Electronic structures of cephalosporins and penicillins. 9. Departure of a leaving group in cephalosporins.
Molecular orbital calculations by the CNDO/2 method are used to study the potential energy surface for the stretching and rupturing of the CH2-OAc bond in a model cephalosporin structure, 7-amino-3-(acetoxymethyl)-3-cephem. The bond is easier to stretch and break when a nucleophilic group is in the vicinity of or attached to the beta-lactam carbonyl carbon (C8). The rate of acylation by a beta-lactam antibiotic at the receptor sites in bacterial cell-wall enzymes will be enhanced by a suitable leaving group at the 3' position. An orientational specificity is predicted for the direction of departure of the leaving group. Regardless of the direction the nucleophile approaches C8, the CH2-OAc bond is easiest to break when the acetate group departs from the alpha face of the molecule.
D002511:Cephalosporins / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D008968:Molecular Conformation; D011789:Quantum Theory; D013816:Thermodynamics
D002511:Cephalosporins