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

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.