7-엑소메칠렌 세팔로스포라네이트 유도체의 합성과 beta-락타메이즈 억제작용

Synthesis and beta-Lactamase Inhibitory Activity of 7-Exomethylene Cephalosporanates

7-Oxocephalosporanate 1 was treated with phosphonium salts 2~4 by Wittig reaction to afford 7-exomethylene cephalosporanates 5-7. They were oxidized to sulfones 8-10 with mCPBA. Deprotection of benzhydryl 7-exomethylene cephalosporanate with AlCl3 and NaHC03 gave sodium salts of 7-exomethylene cephalosporanates 11-16. The beta-lactamase inhibitory activity of synthesized compounds 11~16 were compared with sulbactam, tazobactam and clavulanic acid against Type I, II, III, IV and TEM-2 beta-lactamase in vitro. Compound 15 showed more potent activity than sulbactam and clavulanic acid against Type III, IV beta-lactamase enzyme.