Inhibition of human leukocyte elastase by functionalized N-aryl-3,3-dihalogenoazetidin-2-ones. Stereospecific synthesis and chiral recognition of dissymmetrically C3-substituted β-lactams

✍ Scribed by Caroline Doucet; Isabelle Vergely; Michèle Reboud-Ravaux; Jean Guilhem; Randa Kobaiter; Roger Joyeau; Michel Wakselman

• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 840 KB
• Volume: 8
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/s0957-4166(97)00017-7

✦ Synopsis

3R)-and (3S)-N-(2-chloromethylphenyl)-3-bromo-3-fluoroazetidin-2-ones 2 were synthesized via the separation of diastereoisomeric phenylglycinol derivatives of the starting 2,3-dibromo-2-fluoropropanoic acid. Acidic hydrolysis of the hydroxyamides led to the chiral trihalogenopropanoic acids. Then, an expeditious four step synthesis provided the (3S)-and (3R)-azetidinones 2, both of which behaved as strictly irreversible inhibitors of HLE. The configuration of the bromofluorocarbon was shown to have a significant effect on the partition ratio: kcat/kinact--4.6 and 34.3 for (3S)-and (3R)-2, respectively.