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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
Author(s) -
Merkt Franziska K.,
Mazzone Flaminia,
Sazzadeh Shabnam Shaneh,
Bonda Lorand,
Hinz Larissa K. E.,
Gruber Irina,
Buchholz Karin,
Janiak Christoph,
Pfeffer Klaus,
Müller Thomas J. J.
Publication year - 2021
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202101391
Subject(s) - cycloisomerization , substituent , aryl , trimethylsilyl , chemistry , fluorescence , halogenation , suzuki reaction , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , catalysis , alkyl , physics , quantum mechanics
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 σ p+ 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 IC 50 of up to 0.67±0.13 μM. Thus, these compounds are promising candidates for novel anti‐parasitic therapies.