Experimental and theoretical investigations on the cephalosporin Delta3-Delta2 isomerization.

Cephalosporin esters and amides have been subjected to ?3-?2 isomerization in basic medium. Good agreement between the experimentally obtained thermodynamic equilibrium constants and those calculated by molecular mechanics calculations has been found, suggesting the reliability of the MM2 force field as implemented in the program MODEL for calculations on cephalosporins. The ?3 isomers generally prove to be more stable than the ?2, although the energy difference in the case of esters is small. Reduced accessibility of electrophiles to the ?2 double bond is discussed in terms of 3D structure.