Intramolecular general acid catalysis in the aminolysis of beta-lactam antibiotics.
The rate of aminolysis of benzylpenicillin and cephaloridine by hydroxylamine, unlike other amines, shows only a first order dependence on amine concentration. The rate enhancement compared with that predicted from a Bronsted plot for other primary amines with benzylpenicillin is greater than 10(6). This is much more than an alpha-effect and is compatible with rate-limiting formation of the tetrahedral intermediate due to a rapid intramolecular general acid catalysed breakdown of the intermediate. For cephaloridine, the rate enhancement is greater than 10(4) which demonstrates that beta-lactam C-N bond fission and expulsion of the leaving group at C3' are not concerted.
Llinas
Antonio
A
Department of Chemical and Biological Sciences, University of Huddersfield, Queensgate, Huddersfield, UK HD1 3DH.
Page
Michael I
MI
D000143:Acids / Q000737:chemistry*; D000588:Amines / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D002384:Catalysis; D002509:Cephaloridine / Q000138:chemical synthesis / Q000737:chemistry; D008968:Molecular Conformation; D010400:Penicillin G / Q000138:chemical synthesis / Q000737:chemistry; D047090:beta-Lactams / Q000737:chemistry*
D000143:Acids; D000588:Amines; D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D002509:Cephaloridine; D010400:Penicillin G