Comparison of the mechanisms of reactions of β-Lactams and β-Sultams including their reactions with some serine enzymes

Page, Michael I., Tsang, Wing Y. and Ahmed, Naveed (2006) Comparison of the mechanisms of reactions of β-Lactams and β-Sultams including their reactions with some serine enzymes. Journal of Physical Organic Chemistry, 19 (8-9). pp. 446-451. ISSN 1099-1395

Abstract

The strain energy of the four-membered ring of -lactams is not released in the transition state to lower the activation energy of reactions involving ring-opening. The alkaline hydrolysis of N-aroyl -lactams occurs with competitive exo- and endocyclic CN ring fission, the ratio of which varies with the aryl substituent. -Sultams are four-membered cyclic sulfonamides and are about 103 fold more reactive than analogous -lactams. Nucleophiles usually attack N-acylsulfonamides at the carbonyl centre resulting in CN bond fission, but the hydrolysis of N-acyl -sultams occurs with SN fission and opening of the four-membered ring. The 3-oxo--sultams are a unique combination of both -lactams and -sultams and therefore are susceptible to nucleophilic attack at either the acyl or the sulfonyl centre, but they hydrolyse with exclusive SN bond fission. -Sultams are novel inhibitors of the serine enzymes elastase, transpeptidase and -lactamase due to sulfonylation of the active-site serine residue. Structure-activity relationships are used to identify differences in transition-state structures between -sultams as inhibitors and -lactams as substrates. Copyright © 2006 John Wiley & Sons, Ltd

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