Base-catalyzed hydrolysis of 6-aminopenicillanic acid. The kinetic and thermodynamic products

In the presence of sodium hydroxide or a β-lactamase, 6-APA has been shown to hydrolyze rapidly at room temperature to penicic acid 3 , the kinetic product of the reaction. In a subsequent equilibration 3 isomerizes at C-5, by way of intermediate imine 4 , affording 5-epi-penicic acid 6 as the major hydrolysis product (～ 95% at equilibrium). The pH and temperature parameters of equilibration are discussed and HPLC, optical rotation, proton nmr and ¹³C nmr data are presented.