ES375237A1 - Orally active sulfur-containing cephalosporin antibiotics - Google Patents

Abstract

Novel cephalosporanic acids of Formula I wherein R is phenyl, thienyl or phenyl substituted with OH, Cl, Br, NO 2 , CN, or C 1 -C 6 alkyl or alkoxy are prepared by acylating 3- methylthiomethyl-7-aminocephalosporanic acid or an ester thereof with N-protected phenylglycine, thienylglycine or appropriately substituted phenylglycine or an acid halide or anhydride thereof, and removing the N-protecting group, and the ester group if present. The 3-methylthiomethyl - 7 - aminocephalosporanic acid may be prepared by treating either (a) 7- aminocephalosporanic acid or (b) the corresponding 7-phenylacetamido or 7-phenoxyacetamido acid with methyl mercaptan, and in the case of (b), protecting the carboxyl group by ester formation and then splitting off the phenylacetyl or phenoxyacetyl group by treatment with PCl 5 in the presence of a tertiary amine followed by treatment with a lower alkanol and then with water or aqueous acid. Alternatively a #3-desacetoxycephalosporanic acid ester prepared by heating a penicillin sulphoxide ester under acid conditions, is isomerized to the corresponding #2 compound, converted to the 3-bromomethyl derivative with N-bromosuccinimide, and treated with methyl mercaptan to give the 3-methylthiomethyl derivative which is converted to the corresponding #3 isomer by treatment with a base. The 7-acylating group is then removed as described above to give the required 7-amino-3-methylthiomethyl starting material.. Pharmaceutical compositions having antibacterial activity comprise a cephalosporanic acid of Formula I together with a pharmaceutically acceptable carrier.