Kishore, KG;
Ghashghaei, O;
Estarellas, C;
Mar Mestre, M;
Monturiol, C;
Kielland, N;
Kelly, JM;
... Lavilla, R; + view all
(2016)
Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds.
Angewandte Chemie - International Edition
, 55
(31)
pp. 8994-8998.
10.1002/anie.201604109.
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Abstract
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.
Type: | Article |
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Title: | Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1002/anie.201604109 |
Publisher version: | https://doi.org/10.1002/anie.201604109 |
Language: | English |
Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
Keywords: | Science & Technology, Physical Sciences, Chemistry, Multidisciplinary, Chemistry, azines, isocyanides, multicomponent reactions, silicon, trypanosomiasis, TRYPANOSOMA-CRUZI, DRUG DISCOVERY, CHEMISTRY, HETEROCYCLES, ISONITRILES, ALDEHYDES, CATALYSTS, SALTS, ALKYL |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
URI: | https://discovery.ucl.ac.uk/id/eprint/10062138 |
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