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Merging the Isonitrile-Tetrazine (4+1) Cycloaddition and the Ugi Four-Component Reaction into a Single Multicomponent Process |
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| Authors: | Dr. Yanira Méndez Dr. Aldrin V. Vasco Galway Ivey Ana Laura Dias Dr. Peter Gierth Bárbara B. Sousa Dr. Claudio D. Navo Angel Torres-Mozas Dr. Tiago Rodrigues Dr. Gonzalo Jiménez-Osés Prof. Gonçalo J. L. Bernardes |
| Affiliation: | 1. Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW UK;2. Research Institute for Medicines (iMed), Faculty of Pharmacy, University of Lisbon, Av. Prof Gama Pinto, 1649-003 Lisbon, Portugal;3. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisboa, Portugal;4. Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Bizkaia Technology Park, Building 800, 48160 Derio, Spain |
| Abstract: | Multicomponent reactions are of utmost importance at generating a unique, wide, and complex chemical space. Herein we describe a novel multicomponent approach based on the combination of the isonitrile-tetrazine (4+1) cycloaddition and the Ugi four-component reaction to generate pyrazole amide derivatives. The scope of the reaction as well as mechanistic insights governing the 4H-pyrazol-4-imine tautomerization are provided. This multicomponent process provides access to a new chemical space of pyrazole amide derivatives and offers a tool for peptide modification and stapling. |
| Keywords: | Chemical Biology Multicomponent Reactions Peptides Tetrazines Ugi Reaction |