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

Abstract

An intramolecular Diels−Alder reaction of positionally isomeric indole-2/3-phenylvinyl-N-alkynylated (Nphenylsulfonyl)amines has been successfully exploited for the synthesis of quino [4,3-b]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 in vitro cytotoxicity evaluation of representative quino[4,3-b]carbazoles was performed against NCI-H460 human cancer cell culture. Among the quino[4,3-b]carbazoles evaluated, five of the fluorine-containing quinocarbazoles displayed nano molar range (0.8−2.0 nm) GI 50 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 p-quinonoid like tautomeric forms in a polar protic solvent.

Synthesis of α-, β-, and γ-Carbolines via Intramolecular Cyclization of Azidomethyl(indolyl)acrylates Involving PIFA-BF3·OEt2/DBU-Mediated Cyclization as well as Thermolysis Approaches

“…The required starting material, azidomethyl acrylate 5a was obtained from the respective indole-3-carboxaldehyde 1a employing the Wittig reaction followed by allylic bromination and azide displacement (Scheme ).…”

“…To a solution of 1-phenylsulfonyl-2-bromomethylindole (1.00 g, 2.85 mmol) in DMF (15 mL) at 0 °C, NaN 3 (0.56 g, 8.56 mmol) was added, and then the reaction mixture was stirred at the same temperature for 30 min followed by a workup adopting the above-mentioned procedure B to afford azide 10a (0.696 g, 78%) as a thick brown liquid. 1 H NMR (CDCl 3 , 300 MHz): δ 8.12 (d, J = 8.4 Hz, 1H), 7.90–7.84 (m, 2H), 7.57–7.49 (m, 2H), 7.45–7.40 (m, 2H), 7.34 (dt, J 1 = 7.0 Hz, J 2 = 1.2 Hz, 1H), 7.25 (t, J = 6.6 Hz, 1H), 6.71 (s, 1H), 4.81 (s, 2H) ppm; 13 C { 1 H} NMR (CDCl 3 , 75 MHz): δ 138.6, 137.2, 134.6, 134.0, 129.3, 128.8, 126.5, 125.4, 129.9, 121.2, 114.6, 112.2, 48.5 ppm; DEPT-135 NMR (CDCl 3 , 75 MHz): δ 134.0, 129.3, 126.5, 125.4, 123.9, 121.2, 114.6, 112.2, 48.5 ppm.…”

“…The Wittig reaction of 1-(phenylsulfonyl)-1 H -pyrrole-2-carbaldehyde (3.00 g, 12.75 mmol) with ethyl 2-(triphenylphosphoranylidene)­propionate 2 (5.54 g, 15.30 mmol) in dry DCM (30 mL) was performed at room temperature for 2 h under a N 2 atmosphere. Subsequent removal of the solvent followed by column chromatographic purification on silica gel (230–420 mesh, n -hexane/ethyl acetate, 9:1) afforded ethyl ( E )-2-methyl-3-(1-(phenylsulfonyl)-1 H -pyrrol-2-yl)­acrylate (3.87 g, 95%) as a colorless solid.…”