STUDIES ON ANTIBIOTICS OF SEMISYNTHETIC CEPHALOSPORINS. Ⅱ. SYNTHESIS OF 7-(7- OR 8-SUBSTITUTED COUMARIN-3-FORMAMIDO)-CEPHALOSPORINS

A series of new 7-(7- or 8-substituted coumarin-3-formamido)-cephalosporins has been prepared by acylation of the 7-amino group of 7-ADCA, 7-ACA and 7-ACT with 7- or 8-substituted coumarin-3-carboxylic acids which were made from 3-or 4-substituted salicylaldehyde and malonic acid orbits ester by Knovenagel condensation. Acyl chloride method anti Vilsmeier reagent method were adopted in the reactions. Isolation and purification were fulfilled with the combined methods of Sephadex LH-20 column chromatography and centrifugal-TLC technique. Sixteen new cephalosporin derivatives were synthesized. Their structures have been confirmed by elemental analysis, IR and ¹HNMR. The preliminary antibacterial sensitivity tests showed that V₂, V₃, V₈, V₉, V₁₄ and V₁₅ of these new derivatives exhibited high sensitivity to staphylococcus aureus which was resistant to eight other antibiotics. Further biological evaluation for these compounds was expected to be carried out.