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

doi:10.1002/chem.201803839

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

Chemistry and Pharmaceutical Sciences

Research output: Contribution to Journal › Article › Academic › peer-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 language	English
Pages (from-to)	18075-18081
Number of pages	7
Journal	Chemistry - A European Journal
Volume	24
Issue number	68
DOIs	https://doi.org/10.1002/chem.201803839
Publication status	Published - 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.

Funders	Funder number
Institute of Chemical Immunology
NWO BBoL-grant
Horizon 2020 Framework Programme	639005
European Research Council
Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Keywords

bioorthogonal chemistry
Diels–Alder reactions
elimination
nitrogen heterocycles
pH effects

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/chem.201803839

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title = "Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl-Functionalized Tetrazines",

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.",

keywords = "bioorthogonal chemistry, Diels–Alder reactions, elimination, nitrogen heterocycles, pH effects",

author = "Sarris, {Alexi J.C.} and Thomas Hansen and {de Geus}, {Mark A.R.} and Elmer Maurits and Ward Doelman and Overkleeft, {Herman S.} and Cod{\'e}e, {Jeroen D.C.} and Filippov, {Dmitri V.} and {van Kasteren}, {Sander I.}",

year = "2018",

month = dec,

day = "5",

doi = "10.1002/chem.201803839",

language = "English",

volume = "24",

pages = "18075--18081",

journal = "Chemistry - A European Journal",

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publisher = "Wiley-VCH Verlag",

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TY - JOUR

T1 - Fast and pH-Independent Elimination of trans-Cyclooctene by Using Aminoethyl-Functionalized Tetrazines

AU - Sarris, Alexi J.C.

AU - Hansen, Thomas

AU - de Geus, Mark A.R.

AU - Maurits, Elmer

AU - Doelman, Ward

AU - Overkleeft, Herman S.

AU - Codée, Jeroen D.C.

AU - Filippov, Dmitri V.

AU - van Kasteren, Sander I.

PY - 2018/12/5

Y1 - 2018/12/5

N2 - 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.

AB - 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.

KW - bioorthogonal chemistry

KW - Diels–Alder reactions

KW - elimination

KW - nitrogen heterocycles

KW - pH effects

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U2 - 10.1002/chem.201803839

DO - 10.1002/chem.201803839

M3 - Article

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AN - SCOPUS:85056309246

SN - 0947-6539

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SP - 18075

EP - 18081

JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 68

ER -

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

Abstract

Funding

Keywords

UN SDGs

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