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. Issue 38 (27th May 2021)

• Record Type: Journal Article
• Authors: 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.
• Is Part Of: Chemistry. Volume 27:Issue 38(2021)
• Page Start: 9774
• Page End: 9781
• Publication Date: 2021-05-27
• Subjects: bioactivity -- cycloisomerization -- heterocycles -- iodination -- multicomponent reactions -- Toxoplasma gondii; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.202101391
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: 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 IC50 of up to 0.67±0.13 μM. Thus, these compounds are promising candidates for novel anti‐parasitic therapies. Abstract : Gold catalysis and a one‐pot process gives glowing parasite killers . A gold‐catalyzed cycloisomerization with concomitant 1, 2‐silyl shift forms 6‐(trimethylsilyl)indolo[3, 2‐ a ]phenazines, which furnish 6‐aryl‐indolo[3, 2‐ a ]phenazines in a concise one‐pot ipso ‐iodination‐Suzuki coupling sequence. Structure‐property relationships reveal a novel class of tunable luminophores, which also efficiently kill the parasite T. gondii .