Patents Assigned to API Corporation
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Publication number: 20210403427Abstract: 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.Type: ApplicationFiled: September 24, 2019Publication date: December 30, 2021Applicant: API CORPORATIONInventors: Masato MURAI, Jun TAKEHARA, Daiki OKADO
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Patent number: 11136560Abstract: 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 ?-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 repType: GrantFiled: April 6, 2018Date of Patent: October 5, 2021Assignee: API CORPORATIONInventors: Makoto Hibi, Jun Ogawa, Ryoma Miyake, Hiroshi Kawabata
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Patent number: 11136287Abstract: 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.Type: GrantFiled: November 21, 2017Date of Patent: October 5, 2021Assignee: API CORPORATIONInventors: Masaki Nagahama, Kenta Saito
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Publication number: 20210188904Abstract: 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.Type: ApplicationFiled: March 9, 2021Publication date: June 24, 2021Applicant: API CORPORATIONInventor: Masaki NAGAHAMA
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Publication number: 20210180097Abstract: A novel method of producing high-purity hydroxy-L-pipecolic acids in an efficient and inexpensive manner while suppressing the production of hydroxy-L-proline is provided. The method includes allowing an L-pipecolic acid hydroxylase, a microorganism or cell having the ability to produce the enzyme, a processed product of the microorganism or cell, and/or a culture liquid comprising the enzyme and obtained by culturing the microorganism or cell, to act on L-pipecolic acid as a substrate in the presence of 2-oxoglutaric acid and ferrous ion, wherein the L-pipecolic acid hydroxylase has the properties: (1) the enzyme can act on L-pipecolic acid in the presence of 2-oxoglutaric acid and ferrous ion to add a hydroxy group to the carbon atom at positions 3, 4, and/or 5 of L-pipecolic acid; and (2) the enzyme has a catalytic efficiency (kcat/Km) with L-proline that is equal to or less than 7 times the catalytic efficiency (kcat/Km) with L-pipecolic acid.Type: ApplicationFiled: February 17, 2021Publication date: June 17, 2021Applicant: API CORPORATIONInventors: Ryoma MIYAKE, Hiroshi KAWABATA
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Patent number: 10975117Abstract: 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.Type: GrantFiled: November 11, 2016Date of Patent: April 13, 2021Assignee: API CORPORATIONInventor: Masaki Nagahama
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Patent number: 10954539Abstract: A novel method of producing high-purity hydroxy-L-pipecolic acids in an efficient and inexpensive manner while suppressing the production of hydroxy-L-proline is provided. The method includes allowing an L-pipecolic acid hydroxylase, a microorganism or cell having the ability to produce the enzyme, a processed product of the microorganism or cell, and/or a culture liquid comprising the enzyme and obtained by culturing the microorganism or cell, to act on L-pipecolic acid as a substrate in the presence of 2-oxoglutaric acid and ferrous ion, wherein the L-pipecolic acid hydroxylase has the properties: (1) the enzyme can act on L-pipecolic acid in the presence of 2-oxoglutaric acid and ferrous ion to add a hydroxy group to the carbon atom at positions 3, 4, and/or 5 of L-pipecolic acid; and (2) the enzyme has a catalytic efficiency (kcat/Km) with L-proline that is equal to or less than 7 times the catalytic efficiency (kcat/Km) with L-pipecolic acid.Type: GrantFiled: September 30, 2016Date of Patent: March 23, 2021Assignee: API CORPORATIONInventors: Ryoma Miyake, Hiroshi Kawabata
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Publication number: 20210078940Abstract: 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).Type: ApplicationFiled: April 26, 2019Publication date: March 18, 2021Applicant: API CORPORATIONInventors: Masaki NAGAHAMA, Hideki OOMIYA, Daiki OKADO, Hirotsugu TANIIKE
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Publication number: 20210024905Abstract: 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.Type: ApplicationFiled: March 29, 2019Publication date: January 28, 2021Applicant: API CORPORATIONInventors: Toyokazu YOSHIDA, Koichi ISHIDA, Ryoma MIYAKE, Takanobu IURA, Hiroshi KAWABATA
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Patent number: 10815201Abstract: 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.Type: GrantFiled: April 17, 2020Date of Patent: October 27, 2020Assignee: API CORPORATIONInventors: Naoyuki Watanabe, Takanobu Iura, Hideki Oomiya, Masaki Nagahama
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Publication number: 20200283390Abstract: 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.Type: ApplicationFiled: April 17, 2020Publication date: September 10, 2020Applicant: API CORPORATIONInventors: Naoyuki WATANABE, Takanobu IURA, Hideki OOMIYA, Masaki NAGAHAMA
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Patent number: 10703719Abstract: 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).Type: GrantFiled: April 27, 2018Date of Patent: July 7, 2020Assignee: API CORPORATIONInventors: Jun Takehara, Masato Murai, Takashi Ohtani, Tomoko Maeda, Tsugihiko Hidaka
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Patent number: 10676441Abstract: 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.Type: GrantFiled: August 5, 2016Date of Patent: June 9, 2020Assignee: API CORPORATIONInventors: Naoyuki Watanabe, Takanobu Iura, Hideki Oomiya, Masaki Nagahama
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Publication number: 20200115322Abstract: 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.Type: ApplicationFiled: November 21, 2017Publication date: April 16, 2020Applicant: API CORPORATIONInventors: Masaki NAGAHAMA, Kenta SAITO
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Publication number: 20190315696Abstract: 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.Type: ApplicationFiled: June 17, 2019Publication date: October 17, 2019Applicant: API CORPORATIONInventors: Naoyuki WATANABE, Tomoko MAEDA, Yasumasa DEKISHIMA, Hiroshi KAWABATA, Masaki NAGAHAMA
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Patent number: 10377722Abstract: 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.Type: GrantFiled: May 19, 2017Date of Patent: August 13, 2019Assignee: API CORPORATIONInventors: Naoyuki Watanabe, Tomoko Maeda, Yasumasa Dekishima, Hiroshi Kawabata, Masaki Nagahama, Kosuke Ito
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Patent number: 10370330Abstract: 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).Type: GrantFiled: April 27, 2018Date of Patent: August 6, 2019Assignee: API CORPORATIONInventors: Jun Takehara, Masato Murai, Takashi Ohtani, Tomoko Maeda, Tsugihiko Hidaka
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Publication number: 20180371013Abstract: 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.Type: ApplicationFiled: November 11, 2016Publication date: December 27, 2018Applicant: API CORPORATIONInventor: Masaki NAGAHAMA
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Publication number: 20180282709Abstract: 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 ?-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 repType: ApplicationFiled: April 6, 2018Publication date: October 4, 2018Applicant: API CORPORATIONInventors: Makoto HIBI, Jun OGAWA, Ryoma MIYAKE, Hiroshi KAWABATA
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Patent number: 10087473Abstract: 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-dependent L-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.Type: GrantFiled: November 2, 2015Date of Patent: October 2, 2018Assignee: API CORPORATIONInventors: Ryoma Miyake, Yasumasa Dekishima