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

UN SDGs

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

SDG 6 Clean Water and Sanitation

Keywords

bioorthogonal chemistry
Diels–Alder reactions
elimination
nitrogen heterocycles
pH effects

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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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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

UR - https://www.scopus.com/pages/publications/85056309246

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U2 - 10.1002/chem.201803839

DO - 10.1002/chem.201803839

M3 - Article

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AN - SCOPUS:85056309246

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VL - 24

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

UN SDGs

Keywords

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