Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai

Nippon Kayaku Kabushiki Kaisha

Sanraku-ocean Co., Ltd.

Yamanouchi Pharmaceutical Company Ltd.

Meiji Seika Kaisha, Ltd.

Microbial Chemistry Research Foundation

Sanraku Incorporated

Bristol-myers Company

Banyu Pharmaceutical Co. Ltd

Kowa Company Limited

Kirin Beer Kabushiki Kaisha

Kanegafuchi Chemical Industry Co., Ltd.

Takara Shuzo Co., Inc.

Meiji Seiki Kaisha, Ltd.

Microbiochemical Research Foundation

Hamao Umezawa

Tomio Takeuchi

Sumio Umezawa

Shinichi Kondo

Takaaki Aoyagi

Masa Hamada

Tsutomu Tsuchiya

Masaaki Ishizuka

Toshikazu Oki

Akio Fujii

Hiroshi Naganawa

Taiji Inui

Shunzo Fukatsu

Tomohisa Takita

Teruya Nakamura

Yasuhiko Muraoka

Akira Takamatsu

Tomoyuki Ishikura

Hironobu Iinuma

Akihiro Yoshimoto

Tetsushi Saino

Kenji Maeda

Tsutomu Sawa

Takeyo Fukuoka

Akihiro Tanaka

Katsutoshi Takahashi

Shuichi Sakamoto

Kuniaki Tatsuta

Hajime Morishima

Yoshiro Okami

Daishiro Ikeda

Eiichi Akita

Rinzo Nishizawa

Osamu Tsuchiya

Shuntaro Yasuda

Ikuo Matsumoto

Tokuji Nakatani

Nobuyoshi Shimada

Takashi Osono

Toshiharu Nagatsu

Toshio Yoneta

Takeo Miyazawa

Shigeo Seki

Mitsugu Hachisu

Isamu Watanabe

Hiroshi Tone

Kageaki Kouno

Yoshihisa Umeda

Tadashi Shirai

Norio Shibamoto

Osamu Tanabe

Tetsuya Someno

Masao Suzuki

Kiyoshi Watanabe

Takeo Yoshioka

Yoshiaki Takahashi

Rokuro Okamoto

Yasushi Takagi

Shintaro Suzuki

Takashi Terada

Yasushi Takahashi

Fumihiro Sato

Toshiaki Miyake

Masaji Ohno

Shohachi Nakajima

Hiroshi Yoshikawa

Yasuharu Sekizawa

Junji Yoshizawa

Yoshihiko Oka

Yasutaka Shimauchi

Takashi Yamaguchi

Yoshikazu Takahashi

Junzo Hasegawa

Masao Yamamoto

Yoshinori Kyotani

Takayoshi Hidaka

Toshihito Mori

Akira Obayashi

Kunio Isshiki

Yoshihiko Kobayashi

Fuminori Abe

Shiro Kataoka

Kazuhiro Kamiya

Shigeki Hamaguchi

Hajime Kawaharada

Yoshio Takahashi

Masahiro Ogura

Hirokazu Kotani

Hidenori Iwamoto

Hiroyuki Kawai

Hiroshi Ishihama

Takayuki Usui

Yoso Numasaki

Michinori Koyama

Hiroshi Tanaka

Tadashi Wakazawa

Tetsuji Miyano

Yoshio Watanabe

Tetsuo Shitara

As new compounds are now provided N-methyl-3-(3,4-dihydroxyphenyl)serine alkyl esters which are effective as an .alpha.-adrenergic and .beta.-adrenergic agent to stimulate the .alpha.-adrenergic and .beta.-adrenergic functions of the central nervous system of mammalian animals and are expectable to be useful for therapeutic treatment of disorders as invoked by reduced biological activities or functions of the .alpha.- and/or .beta.-adrenergic neurons. N-methyl-L-threo-3-(3,4-dihydroxyphenyl)serine (C.sub.1 -C.sub.6) alkyl esters are preferred amongst the new compounds of this invention.

N-methylphenylserine alkyl ester derivatives and uses thereof

Mycaminosyl tylonolide derivatives represented by the following general formula ##STR1## (wherein R.sup.1 denotes hydroxyl group, a lower alkanoyloxy group, benzoyloxy group, azido group, or amino group which may optionally be substituted with a lower alkyl or a lower alkanoyl radical; R.sup.2 stands for hydrogen atom or hydroxyl group; R.sup.3 expresses hydrogen atom or formyl group; and means a double bond or a radical represented by ##STR2## and salts thereof.

Mycaminosyl tylonolide derivatives

2,6-Dideoxy-2-fluoro-L-talopyranose and 1-substituted derivatives thereof, including methyl 2,6-dideoxy-2-fluoro-L-talopyranoside and 3,4-di-O-protected-2,6-dideoxy-2-fluoro-L-talopyranosyl halides, are now provided and these new compounds are useful as intermediates for use in the synthesis of new compounds having antitumor activity, especially 7-O-(2,6-dideoxy-2-fluoro-.alpha.-L-talopyranosyl) daunomycinone or -adriamycinone. 2,6-Dideoxy-2-fluoro-L-talopyranose shows antibacterial activity. 2,6-Dideoxy-fluoro-L-talopyranose and the 1-substituted derivatives thereof may be produced by a multi-stage process starting from L-fucose.

Process for producing 2,6-dideoxy-2-fluoro-L-talopyranose

N-[4-(3-Aminopropyl)aminobutyl]-2-(.omega.-guanidino-fatty acid-amido)-2-substituted-ethanamides represented by the general formula ##STR1## wherein Y represents --CH.sub.2 --CH.sub.2 --, --CH.dbd.CH or ##STR2## R represents a hydrogen atom, an alkyl group of 1 to 4 carbon atoms which may have a hydroxyl group as substituent, or a benzyl group, and n is an integer of from 1 to 8, provided that when Y is ##STR3## and n is 4, R represents the groups other than the hydrogen atom; salt thereof having antitumor activity in experimental animal tumors and a process for the preparation thereof is provided.

N-(4-(3-aminopropyl)aminobutyl)-2-(.omega.-gua

Mycaminosyl tylonolide derivatives represented by the following general formula ##STR1## (wherein R.sup.1 denotes hydroxyl group, a lower alkanoyloxy group, benzyloxy group, azido group, or amino group which may optionally be substituted with a lower alkyl or a lower alkanoyl radical; R.sup.2 stands for hydrogen atom or hydroxyl group; R.sup.3 expresses hydrogen atom or formyl group; and  means a double bond or a radical represented by ##STR2## and salts thereof.

Mycaminosyl tylonolide derivatives represented by the following general formula ##STR1## (wherein R.sup.1 denoted hydroxyl group, a lower alkanoyloxy group, benzyloxy group, azido group, or amino group which may optionally be substituted with a lower alkyl or a lower alkanoyl radical; R.sup.2 stands for hydrogen atom or hydroxyl group; R.sup.3 expresses hydrogen atom or formyl group; and  means a double bond or a radical represented by ##STR2## and salts thereof.

The present invention relates to a stable medical composition for injection containing (1) a Spergualin of the formula: ##STR1## [wherein R is ##STR2## (wherein R' is a lower alkyl group having 1 to 4 carbon atoms), ##STR3## or a salt thereof and (2) at least one stabilizer selected from the group consisting of mannitol, maltose, dextran, lactose, cyclodextrin, gelatin, chondroitin sulfate, and human serum albumin; when R is ##STR4## mannitol is excepted. A spergualin is useful as cancer control agents and immunomodulators.

Medical composition for injection containing a spergualin as active

New physiologically active substances, arphamenine A and arphamenine B which are generically termed arphamenine are produced from a new microorganism, BMG361-CF4 strain identified as FERM P-6521 or FERM BP-286 or ATCC No. 39373. Arphamenine is useful as a host defence stimulator having an activity to enhance cell-mediated immunity, and also as an anti-tumor agent.

New physiologically active substance, arphamenine and production thereof

An anthracycline compound, R20X2, of the following formula (II) is produced by a process which comprises subjecting an anthracycline compound, R20X3, of the following formula (I) or a salt thereof to reaction in the co-presence of (1) acetone and/or dimethylformamide and (2) an aqueous solution containing ammonium ion and/or trialkylamine. ##STR1## The anthracycline compound, R20X2, can be produced not only by the cultivation of actinomycetes but also, in accordance with the process as shown above, by chemical conversion of the anthracycline compound, R20X3, in a high yield.

Process for production of anthracycline compound R20X2

New compound, 3',4'-dideoxy-3'-fluorokanamycin B is now provided, which is useful as antibacterial agent. 3',4'-Dideoxy-3'-fluorokanamycin B is prepared by a process comprising halogenating an N,O-protected derivative of 3'-deoxy-3'-fluoro-4'-O-sulfonylkanamycin B with a metal halide, reducing the resulting 4'- halogenated 3'-deoxy-3'-fluorokanamycin B derivative to convert its 4'-halo group into a hydrogen atom, and thereby to produce an N,O-protected derivative of 3',4'-dideoxy-3'-fluorokanamycin B, and removing the remaining amino-protecting groups and the remaining hydroxyl-protecting groups from the reduction product by conventional deprotecting methods.

3'4'-dideoxy-3'-fluorokanamycin B and production thereof

Disclosed is an anthracycline compound of the following formula (I) or an acid addition salt thereof: ##STR1## These compounds are useful as intermediates in the synthesis of an anthracycline compound, M-R20X or M-R20X2, which has antitumor activity.

Anthracycline compound

DL- or L-Threo-3-(3,4-dihydroxyphenyl)-N-methyl-serine which may also be termed as DL- or L-threo-adrenalinecarboxylic acid are now provided, which are new compounds useful for therapeutic treatment of Parkinson's disease and mental depression disease. DL-Adrenalinecarboxylic acid may be produced by a new process comprising reacting glycine with O-protected 3,4-dihydroxybenzaldehyde, hydrolyzing the resultant reaction product under acidic conditions to form O-protected DL-3-(3,4-dihydroxyphenyl)serine, isolating the O-protected DL-3-(3,4-dihydroxyphenyl)serine into the threo isomer and the erythro isomer by recrystallization from a suitable organic solvent, introducing an unsubstituted or substituted benzyl group into the 2-amino group of the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine, then N-methylating the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl )-N-benzylserine, and removing the O-protecting groups as well as the unsubstituted or substituted benzyl group at the 2-methylamino group of the N-methylation product. L-Adrenalinecarboxylic acid may be produced by a new process comprising introducing a p-methoxybenzyloxycarbonyl group into the 2-amino group of the O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine obtained as an intermediate product, optically resolving the resultant O-protected DL-threo-3-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine by reacting the latter with an optically active amine and recrystallizing the resultant amine salt products from a suitable organic solvent, removing the p-methoxy-benzyloxycarbonyl group from the resultant O-protected L-threo-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine, reacting the resultant O-protected L-threo-(3,4-dihydroxyphenyl)serine with dimethyl sulfate in dry acetone to form an O-protected L- or D-threo-(3,4-dihydroxyphenyl)-N-methylserine methyl ester, saponifying this methyl ester and then removing the O-protecting groups from the saponification product.

Threo-adrenalinecarboxylic acid, and the production and uses thereof

Disclosed is a 3-(4'-aminobutylamino) propylaminobleomycin having low pulmonary toxicity, which expressed by the following general formula

Novel 3-(4'-aminobutylamino) propylaminobleomycin derivatives

Mycaminosyl tylonolide derivatives represented by the following general formula ##STR1## (wherein R.sup.1 denotes hydroxyl group, a lower alkanoyloxy group, benzoyloxy group, azido group, or amino group which mat optionally be substituted with a lower alkyl or a lower alkanoyl radical; R.sup.2 stands for hydrogen atom or hydroxyl group; R.sup.3 expresses hydrogen atom or formyl group; and  means a double bond or a radical represented by  ), and salts thereof.

A stable, non-hygroscopic, crystalline .gamma.-form of bestatin is prepared from the .alpha.- or .beta.-form of bestatin by heating at a temperature of from about 148.degree. C. to the melting point of bestatin, or by suspending or kneading in certan specified solvents.

Crystalline upsilon-form bestatin and processes for its preparation

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Tokyo, Japan

Hamao Umezawa