Charting the Chemical Reaction Space around a Multicomponent Combination: Controlled Access to a Diverse Set of Biologically Relevant Scaffolds.

Charting the chemical reaction space around the combination of carbonyls, amines, and isocyanoacetates allows the description of new multicomponent processes leading to a variety of unsaturated imidazolone scaffolds. The resulting compounds display the chromophore of the green fluorescent protein and the core of the natural product coelenterazine. Despite the competitive nature of the pathways involved, general protocols provide selective access to the desired chemotypes. Moreover, we describe unprecedented reactivity at the C-2 position of the imidazolone core to directly afford C, S, and N-derivatives featuring natural products (e.g. leucettamines), potent kinase inhibitors, and fluorescent probes with suitable optical and biological profiles. Charting the reaction space around a known Multicomponent Reaction (MCR) allows the development of new processes. In this way, a detailed study of the parameters involved in the Orru transformation leads to the generation of alternative connectivities featuring diversely substituted imidazolones, including GFP (Green Fluorescent Protein) chromophores, coelenterazine derivatives, natural products, kinase inhibitors, and bioprobes.

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© 2023 The Authors. Angewandte Chemie published by Wiley-VCH GmbH.

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The authors declare no conflict of interest.