51978-94-0

Upstream product

• 123-54-6 acetylacetone 
• 300-87-8 3,5-dimethyl-1,2-oxazole 
• 1123-49-5 3,5-dimethyl-4-nitroisoxazole 
• 100-52-7 benzaldehyde 
• 79510-57-9 3-<1-phenyl-2-(3-methyl-4-nitro-5-isoxazolyl)-ethyl>pentane-2,4-dione 

Downstream Products

• 84735-86-4 C₅H₆N₂O₄ 
• 84735-88-6 2,3-dimethyl-4-nitroisoxazolin-5(2H)-one 
• 84735-85-3 3-methyl-4-nitro-5-methoxyisoxazole 
• 79510-67-1 3,5-diphenyl-4-(3-methyl-4-nitro-5-isoxazolyl)-2-isoxazoline 
• 79510-57-9 3-<1-phenyl-2-(3-methyl-4-nitro-5-isoxazolyl)-ethyl>pentane-2,4-dione 
• 51978-95-1 5-(1,2-dibromo-2-phenylethyl)-3-methyl-4-nitroisoxazole 
• 58935-96-9 1-Nitro-propan-2-one oxime 
• 621-82-9 Cinnamic acid 
• 924650-65-7 3-[2-(3-methyl-4-nitroisoxazol-5-yl)-1-phenylethyl]-1H-indole 
• 98239-35-1 5-[2-(3,5-dimethyl-1H-pyrazol-4-yl)-2-phenylethyl]-3-methyl-4-nitroisoxazole 
• 98239-45-3 5-[2-(3,5-dimethyl-1-phenyl-1H-pyrazol-4-yl)-2-phenylethyl]-3-methyl-4-nitroisoxazole 
• 1205553-81-6 3-methyl-4-nitro-5-((2S,3R)-3-nitro-2-phenylbutyl)isoxazole 
• 1205553-66-7 (S)-3-methyl-4-nitro-5-(3-nitro-2-phenylpropyl)isoxazole 
• 1205553-71-4 (R)-3-methyl-4-nitro-5-(3-nitro-2-phenylpropyl)isoxazole 

Relevant academic research and scientific papers

Chiral 4 and 5 - disubstituted pyrrolidine -2 - ketone compound as well as preparation method and application thereof

The invention belongs to the technical field of organic synthesis, and particularly relates to chiral 4, 5 - disubstituted pyrrolidine -2 - ketone compounds as well as a preparation method and application thereof. The invention firstly uses nitro substituted alkyl (I) and trans α, β - unsaturated 3 - methyl -4 - nitroisoxazole (II) as raw materials, and the asymmetric Michael addition reaction of chiral superbase catalysis I and II is a key step and is hydrolyzed. Esterification and reduction closes the ring, synthesizing a chiral 3, 4 - disubstituted pyrrolidine -2 - ketone compound, including optically pure fenoxone. The asymmetric Michael addition reaction of chiral superbase catalyst for catalyzing 2 -substituted nitroethane (I) and trans α, β -unsaturated 3 - methyl -4 - nitroisoxazole (II) is used for preparing chiral 4 and 5 -disubstituted pyrroli -2 - ketone, and a strapdown is provided for synthesizing chiral 4 and 5 - disubstituted pyrrolidine -2 - ketone skeleton.

Phosphine-Catalyzed [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates with Isoxazole-Based Alkenes

A phosphine-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with 3-methyl-4-nitro-5-styrylisoxazoles has been developed to afford various multifunctional isoxazoles in moderate to good yields with moderate to excellent diastereoselectivities. With a spirocyclic chiral phosphine as the catalyst, up to 89% ee was obtained.

Structure–activity relationships of GPX4 inhibitor warheads

Direct inhibition of GPX4 requires covalent modification of the active-site selenocysteine. While phenotypic screening has revealed that activated alkyl chlorides and masked nitrile oxides can inhibit GPX4 covalently, a systematic assessment of potential electrophilic warheads with the capacity to inhibit cellular GPX4 has been lacking. Here, we survey more than 25 electrophilic warheads across several distinct GPX4-targeting scaffolds. We find that electrophiles with attenuated reactivity compared to chloroacetamides are unable to inhibit GPX4 despite the expected nucleophilicity of the selenocysteine residue. However, highly reactive propiolamides we uncover in this study can substitute for chloroacetamide and nitroisoxazole warheads in GPX4 inhibitors. Our observations suggest that electrophile masking strategies, including those we describe for propiolamide- and nitrile-oxide-based warheads, may be promising for the development of improved covalent GPX4 inhibitors.

Styrylisoxazole-based fluorescent probes for the detection of hydrogen sulfide

Styrylisoxazoles bearing a nitro group linked to bulky aromatic rings have been synthesized and examined for their absorption and emission studies in organic solvents and water. The molecules showed emission in the visible region with significant solvatochromic emission shifts influenced by the extended conjugation of aromatic rings and intramolecular charge transfer. These absorption and emission changes were used for the efficient and sensitive detection of trace concentrations of hydrogen sulfide (H2S) through the reduction of the nitro group to the amine group in the presence of aqueous sodium sulfide. The experimental results indicated that the probes exhibit an excellent emission response with large shifts in the emission and sensitivity with a micromolar detection limit.

Catalytic enantioselective addition of isocyanoacetate to 3-methyl-4-nitro-5-styrylisoxazoles under phase transfer catalysis conditions

The reaction between 3-methyl-4-nitro-5-styrylisoxazoles and ethyl isocyanoacetate proceeded under phase transfer catalysis to give enantioenriched monoadducts in high enantiomeric excess (up to 99% ee). The resulting adducts were subsequently cyclised to give 2,3-dihydropyrroles and substituted pyrrolidines in identical high ees and as a single diastereoisomer.

Trifluoromethylation of aromatic isoxazoles: Regio- and diastereoselective route to 5-trifluoromethyl-2-isoxazolines

It all adds up: The activation of aromatic isoxazoles with a nitro group at the 4-position has enabled the first regio- and diastereoselective trifluoromethylation at the 5-position of isoxazoles by nucleophilic addition using Me3SiCF3 (see scheme; DMF=N,N′- dimethylformamide). The process was demonstrated with a broad range of 3,5-aromatic, heteroaromatic and aliphatic substrates.

Catalytic asymmetric conjugate addition of nitroalkanes to 4-nitro5-styrylisoxazoles

(Chemical equation presented) Nitro versus nitro: 4-Nitro-5- styrylisoxazoles were used as masked α,β-unsaturated carboxylic acids in the titled catalytic asymmetric transformation. The 4-nitroisoxazole core acts as an activator of the conjugated alkene and a latent carboxylate functionality. The reaction proceeded with 5 mol% of a readily prepared phasetransfer catalyst at room temperature with remarkable diastereo- and enantioselectivity (see scheme).

Modular synthesis of isoxazolopyridones and pyrazolopyridones

Herein we described the preparation of two novel heterocyclic nuclei isoxazolopyridone and pyrazolopyridone. The syntheses are modular in nature and fast to execute. The title compounds were obtained pure without intervention of chromatography.

Chemistry of Heterocylces: Part VIII - Synthesis of Isoxazolylethylpyrazoles

The base-catalysed addition of acetylacetone to 3-methyl-4-nitro-5-styrylisoxazoles (II) leads to the Michael adducts 3-pentane-2,4-diones (III).These β-diketones (III) undergo cyclization with hydrazine sulphate and phenylhydrazine to furnish pyrazoles (IV) and N-phenylpyrazoles (V), respectively.

Attempted Heterocyclization of 2-Substituted 1,3-Diketones in Presence of Ethylenediamine

3-pentane-2,4-diones (II) when treated with ethylenediamine undergo retro Michael reaction to give 3-methyl-4-nitro-5-styrylisoxazoles (I).