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

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