Chemistry of cephalosporin antibiotics. 30. 3-Methoxy- and 3-halo-3-cephems

Abstract

The exo-methylene group in esters of 7-acylamido- and 7-amino-3-methylenecephams was ozonized to give 3-hydroxy-3-cephems. Conditions are described to effect a selective N-acylation of a 3-hydroxy-3-cephem nucleus ester. Vilsmeier reagents converted 7-acylamido-3-hydroxy compounds to 3-halo-3-cephem derivatives. Diazomethane converted the 3-hydroxy compounds to 3-methoxy-3-cephem derivatives. Removal of the ester-protecting group at the C4-carboxyl afforded a select group of cephalosporins with direct halo and methoxy substitution at C3. A number of these compounds are potent antibiotics.

p‐Nitrobenzyloxycarbonyl (pNZ) as a Temporary Nα‐Protecting Group in Orthogonal Solid‐Phase Peptide Synthesis – Avoiding Diketopiperazine and Aspartimide Formation

“…Although the most common method for this transformation is catalytic hydrogention,16 it is not useful for SPPS. Other common methods are the use of metals such as Zn,11b Fe,17 or Sn17 in acidic solutions. However, the difficulty of working with metals on solid phase, as well as the highly acidic conditions required for this chemistry, make it problematic for the case at hand.…”

Penicillin Acylase in the Industrial Production of β-Lactam Antibiotics

“…Cefaclor ( 4a in Scheme ) is a d -(−)-PG-derived antibiotic based on the nucleus 7-aminodesacetoxymethyl-3-chlorocephalosporanic acid (7-ACCA) which can be obtained by ozonolysis and chlorination of 3-methylene cephams …”

Studies on .BETA.-lactam antibiotics. XI. Synthesis and structure-activity relationships of new 3-(2,2-dihalovinyl)cephalosporins.

“…General Preparation of Diphenylmethyl 7~-P _henylaceta_mido-3-(2,2-dihalovinyl)-3-cephem-4-carboxylate (5) To a soln of 4 (10 mmol) in DMF (100 ml) was added PCl3 (2.75 g, 20 mmol) at -30°C and the reaction mixture was stirred at -30--20°C for 30 minutes. The resulting mixture was poured into a mixture of EtOAc and H2O.…”