OPTICALLY-ACTIVE 2-AMINO-PHOSPHONOALKANE ACID, OPTICALLY-ACTIVE 2-AMINOPHOSPHONOALKANE ACID SALT, AND HYDRATES OF THESE

• US 20200131207A1
• Filed: 04/13/2018
• Published: 04/30/2020
• Est. Priority Date: 04/17/2017
• Status: Active Grant

• Current Assignee: Kyoto University, Nahls Corporation Co., Ltd.
• Original Assignee: Nahls Corporation Co., Ltd.
• Inventors: WATANABE, Bunta, YOSHIOKA, Ryuzo, ISHIDA, Hideaki
• Granted Patent: US 11,220,521 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 31/662 Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
• CPC Class Codes: A61K 8/55 Phosphorus compounds
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/04 Antipruritics
• CPC Class Codes: A61Q 19/00 Preparations for care of the skin
• CPC Class Codes: C07F 9/3808 Acyclic saturated acids which can have further substituents on alkyl
• CPC Class Codes: C07F 9/3813 N-Phosphonomethylglycine; Salts or complexes thereof

Abstract

A novel compound has pharmacological activities comparable to those of Nahlsgen and is storable excellently stably. The compound can be produced by a method according to the present invention for producing an optically active 2-amino-phosphonoalkanoic acid salt. In the method, a starting material DL-2-amino-phosphonoalkanoic acid represented by Formula (1) or a hydrate thereof is reacted with an optically active basic compound other than an optically active lysine, to give a diastereomeric salt mixture including a first salt (including a hydrate salt) between a D-2-amino-phosphonoalkanoic acid represented by Formula (1-1) and the optically active basic compound, and a second salt (including a hydrate salt) between an L-2-amino-phosphonoalkanoic acid represented by Formula (1-2) and the optically active basic compound. The diastereomeric salt mixture is fractionally crystallized to isolate one of the first and second diastereomeric salts.

Claims

1. A method for producing an optically active 2-amino-phosphonoalkanoic acid salt, the method comprising:

reacting, as a starting material, a DL-2-amino-phosphonoalkanoic acid represented by Formula (1) or a hydrate thereof with an optically active basic compound other than an optically active lysine, to give a diastereomeric salt mixture comprising;

a first salt (including a hydrate salt) between a D-2-amino-phosphonoalkanoic acid represented by Formula (1-1) and the optically active basic compound; and

a second salt (including a hydrate salt) between an L-2-amino-phosphonoalkanoic acid represented by Formula (1-2) and the optically active basic compound; and

subjecting the diastereomeric salt mixture to fractional crystallization to isolate one of the first and second diastereomeric salts, Formulae (1), (1-1), and (1-2) expressed as follows;

2. The method according to claim 1,

wherein the optically active basic compound is a compound selected from the group consisting of cinchonine, cinchonidine, quinine, quinidine, an optically active arginine, an optically active phenylalaninamide, an optically active ornithine, an optically active tyrosine hydrazide, an optically active 1-phenylpropylamine, an optically active 2-phenylpropylamine, an optically active valinol, an optically active p-hydroxyphenylglycine hydrazide, an optically active p-hydroxyphenylglycine methyl ester, an optically active p-hydroxyphenylglycine ethyl ester, an optically active glucamine, an optically active leucinol, an optically active 1-phenylethylamine, and an optically active 2-amino-1-butanol.

3. The method according to claim 1,

wherein the starting material is the DL-2-amino-phosphonoalkanoic acid represented by Formula (1) in which m is 1, 3, or 5, or a hydrate thereof.

4. The method according to claim 1,

wherein the hydrate of the DL-2-amino-phosphonoalkanoic acid represented by Formula (1) is used as the starting material to give, as one of the diastereomeric salts, the first salt between the D-2-amino-phosphonoalkanoic acid represented by Formula (1-1) and the optically active basic compound, or a hydrate of the first salt, or the second salt between the L-2-amino-phosphonoalkanoic acid represented by Formula (1-2) and the optically active basic compound, or a hydrate of the second salt.

7. A method for producing an optically active 2-amino-phosphonoalkanoic acid or a hydrate thereof, the method comprising:

preparing an optically active 2-amino-phosphonoalkanoic acid salt (including a hydrate salt) by the method according to claim 1; and

decomposing the prepared compound to give a corresponding optically active 2-amino-phosphonoalkanoic acid, or a hydrate thereof, having the same configuration as the compound before decomposition.

5. A D-2-amino-phosphonoalkanoic acid salt or a hydrate of the salt, represented by Formula (1-1′

-B);

6. An L-2-amino-phosphonoalkanoic acid salt or a hydrate of the salt, represented by Formula (1-2′

-B);

8. A D-2-amino-phosphonoalkanoic acid hydrate represented by Formula (1-1′

);

9. An L-2-amino-phosphonoalkanoic acid hydrate represented by Formula (1-2′

);