Insertion of Isocyanides into N−Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds

Kranti G. Kishore, Ouldouz Ghashghaei, Carolina Estarellas, M. Mar Mestre, Cristina Monturiol, Nicola Kielland, John M. Kelly, Amanda Fortes Francisco, Shiromani Jayawardhana, Diego Muñoz-Torrero, Belén Pérez, F. Javier Luque, Rocío Gámez-Montaño, Rodolfo Lavilla

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N−Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N−Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles.
Original languageEnglish
Pages (from-to)8994-8998
JournalAngewandte Chemie - International Edition
Volume55
Issue number31
DOIs
Publication statusPublished - 1 Jan 2016

Keywords

  • azines
  • isocyanides
  • multicomponent reactions
  • silicon
  • trypanosomiasis

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