Fluorescent Indolo[3,2-a]phenazines against Toxoplasma gondii: Concise Synthesis by Gold-Catalyzed Cycloisomerization with 1,2-Silyl Migration and ipso-Iodination Suzuki Sequence.

A gold-catalyzed cycloisomerization of 2-indolyl-3-[(trimethylsilyl)ethynyl)]quinoxalines with concomitant 1,2-silyl shift forms 6-(trimethylsilyl)indolo[3,2-a]phenazines in moderate to excellent yield. These silylated heterocycles are readily transformed into 6-aryl-indolo[3,2-a]phenazines in moderate to good yield by one-pot ipso-iodination Suzuki coupling. The title compounds represent a novel type of tunable luminophore. Structure-property relationships for 6-aryl-indolo[3,2-a]phenazines obtained from Hammett correlations with σp+ substituent parameters indicate that emission maxima, Stokes shifts, and fluorescence quantum yields can be fine-tuned by the remote para-aryl substituent. Furthermore, indolo[3,2-a]phenazines were found to exhibit interesting activities against medically relevant pathogens such as the Apicomplexa parasite Toxoplasma gondii with an IC50 of up to 0.67±0.13 µM. Thus, these compounds are promising candidates for novel anti-parasitic therapies.

Sequential Cu-Catalyzed Four- and Five-Component Syntheses of Luminescent 3-Triazolylquinoxalines.

3-Triazolylquinoxalines can be readily synthesized by applying two complementary synthetic protocols starting from heterocyclic π nucleophiles or (hetero)aryl glyoxylic acids in a consecutive four- or five-component reaction. Conceptually, the sequential use of a single cuprous salt for alkynylation and Cu-catalyzed alkyne-azide cycloaddition (CuAAC) in a one-pot fashion sets the stage for activation-alkynylation-cyclocondensation-CuAAC or glyoxylation-alkynylation-cyclocondensation-CuAAC sequences in good yields. The diversity-oriented generation of differently substituted 3-triazolylquinoxalines is an excellent entry to tunable emission solvatorchromic fluorophores with triazole ligation. The electronic structure, corroborated by DFT and TD-DFT calculations, rationalizes the charge transfer character of relevant absorptions and large Stokes shifts as well as the electronic innocence of the triazole substituents.

Synthesis of Water-Soluble Blue-Emissive Tricyclic 2-Aminopyridinium Salts by Three-Component Coupling-(3+3)-Anellation.

The (3+3) anellation of alkynones and cyclic amidines is a novel and unexpected approach to generate intensively blue luminescent tricyclic 2-aminopyridinium salts with quantum yields Φf up to 63 % in water. By implementation into a consecutive three-component reaction, these title compounds are obtained rapidly and efficiently in a diversity-oriented fashion. Most interestingly, these bi- and tricyclic 2-aminopyridinium salts emit in dichloromethane and water solutions, thus making them interesting novel luminophore probes for bioanalytics, as well as in the solid state, thus making them blue emitters with tunable efficiency.

Three-Component Activation/Alkynylation/Cyclocondensation (AACC) Synthesis of Enhanced Emission Solvatochromic 3-Ethynylquinoxalines.

2-Substituted 3-ethynylquinoxaline chromophores can be readily synthesized by a consecutive activation-alkynylation-cyclocondensation (AACC) one-pot sequence in a three-component manner. In comparison with the previously published four-component glyoxylation starting from electron-rich π-nucleophiles, the direct activation of (hetero)aryl glyoxylic acids allows the introduction of substituents that cannot be directly accessed by glyoxylation. By introducing N,N-dimethylaniline as a strong donor in the 2-position, the emission solvatochromicity of 3-ethynylquinoxalines can be considerably enhanced to cover the spectral range from blue-green to deep red-orange with a single chromophore in a relatively narrow polarity window. The diversity-oriented nature of the synthetic multicomponent reaction concept enables comprehensive investigations of structure-property relationships by Hammett correlations and Lippert-Mataga analysis, as well as the elucidation of the electronic structure of the emission solvatochromic π-conjugated donor-acceptor systems by DFT and time-dependent DFT calculations with the PBEh1PBE functional for a better reproduction of the dominant charge-transfer character of the longest wavelength absorption band.