Isoxazoles, mainly 3,5‐disubstituted, are prepared by catalytic condensation of primary nitro compounds with terminal acetylenes by using a copper/base catalytic system. The additional catalytic effect of the copper(II) salts is evidenced by comparing the kinetic profiles. Selectivity dependence on reaction conditions is considered for phenylacetylene in the following competitive processes: oxidative coupling of terminal alkynes to conjugated diynes catalyzed by CuII and base in the presence of air; production of furazans beside condensation with benzoylnitromethane to 3‐benzoylisoxazoles, as a result of the reaction of the dipolarophile with 3,4‐dibenzoylfuroxan; addition of electron‐poor alkynes (e.g., methyl propiolate) with themselves and with the nitro compound. Thus, oxidative coupling is negligible in reactions with “active” nitro compounds, whereas with nitroalkanes both products are observed: only trace amounts of isoxazoles are detected without copper. Similarly, in the presence of copper, 3‐benzoyl‐5‐phenylisoxazole is predominant over the furazan. Furthermore, condensations of electron‐poor alkynes give complex reaction mixtures in the presence of base alone, but cycloadducts are conveniently prepared with copper. The results indicate the practical and general utility of this catalytic method for synthetic practice.

Alzheimer’s disease (AD) is a progressive neurodegenerative condition affecting people in the elderly. Targeting aggregation of β-amyloid peptides (Aβ) is considered a promising approach for the therapeutic treatment of the disease. Peptide based inhibitors of β-amyloid fibrillation are emerging as safe drug candidates as well as interesting compounds for early diagnosis of AD. Peptide conjugation via covalent bond with functional moieties enables the resultant hybrid system to acquire desired functions. Here we report the synthesis, the structural characterization, and the Aβ42 interaction of a p-amino-calix­[4]­arene derivative bearing a GPGKLVFF peptide pendant at the lower rim. We demonstrate that the p-amino-calix­[4]­arene–GPGKLVFF conjugate alters the Aβ42 aggregation pathways by preventing Aβ42’s conformational transition from random coil to β-sheet with concomitant changes of the aggregation kinetic profile as evidenced by circular dichroism (CD), thioflavin T (ThT), and dynamic light scattering (DLS) measurements, respectively. High resolution mass spectrometry (HR-MS) confirmed a direct interaction of the p-amino-calix­[4]­arene–GPGKLVFF conjugate with Aβ42 monomer which provided insight into a possible working mechanism, whereas the alteration of the Aβ42’s fibrillary architecture, by the calix-peptide conjugate, was further validated by atomic force microscopy (AFM) imaging. Finally, the herein proposed compound was shown to be effective against Aβ42 oligomers’ toxicity in differentiated neuroblastoma cells, SH-SY5Y.