PUB - Publikationen an der Universität Bielefeld

In this contribution we demonstrate the feasibility of a recently developed amidation method for a general synthesis of industrially important semi-synthetic cephalosporin antibiotics starting from readily available 7-aminocephalosporanic acid and derivatives thereof. The amidation process is based on the use of 4-toluene-sulfonyl chloride as an economically attractive coupling reagent in combination with methanol or ethyl acetate as one of the solvent components. A broad reaction scope was shown by the successful synthesis of three further cephalosporin antibiotics with different functionalities, which were obtained in high yields of 82-95% in the reactions even under non-optimized conditions. It is noteworthy that also different oxime functionalities in the side chain of the 7-position are tolerated as well as an ester moiety in 4-position and a cationic functionality in 3-position. Thus, this amidation process through an activated anhydride formed by means of 4-toluenesulfonyl chloride is a broadly applicable methodology for the synthesis of industrial semi-synthetic cephalosporin antibiotics.