ABSTRACT
A FRET-based fluorescence turn-on probe is designed, which employs a sydnonimine as the linker to match specific fluorophore and quencher pairs and releases the fluorescence after the "click-and-release" reaction. Furthermore, we realized selective fluorescence labeling by exploiting the mutual orthogonality between sydnonimine-DIBAC and tetrazine-1,3-Cp cycloaddition pairs.
Subject(s)
Fluorescent Dyes , Heterocyclic Compounds , Cycloaddition ReactionABSTRACT
Sulfonamide derivatives have been used in pharmaceutics for decades. Here we report a new approach to release sulfonamides efficiently using a bioorthogonal reaction of sulfonyl sydnonimines and dibenzoazacyclooctyne (DIBAC). The second-order rate constant of the cycloaddition reaction can be up to 0.62 M-1 s-1, and the reactants are highly stable under physiological conditions. Most significantly, we also discovered the mutual orthogonality between the sydnonimine-DIBAC and benzonorbornadiene-tetrazine cycloaddition pairs, which can be used for selective and simultaneous liberation of sulfonamide and primary amine drugs.
Subject(s)
Azabicyclo Compounds/chemistry , Celecoxib/chemical synthesis , Doxorubicin/chemical synthesis , Heterocyclic Compounds, 3-Ring/chemistry , Prodrugs/chemistry , Sydnones/chemistry , Azabicyclo Compounds/chemical synthesis , Celecoxib/chemistry , Click Chemistry , Cycloaddition Reaction , Cyclooxygenase 2/chemistry , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/chemistry , Enzyme Assays , Heterocyclic Compounds, 3-Ring/chemical synthesis , Humans , Models, Chemical , Prodrugs/chemical synthesis , Quantum Theory , Sydnones/chemical synthesisABSTRACT
Halogen substituents increase sydnone cycloaddition reactivities substantially. Fluoro-sydnones are superior to bromo- and chloro-sydnones, and can achieve extremely high second-order rate constants with strained alkynes. Computational studies have revealed the fluorine substituent increases the reactivity of sydnone mainly by lowering its distortion energy.
ABSTRACT
The tandem Michael addition/decarboxylation of (thio)coumarin-3-carboxylic acids with indoles has been developed and the biologically important indole-3-substituted dihydrocoumarins were obtained in good to excellent yields under catalyst-free conditions.
Subject(s)
Coumarins/chemical synthesis , Indoles/chemistry , Indoles/chemical synthesis , Sulfhydryl Compounds/chemistry , Catalysis , Coumarins/chemistry , Decarboxylation , Molecular StructureABSTRACT
The catalyst-free sp(3) C-H functionalization of 2-alkylazaarenes has been achieved in the reaction with (thio)coumarin-3-carboxylic acids. Followed by a tandem decarboxylation, this method provides facile synthesis of biologically important azaarene-substituted 3,4-dihydro(thio)coumarins in a single step in high yields.