Nippon Kayaku Kabushiki Kaisha

Yasuhisa Tashiro

Shigeru Aoki

Tadashi Shirai

Rinzo Nishizawa

Takashi Nagashima

Yoshinobu Miyazawa

Masao Suzuki

Tetsushi Saino

Hideo Sugimura

Ryoichi Hasegawa

Akikazu Mitsunobu

Akihiro Mashiba

Mamoru Katagiri

Noriko Ooishi

Yuzo Aboshi

Toshiro Narita

Toshiaki Arai

Kazuteru Hagita

This invention relates to a process for producing optically active valine, characterized by optically resolving DL-valine hydrochloride in a solvent containing an amine salt, a sulfonic acid or a carboxylic acid and isolating optically active valine after the decomposition of the obtained optically active valine hydrochloride.

Process for producing optically active valine

The present invention relates to new easily filtrable, non-hygroscopic N-benzyloxycarbonyl-L-threonine amide hemihydrate.

N-benzyloxycarbonyl-L-threonine amide hemihydrate

This invention relates to a process for producing optically active phenylalanine, characterized by optically resolving DL-phenylalanine.optically active mandelic acid complexes in an aqueous solvent in the presence of an acidic compound having a pKa value of 0.90 to 2.10 and isolating optically active phenylalanine from the obtained optically active phenylalanine.optically active mandelic acid complex. According to the process of the present invention, it is possible to decrease the amount of a mother liquor of resolution to 1/5 to 1/10 of that when no acidic compound is used and to obtain optically active phenylalanine having an optical purity of as high as 96.5% or above without a step of optical purification when optically active phenylalanine is isolated from the obtained optically active phenylalanine.optically active mandelic acid complex.

Process for producing optically active phenylalanine

The present invention relates to a process for preparing optically active phenylalanine which comprises resolving mixture of a complex of D-phenylalanine and optically active mandelic acid and a complex of L-phenylalanine and optically active mandelic acid in a solvent containing hydrochloric acid, carboxylic acid, phosphoric acid or a salt thereof to obtain the complex having lower solubility, and removing said optically active mandelic acid from the obtained complex to obtain an optically active phenylalanine. In the case of resolving DL-phenylalanine by the process according to the present invention, the amount of mother liquor used in resolution can be made to about 1/2 to 1/6 as compared to the amount of mother liquor of which the acidic compound or the salt thereof is not used in the resolution. Accordingly, the process according to the present invention is extremely profitable as an industrial process for producing an optically active phenylalanine.

Process for preparing optically active phenylalanine

Two optically active amino acid-mandelic acid complexes are obtained by interacting in a solvent under pH conditions of 1.0-4.0 an amino acid expressed by a general formula ##STR1## (in which R represents a methyl group, an ethyl group or a methylthioethyl group) and mandelic acid, one of the acids being an optically active substance and the other being a racemic modification, and optically resolving the resulting complexes into two diastereoisomers by using solubility difference therebetween. The optically active complexes are each decomposed by means of an acid, a strongly acidic ion-exchange resin, or a weakly basis ion-exchange resin to obtain optically active amino acids or optically active mandelic acid.

Process for preparing optically active amino acid or mandelic acid

Two optically active amino acid-mandelic acid complexes are obtained by reacting in a solvent under pH conditions of 1.0-4.0, an amino acid expressed by a general formula ##STR1## (in which R represents a methyl group, an ethyl group or a methylthioethyl group) and mandelic acid, one of the acids being an optically active substance and the other being a racemic modification, and optically resolving the resulting complexes into two diastereomers by using a solubility difference therebetween. The optically active complexes are each decomposed by means of an acid, a strongly acidic ion-exchange resin, or a weakly basic ion-exchange resin to obtain optically active amino acids or optically active mandelic acid.

Optically active amino acid-mandelic acid complexes

DL- .alpha.-phenylglycine can be combined with benzene-sulfonic acid, p-ethylbenzenesulfonic acid or m-xylenesulfonic acid to give the salt. The salt of the racemate may be more soluble in a sulfuric acid solution than the salt of the optically active isomer by suitably choosing the concentration of the sulfuric acid solution, and then the optical resolution by fractional crystallization is carried out. The D- or L- .alpha.-phenylglycine sulfonate is easily liberated of the sulfonic acid portion to give optically active D- or L- .alpha.-phenylglycine.

Process for the preparation of optically active .alpha.-phenylglycine

In order to separate optically active D- or L-.alpha.-phenylglycine hydrochloride from a supersaturated solution of DL-.alpha.-phenylglycine hydrochloride seed crystals of the desired D- or L-isomer are added to the solution in the presence of a metal chloride.

Optical resolution of DL-.alpha.-phenylglycine hydrochloride

Optically active p-hydroxyphenylglycine is prepared by reacting a racemic compound of a specified p-hydroxyphenylglycine derivative with optically active .alpha.-phenylethylamine to form a corresponding salt, obtaining two types of optically active salts therefrom by fractional crystallization, and obtaining optically active p-hydroxyphenylglycine by decomposition and hydrolysis of at least one of the optically active salts.

Process for the preparation of optically active p-hydroxyphenylglycine

Optically active p-hydroxyphenylglycine is manufactured by inoculating a supersaturated solution of a p-hydroxyphenylglycine sulfonic acid derivative salt comprising a mixture of the two optically active enantiomers of said salt with an optically active enantiomer of the same salt, said mixture being either racemic or else one in which the predominant enantiomer is that of the inoculant. In this manner the enantiomer having the form of the inoculant is selectively crystallized. The selectively crystallized salt is thereafter treated for removal of the sulfonic acid derivative.

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Yokohama, Japan

Yasuhisa Tashiro