THE CARBOHYDRATE-CATALYZED HYDROLYSIS OF CEPHALOSPORINS

The decomposition of cephaloridine, cephtazidime, cephaclor, cephaloth in, cephaloglycin, cephalexin and cephradine catalysed by glucose, gal actose, maltose, sucrose, mannitol and alpha-methylglucoside in aqueou s solutions of pH 9-11 is reported. The rate of decomposition depends upon the structure of the cephalosporin, the more important feature be ing the electron withdrawing nature of the substituent attached to the exocyclic C-3 methylene carbon atom. At pH 9.5 a Hammett rho(I) value of 2.9 is obtained from a plot of log k2, the apparent second-order r ate constant, versus sigma(I) for the glucose catalysed reaction. At p H ca. 9 plots of k(o) versus catalyst concentration appear linear, but above pH ca. 10 such plots are curved. The extent of catalysis increa ses at higher pH values. Carbohydrates with a hemiacetal OH group are significantly better catalysts than those that do not contain this fun ctionality, though catalysis by non-hemiacetal groups is evident. The difference in reactivity between the two types of OH at pH 9.5 lies be tween 10 and 15-fold. The results are interpreted in terms of a mechan ism that involves nucleophilic catalysis via the hemiacetal anion of t he carbohydrate. Curvature of the k(o) versus [catalyst] plots is expl ained by the formation of non-catalytic dimer between the anionic and neutral forms of the catalyst.