Chemoenzymatic enantioselective route to get (+) and (−) 4-acetoxy-azetidin-2-one by lipase-catalysed kinetic resolution and their applications

Abstract

4-Acetoxy-azetidin-2-one is an extremely useful intermediate widely applied for the synthesis of several biologically active β-lactam compounds. However, it is available as a racemic mixture that could limit its application in the synthesis of enantiopure products. Herein we evaluated the use of lipases in a kinetic resolution (KR) process to finally obtain 4-acetoxy-zetidin-2-one as separated pure enantiomers. From a preliminary screening on a set of commercial enzymes, Pseudomonas fluorescens emerged as the most suitable lipase that allowed to obtain good conversions and excellent enantiomeric excesses. On the enantiomerically pure 4-acetoxy-azetidin-2-ones some nucleophilic substitutions and N-thio-alkylation reactions were tested in order to evaluate the stereochemical integrity at the C-4 position.