公开(公告)号：US20220275410A1

公开(公告)日：2022-09-01

申请号：US17606123

申请日：2020-05-15

申请人： API CORPORATION

发明人： Masaharu MIZUTANI ,  Ryoma MIYAKE ,  Hiroshi KAWABATA

IPC分类号： C12P13/04 ,  C12N15/70 ,  C12P41/00 ,  C12N9/10

摘要： An object of the present invention is to provide a method of industrially producing a high-purity L-cyclic amino acid more inexpensively and with a high efficiency, from a cyclic amino acid having a double bond at the 1-position. The present invention provides a method in which an L-cyclic amino acid is produced by allowing a cyclic amino acid having a double bond at the 1-position to react with a specific enzyme having a catalytic ability to reduce a cyclic amino acid having a double bond at the 1-position to produce an L-cyclic amino acid.

公开(公告)号：US20210403427A1

公开(公告)日：2021-12-30

申请号：US17277456

申请日：2019-09-24

申请人： API CORPORATION

发明人： Masato MURAI ,  Jun TAKEHARA ,  Daiki OKADO

IPC分类号： C07D211/60

摘要： The present invention aims to provide a method for producing a (2S,5R)-5-(protected oxyamino)-piperidine-2-carboxylic acid derivative at a low cost that can be performed under mild reaction conditions not requiring a facility at an extremely low temperature, is safer, can control the quality of the desired product with ease, and shows good workability in the site of production. A method for producing a compound represented by the formula (2): wherein PG1 is an amino-protecting group, PG2 is an amino-protecting group, PG3 is a hydroxyl-protecting group, LG is a leaving group, and R is a hydrocarbon group having 1-8 carbon atoms and optionally having substituent(s), including a step of reacting a compound represented by the formula (1): wherein each symbol is as defined above, with a hydroxylamine derivative represented by the formula PG2NHOPG3 wherein each symbol is as defined above, in the presence of a base in a solvent.

公开(公告)号：US11136287B2

公开(公告)日：2021-10-05

申请号：US16078889

申请日：2017-11-21

申请人： API CORPORATION

发明人： Masaki Nagahama ,  Kenta Saito

IPC分类号： C07C231/02 ,  C07C231/12 ,  C07C235/06

摘要： The present invention provides an industrially-preferable method for safely producing N-benzyl-2-bromo-3-methoxypropionamide at a high yield but at low cost. The method for producing of the present invention includes: in sequence, an amidation process that causes diacrylic anhydride to react with benzylamine in a solvent to obtain N-benzylacrylamide; a bromination process that causes N-benzylacrylamide to react with bromine in a solvent to obtain N-benzyl-2,3-dibromopropionamide; and a methoxylation process that causes N-benzyl-2,3-dibromopropionamide to react with methanol in the presence of a base to obtain N-benzyl-2-bromo-3-methoxypropionamide.

公开(公告)号：US20200283390A1

公开(公告)日：2020-09-10

申请号：US16851402

申请日：2020-04-17

申请人： API CORPORATION

发明人： Naoyuki WATANABE ,  Takanobu IURA ,  Hideki OOMIYA ,  Masaki NAGAHAMA

IPC分类号： C07D215/14 ,  C12P17/12

摘要： Production of pitavastatin calcium safely on an industrial scale with a high yield and high selectivity at low cost. A method of producing pitavastatin calcium including step (i) for acetalizing a compound represented by the formula (1) to give a compound represented by the formula (3), step (ii) for reacting a compound represented by the formula (3) with an acid to give a compound represented by the formula (4), and step (iii) for hydrolyzing a compound represented by the formula (4) and reacting same with a calcium compound.

公开(公告)号：US10071958B2

公开(公告)日：2018-09-11

申请号：US14888576

申请日：2014-05-01

申请人： API Corporation

发明人： Yuuki Asuma ,  Hisatoshi Uehara ,  Tomoko Maeda ,  Yasuyo Saito ,  Ryoma Miyake ,  Hiroshi Kawabata

IPC分类号： C07C319/06 ,  C07C323/52 ,  C07C323/58 ,  C07D277/14 ,  C07C319/02 ,  C12P13/12 ,  C07C319/14 ,  C07C319/20 ,  C07C323/60

CPC分类号： C07C319/06 ,  C07C319/02 ,  C07C319/14 ,  C07C319/20 ,  C07C323/52 ,  C07C323/58 ,  C07C323/60 ,  C07D277/14 ,  C12P13/12 ,  C07C323/12 ,  C07C323/03

摘要： According to the present invention, it becomes possible to perform a process for converting into an α-substituted cysteine represented by general formula (1) or a salt thereof at low cost and on an industrial scale by employing a process that is routed through a compound represented by general formula (3) to a compound represented by general formula (6). Particularly, by employing a process that is routed through a compound represented by general formula (7-2), it becomes possible to detach a tert-butyl protection group in a simple manner and to produce the compound represented by general formula (1) with high purity. Furthermore, by employing a process that is routed through tert-butylthiomethanol or a process that is routed through a compound represented by general formula (9), it becomes possible to produce a compound represented by general formula (2) without generating bischloromethylether that is an oncogenic substance. In the production of an α-substituted-D-cysteine or a salt thereof, it becomes possible to perform a process for converting the compound represented by general formula (2) into a compound represented by general formula (3S) in one step by allowing an enzyme or the like to act on the compound represented by general formula (2).

公开(公告)号：US20170306367A1

公开(公告)日：2017-10-26

申请号：US15526031

申请日：2015-11-02

申请人： API CORPORATION

发明人： Ryoma MIYAKE ,  Yasumasa DEKISHIMA

IPC分类号： C12P17/12 ,  C12N9/02

CPC分类号： C12P17/12 ,  C12N9/0071 ,  C12N15/09 ,  C12Y114/11

摘要： A method for producing cis-5-hydroxy-L-pipecolic acid, the method comprising allowing a 2-oxoglutarate-dependent L-pipecolic acid hydroxylase to act on L-pipecolic acid to generate cis-5-hydroxy-L-pipecolic acid, wherein the 2-oxoglutarate-dependent L-pipecolic acid hydroxylase comprises the polypeptide (A), (B) or (C) below: (A) a polypeptide comprising the amino acid sequence represented by SEQ ID NO: 4 or 11; (B) a polypeptide comprising the amino acid sequence represented by SEQ ID NO: 4 or 11 except that one or several amino acids are deleted, substituted, and/or added, which polypeptide has 2-oxoglutarate-dependentL-pipecolic acid hydroxylase activity; or (C) a polypeptide comprising an amino acid sequence with an identity of not less than 60% to the amino acid sequence represented by SEQ ID NO: 4 or 11, which polypeptide has 2-oxoglutarate-dependent L-pipecolic acid hydroxylase activity.

公开(公告)号：US20170305867A1

公开(公告)日：2017-10-26

申请号：US15600196

申请日：2017-05-19

申请人： API CORPORATION

发明人： Naoyuki WATANABE ,  Tomoko MAEDA ,  Yasumasa DEKISHIMA ,  Hiroshi KAWABATA ,  Masaki NAGAHAMA ,  Kosuke ITO

IPC分类号： C07D239/42 ,  C12P17/12 ,  C12N9/04

CPC分类号： C07D239/42 ,  C12N9/0006 ,  C12P17/12 ,  C12Y101/01184

摘要： An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.

公开(公告)号：US09695130B2

公开(公告)日：2017-07-04

申请号：US15116861

申请日：2015-02-06

申请人： API CORPORATION

发明人： Naoyuki Watanabe ,  Masaki Nagahama ,  Takashi Ohtani

IPC分类号： C07D239/42 ,  C12P17/12 ,  C12N9/04

CPC分类号： C07D239/42 ,  C12N9/0006 ,  C12P17/12

摘要： An object of the present invention is to provide a novel method capable of producing rosuvastatin calcium and intermediates therefor efficiently, inexpensively and with high purity. The present invention provides a method of efficiently producing rosuvastatin calcium and intermediates therefor having a high purity at an industrial scale, without using an extremely low temperature reaction or a special asymmetric catalyst.

公开(公告)号：US20160318867A1

公开(公告)日：2016-11-03

申请号：US15108141

申请日：2014-12-26

申请人： API CORPORATION

发明人： Jun TAKEHARA ,  Masato MURAI ,  Takashi OHTANI ,  Tomoko MAEDA ,  Tsugihiko HIDAKA

IPC分类号： C07D211/60 ,  C07D498/08

CPC分类号： C07D211/60 ,  C07C233/47 ,  C07C309/66 ,  C07D498/08 ,  Y02P20/55

摘要： A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by formula (10) below: the method including removing the protecting group from the hydroxyl group in a compound represented by formula (7) below: (wherein P represents a protecting group, R3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms) to synthesize a compound represented by formula (8) below: (wherein R3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms).

摘要翻译： （其中R3表示含有1至4个碳原子的烷基，A表示含有1至10个碳原子的烷基，含有6至12个碳原子的芳基，含有1至4个碳原子的烷氧基或芳烷氧基 含有7〜20个碳原子的基团）。

公开(公告)号：US20130289011A1

公开(公告)日：2013-10-31

申请号：US13817672

申请日：2011-08-11

申请人： Masaaki Yoshimaru

发明人： Masaaki Yoshimaru

IPC分类号： A61K8/04 ,  A61K8/81 ,  A61Q5/00 ,  A61K8/73 ,  A61Q5/12 ,  A61K8/86

CPC分类号： A61K8/04 ,  A61K8/27 ,  A61K8/4933 ,  A61K8/731 ,  A61K8/8147 ,  A61K8/8158 ,  A61K8/8176 ,  A61K8/86 ,  A61K2800/58 ,  A61Q5/006 ,  A61Q5/12 ,  A61Q17/005 ,  C08F220/34 ,  C08K5/32 ,  C08K5/56 ,  C08K7/14 ,  C08L33/14 ,  C08L71/02 ,  C08L79/02 ,  C08F2220/282 ,  C08F220/58

摘要： To provide an aqueous antibacterial dispersion which contains a metal pyrithione salt and a cationic polymer and which can maintain a stable dispersed state. An antibacterial dispersion characterized by containing at least one cationic polymer, at least one metal pyrithione salt, and at least one non-anionic surfactant. In an aqueous dispersion of the metal pyrithione salt, the non-anionic surfactant is blended instead of a conventional anionic component, whereby good dispersion stability can be maintained in a cationic polymer blend system.

摘要翻译： 提供含有金属吡啶硫酮盐和阳离子聚合物并且可以保持稳定的分散状态的水性抗菌分散体。 一种抗菌分散体，其特征在于含有至少一种阳离子聚合物，至少一种金属吡啶硫酮盐和至少一种非阴离子表面活性剂。 在金属吡啶硫酮盐的水分散体中，配合非阴离子表面活性剂代替常规的阴离子组分，由此在阳离子聚合物共混体系中可以保持良好的分散稳定性。