Shionogi Company Limited

Yuji Sendo

Mitsuru Yoshioka

Masayuki Murakami

Koji Ishikura

Sadao Miyazaki

Wataru Nagata

Teruji Tsuji

Takashi Maeda

Shoichi Hirai

Takahiro Kataoka

A process for preparing free carboxylic acids which comprises treating an optionally substituted benzyl ester with a Lewis acid, preferably in the presence of a cation acceptor, followed by hydrolysis, if required.

Selective conversion of benzyl alcohol carboxylates to the free acid form

Antibacterial cephalosporins of the following formula: ##STR1## WHEREIN A and B each is a hydrogen or an amino protecting group; X is a hydroxy or a carboxy protecting group; Y is a hydrogen, halogen, alkyl, alkoxy, or an alkylthio; R is a hydrogen or an alkyl; Z is a group of the formula ##STR2## (in which R.sup.1 and R.sup.2 are the same or different and are a hydrogen, optionally substituted hydrocarbon group, organic acyl, or a group of the formula ##STR3## respectively, in which M and M' are the same or different and are an oxygen or sulfur; R.sup.3 is a hydrocarbon group; R.sup.1 and R.sup.2 can be combined together directly or through a hetero atom); m is 0 or 1; and the broken line shows the presence of a double bond at position 2 or 3, preparable from the compounds shown by the above formula in which Z is an oxygen by treatment with a compound shown by the formula H.sub.2 Z; and pharmaceuticals containing these compounds.

Antibacterial hydrazono cephalosporins

Antibacterial cephalosporins of the formula ##STR1## wherein Acyl is an acyl group; R is a hydrogen or methoxy, R.sup.1 is a hydrocarbyl group containing 1 to 8 carbon atoms; R.sup.2 is a hydrogen, alkali metal, alkaline earth metal, halo-alkaline earth metal group or acyl group containing 1 to 12 carbon atoms; R.sup.3 is a hydrogen, pharmaceutically acceptable cation, or ester residue; or when R.sup.2 and R.sup.3 are both hydrogens, they can be combined to form a lactone ring; the broken line shows a double bond at position 2 or 3; and n is zero or one, and processes for preparing them by the reaction of the compound shown by above formula in which R.sup.1 and R.sup.2 combined to show a bond, with a Grignard type or organometallic reagent to introduce R.sup.1, followed by acylation, oxidation, reduction, double bond migration, or other reactions.

Cephalosporins having a metaloxy group in 3-substituent

An antibacterial 7-protected amino-3-oxyiminomethyl-3-cephem-4-carboxylic acid is prepared by the reaction of a 7-protected amino-3-formyl-3-cephem-4-carboxylic acid or its reactive derivatives with a hydroxylamine compound or its reactive derivatives, the process being more suitable for large scale production when coupled with fermentative production of a 3-hydroxymethyl-3-cephem-4-carboxylic acid followed by its direct oxidation.

Intermediates for the preparation of

Antibacterial cephalosporin compounds of the following formula: ##STR1## wherein A and B each is a hydrogen, organic or inorganic acyl, or A and B combined together are a diacyl group derived from a polybasic acid; Y is a hydrogen or methoxy; R is a hydrogen or lower alkyl; R' is a hydrogen, alkali metal, organic base group or easily removable protecting group; m is 0 or 1; Z is an optionally substituted guanylhydrazono group, preparable from the corresponding oxo compound or its reactive derivative by reacting with a guanylhyrazine of the formula H.sub.2 Z or its reactive derivative, or by some other reactions.

Growing community of inventors

Nishinomiya, Japan

Yuji Sendo