Research and Process Development of Cefditoren Pivoxil: an Oral Cephalosporin Antibiotic

摘要

Cefditoren Pivoxil was synthesized in the course of study on a series of cephalosporins having various heterocycles attached to the C3-position of the cephem nucleus through Z-and E-etheno groups. Introduction of the side chains to the cephalosporins was achieved by a Wittig reaction. The reaction showed rather poor Z-E selectivity (Z:E = 1:1 to 4:1) in the stage of screening research. Investigation was started for improvement of the Z-selectivity soon after determining Cefditoren Pivoxil as a development candidate substance, and relatively high Z-selectivity (Z:E = 94:6) was finally achieved. The overall yield of Cefditoren Pivoxil was 49.6% in the established manufacturing synthetic method. Cefditoren, the active form of Cefditoren Pivoxil, has remarkably potent activity to penicillin-resistant Streptococcus pneumoniae (PRSP) and #beta#-lactamase-negative-ampicillin resistant Haemophilus influenzae (BLNAR) among the oral #beta#-lactam antibiotics.