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DOI: 10.1055/s-0036-1590946
Concise Synthesis of Macrocycles by Multicomponent Reactions
The work was financially supported by NIH 2R01GM097082-05, the Innovative Medicines Initiative (grant agreement No.115489), the European Union’s Seventh Framework Programme (FP7/2007-2013), EFPIA companies’ in-kind contribution, the European Union’s Horizon 2020 Research and Innovation Programme under MSC ITN ‘Accelerated Early Stage Drug Discovery’ (No 675555), and CoFund ALERT (No 665250). E.M.M.A. was supported by the Egyptian government.
Publication History
Received: 21 July 2017
Accepted after revision: 08 October 2017
Publication Date:
10 January 2018 (online)
Abstract
A short reaction pathway was devised to synthesize a library of artificial 18–27-membered macrocycles. The five-step reaction sequence involves ring opening of a cyclic anhydride with a diamine, esterification, coupling with an amino acid isocyanide, saponification, and, finally, macro-ring closure using an Ugi or, alternatively, a Passerini multicomponent reaction. Three out of the five steps allow for the versatile introduction of linker elements, side chains, and substituents with aromatic, heteroaromatic, and aliphatic character. The versatile pathway is described for 15 different target macrocycles on a mmol scale. Artificial macrocycles have recently become of great interest due to their potential to bind to difficult post-genomic targets.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1590946.
- Supporting Information
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