Taisho Pharmaceutical Co., Ltd.

Chihiro Yokoo

Yoshiaki Watanabe

Kaoru Sota

Akira Onodera

Hiroshi Fukushima

Mitsuo Murata

Masami Goi

Katsuo Hatayama

Toshifumi Asaka

Jiro Sawada

Kazuyuki Tomisawa

Minoru Taguchi

Kazunori Hanada

Yasuji Yamada

Tatsuhiko Sano

Hisaya Wada

Tomomichi Yoshida

Dai Tatsuta

Hidemichi Mitome

Shigeyuki Sumiya

The present invention provides a safer method for production of a cis-4-fluoro-L-proline derivative under milder conditions and in good yield to give a product of high purity on an industrial scale at low cost. Namely, the present invention provides a method for producing a cis-4-fluoro-L-proline derivative, which comprises reacting a trans-4-hydroxy-L-proline derivative of the following Formula [I]: (wherein Rrepresents a protecting group for an &#x3b1;-amino group, and Rrepresents a protecting group for a carboxyl group) with N,N-diethyl-N-(1,1,2,3,3,3-hexafluoropropyl)amine in the presence of a hydrogen fluoride-scavenger.

Method for production of cis-4-fluoro-L-proline derivatives

To provide novel steroid derivatives having an antitumor action which can be synthesized efficiently and stereoselectively by means of synthetic organic chemistry. A steroid derivative represented by the formula: ##STR1## wherein R is an alkyl group having 1 to 13 carbon atoms, A is a hydroxyl group or a group easily hydrolyzable to a hydroxyl group, X and Y together form an oxo group or an alkylenedioxy group having 2 or 3 carbon atoms, X is a hydroxyl group, an alkoxy group having 1 to 5 carbon atoms or a group easily hydrolyzable to a hydroxyl group, Y is a hydrogen atom or an alkoxy group having 1 to 5 carbon atoms, with the proviso that when X is a hydroxyl group or a group easily hydrolyzable to a hydroxyl group, Y is a hydrogen atom, and when X is an alkoxy group having 1 to 5 carbon atoms, Y is an alkoxy group having 1 to 5 carbon atoms, or a salt thereof.

Steroid derivatives

Epoxysuccinamic acid derivatives

An epoxysuccinic acid derivative represented by the formula ##STR1## wherein R.sup.1 is a hydrogen atom or an alkyl group containing 1 to 4 carbon atoms, and a pharmaceutically acceptable salt are useful as cathepsin B inhibitors.

Epoxysuccinic acid derivatives

A cephalosporin derivative represented by the general formula ##STR1## wherein R.sup.1 is a hydrogen atom or a protecting group of the amino group, R.sup.2 is a hydrogen atom or a protecting group of the hydroxyl group, R.sup.3 is a hydrogen atom or a protecting group of the carboxyl group, and R.sup.4 is a hydrogen atom or an alkyl group having 1 to 4 carbon atoms, and the non-toxic salts thereof are useful as antibacterial agents.

Cephalosporin derivatives

A cephalosporin derivative represented by the formula ##STR1## wherein R.sup.1 is a hydrogen atom or a protecting group of the amino group, R.sup.2 is a hydrogen atom or a protecting group of the hydroxyl group, R.sup.3 is a hydrogen atom or a protecting group of the carboxyl group, X is a halogen atom, a cyano group, a vinyl group, a lower alkoxy group having 1 to 4 carbon atoms or a lower alkylthio group having 1 to 4 carbon atoms and n is an integer of 1 to 3, and a non-toxic salt thereof are useful as antibacterial agents for oral administration.

Cephalosporin derivatives represented by the general formula ##STR1## wherein R is a hydrogen atom or a lower alkyl group having 1 to 4 carbon atoms, R' is a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, a cycloalkyl group having 5 or 6 carbon atoms or a benzyl group, or R and R' together with the nitrogen atom to which they are attached form a tetrahydropyridinyl group, a morpholinyl group or pyrroridinyl group, and the non-toxic salts thereof are disclosed. These compounds are useful as antibacterial agents.

Cephalosporin derivatives represented by the general formula ##STR1## wherein X represents a halogen atom, a hydroxyl group, a cyano group, a trifluoromethyl group, an amino group, a lower alkylcarbonylamino group, a lower alkoxy group, a lower alkylthio group, a lower alkoxycarbonyl group, a carbamoyl group, a substituted carbamoyl group, a carbamoyloxy group, a lower alkylcarbonyl group, a lower alkenyl group, an ethynyl group, a thiocyanate group, an .alpha.-carboxyaminomethyl group, a phenyl group, a pyridinyl group or an aminothiazolyl group, and n is an integer of 1 to 3, and the non-toxic salts thereof, are disclosed. These compounds are useful as antibacterial agents.

Cephalosporin derivatives represented by the general formula ##STR1## Wherein X represents a hydrogen atom, a lower alkyl group having 1 to 4 carbon atoms, an allyl group, a cycloalkyl group having 5 or 6 carbon atoms or a benzyl group, and the non-toxic salts thereof are disclosed. These compounds are useful as antibacterial agents.

Novel cephalosporin compounds having the general formula ##STR1## wherein X represents hydrogen atom or hydroxy group, and the non-toxic pharmacologically acceptable salts thereof are disclosed. These compounds are useful as antibacterial agents.

Cephalosporin compounds

Novel penicillin derivatives of the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R is hydrogen or hydroxy, are produced by acylating ampicillin, amoxicillin or a salt thereof with 4-hydroxy-pyrazino[2,3-f]quinoline-3-carboxylic acid or its functional derivative. They have high anti-pseudomonas activity and other antibacterial activity against gram-positive and gram-negative bacteria, and are of extremely low toxicity.

Growing community of inventors

Gyoda, Japan

Chihiro Yokoo