Kaïss Aouadi

Stereoselective synthesis of enantiopure N-substituted pyrrolidin-2,5-dione derivatives by 1,3-dipolar cycloaddition and assessment of their in vitro antioxidant and antibacterial activities

1,3-Dipolar cycloaddition between a chiral nitrone and N-substituted maleimides afforded unprecedented enantiopure spiro-fused heterocycles in good yields with a high enantio- and diastereoselectivity. The reaction was taking place on the less hindered face of the nitrone. The obtaining heterocycles were screened for their in vitro antioxidant properties and the results revealed that the potent antioxidant activity was generally recorded to compounds (3g) and (3e). The in vitro antibacterial activities of these two compounds were also investigated and the results demonstrated the strongest potential of compound (3g) against all the tested bacteria. Molecular properties were analyzed and showed good oral drug candidate like properties and that could be exploited as a potential antioxidant and antimicrobial agent. Finally, the preliminary results obtained from this investigation attempted to clarify if the structurally different side chains of active compounds interfere with their biological properties.

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

Crystal structure of (1S,2S,2′R,3a′S,5R)-2′-[(5-bromo-1H-indol-3-yl)meth­yl]-2-isopropyl-5,5′-dimethyl­dihydro-2′H-spiro­[cyclo­hexane-1,6′-imidazo[1,5-b]isoxazol]-4′(5′H)-one

The absolute structure for the title compound, which has five chiral centres has been determined in this analysis. The supramolecular architecture comprises parallel zigzag chains formed through N—H⋯N and C—H⋯O hydrogen bonds, as well as intramolecular C—H⋯O, C—H⋯N and C—H⋯π interactions.

Crystal structure of 5-chloro­methyl-N-methyl-4-[(4-phenyl-1,2,3-triazol-1-yl)meth­yl]isoxazolidine-3-carboxamide

The title compound crystallized with two independent molecules in the asymmetric unit. Each molecule has three stereogenic centres with configurations 2(S), 3(S) and 4(R), confirmed by resonant scattering.

Crystal structure of 2-isopropyl-5,7'-dimethyl-1',3',3a',6',8a',8b'-hexa-hydro-spiro-[cyclo-hexane-1,6'-furo[3,4-d]imidazo[1,5-b]isoxazol]-8'(7'H)-one.

Cycloaddition reaction between a menthone-based chiral nitrone and 2,5-dihydrofuran under microwave activation affords a enantiopure cycloadduct in good yields and with high stereoselectivity