Novel base-initiated cascade reactions of hemiindigos to produce dipolar γ-carbolines and indole-fused pentacycles

Novel continuous-flow cascade reactions are developed for producing 1,4-diaryl-disubstituted dipolar γ-carbolines 2 that contain a carboxylate group and their two pentacyclic precursors 6 , 7 from hemiindigos 1 . The nucleophilic and pro-electrophilic chemistry described is new to the hemiindigos 1 , and it led to the discovery of antimycobacterial scaffold characteristic of rimino-type pentacycles 6 , 7 and potent drug clofazimine. The new scaffold like clofazimine appears to be useful in developing lead agents active against drug-resistant/dormant TB. Based on hemiindigos we developed novel reactions for producing γ-carbolines and their precursors that appeared to be active against MTB.