Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl-Functionalized Tetrazines

Alexi J.C. Sarris, Thomas Hansen, Mark A.R. de Geus, Elmer Maurits, Ward Doelman, Herman S. Overkleeft, Jeroen D.C. Codée, Dmitri V. Filippov*, Sander I. van Kasteren

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

The inverse-electron-demand Diels–Alder/pyridazine elimination tandem reaction, in which the allylic substituent on trans-cyclooctene is eliminated following reaction with tetrazines, is gaining interest as a versatile bioorthogonal process. One potential shortcoming of such currently used reactions is their propensity to proceed faster and more efficiently at lower pH, a feature caused by the nature of the tetrazines used. Here, we present aminoethyl-substituted tetrazines as the first pH-independent reagents showing invariably fast elimination kinetics at all biologically relevant pH values.

Original languageEnglish
Pages (from-to)18075-18081
Number of pages7
JournalChemistry - A European Journal
Volume24
Issue number68
DOIs
Publication statusPublished - 5 Dec 2018

Funding

A.J.C.S., D.V.F., and S.I.V.K. were funded by the Institute of Chemical Immunology (NWO Zwaartekracht), M.A.R.D.G. and S.I.V.K. were funded by the European Research Council (ERC-2014-StG-639005), and W.D. was funded by an NWO BBoL-grant. The authors thank the SURFsara for support in using the Dutch national supercomputer, including the Lisa system.

FundersFunder number
Institute of Chemical Immunology
NWO BBoL-grant
Horizon 2020 Framework Programme639005
European Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

    Keywords

    • bioorthogonal chemistry
    • Diels–Alder reactions
    • elimination
    • nitrogen heterocycles
    • pH effects

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