ISSN:
1434-193X
Keywords:
Azetidinones
;
Enzyme inhibitors
;
Kinetics
;
Molecular modelling
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
-Three 1-alkoxycarbonyl-3-bromoazetidin-2-ones have been prepared by reaction of (3S)-3-(tert-butoxycarbonyl)aminoazetidin-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 kcat and Km values. Accordingly, these compounds behave as transient inhibitors of the enzyme.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
