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Insertion of Isocyanides into N−Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds
Author(s) -
Kishore Kranti G.,
Ghashghaei Ouldouz,
Estarellas Carolina,
Mestre M. Mar,
Monturiol Cristina,
Kielland Nicola,
Kelly John M.,
Francisco Amanda Fortes,
Jayawardhana Shiromani,
MuñozTorrero Diego,
Pérez Belén,
Luque F. Javier,
GámezMontaño Rocío,
Lavilla Rodolfo
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201604109
Subject(s) - isocyanide , chemistry , azine , nucleophile , antiparasitic , adduct , combinatorial chemistry , medicinal chemistry , stereochemistry , organic chemistry , medicine , pathology , catalysis
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.