J . Am. Chem. SOC.1991, 113, 3079-3084
3079
thiazolidine, e.g., benzylpenicillin undergoes opening of the 8lidine ring could then be important subsequent to the enzymatic lactam ring to give benzylpenicilloic a ~ i d . * ~This - ~ implies ~ that acylation reaction. The penicillins and cephalosporins are effective bacteriocidal thiazolidine ring opening is unfavorable at those pH values. As seen in the present work the equilibrium for thiazolidine ring agents presumably because they disrupt bacterial cell wall synopening is indeed unfavorable at high pH (>IO), even when the t h e ~ i s . * ~ This * ~ *effect ~ ~ ~ is exerted by the inhibition of enzymes forward reaction is rapid because of significant internal stabilithat catalyze the cross-linking reaction of peptidoglycan zation of the developing carbonium ion. This is because the reverse The process of transpeptidation is thought to involve ring-closure reaction involving nucleophilic attack of the thiol anion the cleavage of the terminal D-alanyl-D-alanine of the peptidois facile. As a consequence, ring opening is only favorable at pH glycan to give an acyl enzyme intermediate with release of D
