The reaction of nitrilimine 6a with ethyl pyridine-2-acetate (7) gave the corresponding pyrrolo[1,2-a]pyridine 8, while the reaction of 6b containing an ester moiety afforded the acyclic adduct 9. The reaction of 6a with 2-aminopyrimidine (10) gave the novel unexpected pyrimido[2,1-d]1,2,3,5-tetrazine 11. Acyclic adducts 16 and 17 were obtained from the reaction of 6b with 2-cyanomethylbenzimid...

The pyridazino[4,5-b]indole (3), which is conveniently available from 3-methylthioindole and the tetrazine (2), undergoes thermally induced inverseelectron-demand Diels-Alder reactions with enamines to afford the cycloalkeneannelated carbazoles (7,8) or the 2-substituted carbazole (9), respectively. We have previously shown that 1,2-diazines annelated to a second π-electron-deficient aromatic r...

A Ag-mediated Pd-catalyzed cross-coupling method for 3-bromo-1,2,4,5-tetrazine with boronic acids is presented. Electronic modification of the 1,1'-bis(diphenylphosphine)ferrocene (dppf) ligand was found to be crucial good turnover. Using this fast method, a variety alkyl-, heteroatom-, and halide-substituted aryl- heteroaryl-tetrazines were prepared (29 examples, up 87% yield).

The Carboni-Lindsey reaction between tetrazines and strained unsaturated hydrocarbons has in recent years become a useful tool bioorthogonal chemistry for labelling biomolecules vitro vivo. Here, we report computational studies on the mechanism of Diels-Alder/Retro-Diels-Alder commercially available tetrazine norbornene. Isomerism with norbornene-amide relevant applications bioconjugation chemi...

A number of non-canonical amino acids (NCAAs) with unstrained olefins are genetically encoded using mutant pyrrolysyl-tRNA synthetase-tRNA(Pyl)(CUA) pairs. These NCAAs readily undergo inverse electron-demand Diels-Alder cycloadditions with tetrazine dyes, leading to selective labeling of proteins bearing these NCAAs in live cells.

Many applications in biotechnology and molecular biology rely on modified nucleotides. Here, we present an approach for the postsynthetic labelling of enzymatically synthesized vinyl-modified DNA by Diels-Alder reaction with inverse electron demand using a tetrazine. Labelling proceeds very efficiently and supersedes several known approaches.

Injectable gelatin hydrogels formed with bioorthogonal click chemistry (ClickGel) are cell-responsive ECM mimics for in vitro and in vivo biomaterials applications. Gelatin polymers with pendant norbornene (GelN) or tetrazine (GelT) groups can quickly and spontaneously crosslink upon mixing, allowing for high viability of encapsulated cells, establishment of 3D elongated cell morphologies, and ...