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

Abstract

Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions,w hich then proceed through akey insertion of the isocyanide into aN À Si bond. The reaction is initiated by Nactivation of the azine,f ollowed by nucleophilic attackofanisocyanide in aReissert-type process. Finally,asecond equivalent of the same or ad ifferent isocyanide inserts into the NÀSi bond leading to the final adduct. The use of distinct nucleophiles leads to av ariety of a-substituted dihydroazines after as elective cascade process. Based on computational studies,amechanistic 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.

Development of Heterocyclic Multicomponent Reactions through Guided Exploration: Direct, Reasonable and Unpredictable Processes

“…The synthesized benzimidazolium salts were confirmed to be potent antiparasitic compounds against Trypanosoma brucei and cruzi . 51…”