Direct sequential C–H iodination/organoyl-thiolation for the benzenoid A-ring modification of quinonoid deactivated systems: a new protocol for potent trypanocidal quinones

Abstract

We report a sequential C-H iodination/organoyl-thiolation of naphthoquinones and their relevant trypanocidal activity. Under a combination of AgSR with a copper source, sulfur-substituted benzenoid quinones were prepared in high yields (generally >90%). This provides an efficient and general method for preparing A-ring modified naphthoquinoidal systems, recognized as a challenge in quinone chemistry.

Ruthenium(II)‐Catalyzed Double Annulation of Quinones: Step‐Economical Access to Valuable Bioactive Compounds

“…However,f urther experimentation revealed DCE as the optimal solvent for this transformation, and, consequently, we decided to probe the presence of additives to generate a cationic ruthenium(II) catalyst. Here, KPF 6 ,K OAc, NaOAc, and NaOPivw eree valuated as additives (entries [11][12][13][14]. Further refinementl ed to the reaction conditions outlined in entries 15 and 18, delivering product 3a in 80 %y ield (see Supporting Information for experimental details).…”

Ruthenium(II)‐Catalyzed C–H Alkenylation of Quinones: Diversity‐Oriented Strategy for Trypanocidal Compounds

“…In this context, the da Silva Júnior and Bower groups have described the application of the [RhCp*Cl 2 ] 2 catalyst to the direct ortho ‐functionalization of 1,4‐NQs with different electrophilic sources . Following the same strategy, the da Silva Júnior group has demonstrated the value of this method for sequential C–H iodination/thiolation of 1,4‐NQs . These methods provided access to quinones with potent trypanocidal activity , .…”

Combination of Aryl Diselenides/Hydrogen Peroxide and Carbon‐Nanotube/Rhodium Nanohybrids for Naphthol Oxidation: An Efficient Route towards Trypanocidal Quinones

“…The da Silva Júnior and Bower groups have used [{RhCp*Cl 2 } 2 ] in the presence of an electrophilic iodine source for directed ortho ‐iodination of 1,4‐NQs . Recently, da Silva Júnior's group has expanded this strategy and synthesised sulfur‐substituted benzenoid quinones in high yields by means of a direct sequential C−H iodination/organoylthiolation method (Scheme A) . These compounds were assayed against Trypanosoma cruzi , the etiologic agent of Chagas disease, and promising results were obtained with IC 50 values at 24 h that are lower than those observed for benznidazole, the current drug used to treat this parasitic disease (Scheme A) …”

“…[4] Recently,d aSilva Jfflnior's group hase xpanded this strategy and synthesised sulfur-substituted benzenoid quinones in high yields by meanso fadirect sequential CÀHi odination/organoylthiolation method (Scheme 1A). [5] These compounds were assayed against Trypanosoma cruzi,t he etiologica gent of Chagas disease, and promising resultsw ere obtained with IC 50 values at 24 ht hat are lower than those observed for benznidazole, the current drug used to treat this parasitic disease (Scheme 1A). [5,6] Am ore careful look also allows us to realise that oxidation processes are among the classical methods for preparing 1,4-NQs.…”

“…[5] These compounds were assayed against Trypanosoma cruzi,t he etiologica gent of Chagas disease, and promising resultsw ere obtained with IC 50 values at 24 ht hat are lower than those observed for benznidazole, the current drug used to treat this parasitic disease (Scheme 1A). [5,6] Am ore careful look also allows us to realise that oxidation processes are among the classical methods for preparing 1,4-NQs. Methodologies commonlyu sed involves oxidation of naphthols with strong oxidants in high quantities, affording in some cases, poor yields and limited scope.…”