The synthesis of anticancer sulfonated indolo[2,1-a]isoquinoline and benzimidazo[2,1-a]isoquinolin-6(5H)-ones derivatives via a free radical cascade pathway

Abstract

A facile CuBr2 induced tandem radical reaction has been achieved, leading to sulfonated indole and benzimidazole derivatives.

The Synthesis of 5,6‐dihydrobenzo[4,5]imidazo[2,1‐a]isoquinoline Derivatives via Metal‐Free Radical Cascade Pathway

“…A possible reaction mechanism is proposed on the basis of the above experimental observations and previous literature reports (Scheme 7). [4b–d,5] Initially, benzoate radical is formed by the thermal cleavage of BPO [6] . Then, the 1,3‐dioxolane is activated by the benzoate radical to generate radical A .…”

Diversely functionalized isoquinolines and their core-embedded heterocyclic frameworks: a privileged scaffold for medicinal chemistry

“…Pan et al reported a one-step synthesis of benzimidazo[2,1- a ]isoquinolinone 79a and indolo[2,1- a ]isoquinoline 79b (Scheme 14). 58 The tert -butoxyl radical attacks the sulfonothiolate 77 to generate a sulfonyl radical that adds to alkene 76 generating radical intermediate 78 which on further cyclization and subsequent oxidation via SET following deprotonation affords the isoquinolinone derivative 79 . The anti-tumour activity of some representative isoquinoline skeletons was examined via the CCK8-assay of MCG-803, T-24 and HeLa tumour cell lines, where significant anti-tumour potential was exhibited by methoxy phenylsulfonyl benzo[4,5]imidazo[2,1- a ]isoquinolinone (IC 50 = 4 μM) against MCG-803 cell lines.…”

“…Pan et al reported a one-step synthesis of benzimidazo[2,1-a] isoquinolinone 79a and indolo[2,1-a]isoquinoline 79b (Scheme 14). 58 The tert-butoxyl radical attacks the sulfonothiolate 77 to generate a sulfonyl radical that adds to alkene 76 generating radical intermediate 78 which on further cyclization and subsequent oxidation via SET following deprotonation affords the isoquinolinone derivative 79. The…”

Recent Advances in the 3 d‐Transition‐Metal‐Catalyzed Synthesis of Isoquinolines and its Derivatives

“…Additionally, the synthesis of isoquinoline alkaloid moxaverine (gastrointestinal drug) under the optimized conditions was also carried out successfully. In 2022, Huang and coworkers [103] demonstrated an efficient synthesis of indolo[2,1-a]isoquinolines/ benzimidazo[2,1-a]isoquinolin-6(5H)-ones 193 via Cucatalyzed radical domino addition/cyclization reaction (Scheme 66). The activated alkenes 191 and substituted thiosulfonates 192 underwent a domino reaction using 10 mmol % CuBr 2 catalyst and 3 equiv.…”

“…In 2022, Huang and coworkers [103] demonstrated an efficient synthesis of indolo[2,1‐ a ]isoquinolines/benzimidazo[2,1‐ a ]isoquinolin‐6(5 H )‐ones 193 via Cu‐catalyzed radical domino addition/cyclization reaction (Scheme 66). The activated alkenes 191 and substituted thiosulfonates 192 underwent a domino reaction using 10 mmol % CuBr 2 catalyst and 3 equiv.…”