Tetrazine (Tz)–trans‐cyclooctene (TCO) ligation is an ultra‐fast and highly selective reaction and it is particularly suited to label biomolecules under physiological conditions. As such, a 3H‐Tz based synthon would have… Click to show full abstract
Tetrazine (Tz)–trans‐cyclooctene (TCO) ligation is an ultra‐fast and highly selective reaction and it is particularly suited to label biomolecules under physiological conditions. As such, a 3H‐Tz based synthon would have wide applications for in vitro/ex vivo assays. In this study, we developed a 3H‐labeled Tz and characterized its potential for application to pretargeted autoradiography. Several strategies were explored to synthesize such a Tz. However, classical approaches such as reductive halogenation failed. For this reason, we designed a Tz containing an aldehyde and explored the possibility of reducing this group with NaBT4. This approach was successful and resulted in [3H]‐(4‐(6‐(pyridin‐2‐yl)‐1,2,4,5‐tetrazin‐3‐yl)phenyl)methan‐t‐ol with a radiochemical yield of 22 %, a radiochemical purity of 96 % and a molar activity of 0.437 GBq/μmol (11.8 Ci/mmol). The compound was successfully applied to pretargeted autoradiography. Thus, we report the synthesis of the first 3H‐labeled Tz and its successful application as a labeling building block.
               
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