公开(公告)号：US20240043887A1

公开(公告)日：2024-02-08

申请号：US18268788

申请日：2021-12-24

Applicant: API CORPORATION

Inventor： Yasuhisa ASANO ,  Suguru SHINODA ,  Junichi ENOKI ,  Ryoma MIYAKE ,  Haruka SASANO

IPC: C12P17/12 ,  C12N9/02 ,  C12N15/70

CPC classification number: C12P17/12 ,  C12N9/0071 ,  C12N15/70 ,  C12Y114/11002 ,  C12R2001/19

Abstract: The present invention aims to provide a mutant L-pipecolic acid hydroxylase for highly productive and highly selective production of cis-5-hydroxy-L-pipecolic acid by hydroxylation of L-pipecolic acid, and to provide a novel method for industrially producing cis-5-hydroxy-L-pipecolic acid from L-pipecolic acid with high productivity at low cost. The present invention provides a mutant L-pipecolic acid hydroxylase having an amino acid sequence that a particular amino acid mutation(s) is/are introduced in the amino acid sequence of SEQ ID NO:2.

公开(公告)号：US20230323317A1

公开(公告)日：2023-10-12

申请号：US18091687

申请日：2022-12-30

Applicant: API CORPORATION

Inventor： Toyokazu YOSHIDA ,  Koichi ISHIDA ,  Ryoma MIYAKE ,  Takanobu IURA ,  Hiroshi KAWABATA

IPC: C12N9/18 ,  C12P7/62 ,  C12P41/00

CPC classification number: C12N9/18 ,  C12P7/62 ,  C12P41/00 ,  C12Y301/01

Abstract: The present invention provides a novel hydrolase that can industrially produce optically highly pure (1S,2S)-1-alkoxycarbonyl-2-vinylcyclopropane carboxylic acid with high efficiency at low costs, and a production method using the hydrolase.

公开(公告)号：US11623943B2

公开(公告)日：2023-04-11

申请号：US17196167

申请日：2021-03-09

Applicant: API CORPORATION

Inventor： Masaki Nagahama

IPC: A61K31/165 ,  C07K5/062 ,  C07B57/00 ,  C07C231/12 ,  C07C231/20 ,  C07C237/06 ,  C07C233/47 ,  C07C231/02

Abstract: The present invention provides a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Adopting a particular isomerization-crystallization condition makes it possible to a method of industrially and safely producing lacosamide high in diastereomeric excess at a high yield and a low cost. Additionally, an intermediate efficacious for producing lacosamide is provided.

公开(公告)号：US20210078940A1

公开(公告)日：2021-03-18

申请号：US17050255

申请日：2019-04-26

Applicant: API CORPORATION

Inventor： Masaki NAGAHAMA ,  Hideki OOMIYA ,  Daiki OKADO ,  Hirotsugu TANIIKE

IPC: C07C253/20 ,  C07C51/06

Abstract: The present invention provides a method for industrially producing a highly pure aromatic nitrile compound and a highly pure aromatic carboxylic acid compound safely and highly efficiently at low costs. Compound (2) is subjected to Willgerodt reaction in the presence of an additive as necessary, and the obtained amide compound (3) is hydrolyzed and neutralized to give carboxylic acid compound (4). Carboxylic acid compound (4) is reacted with a halogenating agent in the presence of a catalyst as necessary in an organic solvent, and further reacted with an amidating agent, and the obtained amide compound (5) or (6) is reacted with a dehydrating agent to give nitrile compound (1). Alternatively, carboxylic acid compound (4) is reacted with a halogenating agent and a compound represented by the formula R6SO2R7 in the presence of a catalyst as necessary in an organic solvent to give nitrile compound (1). Np is a naphthyl group optionally having substituent(s), R5 is an alkylene group having 1-3 carbon atoms, and other symbols are as described in the DESCRIPTION.

公开(公告)号：US10815201B2

公开(公告)日：2020-10-27

申请号：US16851402

申请日：2020-04-17

Applicant: API CORPORATION

Inventor： Naoyuki Watanabe ,  Takanobu Iura ,  Hideki Oomiya ,  Masaki Nagahama

IPC: A61P43/00 ,  A61P3/06 ,  A61K31/47 ,  C07D215/14 ,  C07B61/00 ,  C12P17/12

Abstract: 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：US10703719B2

公开(公告)日：2020-07-07

申请号：US15965289

申请日：2018-04-27

Applicant: API CORPORATION

Inventor： Jun Takehara ,  Masato Murai ,  Takashi Ohtani ,  Tomoko Maeda ,  Tsugihiko Hidaka

IPC: C07D211/60 ,  C07C309/66 ,  C07C233/47 ,  C07D498/08

Abstract: A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the 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).

公开(公告)号：US20180244620A1

公开(公告)日：2018-08-30

申请号：US15965316

申请日：2018-04-27

Applicant: API CORPORATION

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

IPC: C07D211/60 ,  C07C309/66 ,  C07C233/47 ,  C07D498/08

CPC classification number: C07D211/60 ,  C07C233/47 ,  C07C309/66 ,  C07D498/08 ,  Y02P20/55

Abstract: A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below: the method comprising the step of removing the protecting group from the hydroxyl group in a compound represented by the 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 the 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).

公开(公告)号：US09969988B2

公开(公告)日：2018-05-15

申请号：US15115028

申请日：2015-01-27

Applicant: API CORPORATION

Inventor： Makoto Hibi ,  Jun Ogawa ,  Ryoma Miyake ,  Hiroshi Kawabata

IPC: C12P13/04 ,  C12P17/10 ,  C12P17/12 ,  C12N9/02

CPC classification number: C12N9/0071 ,  C12P13/04 ,  C12P17/10 ,  C12P17/12 ,  C12Y114/00 ,  C12Y114/11006

Abstract: The present invention provides a pipecolic acid 4-hydroxylase protein exemplified by the following (A), (B), and (C), having activity to react with L-pipecolic acid in the presence of 2-oxoglutaric acid and iron(II) ions to produce trans-4-hydroxy-L-pipecolic acid, and a method for producing 4-hydroxy amino acid, which method comprises reacting the pipecolic acid 4-hydroxylase protein, cells containing the protein, a treated product of the cells, and/or a culture liquid obtained by culturing the cells, with α-amino acid to produce 4-hydroxy amino acid: (A) a polypeptide comprising the amino acid sequence represented by SEQ ID NO:2, 4, 6, 8, 10, 12, 16, or 18; (B) a polypeptide comprising the amino acid sequence represented by SEQ ID NO:2, 4, 6, 8, 10, 12, 16, or 18 except that one or several amino acids are deleted, substituted, and/or added, and having pipecolic acid 4-hydroxylase activity; and (C) a polypeptide having an amino acid sequence that is not less than 80% identical to the amino acid sequence represented by SEQ ID NO:2, 4, 6, 8, 10, 12, 16, or 18, and having pipecolic acid 4-hydroxylase activity.

公开(公告)号：US20160347718A1

公开(公告)日：2016-12-01

申请号：US15116861

申请日：2015-02-06

Applicant: API CORPORATION

Inventor： Naoyuki WATANABE ,  Yasumasa DEKISHIMA ,  Masaki NAGAHAMA ,  Tomoko MAEDA ,  Takashi OHTANI ,  Kosuke ITO ,  Hiroshi KAWABATA

IPC: C07D239/42 ,  C12P17/12

CPC classification number: C07D239/42 ,  C12N9/0006 ,  C12P17/12

Abstract: 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.

Abstract translation: 本发明的目的是提供能够高效，低成本且高纯度地生产瑞舒伐他汀钙及其中间体的新方法。 本发明提供了在不使用极低温反应或特殊的不对称催化剂的情况下，有效地生产工业规模的高纯度的瑞舒伐他汀钙及其中间体的方法。

公开(公告)号：US09334509B2

公开(公告)日：2016-05-10

申请号：US14637429

申请日：2015-03-04

Applicant: API CORPORATION

Inventor： Hiroshi Kawabata ,  Ryoma Miyake ,  Kuniko Asada ,  Ryouhei Katou

IPC: C12P7/62 ,  C12N9/18 ,  C12P41/00 ,  C12N9/14

CPC classification number: C12P7/62 ,  C12N9/14 ,  C12N9/18 ,  C12P41/005 ,  Y02P20/52

Abstract: It is an object of the present invention to provide a novel hydrolase, which is used when dialkyl 2-vinylcyclopropane-1,1-dicarboxylate is hydrolyzed with an enzyme, so as to efficiently obtain (1S,2S)-1-alkoxycarbonyl-2-vinylcyclopropanecarboxylic acid that is useful as an intermediate for synthesizing therapeutic agents for hepatitis C. According to the present invention, there is provided a hydrolase protein, which consists of the amino acid sequence shown in any one of SEQ ID NOS. 2 to 5 and which has activity of catalyzing, at higher selectivity than the protein consisting of the amino acid sequence shown in SEQ ID NO. 1, a reaction of producing (1S,2S)-1-ethoxycarbonyl-2-vinylcyclopropanecarboxylic acid from diethyl 2-vinylcyclopropane-1,1 -dicarboxylate.

Abstract translation: 本发明的一个目的是提供一种新的水解酶，其在2-乙烯基环丙烷-1,1-二羧酸二烷基酯用酶水解时使用，以有效地获得（1S，2S）-1-烷氧基羰基-2 - 乙烯基环丙烷羧酸，其可用作合成丙型肝炎治疗剂的中间体。根据本发明，提供了水解酶蛋白质，其由SEQ ID NOS中任一项所示的氨基酸序列组成。 2至5，并且其具有以比由SEQ ID NO。所示的氨基酸序列组成的蛋白质更高的选择性催化的活性。 1，从2-乙烯基环丙烷-1,1-二羧酸二乙酯生产（1S，2S）-1-乙氧基羰基-2-乙烯基环丙烷甲酸的反应。