Acylation-Mediated ‘Kinetic Turn-On’ of 3-Amino-1,2,4,5-tetrazines

Stefan Kronister; Dennis Svatunek; Christoph Denk; Hannes Mikula

doi:10.1055/s-0036-1591764

Synlett, Table of Contents

Synlett 2018; 29(10): 1297-1302
DOI: 10.1055/s-0036-1591764

letter

Acylation-Mediated ‘Kinetic Turn-On’ of 3-Amino-1,2,4,5-tetrazines

Stefan Kronister

Institute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Email: hannes.mikula@tuwien.ac.at

,

Dennis Svatunek

Institute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Email: hannes.mikula@tuwien.ac.at

,

Christoph Denk

Institute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Email: hannes.mikula@tuwien.ac.at

,

Hannes Mikula*

Institute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9/163-OC, 1060 Vienna, Austria Email: hannes.mikula@tuwien.ac.at

› Author Affiliations

Abstract

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Published as part of the Special Section 9^th EuCheMS Organic Division Young Investigator Workshop

Abstract

The fast and biocompatible ligation of 1,2,4,5-tetrazines with strained alkenes has found numerous applications in biomedical sciences. The reactivity of a 1,2,4,5-tetrazine can generally be tuned by changing its electronic properties by varying the substituents in the 3- and/or 6-position. An increased reactivity of such bioorthogonal probes upon conjugation or attachment to a target molecule has not previously been described. Such an approach would be beneficial, as it would minimize the impact of residual tetrazine reagents and/or impurities. Herein, we describe such a ‘kinetic turn-on’ of 1,2,4,5-tetrazines upon conjugation. On the basis of the significant increase in reactivity following N-acylation predicted by quantum chemical calculations, we prepared 3-aminotetrazines and their corresponding acetylated derivatives. An investigation of the reaction kinetics indeed revealed a remarkable increase in reactivity upon acylation.

Key words

click chemistry - tetrazines - kinetics - bioorthogonal chemistry - Diels–Alder reaction - acylation

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References

References and Notes
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