Cephalosporin 3-carbonyl-functionalized

A subset of lactams is the P-lactam functionality, the chemistry of which has been studied extensively. The P-lactam functionality has been thoroughly studied because the biological activity of the P-lactam antibiotics (e.g., penicillins, cephalosporins, etc.) is the result of the presence of the P-lactam moiety (Fig. 9). The electrophilic carbonyl of the P-lactam reacts with certain penicillin binding proteins found in bacteria to form a covalent bond (ester-linked) with the protein (23,24). The protein is thereby inactivated, bacterial cell wall... 

Modification at C-6(7).—The discovery of 7-methoxycephalosporins as potent antibacterials, coupled with an early prediction that alkylation at C-6 should enhance the biological activity of penicillin, generated considerable interest in the functionalization a to the p-lactam carbonyl group. Use of an aryl Schiif base to increase the acidity of the C-6 proton permitted the generation of anion (IQ by sodium hydride or other strong bases. Alkylation of (16) by methyl iodide occurred preferentially from the less hindered a face, affording (17) as the major isomer. Similarly, stereoselective methylation of the cephalosporin anions (18 X = H) - and (18 X = OAc) yielded o-methylated products (19 X = H or OAc). 

---