Insertion of Isocyanides into N−Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds
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- 作者：Kranti G. Kishore ; Ouldouz Ghashghaei ; Dr. Carolina Estarellas ; M. Mar Mestre ; Cristina Monturiol ; Dr. Nicola Kielland ; Prof. John M. Kelly ; Dr. Amanda Fortes Francisco ; Shiromani Jayawardhana ; Prof. Diego Muñ ; oz-Torrero ; Prof. Belé ; n Pé ; rez ; Prof. F. Javier Luque ; Prof. Rocí ; o Gá ; mez-Montañ ; o and Prof. Rodolfo Lavilla
- 刊名：Angewandte Chemie
- 出版年：2016
- 出版时间：July 25, 2016
- 年：2016
- 卷：128
- 期：31
- 页码：9140-9144
- 全文大小：1337K
- ISSN：1521-3757
文摘
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.