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Macrocycle compounds with enediyne motif

Multicomponent reactions (MCRs) are powerful tool for introducing chemical diversity and the rapid generation of small-molecule libraries. [1] The main advantage of MCRs is an easy access to libraries of complex and structurally diverse compounds in a single reaction step starting from relatively simple components. Isocyanide-based multicomponent reactions (IMCRs, i.e. Passerini, Ugi reaction) are among the most important MCRs. The Ugi reaction provides a rapid route to peptide-like compounds through coupling of an aldehyde, an amine, a carboxylic acid and an isocyanide. The Ugi reaction can be coupled with a post- condensation reactions, like cyclisation, to increase the number of compounds available for screening.[2] Our aim was synthesis of macrocycle compounds with enediyne motif utilizing the Ugi reaction/Sonogashira reaction approach coupled with intramolecular cyclisation (Scheme 1). The enediyne structural motif was found in natural products with strong anticancer activity.[3] Additionally, enediyne compounds can be used in asymmetric hydrogenation reactions[4] and in metal complexation.[5] The Ugi reaction of aldehyde 1, different C- protected amino acids, commercially available isocyanides and carboxylic acids gave Ugi products 2. Next, the Sonogashira reaction was carried out with 2 unsaturated alcohols yielding acyclic structures 3 and 4. Finally, macrocycle compounds 5 and 6 were synthesized by intramolecular esterification (Scheme 1).

enediyne motif ; macrocyclic compounds ; multicomponent reactions ; Ugi reaction

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