Preparation Of Ceph-3-Em Esters Unaccompanied By δ³To δ²Isomerization Of The Cephalosporin Derivatives

Exploitation of Antibiotic Resistance as a Novel Drug Target: Development of a β-Lactamase-Activated Antibacterial Prodrug

“…First, 7-ACA was reacted with acetic anhydride to give N -acetyl 26 . Protection of the carboxylic acid as the tert -butyl ester was then performed using tert -butyl 2,2,2-trichloroacetimidate (TBTA) enabling formation of the tert -butyl ester 29 in the absence of base, which has previously been reported to be associated with isomerization from the Δ 3 -cephem to the biologically inactive Δ 2 -cephem. − Iodination at the 3′-position with TMSI gave the activated iodocephalosporin 30 ready for coupling . The ciprofloxacin component was prepared by BOC protection of the piperazine NH to give 32 and subsequent conversion of the carboxylic acid to the sodium salt 33 .…”

“…The ciprofloxacin component was prepared by BOC protection of the piperazine NH to give 32 and subsequent conversion of the carboxylic acid to the sodium salt 33 . Coupling of compounds 30 and 33 was performed in 3:1 1,4-dioxane/DMF to give the protected cephalosporin–ciprofloxacin conjugate 34 . , Finally, global deprotection with TFA to remove the BOC and tert -butyl ester afforded the final prodrug 35 . Synthesis of 35 was achieved in seven steps from commercially available materials without the requirement for toxic metal reagents.…”