Synthesis of Cytotoxic Quino[4,3-]carbazole Frameworks through an Intramolecular Diels-Alder Reaction.

An intramolecular Diels-Alder reaction of positionally isomeric indole-2/3-phenylvinyl--alkynylated (-phenylsulfonyl)amines has been successfully exploited for the synthesis of quino[4,3-]carbazole and its analogues. This reaction proceeds through a [4 + 2] cycloaddition followed by elimination and deprotection of phenylsulfonyl units to afford the quinocarbazoles in moderate to good yields. The reaction features a broad substrate scope and remarkable functional group forbearance. A preliminary cytotoxicity evaluation of representative quino[4,3-]carbazoles was performed against NCI-H460 human cancer cell culture. Among the quino[4,3-]carbazoles evaluated, five of the fluorine-containing quinocarbazoles displayed nano molar range (0.8-2.0 nm) GI values. The UV-vis and fluorescence spectral studies of representative quinocarbazoles were also performed. Like ellipticine, four of the quinocarbazoles displayed dual emissions confirming the existence of -quinonoid like tautomeric forms in a polar protic solvent.