Synthesis and Evaluation of Nicotinic Acid Derived Tetrazines for Bioorthogonal Labeling

Abstract

A set of nicotinic acid derived tetrazines were synthesized and evaluated for activity in inverse-electron-demand Diels–Alder (IEDDA­) reactions with various dienophiles. It was found that the performance of these tetrazines is governed by two factors. Theoretical and experimental investigations showed that steric effects may override the energetically predicted order of reactivity. Making a compromise between reactivity and stability, a selected tetrazine was incorporated into a deoxynucleotide to afford a bioorthogonalized building block enabling IEDDA-based tagging schemes of nucleic acids.

Key words

tetrazine - inverse-electron-demand Diels–Alder reaction - biorthogonal - nucleic acid - labeling

• References

• 1 These two authors contributed equally to the work.
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