Kanegafuchi Kagaku Kogyo Kabushiki Kaisha

Yoshio Shimada

Kiyoshi Watanabe

Tadayoshi Shiraishi

Takayoshi Hidaka

Ikuo Katsumi

Keiji Kameyama

Yutaka Ariki

Takeshi Domoto

Naohiro Imai

Masaji Kawatsu

Yasuyoshi Ueda

Satomi Takahashi

Kazunori Hosoe

Yoshio Nakamura

Hideyuki Takahashi

Takehisa Ohashi

Yukio Yamada

Masahiro Ogura

Kenji Inoue

Shigeki Hamaguchi

Hajime Kawaharada

Michio Nomura

Takehiko Yamane

Yoshifumi Yanagita

Kazuhiko Yamada

Kenji Takahara

Yasuhiro Katayama

Hidetoshi Katsuki

Masanori Asada

Kazunoro Hosoe

Satoru Tsuda

Keiichi Kagotani

Norio Noda

A process for preparing optically active (R)-3-chloro-1,2-propanediol, which comprises subjecting (R,S)-3-chloro-1,2-propanediol to the reaction of a microorganism belonging to genus Serratia in a reaction mixture, and then collecting the residual (R)-3-chloro-1,2-propanediol. According to the process of the present invention, (R)-3-chloro-1,2-propanediol can be efficiently prepared starting from low cost (R,S)-3-chloro-1,2-propanediol.

Microbial process for biotransformation to (R)-3-chloro-1,2-propanediol

A hydroxystyrene derivative represented by the formula (I): ##STR1## wherein when R.sup.1 and R.sup.2 : phenyl group, benzyl group or phenethyl group, or R.sup.1 : R.sup.5 O- (R.sup.5 : H, a C.sub.1 to C.sub.5 alkyl group or benzyl group) and R.sup.2 : benzyl group or PhSCH.sub.2, R.sup.3 and R.sup.4 are taken together to represent --CONH--CS--S--, ##STR2## (X.sup.1 : H, a halogen, methyl group, ethyl group, R.sup.7 O-- (R.sup.7 : methyl or ethyl group), nitro group, aminosulfonyl group or amino group, m.sup.1 : 1 or 2), pyridyl group, furyl group or thienyl group, n.sup.1 : an integer of 0 to 3); when R.sup.1 and R.sup.2 : phenyl group, benzyl group or phenethyl group, or R.sup.1 : R.sup.5 O-- (R.sup.5 : as defined above) and R.sup.2 : benzyl group, R.sup.3 : cyano group and R.sup.4 : a carbamoyl group, or R.sup.3 and R.sup.4 are taken together to represent --CO--Y--CH.sub.2 CH.sub.2 -- (Y: O or --NH--) or ##STR3## and when R.sup.1 and R.sup.2 : a C.sub.1 to C.sub.3 alkyl group, R.sup.3 and R.sup.4 are taken together to represent ##STR4## (n.sup.1, R.sup.6 : as defined above), or a salt thereof. The hydroxystyrene derivative or a salt thereof is a compound which is useful as an active ingredient of an antiallergic agent, a 5-lipoxygenase inhibiting agent, an antibacterial agent, a tyrosine kinase inhibiting agent, an ultraviolet absorber or a reverse transcriptase inhibiting agent, and also is useful as an intermediate for preparing various organic compounds.

Hydroxystyrene compounds having tyrosine kinase inhibiting activity

A hydroxystyrene derivative represented by the formula (I): ##STR1## wherein when R.sup.1 and R.sup.2 : phenyl group, benzyl group or phenethyl group, or R.sup.1 : R.sup.5 O-- (R.sup.5 : H, a C.sub.1 to C.sub.5 alkyl group or benzyl group) and R.sup.2 : benzyl group or PhSCH.sub.2, R.sup.3 and R.sup.4 are taken together to represent --CONH--CS--S--, ##STR2## (X.sup.1 : H, a halogen, methyl group, ethyl group, R.sup.7 O-- (R.sup.7 : methyl or ethyl group), nitro group, aminosulfonyl group or amino group, m.sup.1 : 1 or 2), pyridyl group, furyl group or thienyl group, n.sup.1 : an integer of 0 to 3); when R.sup.1 and R.sup.2 : phenyl group, benzyl group or phenethyl group, or R.sup.1 : R.sup.5 O-- (R.sup.5 : as defined above) and R.sup.2 : benzyl group, R.sup.3 : cyano group and R.sup.4 : a carbamoyl group, or R.sup.3 and R.sup.4 are taken together to represent --CO--Y--CH.sub.2 CH.sub.2 -- (Y: O or --NH--) or ##STR3## and when R.sup.1 and R.sup.2 : a C.sub.1 to C.sub.3 alkyl group, R.sup.3 and R.sup.4 are taken together to represent ##STR4## (n.sup.1, R.sup.6 : as defined above), or a salt thereof. The hydroxystyrene derivative or a salt thereof is a compound which is useful as an active ingredient of an antiallergic agent, a 5-lipoxygenase inhibiting agent, an antibacterial agent, a tyrosine kinase inhibiting agent, an ultraviolet absorber or a reverse transcriptase inhibiting agent, and also is useful as an intermediate for preparing various organic compounds.

1-phenyl-3,5-pyrazolidinedione hydroxystyrene compounds which have

A hydroxystyrene derivative represented by the formula (I): ##STR1## Wherein when R.sup.1 and R.sup.2 : phenyl group, benzyl group or phenethyl group, or R.sup.1 : R.sup.5 O--(R.sup.5 : H, a C.sub.1 to C.sub.5 alkyl group or benzyl group) and R.sup.2 : benzyl group or PhSCH.sub.2, R.sup.3 and R.sup.4 are taken together to represent --CONH--CS--S--, ##STR2## (X.sub.1 : H, a halogen, methyl group, ethyl group, R.sup.7 O--(R.sup.7 : methyl or ethyl group), nitro group, aminosulfonyl group or amino group, m.sup.1 : 1 or 2), pyridyl group, furyl group or thienyl group, n.sup.1 : an integer of 0 to 3); when R.sup.1 and R.sup.2 : phenyl group, benzyl group or phenethyl group, or R.sup.1 : R.sup.5 O--(R.sup.5 : as defined above) and R.sup.2 : benzyl group, R.sup.3 : cyano group and R.sup.4 : a carbamoyl group, or R.sup.3 and R.sup.4 are taken together to represent --CO--Y--CH.sub.2 CH.sub.2 --(Y: O or --NH--) or ##STR3## and when R.sup.1 and R.sup.2 : a C.sub.1 to C.sub.3 alkyl group, R.sup.3 and R.sup.4 are taken together to represent ##STR4## (n.sup.1, R.sup.6 : as defined above), or a salt thereof. The hydroxystyrene derivative or a salt thereof is a compound which is useful as an active ingredient of an antiallergic agent, a 5-lipoxybenase inhibiting agent, an antibacterial agent, a tyrosine kinase inhibiting agent, an ultraviolet absorber or a reverse transcriptase inhibiting agent, and also is useful as an intermediate for preparing various organic compounds.

Hydroxystyrene compounds which have useful pharmaceutical utility

A process for preparing an optically active 3-chloro-1, 2-propanediol by employing microorganism which can selectively metabolize (R)- or (S)-3-chloro-1,2-propanediol. The decomposition rate of the substrate can be accelerated and the substrate concentration can be increased by adding a compound having SH group to the reaction solution. According to the process of the present invention, the optically active 3-chloro-1,2-propanediol can be easily prepared starting from low-cost (R,S)-3-chloro-1, 2-propanediol.

Process for preparing 3-chloro-1,2-propanediol

Hydroxystyrene compounds which are useful as tyrosine kinase inhibitors

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 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 hydantoins having the general formula (II): ##STR1## wherein R.sup.1 and R.sup.2, which are different from each other, are independently alkyl group, aralkyl group, aryl group, substituted alkyl group, substituted aralkyl group, or substituted aryl group, or R.sup.1 and R.sup.2 form an asymmetric cyclic compound, characterized in that one configuration of racemic N-carbamoyl-.alpha.-amino acid having the general formula (I): ##STR2## wherein R.sup.1 and R.sup.2 are as above, is enzymatically converted into the corresponding hydantoins. The present invention provides a process for an optical resolution with a high efficiency which can be used for the synthesis of (S)-6-fluoro-spiro-[chroman-4,4'-imidazolidine]-2',5'-dione (USAN; Sorbinil), which is an optically active hydrantoins attracting public attention as a preventive or a remedy for the particular chronic symptoms of diabetes such as cataract and neuropathy, and (S)-.alpha.-methyl-3,4-dihydroxyphenylalanine (L-methyldopa), which is an optically active amino acid widely used as antihypertensives. Further, the present invention provides a novel finding that N-carbamoyl-.alpha.-amino acid having no hydrogen atom on its .alpha.-carbon atom can be biochemically converted into hydantoins by an enzymatic cyclization reaction.

Process for preparing optically active hydantoins

The present invention relates to 3-(4-fluorophenoxy)propionitrile having the formula (I): ##STR1## a process for preparing 3-(4-fluorophenoxy)propionitrile having the formula (I) which comprises reacting 4-fluorophenol and acrylonitrile in the presence of a tertiary amine, a process for preparing 6-fluoro-4-chromanone having the formula (II): ##STR2## which comprises reacting 3-(4-fluorophenoxy)propionitrile having the formula (I) with an acid, and a process for preparing 6-fluoro-4-chromanone having the formula (II) which comprises reacting 4-fluorophenol with acrylonitrile in the presence of a catalyst to give 3-(4-fluorophenoxy)propionitrile having the formula (I), which is then reacted with an acid. 6-Fluoro-4-chromanone is an important intermediate for the synthesis of (S)-2,3-dihydro-6-fluoro-spiro[4H-1-benzopyran-4,4'-imidazolidine]-2',5'di one (USAN: sorbinil).

Process for preparing 6-fluoro-4-chromanone using

A process is disclosed wherein yeast cells containing coenzyme Q in large quantities are efficiently produced by aerobically cultivating a yeast, in which maximum specific growth rate is not less than 0.15 hr.sup.-1 under optimum cultural conditions, in a nutrient medium in which said yeast can grow, while maintaining the dissolved oxygen concentration in the culture broth at not less than 2 ppm and controlling the average specific growth rate through the whole period of cultivation at not more than 0.1 hr.sup.-1, and coenzyme Q is recovered from the resulting yeast cells.

Process for producing coenzyme Q

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Kakogawa, Japan

Yoshio Shimada