Kaneka Corporation

Ono Pharmaceutical Co., Ltd.

Stealth Biotherapeutics Inc.

Masaru Mitsuda

Kenji Inoue

Akira Nishiyama

Susumu Amano

Akio Fujii

Yoshihiko Yasohara

Noriyuki Kizaki

Noboru Ueyama

Makoto Miyazaki

Kazumi Okuro

Naoaki Taoka

Yukio Yamada

Hiroshi Murao

Ken-ichiro Morio

Takeshi Kondo

Shohei Yamamoto

Yasuyoshi Ueda

Masakatsu Shibasaki

Junzo Hasegawa

Takehisa Ohashi

Koichi Kinoshita

Toshihiro Takeda

Tatsuyoshi Tanaka

Tatsuya Honda

Noriyuki Ito

Hiroaki Yasukouchi

Yasuhiro Saka

Koki Yamashita

Masatoshi Ohnuki

Hirofumi Maeda

Teruaki Takesue

Shigeo Hayashi

Yoshinori Hirai

Makoto Funabashi

Ken-Ichiro Morio

The present disclosure provides a reaction of a chlorine-containing compound using a flow reactor which is less restricted by a solvent to be used. In the present disclosure, an organic compound is produced by supplying a reaction substrate having at least one functional group which can react with chlorine and is selected from the group consisting of hydroxy group, a thiol group, an amino group, a carboxyl group, a thiocarboxyl group, and an acid amide group, and a chlorine-containing compound to a flow reactor together with a trialkyl amine having 9 to 40 carbon atoms and an organic solvent, and allowing the reaction substrate and the chlorine-containing compound to react with each other.

Process for producing organic compound

The present invention is to provide a method for the efficient production on an industrial scale of SS-31 (D-Arg-Dmt-Lys-Phe-NH), which is an SS peptide. According to the present invention, the desired SS-31 is produced by efficiently synthesizing a tetrapeptide compound as a precursor of SS-31 and improving the tetrapeptide purity by crystallization.

Tetrapeptide compound and method for producing same

The present invention is related to a method of producing a peptide, characterized in contacting a reaction mixture with a base after a condensation reaction to hydrolyze while a basic condition is maintained until a ratio of a remaining unreacted active ester of an acid component is decreased to 1% or less in a liquid phase peptide synthesis method. According to the invention, a target peptide of high purity can be simply and efficiently produced by a continuous liquid phase synthesis method. Further, the present invention is related to a method of producing a peptide, characterized in using an amide-type solvent immiscible with water in a liquid phase peptide synthesis method. According to the invention, various peptides can be produced by the liquid phase synthesis method without being restricted by the amino acid sequence of the target peptide.

Method of producing peptide

The present application relates to a method for producing an optically active &#x3b1;-amino acid derivative, comprising steps of reacting an &#x3b1;-haloester derivative represented by the general formula (1): of which alcohol part of the ester group is an optically active alcohol derivative,with an amine compound; then deprotecting the obtained compound; further carrying out an ester exchange reaction. According to the present invention method, it is possible to easily produce an optically active &#x3b1;-amino acid ester derivative which is useful as an intermediate for drugs with high selectivity.

Method for producing optically active amino acid derivative

The objective of the present invention is to produce an optically active 2-arylpiperazine derivative useful as a synthetic intermediate for pharmaceutical products and agricultural chemicals from inexpensive and readily available starting material by an industrially practicable method. The objective can be accomplished by treating an optically active substituted aminodiol derivative produced from an optically active styrene oxide derivative with a sulfonating agent in the presence of a base, and then reacting an amine compound to obtain the 2-arylpiperazine derivative. Especially, an optically active 1-unsubstituted-2-arylpiperazine derivative can be produced by treating an optically active 1-allyl-2-arylpiperazine derivative with water in the presence of a transition metal catalyst for deallylation.

Method for producing optically active 2-arylpiperazine derivative

The present invention relates to a method for producing a 2'-hydroxy-protected nucleoside derivative by reacting a ribonucleoside with an acylating or a carbamoylating reagent in the presence of a metal complex consisting of a copper compound and an optically active ligand. By the method according to the present invention, a 2&#x2032;-hydroxy-protected ribonucleoside derivative, which is an important intermediate for producing an oligonucleoside, can be easily produced with good regioselectivity from a nucleoside derivative of which 2&#x2032;,3&#x2032;-hydroxy groups are not protected.

2'-hydroxy-protected ribonucleoside derivative and production method thereof

It is an objective of the present invention to produce an anti-form of an optically active &#x3b2;-hydroxy-&#x3b1;-aminocarboxylic acid ester efficiently, simply and industrially advantageously. The objective can be accomplished by directly and selectively producing the anti-form of the optically active &#x3b2;-hydroxy-&#x3b1;-aminocarboxylic acid ester by asymmetric reduction of a &#x3b2;-keto-&#x3b1;-aminocarboxylic acid ester using an optically active amine complex as a catalyst. Further, the &#x3b2;-keto-&#x3b1;-aminocarboxylic acid ester as a raw material can be produced at a high yield by reacting a glycine derivative with a carboxylic acid derivative.

Process for producing optically active beta-hydroxy-alpha-aminocarboxylic acid ester

The present invention has its object to provide a method for producing an optically active hydroxycarboxylic acid derivative which is an intermediate important for production of medicines, agrochemicals, chemical products, and so on. The production method of the present invention comprises: carrying out a hydrogen-transfer reduction of a ketocarboxylic acid or a salt thereof by the reaction of an optically active diamine complex to produce an optically active hydroxycarboxylic acid derivative. According to the present invention, it is possible to safely and efficiently produce an industrially-useful optically active hydroxycarboxylic acid derivative.

Method for producing optically active hydroxycarboxylic acid derivatives or salts thereof

The objective of the present invention is to provide an optically active imidazolidinone derivative widely usable for synthesizing an optically active amino acid, a method of easily producing the derivative, and a method of easily producing an optically active amino acid by using the derivative. The objective can be achieved by producing an optically active amino acid using a novel optically active imidazolidinone derivative represented by a general formula (3) and the like. According to the method of the present invention, an optically active imidazolidinone derivative can be obtained by preferential crystallization from a mixture of isomers of the imidazolidinone derivative. Therefore, an optically active amino acid can be easily and stereoselectively produced without cumbersome procedures required for the conventional methods, such as resolution of diastereomers, synthesis from an optically active amino acid and resolution of isomers by silica gel column chromatography.

Imidazolidinone derivative, method of producing the same and method of producing optically active amino acid

The present invention provides an industrially safe, easily operable process for producing an optically active epoxy alcohol derivative useful as an intermediate for pharmaceuticals from inexpensively available materials, and also provides a novel halohydrin derivative serving as an important intermediate for the epoxy alcohol derivative. Furthermore, the present invention provides a process for producing an intermediate for a triazole antifungal agent by allowing a halohydrin to react with a triazole sulfonamide, the process including a small number of steps. A process for producing an optically active epoxy alcohol derivative includes allowing an optically active &#x3b1;-substituted propionate derivative to react with a haloacetic acid derivative in the presence of a base to prepare an optically active haloketone derivative, allowing the resulting haloketone derivative to react with an aryl metal compound to stereoselectively prepare a halohydrin derivative, eliminating a substituent for the hydroxy group of the halohydrin derivative, and performing epoxidation with a base. Furthermore, a process for producing an intermediate for a triazole antifungal agent includes allowing a halohydrin derivative to react with a triazole sulfonamide, the process including a small number of steps.

Optically active halohydrin derivative and process for producing optically active epoxy alcohol derivative from the same

The present invention provides a process for producing an optically active 2-allylcarboxylic acid derivative, which is useful as a pharmaceutical intermediate, from readily available and inexpensive starting materials by the process which can be practiced on a commercial scale in a simple and easy manner, and certain 2-allylcarboxamide derivatives, which are novel and important intermediates in that process. An N-allylcarboxamide derivative undergoes rearrangement reaction diastereoselectively in the presence of a base to give a 2-allylcarboxamide derivative, the resulting derivative is subjected to a carbamation reaction and solvolysis to give an optically active 2-allylcarboxylic acid ester, and then the ester obtained is stereoselectively hydrolyzed using an enzyme to produce 2-allylcarboxylic acid having a high optical purity. In addition, the present invention provides a 2-allylcarboxamide derivative compound which is a novel intermediate in the process of the present invention.

Optically active 2-allylcarboxylic acid derivative and process for producing the same

A nitrous acid salt is added at a temperature of 10 to 80&#xb0; C. to an aqueous solution which contains an optically active 2-aminocarboxylic acid (4) and a protonic acid, the amount of the latter acid being 1 to 3 equivalents to the former, and which has a proton concentration of 0.5 to 2 mol/kg to conduct a reaction to thereby produce an optically active 2-hydroxycarboxylic acid (1). Thionyl chloride and a basic compound are caused to act on the compound (1) to chlorinate it and simultaneously invert the configuration in the 2-position. Thus, an optically active 2-chlorocarboxylic acid chloride (5) is induced. The compound (5) is hydrolyzed to induce an optically active 2-chlorocarboxylic acid (2). The compound (2) is reacted with a thioacetic acid salt to incorporate an acetylthio group thereinto and simultaneously invert the configuration in the 2-position to thereby produce an optically active 2-acetylthiocarboxylic acid (3). 

Process for producing optically active carboxylic acid substituted in 2-position

This invention provides a process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives, which are of value as intermediates of drugs, from inexpensive starting materials without using any special equipment such as that required for super-low temperature reactions. A process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives which comprises

Process for producing optically active 2-[6-(hydroxymethyl)-1,3-dioxan-4-yl]acetic acid derivatives

It is an objective to produce intermediates of optically active beta-3 adrenaline receptor agonists from readily available raw materials in a safe, efficient and industrially advantageous manner. A substituted acetylpyridine derivative represented by the general formula (9) is reduced by enantioselective reduction to produce an optically active hydroxyethylpyridine derivative represented by the general formula (10) (wherein * represents an asymmetric carbon atom), and it is further derivatized to an intermediate of an optically active beta-3 adrenaline receptor agonist, such as an optically active dihydroxyethylpyridine derivative represented by the general formula (14) or an optically active oxirane derivative represented by the general formula (16)

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Takasago, Japan

Masaru Mitsuda