Takasago International Corporation

Tsukasa Sotoguchi

Yoshifumi Yuasa

Hidenori Kumobayashi

Takashi Miura

Hideki Nara

Nobuo Seido

Motonobu Takenaka

Kazuhiko Matsumura

Kenji Yagi

Toshiyuki Murayama

Tohru Yokozawa

Wataru Kuriyama

Takenobu Nishikawa

Takashi Moroi

Noboru Sayo

Tetsuro Yamasaki

Takahiro Fujiwara

Takaji Matsumoto

Akio Tachikawa

Shunichi Harada

Sigeru Mitsuhashi

Disclosed is an industrially advantageous production method of optically active &#x3b2;-amino acid of formula (5), which includes subjecting an enaminoester of formula (4) to an asymmetric hydrogenation: 

Method for producing an optically active tetrahydroquinoline

The present invention provides an industrially advantageous production method of optically active tetrahydroquinolines of formula (1), which comprises:      

An object of the present invention is to provide a process for the production of an optically active amino alcohol, particularly an optically active amino alcohol of a trans-form, being excellent in economy and efficiency, and suitable for industry using easily available and less expensive materials. The present invention relates to a process for the production of an optically active amino alcohol comprising the steps that an optically active hydroxy ester in a trans-form obtained by an asymmetric hydrogenation of an easily available &#x3b2;-keto ester is reacted with hydrazine, the resulting optically active hydrazinocarbonyl alcohol is subjected to a Curtius rearrangement in the presence of alcohol and protective group of amino group of the resulting optically active alkoxycarbonylamino alcohol is deprotected. As a result of the process for the production in accordance with the present invention, the objected substance is able to be prepared in a high optical purity and in a high yield.

Process for the production of optically active amino alcohols

Process for producing optically active &ggr;-butyrolactone

A novel process for producing 3-oxocarboxylic acid esters, which are useful as intermediates in the synthesis of ceramides to be used as a humectant, biodegradable polymers, drugs, etc., at a high purity and a high yield without requiring any troublesome procedure, is disclosed. The process comprises reacting an acetoacetic ester with a calcium compound, a barium compound or a strontium compound in the presence of an organic solvent at a temperature of 10 to 120.degree. C., further reacting the obtained product with a carboxylic acid chloride to thereby acylate it, and then adding thereto an alcohol in an amount 1 to 5 times by mol as much as the calcium compound, barium compound or strontium compound to thereby deacetylate the same.

Process for producing 3-oxocarboxylic acid esters

A production process for obtaining optically active (3R,1'S)-1-benzyl-3-�(1'-N-methylamino)ethyl!pyrrolidine or (3R,1'S)-3-�(1'-N-methylamino)ethyl!pyrrolidine used as an intermediate for the synthesis of pharmaceutical preparations such as anti-fungal agents in high purity and in high yield using a reduced number of processing steps. The process comprises asymmetrically hydrogenating 3-acetyl-1-benzyl-2-pyrrolidinone in the presence of a complex formed from bidentate phosphine and ruthenium as a catalyst to provide (3S,1'R)-1-benzyl-3-�(1'-hydroxy)ethyl!-2-pyrrolidinone, then reducing with a hydride to provide (3R,1'R)-1-benzyl-3-�(1'-hydroxy)ethyl!pyrrolidine, mesylating or tosylating to provide (3R,1'R)-1-benzyl-3-�(1'-methanesulfonyloxy)ethyl!pyrrolidine or (3R,1'R)-1-benzyl-3-�(1'-p-toluenesulfonyloxy)ethyl!pyrrolidine, and reacting with methylamine to obtain (3R,1'S)-1-benzyl-3-�(1'-N-methylamino)ethyl!pyrrolidine. The prcess may further comprise de-benzylating (3R,1'S)-1-benzyl-3-�(1'-N-methylamino)ethyl!pyrrolidine to obtain (3R,1'S)-3-�(1'-N-methylamino)ethyl!pyrrolidine.

Process for producing optically active pyrrolidine derivatives

Disclosed is a 2-phenyl-2-(2'-piperidinylidene)acetate derivative suitably used for a raw material of a 2-phenyl-2-(2'-piperidinyl)acetate derivative and a process for manufacturing the same. Also disclosed is a process for manufacturing an optically active 2-phenyl-2-(2'-piperidinyl)acetate derivative which is a major intermediate for an antidepressant. The 2-phenyl-2-(2'-piperidinylidene)acetate derivative is manufactured by cyclizing a 7-(N-substituted amino)-3-oxo-2-heptanoate derivative. The optically active 2-phenyl-2-(2'-piperidinyl)acetate derivative is manufactured by asymmetrically hydrogenating the 2-phenyl-2-(2'-piperidinylidene)acetate derivative in the presence of a complex of a Group VIII transition metal or an acid.

2-phenyl-2-(2'-piperidinylidene)acetate derivative, process for

Disclosed is a 7-(N-substituted amino)-3-oxo-2-phenylheptanoate derivative, 7-(N-substituted amino)-3-hydroxy-2-phenylheptanoate derivative, and 7-(N-substituted amino)-3-benzenesulfonyloxy-2-phenylheptanoate derivative, which are quite important major intermediates for an antidepressant. The 7-(N-substituted amino)-3-oxo-2-phenylheptanoate derivative can be manufactured by condensing an enolate of phenylacetates with a 5-(N-substituted amino) pentanoate derivative.

7-(n-substituted amino)-2-phenylheptanoic acid derivative and process

Compounds represented by the following general structural formula (1) and methods for producing the compounds: ##STR1## R.sup.1 represents a group such as benzyloxycarbonyl, R.sup.2 represents a lower alkyl group, R.sup.3 represents a hydrogen atom or a protecting group, each of M.sup.1 and M.sup.2 represents a metal atom, and n represents the atomic valence of M.sup.1. Intermediates for HMG-CoA reductase inhibitors can be prepared safely and easily from these compounds.

N-substituted-7-amino-5-hydroxy-3-oxoheptanoic acid derivatives and

A process for preparing an optically active (2S,3S)-allophenylnorstatin derivative (I) is disclosed, comprising asymmetrically hydrogenating a 4-phenyl-2-halogeno-3-oxobutyric ester (III) in the presence of a ruthenium-phosphine complex to obtain a 4-phenyl-(2S)-halogeno-(3R)-hydroxybutyric ester (IV), epoxidizing the ester (IV) in the presence of a base to obtain a 4-phenyl-(2S,3R)-epoxybutyric ester (V), reacting the ester (V) with a tri(lower alkyl)silylazide or a (lower alkyl)diarylsilylazide in the presence of a Lewis to obtain a (3S)-azido-4-phenyl-(2S)-trisubstituted silyloxybutyric ester (VI), hydrogenolyzing the ester (VI) into a (2S,3S)-allophenylnorstatin derivative (VII), protecting the amino group of the compound (VII), and, if desired, hydrolyzing the compound before or after the amino group protection. Compounds (I) can be obtained at high optical purity safely and in good yield.

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Kanagawa, Japan

Tsukasa Sotoguchi