Synthetic Approaches to Cytotoxic Quino[4,3-b]carbazole Frameworks Involving Thermal Electrocyclization of...

Thermal electrocyclization of N-phenylsulfonyl-2,3-divinylindoles has been employed as an effective strategy for synthesizing quino[4,3-b]carbazole and their analogues. The synthesis begins with the preparation of 2,3-divinylindoles via consecutive Wittig reactions. The further key transformation involves thermal electrocyclization, followed by MnO₂-mediated dehydrogenation to yield carbazole intermediates. These intermediates undergo reductive cyclization and phenylsulfonyl deprotection to afford the desired quinocarbazoles in moderate to good yields. This method demonstrates a wide substrate scope and exceptional functional group tolerance. Preliminary in vitro cytotoxicity studies against NCI-H460 human lung cancer lines confirmed that at least three of the fluorine-containing quinocarbazoles exhibited potent nanomolar IC₅₀ values (0.8-2.0 nM) suggesting their potential as promising anticancer agents.