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1-alkoxycarbonyl-3-bromoazetidin-2-ones as potential elastase inhibitors

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Beauve, C Tjoens, G Touillaux, Roland Lamotte-Brasseur, J Marchand-Brynaert, Jacqueline [UCL] Fastrez, Jacques [UCL]

Three 1-alkoxycarbonyl-3-bromoazetidin-2-ones have been prepared by reaction of (3S)-3-(tert-butoxycarbonyl) amino azetidin-2-one with benzyl, trichloroethyl, and trifluoroethyl chloroformates followed by tBoc deprotection, diazotation of the exocyclic amino function and its substitution with potassium bromide. The 3-bromoazetidin-2-ones were obtained as racemic mixtures. Their hydroxide-catalyzed hydrolysis exclusively affords ring-opening products. Porcine pancreatic elastase (PPE) catalyzes the same reaction stereospecifically. Model building suggests that it is the (R) isomer that is enzymatically hydrolysed, The PPE-catalyzed hydrolysis is characterised by low k(cat) and K-m values. Accordingly, these compounds behave as transient inhibitors of the enzyme.

Document type Article de périodique (Journal article) – Article de recherche
Publication date 1999
Language Anglais
Journal information "European Journal of Organic Chemistry" - , no. 6, p. 1441-1447 (1999)
Peer reviewed yes
Publisher Wiley-v C H Verlag Gmbh (Berlin)
issn 1434-193X
e-issn 1099-0690
Publication status Publié
Affiliation UCL - SC/CHIM - Département de chimie
Keywords azetidinones ; enzyme inhibitors ; kinetics ; molecular modelling
Links
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Bibliographic reference Beauve, C ; Tjoens, G ; Touillaux, Roland ; Lamotte-Brasseur, J ; Marchand-Brynaert, Jacqueline ; et. al. 1-alkoxycarbonyl-3-bromoazetidin-2-ones as potential elastase inhibitors. In: European Journal of Organic Chemistry, , no. 6, p. 1441-1447 (1999)
Permanent URL http://hdl.handle.net/2078.1/44403