Asahi Kasei Kogyo Kabushiki Kaisha

Asahi Chemical Industry Co., Ltd.

Masahiro Murakami

Chisei Shibuya

Masateru Kobayashi

Takanori Sone

Kimiyo Yamamoto

Tsuneo Sowa

Nobuyuki Suzuki

Novel thioesters effective as acylating agents for amines or hydrazines, especially effective as active esters in synthesis of cephalosporin compounds are disclosed. The novel thioester of the present invention can be prepared by reacting a thiol or a derivative thereof with an acetic acid derivative or a reactive derivative thereof. By reacting the thioester of the present invention with a 7-aminocephalosporin derivative or a salt thereof, cephalosporin derivatives or pharmacologically acceptable salts thereof which are excellent antibiotic substances having a high antimicrobial activity can be obtained in high yield very safely.

1H-1,2,3-triazol-5-ylthio ester of

Process for the preparation of cephalosporin derivatives using thioesters

1-Methyltetrazol-5-ylthio ester of cyanomethylthioacetic acid

This invention relates to a tetrazole-5-thiol ester having D-configuration of the formula, ##STR1## a process for the preparation of the thiol ester and a process for the preparation of cefamandole using the thiol ester.

Novel tetrazole-5-thiol ester and process for preparing cefamandole

Tetrazole derivative

A method for preparing a cephalosporin compound represented by the general formula (III) ##STR1## (wherein R represents hydrogen or methyl group) or a pharmaceutically acceptable salt thereof, which is characterized by reacting 7-amino-3-(benzimidazol-2-yl)-thiomethyl-3-cephem-4-carboxylic acid represented by the general formula (I) ##STR2## or a salt thereof with a compound represented by general formula (II) ##STR3## wherein R represents hydrogen or methyl group.

Method for preparation of cephalosporin compounds

7-Aminocephalosporanic acid derivatives represented by the general formula (III), ##STR1## wherein X is hydrogen, hydroxyl, acetate or a nucleophilic residue, which are useful as a starting material for the synthesis of cephalosporin type antibiotics low in toxicity and broad in pharmacological effect can be easily prepared by allowing to react cephalosporin C or its derivative represented by the general formula (I), ##STR2## wherein X is as defined above, or a salt thereof with an .alpha.-keto derivative represented by the general formula (II), ##STR3## wherein R.sub.1 is carboxyl, aroyl or amide when R.sub.2 is hydrogen, and is carboxyl when R.sub.2 is alkyl or aryl, or its salt. In this case, the yield of the 7-aminocephalosporanic acid derivatives can be remarkably improved by carrying out the reaction in the presence of hydrogen peroxide. The yield can be further improved by adding thiosulfuric acid or a salt thereof after the completion of the reaction to decompose the unreacted hydrogen peroxide.

Process for preparing 7-aminocephalosporanic acid derivatives

Growing community of inventors

Nobeoka, Japan

Masahiro Murakami