Process for the preparation of 7α-methoxy-7β-(1,3-diethietane-2-carboxyamido)cephalosporanic acid derivatives

Abstract

The invention relates to novel 7α-methoxycephalosporin derivatives having at the 7β-position an amido group acylated by a 1,3-dithietane carboxylic acid residue and to 7β-isothiazolylthioacetamido-7α-methoxycephalosporins having antibacterial activity by themselves and, as the case may be, capable of being converted into the aforesaid 7α-methoxycephalosporin derivatives. The compounds of this invention exhibit excellent antibacterial activity and are particularly effective against gram negative bacteria.

What is claimed is: 
     
       1. A process for the preparation of a 7α-methoxy-7β-(4-substituted methylene-1,3-.[.dithientane.]..Iadd.dithietane-.Iaddend.2-yl) carboxamido-3-heterocyclic thiomethyl-Δ 3  -cephem-4-carboxylic acid represented by the formula ##STR114## wherein R 2  represents a hydrogen atom, a lower alkyl group, a lower alkoxy group, R 4  S(O) n  group wherein R 4  represents a lower alkyl gorup and n represents 0, 1 or 2, a lower alkanoyl group, a phenyl group, a naphthyl group, a benzoyl group, a naphthoyl group, .Iadd.a carboxyl group, a derivative thereof selected from the group consisting of lower alkyl, phenyl lower alkyl and naphthyl lower alkyl esters of said carboxyl group and carbamoyl, carbazolyl and cyano groups, .Iaddend.a lower alkenyl group a sulfamoyl group, or a pyridyl group, or a thiadiazolyl group, and R 3  represents a lower alkyl-substituted tetrazolyl group or a lower alkyl-substituted thiadiazolyl group, and R 8  represents a hydrogen atom or an alkyl group .[.which may have substituents selected from N-monoalkyl carbamoyl, N-dialkyl carbamoyl, and alkoxy carbonyl amino.]., which comprises treating the 7α-methoxy-3-heterocyclic thiomethylcephalosporin derivatives represented by the formula ##STR115## wherein R 2 , R 3  and R 8  have the same significance as above, with a base. 
     
     
       2. The method of claim 1, wherein said base is selected from sodium hydrogen carbonate, potassium hydrogen carbonate, and sodium carbonate. .Iadd. 
     
     
       3.  The method of claim 1, wherein R 2  represents a carboxyl group, a derivative thereof selected from the group consisting of lower alkyl, phenyl lower alkyl and naphthyl lower alkyl esters of said carboxyl group and, carbamoyl, carbazolyl, and cyano groups. .Iaddend. .Iadd.4. The method of claim 1, wherein R 8  represents a hydrogen atom, and R 2  represents a carboxyl group. .Iaddend. .Iadd.5. The method of claim 1, wherein R 3  represents a lower alkyl-substituted tetrazolyl group. .Iaddend. .Iadd.6. The method of claim 1, wherein R 8  represents a hydrogen atom, R 2  represents a carboxyl group, and R 3  represents a 1-methyltetrazol-5-yl group. .Iaddend. .Iadd.7. The method of claim 1, wherein R 8  represents an alkyl group. .Iaddend.