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1. 发明申请

US20140004575A1 MODIFIED AMINOTRANSFERASE, GENE THEREOF, AND METHOD FOR PRODUCING OPTICALLY ACTIVE AMINO COMPOUND USING SAME 有权
标题翻译：改性氨基转移酶及其基因及其生产使用其的光学活性氨基化合物的方法
公开(公告)号：US20140004575A1
公开(公告)日：2014-01-02
申请号：US14004293
申请日：2012-03-09
申请人： Noriyuki Ito , Shigeru Kawano , Yoshihiko Yasohara
发明人： Noriyuki Ito , Shigeru Kawano , Yoshihiko Yasohara
IPC分类号： C12N9/10
CPC分类号： C12N9/1096 , C12P13/001 , C12P13/04 , C12P41/006
摘要： Provided is a method for efficiently producing from a ketone compound an optically active amino compound useful as an intermediate of a drug, an agricultural chemical, or the like. Provided are: a polypeptide having aminotransferase activity that is increased in stereoselectivity, heat resistance, and resistance to amine compounds compared to the wild type enzyme by means of modifying an aminotransferase derived from Pseudomonas fluorescens; a gene encoding the polypeptide; and a transformant that expresses the gene at a high level.
摘要翻译：提供一种从酮化合物有效地制备用作药物，农药等的中间体的光学活性氨基化合物的方法。提供：通过修饰衍生自荧光假单胞菌的氨基转移酶，与野生型酶相比，具有增加立体选择性，耐热性和耐胺性化合物的氨基转移酶活性的多肽; 编码该多肽的基因; 以及高水平表达基因的转化体。

2. 发明授权

US08168412B2 Method for producing optically-active amine compound, recombinant vector, and transformant containing the vector 有权
标题翻译：生产光学活性胺化合物，重组载体和含有该载体的转化体的方法
公开(公告)号：US08168412B2
公开(公告)日：2012-05-01
申请号：US12302460
申请日：2007-05-28
申请人： Shigeru Kawano , Noriyuki Ito , Yoshihiko Yasohara
发明人： Shigeru Kawano , Noriyuki Ito , Yoshihiko Yasohara
IPC分类号： C12P13/00
CPC分类号： C12P13/008 , C12N9/0004 , C12N9/0006 , C12N9/1096 , C12P13/001 , C12P13/002 , C12P17/10
摘要： The present invention relates to a method for producing an optically-active amine compound. The method is characterized by using a transaminase (A), an α-keto acid reductase (B), and an enzyme (C), each having specific properties, in an identical reaction system to convert a ketone compound into a corresponding optically-active amine compound in which a carbon atom with an amino group bonded thereto serves as an asymmetric point. The present invention also relates to a recombinant vector for use in the method. The present invention makes it possible to efficiently produce an optically-active amine compound.
摘要翻译：本发明涉及一种光学活性胺化合物的制造方法。该方法的特征在于在相同的反应体系中使用转氨酶（A），α-酮酸还原酶（B）和具有特定性质的酶（C），以将酮化合物转化为相应的光学活性具有与其结合的氨基的碳原子作为不对称点的胺化合物。本发明还涉及用于该方法的重组载体。本发明使得有效地制备光学活性胺化合物成为可能。

3. 发明授权

US08008461B2 Carbonyl reductase, gene therefor and use thereof 失效
标题翻译：羰基还原酶，其基因及其用途
公开(公告)号：US08008461B2
公开(公告)日：2011-08-30
申请号：US11665065
申请日：2005-10-20
申请人： Noriyuki Kizaki , Makoto Ueda , Daisuke Moriyama , Naoaki Taoka , Yoshihiko Yasohara
发明人： Noriyuki Kizaki , Makoto Ueda , Daisuke Moriyama , Naoaki Taoka , Yoshihiko Yasohara
IPC分类号： C07H21/04 , C12N9/02 , C12P21/02 , C12P13/00 , C07C255/01
CPC分类号： C12N9/0006 , C12P7/04 , C12P7/62 , C12P13/002 , C12P41/002
摘要： 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.
摘要翻译：本发明提供一种有效制备包含（R）-3-羟基-3-苯基丙腈的光学活性醇的方法。本发明的特征之一是具有不对称还原从属于念珠菌属的微生物分离的3-氧代-3-苯基丙腈的活性的多肽，以产生（R）-3-羟基-3-苯基丙腈，编码多肽和产生多肽的转化体。本发明的另一个特征是通过使用多肽或转化体还原羰基化合物如3-氧代-3-苯基丙腈来制备光学活性醇如（R）-3-羟基-3-苯基丙腈的方法。

4. 发明申请

US20090029429A1 Process for Producing Optically Active 2-Substituent-Oxy-3-(4-Substituent-Oxyphenyl) Propionic Acid Derivative 审中-公开
标题翻译：制备光学活性2-取代基 - 氧基-3-（4-取代基 - 氧代苯基）丙酸衍生物的方法
公开(公告)号：US20090029429A1
公开(公告)日：2009-01-29
申请号：US11573602
申请日：2005-08-04
申请人： Tatsuya Honda , Hirofumi Maeda , Nobuo Nagashima , Shigeru Kawano , Yoshihiko Yasohara
发明人： Tatsuya Honda , Hirofumi Maeda , Nobuo Nagashima , Shigeru Kawano , Yoshihiko Yasohara
IPC分类号： C12P7/40
CPC分类号： C07C59/90 , C07B2200/07 , C07C67/11 , C07C69/734 , C12P7/42 , C12P7/62 , Y02P20/55
摘要： 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.
摘要翻译：本发明涉及一种光学活性2-取代基 - 氧基-3-（4-取代基 - 氧基苯基）丙酸衍生物的制备方法，其包括立体选择性还原2-氧代-3-（4-取代基 - 苯氧基）丙酸通过酶将由此获得的光学活性2-羟基-3-（4-取代基 - 氧基苯基）丙酸根据需要进行羧基酯化，然后进行羟基的烷基化，如果需要，进行脱保护的醚类保护基。本发明可以制备光学活性的2-取代基 - 氧基-3-（4-取代基 - 氧基苯基）丙酸衍生物，其有效地用于合成药用化合物的中间体，简单易行方式和商业上有利地。

5. 发明授权

US07332312B2 Carbonyl reductase, gene thereof and use of the same 有权
标题翻译：羰基还原酶，其基因及其用途
公开(公告)号：US07332312B2
公开(公告)日：2008-02-19
申请号：US10512908
申请日：2003-04-30
申请人： Noriyuki Kizaki , Miho Horikawa , Yoshihiko Yasohara
发明人： Noriyuki Kizaki , Miho Horikawa , Yoshihiko Yasohara
IPC分类号： C12N1/20 , C12N9/02 , C12N1/21 , C12N15/00 , C07H21/04 , C12P7/22
CPC分类号： C12N9/0006 , C12Y101/01184
摘要： 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.
摘要翻译：本发明提供形成（R）-2-氯-1-（3'-氯苯基）乙醇的新型多肽，编码所述多肽的多核苷酸及其用途。本发明涉及具有以下物理和化学性质（1）至（4）的多肽：（1）活性：以NADPH或NADH作为辅酶作用于2-氯-1-（3'-氯苯基）乙酮，形成（R）-2-氯-1-（31-氯苯基）乙醇; （2）活性最佳pH：5.0〜6.0; （3）最适温度为40℃〜50℃。（4）分子量：约40,000，通过凝胶过滤分析测定，约30,000，通过SDS聚丙烯酰胺凝胶电泳分析测定。本发明还涉及包含序列表中SEQ ID NO：1所示氨基酸序列的多肽，编码所述多肽的多核苷酸，以及以高水平产生所述多肽的转化体。

6. 发明授权

US07148055B2 Process for production of optically active 3-hydroxypentanenitrile 失效
标题翻译：光学活性3-羟基戊腈的制备方法
公开(公告)号：US07148055B2
公开(公告)日：2006-12-12
申请号：US10491115
申请日：2002-10-03
申请人： Shigeru Kawano , Yoshihiko Yasohara
发明人： Shigeru Kawano , Yoshihiko Yasohara
IPC分类号： C12P41/00
CPC分类号： C07C253/30 , C12P13/002 , C12P13/004 , C07C255/17
摘要： 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.
摘要翻译：本发明提供了一种以高产率制备光学活性3-羟基戊腈的方法。通过酶的作用立体选择性还原3-酮戊腈制备光学活性3-羟基戊腈，其将3-酮戊腈不对称地还原成光学活性3-羟基戊腈。此外，可以有效地获得作为没有储存问题的稳定化合物的3-酮戊腈的碱金属盐。

7. 发明申请

US20060046289A1 Novel carbonyl reductase, gene thereof and use of the same 有权
标题翻译：新型羰基还原酶，其基因及其用途
公开(公告)号：US20060046289A1
公开(公告)日：2006-03-02
申请号：US10512908
申请日：2003-04-30
申请人： Noriyuki Kizaki , Miho Horikawa , Yoshihiko Yasohara
发明人： Noriyuki Kizaki , Miho Horikawa , Yoshihiko Yasohara
IPC分类号： C12P7/22 , C07H21/04 , C12P21/06 , C12N9/02 , C12N1/21
CPC分类号： C12N9/0006 , C12Y101/01184
摘要： 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.
摘要翻译：本发明提供形成（R）-2-氯-1-（3'-氯苯基）乙醇的新型多肽，编码所述多肽的多核苷酸及其用途。本发明涉及具有以下物理和化学性质（1）至（4）的多肽：（1）活性：以NADPH或NADH作为辅酶作用于2-氯-1-（3'-氯苯基）乙酮，形成（R）-2-氯-1-（31-氯苯基）乙醇; （2）活性最佳pH：5.0〜6.0; （3）最适温度为40℃〜50℃。（4）分子量：约40,000，通过凝胶过滤分析测定，约30,000，通过SDS聚丙烯酰胺凝胶电泳分析测定。本发明还涉及包含序列表中SEQ ID NO：1所示氨基酸序列的多肽，编码所述多肽的多核苷酸，以及以高水平产生所述多肽的转化体。

8. 发明申请

US20050080277A1 Process for preparing optically active 2-[6-(hydroxy-methyl)-1,3-dioxan-4-yl] acetic acid derivatives 失效
标题翻译：光学活性的2- [6-（羟基 - 甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法
公开(公告)号：US20050080277A1
公开(公告)日：2005-04-14
申请号：US10048553
申请日：2001-06-05
申请人： Akira Nishiyama , Miho Horikawa , Yoshihiko Yasohara , Noboru Ueyama , Kenji Inoue
发明人： Akira Nishiyama , Miho Horikawa , Yoshihiko Yasohara , Noboru Ueyama , Kenji Inoue
IPC分类号： C07D319/06 , C12P7/42 , C12P17/06
CPC分类号： C07D319/06 , C12P7/42 , C12P17/06
摘要： 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)-β-hydroxy-γ-butyrolactone at a temperature not lower than −30° C. to give a dihydroxyoxohexanoic acid derivative, treating the same with an acylating agent in the presence of a base to produce a dihydroxyoxohexanoic acid monoacyl derivative, reducing this compound with a microorganism to produce a trihydroxyhexanoic acid monoacyl derivative, treating this compound with an acetal-forming reagent in the presence of an acid catalyst to produce an acyloxymethyldioxanylacetic acid derivative, and finally, subjecting this compound to solvolysis in the presence of a base.
摘要翻译：本发明提供一种生产技术，通过该技术，可以以廉价的方式生产价值为医药中间体的光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物和容易获得的起始材料，而不使用任何非常设备，例如超低温反应器。本发明是光学活性的2- [6-（羟甲基）-1,3-二恶烷-4-基]乙酸衍生物的制备方法，该方法包括使通过使碱或0价金属在不低于-30℃的温度下用（S）-β-羟基-γ-丁内酯在乙酸酯衍生物上作用，得到二羟基氧代己酸衍生物，在酰化剂存在下用酰化剂处理碱化以制备二羟基氧己基单酰基衍生物，用微生物还原该化合物以产生三羟基己酸单酰基衍生物，在酸催化剂存在下用缩醛形成试剂处理该化合物，得到酰氧基甲基二恶烷基乙酸衍生物，最后，该化合物在碱存在下溶剂解。

9. 发明申请

US20050014818A1 Process for producing optically active chroman derivative and intermediate 审中-公开
标题翻译：光学活性苯并二氢吡喃衍生物和中间体的制备方法
公开(公告)号：US20050014818A1
公开(公告)日：2005-01-20
申请号：US10494671
申请日：2002-11-07
申请人： Masaru Mitsuda , Tatsuyoshi Tanaka , Yoshihiko Yasohara
发明人： Masaru Mitsuda , Tatsuyoshi Tanaka , Yoshihiko Yasohara
IPC分类号： C07C39/24 , C07C303/28 , C07C303/30 , C07C309/66 , C07C309/73 , C07D311/20 , C07D405/06 , C12P7/22 , C07D311/74 , A61K31/353
CPC分类号： C07D405/06 , C07C39/24 , C07C39/245 , C07C303/28 , C07C309/66 , C07C309/73 , C07D311/20 , C12P7/22
摘要： A process for easily producing various optically active chroman derivatives that are useful as pharmaceutical intermediates from inexpensive starting materials is provided. Cyclic hemiacetal (1) obtained from dihydrocoumarin through one step is asymmetrically reduced to produce an optically active halohydrin derivative (3), and the optically active halohydrin derivative (3) is cyclized to produce an optically active chroman derivative (13):
摘要翻译：提供了一种易于制备可用作廉价起始材料的药物中间体的各种光学活性苯并二氢吡喃衍生物的方法。通过一步从二氢香豆素获得的环状半缩醛（1）被不对称地还原以产生光学活性的卤代醇衍生物（3），并将光学活性卤代醇衍生物（3）环化以产生光学活性苯并二氢吡喃衍生物（13）：

10. 发明授权

US5654472A Triazole derivatives 失效
标题翻译：三唑衍生物
公开(公告)号：US5654472A
公开(公告)日：1997-08-05
申请号：US553558
申请日：1995-12-18
申请人： Yoshihiko Yasohara , Kenji Miyamoto , Noriyuki Kizaki , Shigeru Kawano , Junzo Hasegawa
发明人： Yoshihiko Yasohara , Kenji Miyamoto , Noriyuki Kizaki , Shigeru Kawano , Junzo Hasegawa
IPC分类号： C07C33/26 , C07C33/46 , C07C69/28 , C07C69/30 , C07C69/63 , C07C309/66 , C07C309/73 , C07D249/08 , C07D301/30 , C07D303/14 , C07D521/00 , C12P7/20 , C12P7/62 , C12P41/00 , C07C51/36 , C07C31/20 , C07C69/66
CPC分类号： C07D249/08 , C07C309/66 , C07C309/73 , C07C33/26 , C07C33/46 , C07C69/28 , C07C69/30 , C07C69/63 , C07D231/12 , C07D233/56 , C07D303/14 , C12P41/004 , C12P7/20 , C12P7/62
摘要： The present invention relates to a novel glycerol derivative and a process for preparing the same, and a process for preparing a triazole derivative.According to the present invention, an optical active 2-arylglycerol derivative which is a novel and useful as a synthetic intermediate of medicament can be provided and furthermore, (R)-2-(2,4-difluorophenyl)-3-(1H-1,2,4-triazole-1-yl)-propane-1,2-diol which is useful as an antifungal agent can be prepared.
摘要翻译： PCT No.PCT / JP95 / 00749 Sec。 371 1995年12月18日第 102（e）1995年12月18日日期PCT提交1995年4月17日PCT公布。出版物WO95 / 28374 日期：1995年10月26日本发明涉及新型甘油衍生物及其制备方法，以及制备三唑衍生物的方法。根据本发明，可以提供新的可用作药物合成中间体的光学活性2-芳基甘油衍生物，此外，（R）-2-（2,4-二氟苯基）-3-（1H- 1,2,4-三唑-1-基） - 丙烷-1,2-二醇，可用作抗真菌剂。

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