Horner, KA, Valette, NM and Webb, ME (2015) Strain-promoted reaction of 1,2,4-triazines with bicyclononynes. Chemistry - A European Journal, 21 (41). 14376 - 14381. ISSN 0947-6539
Abstract
Strain-Promoted Inverse Electron Demand Diels-Alder Cycloaddition (SPIEDAC) reactions between 1,2,4,5-tetrazines and strained dienophiles such as bicyclononynes are among the fastest biorthogonal reactions. However the synthesis of 1,2,4,5-tetrazines is complex and can involve volatile reagents. 1,2,4-triazines also undergo cycloaddition reactions with acyclic and unstrained dienophiles at elevated temperatures but their reaction with strained alkynes has not been described. We postulated that 1,2,4-triazines would react with strained alkynes at low temperatures and therefore provide an alternative to the tetrazine-cycloaddition reaction for use in in vitro or in vivo labelling experiments. We describe the synthesis of a 1,2,4 triazin-3-ylalanine derivative fully compatible with the Fmoc strategy for peptide synthesis and demonstrate its reaction with strained bicyclononynes at 37 °C with rates comparable to the reaction of azides with the same substrates. The synthetic route to triazinylalanine is readily adaptable to late-stage functionalization of other probe molecules and the 1,2,4-triazine-SPIEDAC therefore has potential as an alternative to tetrazine-cycloaddition for applications in cellular and biochemical studies.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Bioorthogonal Chemistry; 1,2,4-triazine; Strain-promoted reaction |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) |
Funding Information: | Funder Grant number EPSRC EP/I013083/1 |
Depositing User: | Symplectic Publications |
Date Deposited: | 30 Jul 2015 12:21 |
Last Modified: | 08 Mar 2016 21:51 |
Published Version: | http://dx.doi.org/10.1002/chem.201502397 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/chem.201502397 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:88294 |