20130030164A1

公开(公告)日：2013-01-31

申请号：US13574458

申请日：2011-01-19

申请人： Shinichi Yoshida ,  Akira Iwasaki ,  Motohisa Washida ,  Tozo Nishiyama ,  Daisuke Moriyama ,  Naoaki Taoka

发明人： Shinichi Yoshida ,  Akira Iwasaki ,  Motohisa Washida ,  Tozo Nishiyama ,  Daisuke Moriyama ,  Naoaki Taoka

IPC分类号： C12N9/02 ,  C12N15/63 ,  C07H21/02 ,  C12N1/19 ,  C12N5/10 ,  C12P19/36 ,  C12N15/53 ,  C12N1/21

CPC分类号： C12N9/0036 ,  C12N9/0065 ,  C12P7/02 ,  C12P7/18 ,  C12P7/42 ,  C12P13/04 ,  C12P19/36 ,  C12Y106/03 ,  C12Y106/03001 ,  C12Y111/01001

摘要： Water-forming NADH oxidase derived from Streptococcus mutans should be further improved in terms of stability for practical use in industrial production. An object of the present invention is to provide an enzyme that is obtained through modification of a water-forming NADH oxidase, which is useful as an NAD+ regeneration system for stereoselective oxidation catalyzed by an oxidoreductase, by protein engineering techniques so that the enzyme can withstand long-term use without exhibiting a reduction of its activity for the regeneration of NAD+, that is, an enzyme having improved stability, and to provide a method for efficiently producing a useful substance such as an optically active alcohol or amino acid. The present invention relates to an enzyme modification method that can improve the stability of water-forming NADH oxidase derived from Streptococcus mutans by appropriately introducing mutation.

摘要翻译： 来自变形链球菌的成水NADH氧化酶在工业生产实际使用的稳定性方面应进一步提高。 本发明的目的是提供通过蛋白质工程技术，通过改性水合NADH氧化酶获得的酶，其可用作由氧化还原酶催化的用于立体选择性氧化的NAD +再生系统，使得酶能够承受 长期使用而不显示其NAD +再生活性的活性降低，即稳定性提高的酶，以及提供有效生产光学活性醇或氨基酸等有用物质的方法。 本发明涉及通过适当地引入突变来提高来自变形链球菌的水形成NADH氧化酶的稳定性的酶修饰方法。

公开(公告)号：US08338142B2

公开(公告)日：2012-12-25

申请号：US12449645

申请日：2008-02-18

申请人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

发明人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

IPC分类号： C12P17/12

CPC分类号： C07D211/60 ,  C07B57/00 ,  C07D211/56 ,  C12P17/12 ,  C12P41/006

摘要： The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.

摘要翻译： 本发明涉及一种光学活性3-氨基哌啶或其盐的制备方法。 在该方法中，外消旋的丙内酰胺立体选择性地水解，得到光生活性的哌甲酰胺和光学活性的啮齿二甲酸，在衍生自生物体的酶源存在下，然后将光学活性的哌甲酰胺衍生成光学活性的氨基哌啶或其盐 通过酰化，Hofmann重排，氨基脱保护和进一步去保护; 或通过用BOC，霍夫曼重排和进一步去保护的选择性保护将光学活性的哌甲酰胺衍生成光学活性氨基哌啶或其盐。 通过本发明可以通过适用于工业制造的容易的方法从廉价且容易获得的原料中制备用作药物中间体的光学活性3-氨基哌啶或其盐。

公开(公告)号：US20110229940A1

公开(公告)日：2011-09-22

申请号：US13126534

申请日：2009-10-28

申请人： Masutoshi Nojiri ,  Tozo Nishiyama ,  Naoaki Taoka

发明人： Masutoshi Nojiri ,  Tozo Nishiyama ,  Naoaki Taoka

IPC分类号： C12P13/04 ,  C07C229/36 ,  C07C229/30

CPC分类号： C12P13/04 ,  C07C227/30 ,  C07C233/47 ,  C12N9/104 ,  C12N9/90 ,  C12P13/222 ,  C12P41/007 ,  Y02P20/52 ,  C07C229/30 ,  C07C229/32 ,  C07C229/36

摘要： The present invention relates to a method for producing an L-amino acid by reacting an enantiomeric mixture of an N-succinyl amino acid with L-succinylase in the presence of N-acylamino acid racemase to specifically hydrolyze the L-form. In particular, the present invention relates to a method for producing an L-amino acid in high yield by using an N-succinyl amino acid whose dissolved concentration is particularly low as a raw material to perform a reaction while precipitating the produced L-amino acid out of the reaction system. The present invention enables efficient production of an L-amino acid having high optical purity, particularly an L-amino acid useful as a raw material for products such as pharmaceutical products and agricultural chemicals.

摘要翻译： 本发明涉及通过在N-酰基氨基酸消旋酶存在下使N-琥珀酰氨基酸与L-琥珀酰基酶的对映异构体混合物反应以特异性水解L型而生产L-氨基酸的方法。 特别地，本发明涉及通过使用溶解浓度特别低的N-琥珀酰氨基酸作为原料进行反应，同时使生成的L-氨基酸沉淀而以高产率生产L-氨基酸的方法 出了反应体系。 本发明能够有效地生产具有高光学纯度的L-氨基酸，特别是可用作药物产品和农药等产品的原料的L-氨基酸。

公开(公告)号：US20100105917A1

公开(公告)日：2010-04-29

申请号：US12449645

申请日：2008-02-18

申请人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

发明人： Kohei Mori ,  Masutoshi Nojiri ,  Akira Nishiyama ,  Naoaki Taoka

IPC分类号： C07D211/98 ,  C12P17/12 ,  C07D211/60

CPC分类号： C07D211/60 ,  C07B57/00 ,  C07D211/56 ,  C12P17/12 ,  C12P41/006

摘要： The present invention relates to a method for producing an optically active 3-aminopiperidine or salt thereof. In the method, a racemic nipecotamide is stereoselectively hydrolyzed to obtain an optically active nipecotamide and an optically active nipecotic acid in the presence of an enzyme source derived from an organism, and then the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by aroylation, Hofmann rearrangement, deprotection of the amino group and further deprotection; or the optically active nipecotamide is derived into an optically active aminopiperidine or salt thereof by selective protection with BOC, Hofmann rearrangement and further deprotection. It is possible by the present invention to produce an optically active 3-aminopiperidine or salt thereof useful as a pharmaceutical intermediate from an inexpensive and easily available starting material by easy method applicable to industrial manufacturing.

摘要翻译： 本发明涉及一种光学活性3-氨基哌啶或其盐的制备方法。 在该方法中，外消旋的丙内酰胺立体选择性地水解，得到光生活性的哌甲酰胺和光学活性的啮齿二甲酸，在衍生自生物体的酶源存在下，然后将光学活性的哌甲酰胺衍生成光学活性的氨基哌啶或其盐 通过酰化，Hofmann重排，氨基脱保护和进一步去保护; 或通过用BOC，霍夫曼重排和进一步去保护的选择性保护将光学活性的哌甲酰胺衍生成光学活性氨基哌啶或其盐。 通过本发明可以通过适用于工业制造的容易的方法从廉价且容易获得的原料中制备用作药物中间体的光学活性3-氨基哌啶或其盐。

公开(公告)号：US20100003732A1

公开(公告)日：2010-01-07

申请号：US11916152

申请日：2006-05-30

申请人： Takashi Yoshida ,  Naoaki Taoka

发明人： Takashi Yoshida ,  Naoaki Taoka

IPC分类号： C12P7/24

CPC分类号： C12P7/24 ,  C12P41/002

摘要： The present invention relates to a process for producing an optically active 2-substituted propanal derivative, and more particularly, a process for producing an optically active 2-substituted propanal derivative which comprises stereoselectively reducing a carbon-carbon double bond of a 2-substituted acrolein derivative by using an enzyme source capable of stereoselectively reducing said carbon-carbon double bond. According to the present invention, it becomes possible to produce an optically active 2-substituted propanal derivative, in particular an optically active 2-alkylpropanal derivative, which is useful as an intermediate of pharmaceutical products, sweetening agents, etc., in a convenient manner from inexpensive and easily available materials.

摘要翻译： 本发明涉及一种光学活性2-取代的丙醛衍生物的制造方法，更具体地说，涉及一种光学活性2-取代的丙醛衍生物的制备方法，该方法包括立体选择性还原2-取代的丙烯醛的碳 - 碳双键 衍生物通过使用能够立体选择性还原所述碳 - 碳双键的酶源。 根据本发明，可以以便利的方式制造光学活性的2-取代的丙醛衍生物，特别是光学活性的2-烷基丙醛衍生物，其可用作药物产品，甜味剂等的中间体 从廉价和易于获得的材料。

公开(公告)号：US20070292926A1

公开(公告)日：2007-12-20

申请号：US10586337

申请日：2005-01-19

申请人： Akira Nishiyama ,  Naoaki Taoka ,  Narumi Kishimoto ,  Nobuo Nagashima

发明人： Akira Nishiyama ,  Naoaki Taoka ,  Narumi Kishimoto ,  Nobuo Nagashima

IPC分类号： C12P7/18 ,  C07C31/20 ,  C07D207/04

CPC分类号： C12P17/10 ,  C07C303/28 ,  C12P7/18 ,  C12P11/00 ,  C07C309/66

摘要： The present invention relates to a process for producing an optically active 1,4-pentanediol by asymmetrically reducing 5-hydroxy-2-pentanone, which is easily available at low cost. The present invention also relates to a process for producing an optically active 1-substituted 2-methylpyrrolidine including sulfonylating the optically active 1,4-pentanediol to convert it to an optically active sulfonate compound, and reacting the compound with an amine. According to the processes of the present invention, an optically active 1,4-pentanediol and an optically active 1-substituted 2-methylpyrrolidine, which are useful as an intermediate for medicines and an intermediate for agricultural chemicals, can be simply produced from an inexpensive starting material.

摘要翻译： 本发明涉及通过不对称地还原5-羟基-2-戊酮来制备光学活性的1,4-戊二醇的方法，该方法容易以低成本获得。 本发明还涉及一种光学活性1-取代的2-甲基吡咯烷的制备方法，其包括使光学活性的1,4-戊二醇磺酰化以将其转化成光学活性的磺酸盐化合物，并使该化合物与胺反应。 根据本发明的方法，用作药物中间体和农药中间体的光学活性的1,4-丁二醇和光学活性的1-取代的2-甲基吡咯烷可以简便地从廉价的 起始材料

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：US06174707B1

公开(公告)日：2001-01-16

申请号：US09202901

申请日：1999-03-04

申请人： Naoaki Taoka ,  Takehiko Matsumoto ,  Kenji Inoue

发明人： Naoaki Taoka ,  Takehiko Matsumoto ,  Kenji Inoue

IPC分类号： G01N3853

CPC分类号： C12P7/40 ,  C12P13/04 ,  C12P41/006

摘要： The present invention has for its object to provide a method for producing an L-allysine acetal which involves a fewer steps and is efficient. This invention relates to method for producing an L-allysine acetal which comprises; converting a D,L-allysine acetal of the following general formula (1) (wherein R1 and R2 are the same or different, and each of them represents an alkyl group having 1 to 8 carbon atoms, or they combinedly form a ring and represent an alkylene group having 2 to 8 carbon atoms) to a mixture of a 2-oxo-6,6-dialkoxyhexanoic acid of the following general formula (2) (wherein R1 and R2 are as defined above) and an L-allysine acetal of the following general formula (3) (wherein R1 and R2 are as defined above) by reacting in the presence of an enzyme capable of stereoselective oxidative deamination of D-amino acids and; isolating said L-allysine acetal after said converting.

摘要翻译： 本发明的目的是提供一种生产L-赖氨酸缩醛的方法，该方法涉及较少的步骤并且是有效的。本发明涉及L-赖氨酸缩醛的制备方法，其包括：将D，L-烯丙基乙缩醛 的下述通式（1）（其中，R 1和R 2相同或不同，它们各自表示碳原子数1〜8的烷基，或者它们组合形成环，表示碳原子数2〜8的亚烷基 原子）与下述通式（2）的2-氧代-6,6-二烷氧基己酸（其中R 1和R 2如上定义）和下列通式（3）的L-烯丙基缩醛的混合物 其中R1和R2如上所定义）通过在能够进行D-氨基酸的立体选择性氧化脱氨作用的酶存在下反应;和在所述转化后分离所述L-赖氨酸缩醛。

公开(公告)号：US5750382A

公开(公告)日：1998-05-12

申请号：US809431

申请日：1997-06-13

申请人： Naoaki Taoka ,  Mizuho Honda ,  Kenji Inoue ,  Kazunori Kan

发明人： Naoaki Taoka ,  Mizuho Honda ,  Kenji Inoue ,  Kazunori Kan

IPC分类号： C12N9/20 ,  C07C43/196 ,  C07C67/03 ,  C07C67/08 ,  C07C69/06 ,  C07C69/14 ,  C07C69/24 ,  C12P7/02 ,  C12P41/00 ,  C12R1/05 ,  C12R1/38 ,  C12R1/72 ,  C12R1/785 ,  C12P7/62 ,  C12N9/14

CPC分类号： C12P41/004 ,  C12P7/02 ,  Y10S435/829 ,  Y10S435/874 ,  Y10S435/921 ,  Y10S435/931

摘要： A process for efficiently producing (S,S)-2-alkoxycyclohexanols in a single step by using (.+-.)-trans-2-alkoxycyclohexanols which are inexpensive and can be easily obtained. The process comprises treating a (.+-.)-trans-2-alkoxycyclohexanol with a hydrolase originating in a microorganism and being capable of esterifying stereospecifically the R-isomer in the presence of an acyl donor under such conditions that no hydrolysis occurs substantially to thereby give (S,S)-2-alkoxycyclohexanols and (R,R)-2-alkoxycyclohexanol carboxylate and then taking up the (S,S)-2-alkoxycyclohexanols.

摘要翻译： PCT No.PCT / JP96 / 02174 Sec。 371日期：1997年6月13日 102（e）日期1996年6月13日PCT 1996年8月2日PCT公布。 公开号WO97 / 06275 日期：1997年2月20日利用（+/-） - 反式-2-烷氧基环己醇，在一个步骤中有效地生产（S，S）-2-烷氧基环己醇的方法是廉价且易于获得的。 该方法包括用起源于微生物的水解酶处理（+/-） - 反式-2-烷氧基环己醇，并且在酰基供体存在下能够立即特异性酯化R-异构体的条件下，基本上不发生水解 （S，S）-2-烷氧基环己醇和（R，R）-2-烷氧基环己醇羧酸酯，然后加入（S，S）-2-烷氧基环己醇。

公开(公告)号：US5179212A

公开(公告)日：1993-01-12

申请号：US619974

申请日：1990-11-30

申请人： Satomi Takahashi ,  Shigeo Hayashi ,  Naoaki Taoka ,  Noboru Ueyama

发明人： Satomi Takahashi ,  Shigeo Hayashi ,  Naoaki Taoka ,  Noboru Ueyama

IPC分类号： B01J23/40 ,  B01J25/00 ,  C07B61/00 ,  C07C303/30 ,  C07C309/06 ,  C07C309/65 ,  C07C309/66 ,  C07C309/73 ,  C07D207/12

CPC分类号： C07D207/12 ,  C07C309/06 ,  C07C309/66 ,  C07C309/73

摘要： 3-Pyrrolidinol or its salt is economically produced by cyclizing an aminobutanol derivative of the formula: ##STR1## wherein R is an alkyl or a substituted or unsubstituted phenyl group, or its salt.