Synthesis of C3-Substituted N1-tert-Butyl 1,2,4-Triazinium Salts via the Liebeskind–Srogl Reaction for Fluorogenic Labeling of Live Cells

0581624 - ÚOCHB 2025 RIV US eng J - Journal Article
Šlachtová, Veronika - Bellová, Simona - Vrábel, Milan
Synthesis of C3-Substituted N1-tert-Butyl 1,2,4-Triazinium Salts via the Liebeskind–Srogl Reaction for Fluorogenic Labeling of Live Cells.
Journal of Organic Chemistry. (2024). ISSN 0022-3263. E-ISSN 1520-6904
R&D Projects: GA ČR(CZ) GF20-30494L; GA MŠMT(CZ) LX22NPO5104
Institutional support: RVO:61388963
Keywords : liebeskind-Srogl cross-coupling * triazinium ligation * strained alkyne * bioorthogonal labeling * fluorogenic reaction
Impact factor: 3.6, year: 2022
Method of publishing: Open access
https://doi.org/10.1021/acs.joc.3c02454

We recently described the development and application of new bioorthogonal conjugation, the triazinium ligation. To explore the wider application of this reaction, in this work we introduce a general method for synthesizing C3-substituted triazinium salts based on the Liebeskind-Srogl cross-coupling reaction and catalytic thioether reduction. These methods enabled the synthesis of triazinium derivatives for investigating the effect of different substituents on the ligation kinetics and stability of the compounds under biologically relevant conditions. Finally, we demonstrate that the combination of coumarin fluorophore attached to position C3 with a C5-(4-methoxyphenyl) substituent, yields a fluorogenic triazinium probes suitable for no-wash, live-cell labeling. The developed methodology represents a promising synthetic approach to the late-stage modification of triazinium salts, potentially widening their application in bioorthogonal reactions.
Permanent Link: https://hdl.handle.net/11104/0349735