SYNTHESIS OF 7β-(6-SUBSTITUTED-2-QUINOLONE-3-ACETAMIDO) CEPHALOSPORINS

A series of new 7β- (6-substituted-2-quinolone-3-acetamido)-cephalos porins has been prepared by acylation of the 7β-amino group of 7-ADCA, 7-ACA, 7-ACT and 7-ACD with 6-subsbstituted-2-quinolone-3-acetic acids. CDI (N,N'-Carbonyldiimidazole) method was mainly adopted and active ester method was also employed in the reactions. Isolation and purification were fulfilled with the combined methods of Sephadex LH-20 column chromatography and centifugal-TLC technique. Sixteen new cephalosporin derivatives were synthesized. Their structures have been confirmed by elemental analysis, IR and ¹HNMR. The preliminary in vitro antibacterial tests showed that these new compounds exhibited high activity to gram-positive and some negative bacteria. Bacteriostasis of most of the compounds was equal to cefazolin and sodium penicllin G. Compound Ⅲ₃, Ⅲ₄, Ⅲ₈,Ⅲ₁₀ and Ⅲ₁₁ possessed higher activity on the resistant Staphylococcus aureus S22 and Proteus vulgaris OX19 than cefazolin and sodium penicillin G. Further biological evaluation for these compounds is expected to be carried out.