Intramolecular general acid catalysis in the aminolysis of β-lactam antibiotics

Antonio Llinás, Michael I. Page

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

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 106. This is much more than an α-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 104 which demonstrates that β-lactam C-N bond fission and expulsion of the leaving group at C3′ are not concerted.

LanguageEnglish
Pages651-654
Number of pages4
JournalOrganic and Biomolecular Chemistry
Volume2
Issue number5
Early online date9 Feb 2004
DOIs
Publication statusPublished - 7 Mar 2004

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antibiotics
beta-Lactams
Catalysis
Cephaloridine
catalysis
Amines
Penicillin G
Anti-Bacterial Agents
amines
acids
Acids
Hydroxylamine
expulsion
augmentation
fission
breakdown
plots

Cite this

Llinás, Antonio ; Page, Michael I. / Intramolecular general acid catalysis in the aminolysis of β-lactam antibiotics. In: Organic and Biomolecular Chemistry. 2004 ; Vol. 2, No. 5. pp. 651-654.
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Intramolecular general acid catalysis in the aminolysis of β-lactam antibiotics. / Llinás, Antonio; Page, Michael I.

In: Organic and Biomolecular Chemistry, Vol. 2, No. 5, 07.03.2004, p. 651-654.

Research output: Contribution to journalArticle

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