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Synthesis of oxazolidinone drugs Linezolid and Rivaroxaban via asymmetric Henry reaction

Authors: Vrbický Martin | Drabina Pavel

Year: 2021

Type of publication: ostatní - přednáška nebo poster

Page from-to: nestránkováno

Titles:

Language	Name	Abstract	Keywords
eng	Synthesis of oxazolidinone drugs Linezolid and Rivaroxaban via asymmetric Henry reaction	Oxazolidinones are new class of antibiotics used to treat serious skin and bacterial infections. They are active against large spectrum of gram-positive bacteria, including methicillin- and vancomycin-resistant staphylococci. An oxazolidinone derivative for other purposes is Rivaroxaban, which is approved by the FDA for venous thromboembolism prophylaxis.1 Herein, we are presenting significant improvement in synthesis of antibacterial agent Linezolid, previously reported by Piccionello et al.,2 and anticoagulant drug Rivaroxaban. Both reaction sequences involve six steps overall, starting from commercially available and inexpensive materials. The stereogenic center was introduced by asymmetric Henry reaction catalyzed by the complexes of copper(II) acetate and selected ligands. The use of imidazolidin-4-one or bis(oxazoline) ligands provide high yields and enantioselectivities of the chiral precursors of both drugs (up to 94%, up to 90% ee). With regard to obtained results, the most efficient catalysts and appropriate reaction conditions were selected for subsequent research that deals with the modification of the carbamate functional group of starting aldehydes and its influence on the enantioselectivity of asymmetric Henry reaction.	Linezolid; Rivaroxaban; Henry reaction; copper(II) acetate; imidazolidin-4-one; bis(oxazoline)