title: Facile and efficient Lewis acid catalyzed synthesis of an asymmetric tetrazine useful for bio-orthogonal click chemistry applications.
abstract: Bio-orthogonal tetrazine click reactions have recently attracted significant interest for applications spanning biological imaging, cancer targeting, and biomaterials science. Here, we report a simple and efficient two-step scheme for the synthesis of an asymmetric tetrazine molecule containing a carboxylic acid handle for subsequent macromolecular conjugation. Yields as high as 75% were achieved using as little as 0.005 equivalents of nickel triflate catalyst, which is a significant improvement over previous methodologies.
authors.affiliation: Unversity of Colorado at Boulder, Department of Chemical and Biological Engineering and the BioFrontiers Institute, Boulder, CO 80303, USA ; Howard Hughes Medical Institute, Boulder, CO 80303, USA.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Alge
authors.forename: Dillon F
authors.initials: DF
authors.lastname: Donohue
authors.forename: Kristi S
authors.initials: KS
authors.lastname: Anseth
keywords: Lewis acid catalysis; bio-orthogonal chemistry; click chemistry; tetrazine