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

Giulia Martelli; Martina Cirillo; Valentina Giraldi; Daria Giacomini

doi:10.1016/j.bioorg.2021.105580

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

Bioorg Chem. 2022 Mar:120:105580. doi: 10.1016/j.bioorg.2021.105580. Epub 2021 Dec 31.

Authors

Giulia Martelli¹, Martina Cirillo¹, Valentina Giraldi¹, Daria Giacomini²

Affiliations

¹ Department of Chemistry "G. Ciamician", Alma Mater Studiorum University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
² Department of Chemistry "G. Ciamician", Alma Mater Studiorum University of Bologna, Via Selmi 2, 40126 Bologna, Italy. Electronic address: daria.giacomini@unibo.it.

PMID: 35066318
DOI: 10.1016/j.bioorg.2021.105580

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.

Keywords: 4-acetoxy-azetidinone; Azetidinones; Biocatalysis; Kinetic resolution; Lactams; Lipases; Single-enantiomer drugs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biocatalysis
Catalysis
Kinetics
Lipase* / metabolism
Stereoisomerism

Substances

Lipase