Kanegafuchi Kagaku Kogyo Kabushiki Kaisha

Kanegafuchi Chemical Industry Co., Ltd.

Kaneka Corporation

Takehisa Ohashi

Kiyoshi Watanabe

Satomi Takahashi

Kazunori Kan

Noboru Ueyama

Shigeki Hamaguchi

Isao Sada

Kenji Inoue

Yoshifumi Yanagida

Koji Yoneda

Masami Shimazaki

Yasuyoshi Ueda

Yukio Yamada

Masaaki Azuma

Yoshio Shimada

Akimasa Miyama

Hirotaka Fukumitsu

Kazuhiko Yamada

Kenji Nomura

Masakatsu Shibasaki

Junzo Hasegawa

Masaru Mitsuda

Kazuyoshi Yajima

Kazuhiko Katayama

Nobuo Nagashima

Yasuhiro Ikenaka

Masayuki Takano

Hirokazu Nanba

Michio Nomura

Shingo Matsumoto

Takehiko Yamane

Mitsunori Matsumoto

Shigeo Hayashi

Hideo Kondo

Yoshio Nakamura

Hideyuki Takahashi

Yoshifumi Yanagita

Hayashi Uchino

Kenji Takahara

Hiroshi Murakami

Namito Yoshio

Tomoaki Nagamachi

Masami Onishi

Yasushi Nose

Yoshikazu Kogame

Hidetoshi Katsuki

Masanori Asada

Yoshio Namito

Process for producing D-amino acids with composite immobilized enzyme

Optically active aminoalcohol derivatives and method of producing same

Process for preparing an enol silyl ether compound

A novel process for effectively preparing an optically active cyanohydrin comprising asymmetrically cyanating an aldehyde by reacting the aldehyde with a cyanating agent in the presence of a titanate of an optically active tartaric acid derivative.

Process for preparing optically active cyano compound

A process for preparing trans-.beta.-benzoylacrylic acid ester having the general formula (I): ##STR1## wherein R is alkyl group or aralkyl group, which comprises dealcoholizing .beta.-benzoyl-.alpha.-alkoxypropionic acid ester having the general formula (II): ##STR2## wherein R is above, in the presence of an acid catalyst to give trans-.beta.-benzoylacrylic acid ester having the general formula (I). According to the process of the present invention, the by-product (II) produced in the esterification reaction of .beta.-benzoylacrylic acid (III) with the alcohol (V) by the dehydration reaction can be converted into the compound (I) by the dealcoholization reaction in the presence of the acid catalyst and thus trans-.beta.-benzoylacrylic acid ester (I) with a high purity can be produced in an industrially advantageous manner.

Process for preparing trans-.beta.-benzoylacrylic acid ester

Ethyl-.beta.-benzoyacrylate is reacted with an alkali metal salt of (S)-alanine or an alkali metal salt of N.sup.6 -trifluoroacetyl-L-lysine to form the corresponding Michael addition product, and not less than an equivalent amount of acid is added after completion of the Michael addition to prevent conversion of the (S,S) form of the product to the (R,S) form.

Process for preparing ethyl-alpha-amino-gamma-oxo-gamma-phenybutyrate

A process for preparing a 4-acetoxy-3-hydroxyethylazetidin-2-one derivative having the formula (II): ##STR1## wherein R.sup.1 is a protective group for the hydroxyl group, which comprises reacting a .beta.-lactam compound having the formula (I): ##STR2## wherein R.sup.1 is as defined above, and R.sup.2, R.sup.3 and R.sup.4 are a lower alkyl group having 1 to 6 carbon atoms, phenyl group or an aralkyl group, with acetic anhydride in an organic solvent in the presence of a low concentration of a substituted pyridine. According to the present invention, there can be obtained 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives, which are useful intermediates for preparing carbapenem .beta.-lactam antibiotics.

Process for preparing 4-acetoxy-3-hydroxyethylazetidin-2-one derivatives

A process for preparing a 4-acetoxy-3-hydroxyethylazetidin-2-one derivative having the formula (II): ##STR1## wherein R.sup.1 is a protective group for the hydroxyl group, which comprises reactig a .beta.-lactam compound having the formula (I): ##STR2## wherein R.sup.1 is as difined above and R.sup.2, R.sup.3 and R.sup.4 are the same or different and each is a lower alkyl group having 1 to 4 carbon atoms or an aralkyl group, with acetic anhydride in the presence of a base and a catalyst selected from the group consisting of an organic strong acid, a mineral acid, a Lewis acid, a halogenated acyl compound having the formula (IV):

A process for preparing optically active indoline-2-carboxylic acid by an optical resolution, which comprises subjecting a racemic ester of (R,S)-indoline-2-carboxylic acid having the general formula [(R,S)-I] to the action of an enzyme or a microorganism having a stereo-selective esterase activity, which is capable of asymmetrically hydrolyzing the racemic ester [(R,S)-I] to give optically active indoline-2-carboxylic acid having the formula [II*] so as to produce the hydrolysis product, i.e. optically active indoline-2-carboxylic acid [II*] and an unreacted optically active ester of indoline-2-carboxylic acid having the general formula [I*], isolating each optically active form, and further, if necessary, hydrolyzing the obtained optically active ester [I*] to give an optical antipode of the acid [II*]. According to the process of the present invention, optically active indoline-2-carboxylic acid with a high optical purity can be prepared in a simple process with a good yield.

Process for preparing optically active indoline-2-carboxylic acid

A process for preparing optically active glycerol derivatives by a biochemical resolution which comprises (i) subjecting an ester having the general formula [(R,S)-I]: ##STR1## wherein X is a halogen atom, R is an aliphatic hydrocarbon group of C.sub.1 to C.sub.8 and R' is an aromatic hydrocarbon group or an aliphatic hydrocarbon group of C.sub.1 to C.sub.2, to the action of enzymes derived from either microorganisms or animal organs, wherein said enzymes have a stereo selective esterase activity to asymmetrically hydrolyze the ester having the general formula [(R,S)-I] to give a mixture of an optically active alcohol having the general formula (II)*: ##STR2## wherein X and R' are as above and an optically active ester having the general formula (I)*: ##STR3## wherein X, R and R' are as above, and (ii) obtaining the optically active alcohol having the general formula (II)* and the optically active ester having the general formula (I)* by separating operations. In accordance with the present invention, there can be provided a process for preparing optically active glycerol derivatives, wherein the optically active ester having the general formula (I)* and the optically active alcohol having the general formula (II)* can be easily obtained.

Process for preparing optically active glycerol derivatives

A process for preparing a 4-acetoxy-3-hydroxyethylazetidin-2-one derivative having the formula (II): ##STR1## wherein R.sup.1 is a protective group for the hydroxyl group, which comprises reacting a .beta.-lactam compound having the formula (I): ##STR2## wherein R.sup.1 is as defined above, R.sup.2, R.sup.3 and R.sup.4 are a lower alkyl group having 1 to 6 carbon atoms, phenyl group or an aralkyl group and R is a protective group for N, with acetic anhydride in an organic solvent in the presence of a base, and removing the protective group for N. 4-Acetoxy-3-hydroxyethylazetidin-2-one derivatives are useful intermediates for preparing carbapenem .beta.-lactam antibiotics such as thienamycin and penem .alpha.-lactam antibiotics.

A process for preparing 3-halogeno-2-hydroxy-propyltrimethylammonium halide or especially one having the (S)-configuration, which comprises reacting 2,3-dihydroxypropyltrimethylammonium halide or one having the (S)-configuration, which is obtained by reacting (R)-3-halogeno-1,2-propanediol with trimethylamine, with a halogenating reagent. According to the present invention, 3-halogeno-2-hydroxypropyltrimethylammonium halide or one having the (S)-configuration, which is a useful intermediate for the synthesis of carnitine or especially (l)-carnitine, can be obtained economically, efficiently and easily.

Process for preparing 3 halogeno-2-hydroxypropyltrimethylammonium halide

The present invention relates to .beta.-lactam compound having the formula (I): ##STR1## wherein R.sup.1 is a trialkylsilyl group, dimethyl-1,1,2-trimethylpropylsilyl group, acetyl group, benzyloxycarbonyl group, O-nitrobenzyloxycarbonyl group, p-nitrobenzyloxycarbonyl group or t-butyl group, R.sup.2, R.sup.3 and R.sup.4 are a member selected from the group consisting of a lower alkyl group having 1 to 6 carbon atoms, phenyl group and an aralkyl group and a process for preparing the compound which comprises reacting enolsilylethers having the formula (III): ##STR2## wherein R.sup.1, R.sup.2, R.sup.3 and R.sup.4 are as above, with chlorosulfonylisocyanate and then reducing the obtained product. The .beta.-lactam compound of the present invention is a useful intermediate for preparing carbapenem .beta.-lactam compound.

Beta-lactam compound and preparation thereof

An inorganic acid salt of N-[1(S)-ethyoxycarbonyl-3-phenylpropyl]-L-alanylchloride having the formula (I): ##STR1## A process for preparing an inorganic acid salt of N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanylchloride having the formula (I) ##STR2## which comprises reacting an inorganic acid salt of N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-L-alanine with phosphorous pentachloride in an inactive organic solvent. According to the present invention, ACEI can be economically and easily prepared.

Inorganic acid salt of

A method for producing optically active glycol derivatives by biochemical resolution which comprises contacting a racemic ester of the general formula 1 ##STR1## (wherein R.sub.1 is an aliphatic hydrocarbon group of 1 to 16 carbon atoms, R.sub.2 is an aliphatic hydrocarbon group of 1 to 8 carbon atoms, and R.sub.3 is an aromatic hydrocarbon group such as phenyl, tolyl or naphtyl) with a microorganism- or animal organ-derived enzyme having stereoselective hydrolytic activity to asymmetrically hydrolyze said racemic ester of general formula 1 to produce an optically active alcohol of general formula 2* ##STR2## (wherein R.sub.1 and R.sub.3 have the same meanings as defined above) and an unreacted ester of the general formula 1* ##STR3## (wherein R.sub.1, R.sub.2 and R.sub.3 have the same meanings as defined hereinbefore), separating the optically active compounds from each other, hydrolyzing said ester of general formula 1* to give an optically active glycol derivative which is antipodal to the alcohol of general formula 2* and, then, isolating the same optically active glycol derivative. The invention provides a method for producing optically active glycol derivatives, which is expedient, does not require costly reagents and is suited to commercial scale production.

Method for producing optically active glycol derivatives

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Kobe, Japan

Takehisa Ohashi