Unprecedented stereoselective synthesis of 3-methylisoxazolidine-5-aryl-1,2,4-oxadiazoles via 1,3-dipolar cycloaddition and study of their in vitro antioxidant activity

ABSTRACT

The stereoselective 1,3-dipolar cycloaddition between allyl cyanide and a menthone-derived nitrone led to the desired isoxazolidine in good yield. Once the nitrile group transformed to an amidoxime group, the cyclocondensation of various aldehydes with chiral amidoxime led to unprecedented enantiopure 3-methylisoxazolidine-5-aryl-1,2,4-oxadiazoles. The menthone chiral auxiliary was then removed with acid hydrolysis. The new compounds were also screened for their in vitro antioxidant activity using DPPH and FRAP assays. Some of the compounds showed promising antioxidant activity.

GRAPHICAL ABSTRACT

KEYWORDS:

• Antioxidant activity
• 1,3-dipolar cycloaddition
• isoxazolidine
• microwaves
• 1,2,4-oxadiazole

Acknowledgments

Financial support from the University of Monastir, Faculty of Sciences of Monastir Tunisia, University of Lyon, and Centre national de la recherche scientifique (CNRS) are gratefully acknowledged. The authors thank R. Simon and C. Duchamp from the Centre Commun de Spectrométrie de Masse (ICBMSUMR-5246) for their assistance and access to mass spectrometry facilities.