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General Synthesis of Industrial Cephalosporin‐Based Antibiotics Through Amidation with Tosyl Chloride as a Coupling Reagent
Author(s) -
Pieper Matthias,
Schleich Herbert,
Gröger Harald
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900277
Subject(s) - chemistry , cephalosporin antibiotic , reagent , moiety , benzoyl chloride , combinatorial chemistry , sulfonyl , organic chemistry , solvent , cephalosporin , oxime , toluene , antibiotics , alkyl , biochemistry
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.