Functionalized Triazines and Tetrazines: Synthesis and Applications

Acyclic and Heterocyclic Azadiene Diels–Alder Reactions Promoted by Perfluoroalcohol Solvent Hydrogen Bonding: Comprehensive Examination of Scope

“…They have been widely used in organic synthesis, ,, natural product total synthesis, , medicinal chemistry, and chemical biology for decades now. In fact, it was their discovery that led to the now classical definition of an inverse electron demand versus normal Diels–Alder reaction. , Today, there are countless publications on their synthesis, cycloaddition reactions and reactivity patterns, and applications. , Many of the reactions already proceed at room temperature or lower even under dilute reaction conditions required of bioconjugation studies for which they are presently the fastest and most efficient of all such bioorthogonal click reactions. − Electron-withdrawing and conjugating C3/C6 substituents accelerate their cycloaddition reactions and pair best with electron-rich or strained dienophiles. These were not examined in our survey.…”

“…Because of the significant improvements in the reactions of the modestly strained norbornadiene with the 1,2,4,5-tetrazines, kinetic studies of the cycloaddition of 3-phenyl-1,2,4,5-tetrazine ( 9n ) and cyclooctyne 5d were conducted to probe the potential HFIP acceleration of a representative example of a tetrazine ligation reaction. To date, the tetrazine ligation reactions are the most general of the bioorthogonal reactions because of their remarkable reaction rates and efficiencies at the needed low concentrations, and because of their effective use in not only cell-free systems but also in cell-based systems and in vivo . Kinetic studies were conducted in THF, DMSO, and HFIP (5 mM 9n , 25 °C), where the amount of cyclooctyne in HFIP was half that used with THF and DMSO (1.2 equiv vs 2.4 equiv).…”

First representatives of C-glycosyl 1,2,4,5-tetrazines: synthesis of 3-β-d-glucopyranosyl 1,2,4,5-tetrazines and their transformation into 3-β-d-glucopyranosyl pyridazines

“…1 For the preparation of 1,2,4,5-tetrazine derivatives (Scheme 1, I ) basically two main synthetic approaches exist. 2–6 One of them aims at the construction of the 1,2,4,5-tetrazine ring itself via the formation of a 1,4-dihydrotetrazine intermediate obtained by cyclocondensation of electrophilic carbon precursors ( e.g. nitriles, iminoesters, carboxamidines, 1,2-bis-chloroalkylidene-hydrazines) with hydrazine, followed by an oxidative aromatization (Type A).…”

“…Despite the growing interest in variously functionalized s -tetrazines for bioorthogonal 11–15,20,21 and other applications 2,3,6 there is no example in the literature for the preparation of C -glycosyl 1,2,4,5-tetrazines. Therefore, we set out to investigate the possibilities for the synthesis of this hitherto unknown compound class.…”

Designing, Synthesis, and Anti‐Breast Cancer Activity of a Series of New Quinazolin‐4(1H)‐one Derivatives

“…The inability of chemotherapy in distinguishing the cancer cells and normal cells leads to significant side effects and acute toxicity [1–6] . In this regard, numerous N‐heterocyclic molecules have been designed and investigated to check their ability as targeted anti‐cancer drug candidates [7–14] . According to the World Cancer Report, breast cancer is the leading cause of mortality for women around the globe [15] .…”