Taiiti Okada

Electrochemical reduction of cephalosporanic acids

Electrochemical reduction of cephalosporanic acid derivatives (I) bearing various substituents at the 3-position gave the corresponding 3-methylenecepham derivatives (II), a new class of cephalosporins. Reductive opening of the 3-hydroxymethyl-3-cephem-4-carboxylic acid lactone (IV) was effected to give (II) by cathodic reaction. The 3-methylenecepham derivatives (II) were readily isomerized to the 3-methyl-3-cephem derivatives (III) providing a new synthesis of cephalexin [7-(D-2-amino-2-phenylacetamido)-3-methyl-3-cephem-4-carboxylic acid](IIIc). The reaction mechanism is discussed on the basis of deuteriation and polarography of the cephalosporins involved.

SYNTHESIS AND STRUCTURE-ACTIVITY RELATIONSHIPS OF 7β-[2-(2-AMINOTHIAZOL-4-YL)ACETAMIDO]CEPHALOSPORIN DERIVATIVES

In an effort to improve the antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)acetamido]-cephalosporins by introducing a methoxyimino group into the 7-acyl side chain, geometrically isomeric 2-(2-aminothiazol-4-yl)-2-methoxyiminoacetic acids and their derivatives were selectively synthesized. Structurally related acid derivatives were also synthesized. A facile and practical synthesis of an important starting material, 2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-methoxyiminoacetic acid, for the preparation of SCE-1365 which is now under extensive clinical trial was achieved.

Reduction of cephalosporanic acids with chromium(II) salts : Synthesis of 3-methylenecepham derivatives☆

Abstract 7-Acylaminocephalosporanic acid derivatives (1) were converted into 7-acylamino-3-methylenecepham-4-carboxylic acids (2) by treatment with chromium(II) salts in aqueous media. The esters (4a or 4b) of 7-acylamino-3-methylenecepham compounds were readily isomerized to the 3-methyl-3-cephem compounds (5a or 5b) under basic conditions. The reaction mechanism is discussed.

Nucleophilic displacement reactions of 3,6-dichloropyridazine 1-oxide with sulphur nucleophiles

The displacement reaction of 3,6-dichloropyridazine 1-oxide with sodium sulphide took place at the 6-position to give 3-chloropyridazine-6-thiol 1-oxide, in contrast to the results with oxygen and nitrogen nucleophiles. Other sulphur nucleophiles (thiourea and phenylmethanethiol) also reacted at the 6-position; this is inconsistent with a previously reported reaction with potassium methanethiolate.