Double Click: Unexpected 1:2 Stoichiometry in a Norbornene-Tetrazine Reaction.
J Org Chem
; 88(9): 5341-5347, 2023 May 05.
Article
em En
| MEDLINE
| ID: mdl-37058436
ABSTRACT
We report a new reactivity for the inverse electron demand Diels-Alder (iEDDA) reaction between norbornene and tetrazine. Instead of simple 11 condensation between norbornene- and tetrazine-conjugated biomolecules, we observed that dimeric products were preferentially formed. As such, an olefinic intermediate formed after the addition of the first tetrazine unit to norbornene rapidly undergoes a consecutive cycloaddition reaction with a second tetrazine unit to result in a conjugate with a 12 stoichiometric ratio. This unexpected dimer formation was consistently observed in the reactions of both small-molecule norbornenes and tetrazines, as well as oligonucleotide conjugates. When norbornene was replaced with bicyclononyne to bypass the formation of this olefinic reaction intermediate, the reactions resulted exclusively in rapid formation of the expected 11 stoichiometric conjugates.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article